Evidence-based uses of non-conventional … in mental health care: research update U.S. Psychiatric Congress 2005 James Lake M.D. Pacific Grove, CA Adjunct clinical faculty, Stanford

Uses of nonUses of non--conventional conventional approaches in mental health approaches in mental health

care: care: research updateresearch update

U.S. Psychiatric CongressU.S. Psychiatric Congress20052005

James Lake M.D.James Lake M.D.www.IntegrativeMentalHealth.netwww.IntegrativeMentalHealth.net

Pacific Grove, CAPacific Grove, CAAdjunct clinical faculty, StanfordAdjunct clinical faculty, Stanford

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http://www.integrativementalhealth.net/



AssessmentAssessment

•• Emerging approaches may enhance Emerging approaches may enhance diagnostic accuracy or specificity diagnostic accuracy or specificity permitting improved treatment planningpermitting improved treatment planning

•• Assessment in mental health care is often Assessment in mental health care is often overover--looked or minimizedlooked or minimized

•• Emerging assessment approaches include Emerging assessment approaches include QEEG, serologic studies, VR testing QEEG, serologic studies, VR testing environments and othersenvironments and others

Emerging assessment methodsEmerging assessment methods

•• DepressionDepression•• Mania and cyclic mood changesMania and cyclic mood changes•• AnxietyAnxiety•• psychosispsychosis

Assessment: depression Assessment: depression

•• Low serum Low serum folatefolate levels predict more severe levels predict more severe depressed mood and nondepressed mood and non--response to response to fluoxetinefluoxetine, other conventional antidepressants, , other conventional antidepressants, lithium augmentation and thyroid hormone lithium augmentation and thyroid hormone ((FavaFava et al. 1997; et al. 1997; PapakostasPapakostas 2004a)2004a)

•• A significant percentage of severely depressed A significant percentage of severely depressed patients have low serum patients have low serum folatefolate levels. levels.

•• Many treatment refractory depressed patients Many treatment refractory depressed patients respond to conventional or nonrespond to conventional or non--conventional conventional treatments when treatments when folatefolate in the form of in the form of folinicfolinic acid acid is added to their existing regimen (is added to their existing regimen (PapakostasPapakostas2004a). 2004a).

Assessment: depressionAssessment: depression

•• QEEG is helpful in differentiating QEEG is helpful in differentiating UnipolarUnipolar and Bipolar depressed moodand Bipolar depressed mood

•• Abnormal EEG findings occur in up to 40% Abnormal EEG findings occur in up to 40% of depressed patients (Small 1993). EEG of depressed patients (Small 1993). EEG changes described as “small sharp spikes” changes described as “small sharp spikes” are often present in severely depressed are often present in severely depressed suicidal patients (Small 1993). suicidal patients (Small 1993).


•• QEEG analysis of QEEG analysis of UnipolarUnipolar depressed patients typically depressed patients typically reveals increased alpha or theta power, and decreased reveals increased alpha or theta power, and decreased interinter--hemispheric coherence (hemispheric coherence (NieberNieber 1992; 1992; PrinchepPrinchep1990). 1990).

•• In contrast, Bipolar depressed patients often have In contrast, Bipolar depressed patients often have reduced alpha activity and increased beta power (John reduced alpha activity and increased beta power (John 1988). 1988).

•• Bipolar patients often come to treatment after Bipolar patients often come to treatment after experiencing a single major depressive episode, but have experiencing a single major depressive episode, but have not had a manic episode. In such cases a QEEG brain not had a manic episode. In such cases a QEEG brain map provides valuable diagnostic information that can map provides valuable diagnostic information that can inform the most appropriate treatment. inform the most appropriate treatment.


•• Abnormal high auditory evoked response (AER) and Abnormal high auditory evoked response (AER) and decreased predecreased pre--frontal frontal cordancecordance predict enhanced predict enhanced antidepressant response ratesantidepressant response rates

•• Response rates to conventional antidepressants can be predicted Response rates to conventional antidepressants can be predicted on on the basis of differences in brain electrical activity evoked by the basis of differences in brain electrical activity evoked by sounds sounds of various intensities. of various intensities.

•• Relatively greater auditory evoked potentials (AER) correspond tRelatively greater auditory evoked potentials (AER) correspond to o lower brain serotonin levels, and predict improved response of lower brain serotonin levels, and predict improved response of UnipolarUnipolar depressed patients (depressed patients (GallinatGallinat, et al., 2000) to serotonin , et al., 2000) to serotonin reuptake inhibitors (reuptake inhibitors (SSRIsSSRIs). ).

•• CordanceCordance is a measure of localized electrical brain activity relative tois a measure of localized electrical brain activity relative toaveraged brain EEG patterns. Prospective studies show a averaged brain EEG patterns. Prospective studies show a relationship between relationship between cordancecordance and response to antiand response to anti--depressants depressants that increase brain serotonin levels (that increase brain serotonin levels (SuffinSuffin 1997).1997).


•• Over half of patients with severe depressed mood who Over half of patients with severe depressed mood who subsequently had the highest response rates to subsequently had the highest response rates to SSRIsSSRIsshowed significant decreases in preshowed significant decreases in pre--frontal frontal cordancecordanceduring the first 48 hours of therapy, suggesting that during the first 48 hours of therapy, suggesting that improvement was due to normalization of low brain improvement was due to normalization of low brain serotonin levels (serotonin levels (DemottDemott, 2002; Cook, et al., 2002). , 2002; Cook, et al., 2002).

•• NonNon--responders to responders to SSRIsSSRIs or placebo did not show or placebo did not show negative prenegative pre--frontal frontal cordancecordance following treatment, following treatment, suggesting that low serotonin was not the primary cause suggesting that low serotonin was not the primary cause of depressed mood in these cases. of depressed mood in these cases.

•• Differences in prefrontal EEG Differences in prefrontal EEG cordancecordance also predict also predict response differences of depressed patients to response differences of depressed patients to homeopathic remedies (Bell 2004). homeopathic remedies (Bell 2004).


•• Low RBC membrane fatty acids may be correlated Low RBC membrane fatty acids may be correlated with increased severity of depressed mood with increased severity of depressed mood

•• Red blood cell membrane levels and serum levels of Red blood cell membrane levels and serum levels of DHA, an OmegaDHA, an Omega--3 fatty acid, are consistently lower in 3 fatty acid, are consistently lower in depressed individuals (depressed individuals (PeetPeet et al. 1998; et al. 1998; TiemeierTiemeier 2003).2003).

•• Preliminary findings suggest that the average dietary Preliminary findings suggest that the average dietary ratio of Omegaratio of Omega--6 to Omega6 to Omega--3 3 EFAsEFAs is correlated with is correlated with incidence of depression. Lower dietary intake of foods incidence of depression. Lower dietary intake of foods rich in Omegarich in Omega--3 fatty acids resulted in relatively higher 3 fatty acids resulted in relatively higher ratios of AA (an Omegaratios of AA (an Omega--6) to EPA (an Omega6) to EPA (an Omega--3) in red 3) in red blood cells, which in turn were positively correlated with blood cells, which in turn were positively correlated with greater severity of depressed mood (Adams et al, 1996; greater severity of depressed mood (Adams et al, 1996; Edwards et al 1998). Edwards et al 1998).


•• Low serum cholesterol levels are correlated with Low serum cholesterol levels are correlated with severity of depressed mood and suicide riskseverity of depressed mood and suicide risk

•• Depressed patients who attempt suicide have abnormal Depressed patients who attempt suicide have abnormal low serum total cholesterol and triglyceride levels, which low serum total cholesterol and triglyceride levels, which may provide future clinical markers for suicide risk may provide future clinical markers for suicide risk ((BocchettaBocchetta 2001). 2001).

•• Low serum lipid levels are associated with persistently Low serum lipid levels are associated with persistently low platelet serotonin levels in depressed suicidal low platelet serotonin levels in depressed suicidal patients (patients (SteegmansSteegmans 1996; Alvarez 1999). 1996; Alvarez 1999).

•• Low cholesterol levels indirectly lead to reduced brain Low cholesterol levels indirectly lead to reduced brain serotonin because of the requirement of adequate serotonin because of the requirement of adequate cholesterol in nerve cell membranes in order to maintain cholesterol in nerve cell membranes in order to maintain the functional integrity of serotonin receptors the functional integrity of serotonin receptors ((SarchiaponeSarchiapone 2001; 2001; SteegmansSteegmans 1996). 1996).


•• Total serum cholesterol and triglyceride levels are Total serum cholesterol and triglyceride levels are significantly decreased in patients who are considering significantly decreased in patients who are considering suicide or who have recently attempted suicide (Yongsuicide or who have recently attempted suicide (Yong--Ku Ku 2003). 2003).

•• Individuals afflicted with a rare genetic syndrome that Individuals afflicted with a rare genetic syndrome that causes an enzyme deficiency resulting in abnormal low causes an enzyme deficiency resulting in abnormal low serum cholesterol have a high rate of severe depression serum cholesterol have a high rate of severe depression and suicide (and suicide (LalovicLalovic 2004).2004).

•• NonNon--suicidal depressives tend to have cholesterol levels suicidal depressives tend to have cholesterol levels in the range of 180mg/dl, and severely depressed in the range of 180mg/dl, and severely depressed suicidal patients tend to have serum total cholesterol suicidal patients tend to have serum total cholesterol levels in the range of 150mg/dl (Kim 2004) levels in the range of 150mg/dl (Kim 2004)

Mania and cyclic mood changes Mania and cyclic mood changes

•• Low red blood cell (RBC) folic acid levels but Low red blood cell (RBC) folic acid levels but normal serum levels are common in Bipolar normal serum levels are common in Bipolar patientspatients

•• Folic acid deficiency may be a common nutritional factor Folic acid deficiency may be a common nutritional factor in manic patients diagnosed with Bipolar disorder in manic patients diagnosed with Bipolar disorder ((CoppenCoppen 1986). 1986).

•• Chronic Chronic folatefolate deficiency is believed to interfere with deficiency is believed to interfere with normal synthesis of serotonin. Manic patients often have normal synthesis of serotonin. Manic patients often have abnormal low red blood cell folic acid levels but normal abnormal low red blood cell folic acid levels but normal serum folic acid levels (Lee 1992; serum folic acid levels (Lee 1992; HasanahHasanah 1997).1997).

•• Chronic Chronic folatefolate deficiency is associated with both phases deficiency is associated with both phases of Bipolar illness however of Bipolar illness however

•• Bipolar patients who are taking lithium often have Bipolar patients who are taking lithium often have normal red blood cell normal red blood cell folatefolate levels (McKeon 1991). levels (McKeon 1991).

Assessment: maniaAssessment: mania•• LeftLeft--sided QEEG abnormalities may predict sided QEEG abnormalities may predict

improved response to conventional treatments of improved response to conventional treatments of maniamania

•• Abnormal EEG findings are more common in mania than Abnormal EEG findings are more common in mania than depressed mood (Hughes 1999). depressed mood (Hughes 1999).

•• Depressed mood, psychosis and acute mania are Depressed mood, psychosis and acute mania are associated with distinctive patterns of brain electrical associated with distinctive patterns of brain electrical activity on QEEG mapping.activity on QEEG mapping.

•• Global disturbances in EEG synchronization are similar in Global disturbances in EEG synchronization are similar in schizophrenia and Bipolar Disorder. However, in contrast schizophrenia and Bipolar Disorder. However, in contrast to schizophrenics, Bipolar patients do not show to schizophrenics, Bipolar patients do not show disorganization in the superior temporal lobes. disorganization in the superior temporal lobes.

•• NonNon--medicated manic patients have lower EEG medicated manic patients have lower EEG amplitudes in the left anterior and temporal brain amplitudes in the left anterior and temporal brain regions (Small 1998). QEEG findings may predict regions (Small 1998). QEEG findings may predict differential response rates to conventional treatments differential response rates to conventional treatments (Small 1999). (Small 1999).

Assessment: maniaAssessment: mania

•• NonNon--responders to conventional medications are responders to conventional medications are more likely to have diffuse theta activity at more likely to have diffuse theta activity at baseline, and higher amplitudes in the left baseline, and higher amplitudes in the left temporotemporo--parietal regions during treatment parietal regions during treatment (Small 1998; 1999).(Small 1998; 1999).

•• Acutely manic inpatients who responded to Acutely manic inpatients who responded to subsequent conventional treatments were more subsequent conventional treatments were more likely to have left sided abnormalities. The likely to have left sided abnormalities. The significance of these findings is limited by the significance of these findings is limited by the low rate of cooperation of acutely manic low rate of cooperation of acutely manic inpatients in studies completed to date. inpatients in studies completed to date.

Assessment: maniaAssessment: mania

•• Elevated serum GABA levels predict Elevated serum GABA levels predict improved response of mania to improved response of mania to divalproexdivalproex

•• High serum GABA levels may predict improved High serum GABA levels may predict improved response of manic symptoms to response of manic symptoms to divalproexdivalproex((DepakoteDepakote™) however, pre™) however, pre--treatment GABA treatment GABA levels do not predict improved response to levels do not predict improved response to lithium. lithium.

•• In a large placeboIn a large placebo--controlled doublecontrolled double--blind trial, blind trial, acutely manic patients who had abnormal high acutely manic patients who had abnormal high serum GABA levels responded differentially to serum GABA levels responded differentially to divalproexdivalproex (Petty 1996). GABA levels normalized (Petty 1996). GABA levels normalized with clinical response to treatment. with clinical response to treatment.

Assessment: mania Assessment: mania

•• Children with low brain NChildren with low brain N--acetylaspartateacetylaspartatelevels may be at increased risk of levels may be at increased risk of developing Bipolar Disorderdeveloping Bipolar Disorder

•• Findings from a functional brain imaging study Findings from a functional brain imaging study using proton magnetic resonance spectroscopy using proton magnetic resonance spectroscopy suggest that children at risk of developing suggest that children at risk of developing Bipolar Disorder have abnormally low brain Bipolar Disorder have abnormally low brain levels of Nlevels of N--acetylaspartateacetylaspartate (Chang 2003).(Chang 2003).

•• Children with low brain levels of this amino acid Children with low brain levels of this amino acid may be at increased risk of developing Bipolar may be at increased risk of developing Bipolar disorder at an early age disorder at an early age

•• More studies neededMore studies needed

Assessment: anxietyAssessment: anxiety

•• EEG changes may correlate with specific anxiety EEG changes may correlate with specific anxiety symptoms and QEEG findings may predict symptoms and QEEG findings may predict differential response to conventional treatments differential response to conventional treatments

•• Anxiety symptoms frequently correlate with abnormal Anxiety symptoms frequently correlate with abnormal EEG or electroEEG or electro--cardiogram findings. cardiogram findings.

•• EEG changes typically associated with anxiety include EEG changes typically associated with anxiety include decreased alpha activity in generalized anxiety, decreased alpha activity in generalized anxiety, increased theta activity in obsessiveincreased theta activity in obsessive--compulsive patients, compulsive patients, and paroxysmal activity in patients who experience panic and paroxysmal activity in patients who experience panic attacks (Hughes 1999). attacks (Hughes 1999).

•• EKG findings in anxious patients typically reveal EKG findings in anxious patients typically reveal increased sympathetic activity and decreased increased sympathetic activity and decreased parasympathetic activity. parasympathetic activity.


•• QEEG findings may predict differential response QEEG findings may predict differential response rates of OCD patients to conventional rates of OCD patients to conventional medications. In one series, approximately 80% medications. In one series, approximately 80% of OCD patients who exhibited increased alpha of OCD patients who exhibited increased alpha power responded to power responded to SSRIsSSRIs, compared to 80% of , compared to 80% of OCD patients with increased theta activity who OCD patients with increased theta activity who did not respond to did not respond to SSRIsSSRIs ((PrinchepPrinchep 1993).1993).

•• Abnormal QEEG findings associated with other Abnormal QEEG findings associated with other anxiety symptoms are highly inconsistent, and anxiety symptoms are highly inconsistent, and the future role of QEEG in the assessment of the future role of QEEG in the assessment of other anxiety symptom patterns remains other anxiety symptom patterns remains unclear.unclear.

Assessment: anxietyAssessment: anxiety•• Elevated serum cholesterol may be a Elevated serum cholesterol may be a

marker for many anxiety symptoms marker for many anxiety symptoms •• Elevated serum cholesterol may be a biological Elevated serum cholesterol may be a biological

marker for different anxiety syndromes including marker for different anxiety syndromes including generalized anxiety, panic attacks and possibly generalized anxiety, panic attacks and possibly also obsessivealso obsessive--compulsive disorder (Peter 2000). compulsive disorder (Peter 2000).

•• In contrast to high cholesterol levels in In contrast to high cholesterol levels in chronically anxious patients, many chronically chronically anxious patients, many chronically depressed individuals have low serum depressed individuals have low serum cholesterol levels.cholesterol levels.


•• Patients diagnosed with ObsessivePatients diagnosed with Obsessive--compulsive Disorder (OCD) have higher compulsive Disorder (OCD) have higher serum cholesterol levels compared to serum cholesterol levels compared to individuals diagnosed with Panic Disorder individuals diagnosed with Panic Disorder (Peter 1997). (Peter 1997).

•• Successful response of anxiety symptoms Successful response of anxiety symptoms to conventional medications is associated to conventional medications is associated with a reduction of total serum cholesterol with a reduction of total serum cholesterol to normal levels.to normal levels.


•• Chronically anxious patients are often Chronically anxious patients are often deficient in magnesium, selenium or deficient in magnesium, selenium or phosphorousphosphorous

•• Chronically anxious patients are often deficient Chronically anxious patients are often deficient in magnesium, selenium or phosphorous in magnesium, selenium or phosphorous ((DurlachDurlach 1994; Webb 1981; 1994; Webb 1981; McCleaneMcCleane 1990). 1990).

•• Mineral deficiencies often occur in patients who Mineral deficiencies often occur in patients who are malnourished in general. are malnourished in general.

•• Always check serum chemistries of chronically Always check serum chemistries of chronically anxious patients, and especially those who may anxious patients, and especially those who may be malnourished and who do not take quality be malnourished and who do not take quality vitamin and mineral supplements. vitamin and mineral supplements.


•• ElectrodermalElectrodermal skin testing (EDST) may help skin testing (EDST) may help determine whether Healing Touch is helpful for determine whether Healing Touch is helpful for stress reduction stress reduction

•• ElectrodermalElectrodermal skin testing (EDST) may prove to be a skin testing (EDST) may prove to be a useful assessment approach when determining whether useful assessment approach when determining whether conventional or subtle energy treatments of anxiety will conventional or subtle energy treatments of anxiety will be effective for a particular patient (Forbes 2004). be effective for a particular patient (Forbes 2004).

•• Healing Touch (HT) practitioners conducted six trials Healing Touch (HT) practitioners conducted six trials comparing the anxiety reducing efficacy of conventional comparing the anxiety reducing efficacy of conventional relaxation with Healing Touch. They concluded that relaxation with Healing Touch. They concluded that electrodermalelectrodermal skin testing (EDST) reliably measured skin testing (EDST) reliably measured changes in “changes in “bioenergybioenergy” in meridians (according to ” in meridians (according to Chinese medical theory) following both conventional and Chinese medical theory) following both conventional and subtle energy treatments of anxiety (Stouffer in press). subtle energy treatments of anxiety (Stouffer in press).

Assessment: psychosisAssessment: psychosis

•• Consistently reduced red blood cell Consistently reduced red blood cell membrane levels of two fatty acids: membrane levels of two fatty acids: arachidonicarachidonic acid (AA) and acid (AA) and decosahexanoicdecosahexanoicacid (DHA) have been reported in nonacid (DHA) have been reported in non--medicated schizophrenics compared to medicated schizophrenics compared to medicated schizophrenics and normal medicated schizophrenics and normal controls (controls (HorrobinHorrobin 1998; 1998; ArvindakshanArvindakshan2003; 2003; AssiesAssies 2001). 2001).


•• An open study compared serum lipid levels in 16 patients An open study compared serum lipid levels in 16 patients diagnosed with diagnosed with DissociativeDissociative Disorder according to DSMDisorder according to DSM--IV criteria with 16 normal controls. IV criteria with 16 normal controls.

•• Patients diagnosed with Patients diagnosed with dissociativedissociative disorder had disorder had consistently lower total serum cholesterol, triglycerides, consistently lower total serum cholesterol, triglycerides, LDL and VLDL levels compared to matched controls.LDL and VLDL levels compared to matched controls.

•• The relationship between red blood cell (RBC) levels of The relationship between red blood cell (RBC) levels of OmegaOmega--3 fatty acids is confounded by the high rate of 3 fatty acids is confounded by the high rate of smoking in schizophrenics and patients with other smoking in schizophrenics and patients with other chronic psychotic syndromes. Smoking is correlated with chronic psychotic syndromes. Smoking is correlated with reduced consumption of foods rich in Omegareduced consumption of foods rich in Omega--3s and also 3s and also with abnormally low RBC Omegawith abnormally low RBC Omega--3s levels (3s levels (LengLeng 1994; 1994; HibbelnHibbeln 2003). 2003).

Assessment: psychosisAssessment: psychosisserum DHEA levelserum DHEA level•• Abnormal low serum DHEA level may be a Abnormal low serum DHEA level may be a

marker for vulnerability to depression, anxiety, marker for vulnerability to depression, anxiety, and schizophrenia. and schizophrenia.

•• Serum DHEA (but Serum DHEA (but notnot cortisolcortisol) levels increased ) levels increased significantly in chronically psychotic patients who significantly in chronically psychotic patients who improved when treated with DHEA. improved when treated with DHEA.

•• Lower serum DHEA may correlate with increased Lower serum DHEA may correlate with increased severity of psychotic symptoms on standardized severity of psychotic symptoms on standardized scales (Harris 2001). scales (Harris 2001).

•• Increases in serum DHEA correlated with Increases in serum DHEA correlated with reductions in negative psychotic symptoms reductions in negative psychotic symptoms ((StrousStrous 2003). 2003).

Assessment: psychosisAssessment: psychosisDHEA and estrogen levelDHEA and estrogen level•• In a prospective study of 26 active duty military In a prospective study of 26 active duty military

personnel, higher serum DHEA levels correlated with personnel, higher serum DHEA levels correlated with fewer symptoms of dissociation and overall improved fewer symptoms of dissociation and overall improved performance during periods of extreme stress (Morgan performance during periods of extreme stress (Morgan 2004). 2004).

•• Women diagnosed with schizophrenia or other chronic Women diagnosed with schizophrenia or other chronic psychotic syndromes frequently have abnormal low psychotic syndromes frequently have abnormal low serum serum estradiolestradiol levels, and it has been suggested that levels, and it has been suggested that women may be more susceptible to developing a women may be more susceptible to developing a psychotic syndrome when estrogen levels are low, psychotic syndrome when estrogen levels are low, including the premenstrual, postincluding the premenstrual, post--partum periods, and partum periods, and following discontinuation of oral contraceptives (Huber following discontinuation of oral contraceptives (Huber 2001).2001).

Assessment: psychosisAssessment: psychosisniacin challenge testniacin challenge test•• Emerging evidence suggests that the flushing response Emerging evidence suggests that the flushing response

to niacin (and associated elevation in skin temperature) to niacin (and associated elevation in skin temperature) is attenuated in schizophrenia and other chronic is attenuated in schizophrenia and other chronic psychotic syndromes. psychotic syndromes.

•• The mechanism of action probably involves The mechanism of action probably involves dysregulationdysregulation of of phospholipidphospholipid--dependent signal dependent signal transduction and increased transduction and increased phospholipasephospholipase A2 activity A2 activity ((MessamoreMessamore 2003; Tavares 2003). 2003; Tavares 2003).

•• Approximately 80% of schizophrenics do not flush when Approximately 80% of schizophrenics do not flush when challenged with niacin compared to healthy controls. In challenged with niacin compared to healthy controls. In one series, 43% of schizophrenics experienced abnormal one series, 43% of schizophrenics experienced abnormal low low vasodilationvasodilation in response to a 200mg challenge dose in response to a 200mg challenge dose of niacin, compared to only 6% of individuals diagnosed of niacin, compared to only 6% of individuals diagnosed with Bipolar disorder. with Bipolar disorder.


•• Response to niacin is significantly affected by Response to niacin is significantly affected by the dose used, age and gender. At low doses the dose used, age and gender. At low doses healthy men are more likely to be nonhealthy men are more likely to be non--responders compared to women, suggesting responders compared to women, suggesting that these factors should be considered when that these factors should be considered when determining normative responses to a niacin determining normative responses to a niacin challenge in male versus female schizophrenics. challenge in male versus female schizophrenics.

•• Continued refinement of the niacin challenge Continued refinement of the niacin challenge test may eventually provide a specific and test may eventually provide a specific and sensitive clinical method for differentiating sensitive clinical method for differentiating schizophrenia from other severe psychiatric schizophrenia from other severe psychiatric syndromes (Hudson 1997; syndromes (Hudson 1997; PuriPuri 2002).2002).

Assessment: psychosisAssessment: psychosisQEEG brain mappingQEEG brain mapping

•• QEEG may prove a useful adjunct to conventional QEEG may prove a useful adjunct to conventional assessment methods when the underlying causes of assessment methods when the underlying causes of psychotic symptoms are not clearly established, or when psychotic symptoms are not clearly established, or when a psychotic patient fails to respond to conventional a psychotic patient fails to respond to conventional treatment. treatment.

•• Decreased alpha power in the frontal lobes is a typical Decreased alpha power in the frontal lobes is a typical finding in chronically psychotic schizophrenic patients finding in chronically psychotic schizophrenic patients who exhibit positive symptoms (who exhibit positive symptoms (MerrinMerrin 1992) and 1992) and conventional antipsychotic medications are known to conventional antipsychotic medications are known to increase alpha power (increase alpha power (GalderisiGalderisi 1994). 1994).

•• Conversely, negative psychotic symptoms are more often Conversely, negative psychotic symptoms are more often associated with changes in slow wave (delta) activity in associated with changes in slow wave (delta) activity in the temporal lobes (the temporal lobes (GattazGattaz 1992).1992).

Assessment: psychosisAssessment: psychosisQEEG brain mappingQEEG brain mapping•• However, research findings are inconsistent suggesting However, research findings are inconsistent suggesting

that there are no simple correlations between EEG that there are no simple correlations between EEG changes and psychosis (changes and psychosis (LifshitzLifshitz 1974).1974).

•• The range of findings suggests wide variation in the The range of findings suggests wide variation in the neurophysiologicalneurophysiological correlates of disparate psychotic correlates of disparate psychotic symptom patterns (John 1994). symptom patterns (John 1994).

•• This model is consistent with differential response rates This model is consistent with differential response rates to conventional antipsychotic drugs in psychotic patients to conventional antipsychotic drugs in psychotic patients exhibiting different QEEG findings (exhibiting different QEEG findings (CzoborCzobor 1991, 1993).1991, 1993).

•• Differences in interDifferences in inter--hemispheric EEG coherence may hemispheric EEG coherence may prove useful in differentiating depressed or Bipolar prove useful in differentiating depressed or Bipolar patients who are psychotic from patients who are patients who are psychotic from patients who are schizophrenic (schizophrenic (PockbergerPockberger 1989).1989).

Assessment: psychosisAssessment: psychosisserum serum phospholipasephospholipase A2A2

•• High serum High serum phospholipasephospholipase A2 levels may be A2 levels may be correlated with increased risk of developing correlated with increased risk of developing schizophrenia or other severe psychiatric schizophrenia or other severe psychiatric syndromessyndromes

•• Preliminary evidence suggests that serum levels of Preliminary evidence suggests that serum levels of phosophlipasephosophlipase A2 are abnormally high in patients A2 are abnormally high in patients diagnosed with schizophrenia.diagnosed with schizophrenia. In normal individuals this In normal individuals this enzyme is involved in the turnenzyme is involved in the turn--over of phospholipids in over of phospholipids in nerve cell membranes. nerve cell membranes.

•• schizophrenia and other severe psychiatric syndromes schizophrenia and other severe psychiatric syndromes may be caused by abnormal high levels of this enzyme may be caused by abnormal high levels of this enzyme in the brain, resulting in a general deficiency of in the brain, resulting in a general deficiency of phosophlipidsphosophlipids in nerve cell membranes, and associated in nerve cell membranes, and associated abnormalities in neurotransmission abnormalities in neurotransmission HorrobinHorrobin 1996; 1996; 1998). 1998).

Assessment: psychosisAssessment: psychosisserum HVA levelserum HVA level•• Abnormal high serum Abnormal high serum homovanillichomovanillic acid (HVA) acid (HVA)

levels may correspond to lower effective doses of levels may correspond to lower effective doses of first generation first generation antipsychoticsantipsychotics

•• Pretreatment serum Pretreatment serum homovanillichomovanillic acid (HVA) levels may acid (HVA) levels may predict response to certain conventional antipsychotic predict response to certain conventional antipsychotic medications in the treatment of acutely manic or medications in the treatment of acutely manic or psychotic inpatients. psychotic inpatients.

•• Abnormal high serumAbnormal high serum HVA levels may reflect an HVA levels may reflect an increased turnover rate of brain dopamine, and increased turnover rate of brain dopamine, and correspond to lower effective doses of dopamine correspond to lower effective doses of dopamine blocking blocking antipsychoticsantipsychotics in the management of psychotic in the management of psychotic symptoms. symptoms.

Assessment: psychosisAssessment: psychosisserum HVA levelserum HVA level•• Higher serum HVA levels predicted an improved Higher serum HVA levels predicted an improved

response rate to lower doses of first generation response rate to lower doses of first generation antipsychoticsantipsychotics including haloperidol (including haloperidol (egeg, , 5mg/day). 5mg/day).

•• In contrast, lower preIn contrast, lower pre--treatment HVA levels treatment HVA levels correlated with a need for higher dosing correlated with a need for higher dosing strategies of typical strategies of typical antipsychoticsantipsychotics ((egeg, up to , up to 25mg/day) (Chou 2000). 25mg/day) (Chou 2000).

•• It is unclear whether these findings generalize to It is unclear whether these findings generalize to treatment strategies using atypical treatment strategies using atypical antipsychoticsantipsychotics or other conventional or other conventional medications. medications.

Treatment Treatment

•• NonNon--conventional and integrative treatments conventional and integrative treatments may improve outcomes, enhance compliance, may improve outcomes, enhance compliance, reduce adverse effects, and improve costreduce adverse effects, and improve cost--effectivenesseffectiveness

•• Emerging treatments include OmegaEmerging treatments include Omega--3 3 EFAsEFAs, , DHEA, 5DHEA, 5--HTP, HTP, glycineglycine, acetyl, acetyl--LL--carnitinecarnitine, L, L--theaninetheanine, EEG biofeedback, spiritually oriented , EEG biofeedback, spiritually oriented support groups, acupuncture, VR exposure support groups, acupuncture, VR exposure therapy, high density negative ions, qigong and therapy, high density negative ions, qigong and others others

Emerging treatment approachesEmerging treatment approaches

••DepressionDepression••Mania and cyclic mood changesMania and cyclic mood changes••AnxietyAnxiety•• psychosispsychosis

Treatment: depressionTreatment: depressionOmegaOmega--3 fatty acids3 fatty acids

•• OmegaOmega--3 Fatty acids are an effective 3 Fatty acids are an effective adjunctive treatment when combined with adjunctive treatment when combined with conventional antidepressantsconventional antidepressants

•• Research findings suggest that several Research findings suggest that several mechanisms of action may underlie the putative mechanisms of action may underlie the putative antidepressant effects of Omegaantidepressant effects of Omega--3 fatty acids, 3 fatty acids, including increased CNS serotonin activity including increased CNS serotonin activity ((HibbelnHibbeln 1998), anti1998), anti--inflammatory effects inflammatory effects (Calder 1997), suppression of (Calder 1997), suppression of phosphatidylphosphatidyl--inositolinositol second messenger activity (second messenger activity (KinsellaKinsella1990), and possibly increased heart rate 1990), and possibly increased heart rate variability (Villa 2002). variability (Villa 2002).


•• The mechanism of action may be similar to that The mechanism of action may be similar to that of conventional antidepressants including triof conventional antidepressants including tri--cyclicscyclics (TCA) and (TCA) and SSRIsSSRIs, which are known to , which are known to suppress release of many prosuppress release of many pro--inflammatory inflammatory cytokines by immune cells, possibly causing cytokines by immune cells, possibly causing beneficial changes in the brain that manifest as beneficial changes in the brain that manifest as improved mood (improved mood (MaesMaes 1998). 1998).

•• Increased production of proIncreased production of pro--inflammatory inflammatory cytokines takes place in the initial or “acute cytokines takes place in the initial or “acute phase” of severe depressed mood (phase” of severe depressed mood (MaesMaes 1996).1996).

Treatment: depressionTreatment: depressionOmegaOmega--3 3 EFAsEFAs

•• one small doubleone small double--blind study has blind study has evaluated the efficacy of DHA alone as a evaluated the efficacy of DHA alone as a treatment of severe depressed mood treatment of severe depressed mood ((MarangellMarangell 2003). Patients treated with 2003). Patients treated with DHA 2g/day or placebo improved at the DHA 2g/day or placebo improved at the same rate. same rate.

Treatment: depressionTreatment: depressionOmegaOmega--3 fatty acids3 fatty acids•• Three small doubleThree small double--blind controlled studies have blind controlled studies have

evaluated Omegaevaluated Omega--3s in combination with conventional 3s in combination with conventional antianti--depressant medications (depressant medications (PeetPeet 2001; 2001; NemetsNemets 2002; 2002; Su 2003). Su 2003).

•• In two studies EPA (1g/day or 2g/day) was added to the In two studies EPA (1g/day or 2g/day) was added to the onon--going conventional treatment. In the third study going conventional treatment. In the third study patients were treated with a mixture of EPA and DHA patients were treated with a mixture of EPA and DHA (9.6g/day) in addition to their conventional medication. (9.6g/day) in addition to their conventional medication.

•• In all three studies treatment response was significantly In all three studies treatment response was significantly greater in the combined Omegagreater in the combined Omega--3/antidepressant groups 3/antidepressant groups compared to groups treated with antidepressants only. compared to groups treated with antidepressants only.


•• Some patients who had previously been Some patients who had previously been refractory to conventional antidepressants refractory to conventional antidepressants improved significantly when Omegaimproved significantly when Omega--3s were 3s were added to their conventional treatments. added to their conventional treatments.

•• Patients in the combined OmegaPatients in the combined Omega--3/antidepressant groups reported significant 3/antidepressant groups reported significant improvements in insomnia, and reduced feelings improvements in insomnia, and reduced feelings of guilt and worthlessness. of guilt and worthlessness.

•• Severe side effects were not reported in the Severe side effects were not reported in the combined treatment groups or the conventional combined treatment groups or the conventional treatment groups.treatment groups.

Treatment: depressionTreatment: depressionexerciseexercise•• Regular exercise is as effective as most Regular exercise is as effective as most

conventional and nonconventional and non--conventional treatmentsconventional treatments•• Case reports, randomized controlled trials and two metaCase reports, randomized controlled trials and two meta--

analyses confirm that regular exercise has beneficial analyses confirm that regular exercise has beneficial effects on depressed mood (effects on depressed mood (LawlorLawlor 2001; 2001; TkachukTkachuk1999). 1999).

•• Increased brain levels of moodIncreased brain levels of mood--elevating endorphins, elevating endorphins, dopamine, dopamine, norepinephrinenorepinephrine and serotonin following and serotonin following sustained exercise have been proposed as possible sustained exercise have been proposed as possible antidepressant mechanisms. antidepressant mechanisms.

•• Regular exercise enhances selfRegular exercise enhances self--sufficiency and ensures sufficiency and ensures positive social interactions with other people. positive social interactions with other people.

Treatment: depressionTreatment: depressionexerciseexercise

•• It is difficult to separate beneficial effects of It is difficult to separate beneficial effects of exercise from other life style factors, and it is exercise from other life style factors, and it is possible that exercise contributes to overall possible that exercise contributes to overall feelings of wellness while not having specific feelings of wellness while not having specific mood elevating effects.mood elevating effects.

•• The optimum duration or frequency of exercise The optimum duration or frequency of exercise in depressed mood has not yet been determined in depressed mood has not yet been determined but probably varies with age and conditioning. but probably varies with age and conditioning.

•• Both aerobic exercise and nonBoth aerobic exercise and non--aerobic aerobic strengthening exercises are equally efficacious. strengthening exercises are equally efficacious.


•• Exercise is probably comparable to individual Exercise is probably comparable to individual cognitive therapy and group therapy for cognitive therapy and group therapy for depressed mood (depressed mood (TkachukTkachuk 1999). 1999).

•• The therapeutic benefits of regular exercise are The therapeutic benefits of regular exercise are also comparable to validated nonalso comparable to validated non--conventional conventional treatments of depressed mood including St. treatments of depressed mood including St. John’s John’s WortWort (Ernst 1998). (Ernst 1998).

•• Running 45 minutes twice each week, regular Running 45 minutes twice each week, regular relaxation, meditation or group psychotherapy relaxation, meditation or group psychotherapy probably have equivalent antidepressant effects probably have equivalent antidepressant effects ((IntInt J J MentMent Health, 1986, 13:148Health, 1986, 13:148--177). 177).


•• Depressed patients who exercise in a brightly lit Depressed patients who exercise in a brightly lit (2500 to 4000 (2500 to 4000 luxlux) indoor environment ) indoor environment experience more significant improvements in experience more significant improvements in mood and greater feelings of vitality compared mood and greater feelings of vitality compared to depressed individuals who exercise indoors in to depressed individuals who exercise indoors in ordinary room light (400 to 600 ordinary room light (400 to 600 luxlux) () (PartonenPartonen1998). 1998).

•• Depressed women patients who combined Depressed women patients who combined exercise with bright light exposure while taking a exercise with bright light exposure while taking a daily vitamin regimen reported significant daily vitamin regimen reported significant improvements in mood (Brown 2001). improvements in mood (Brown 2001).


•• In a 16 week study one hundred fifty six In a 16 week study one hundred fifty six depressed patients over the age of 50 were depressed patients over the age of 50 were randomized to aerobic exercise three times a randomized to aerobic exercise three times a week, medications (week, medications (sertralinesertraline (Zoloft™) up to (Zoloft™) up to 200mg), or exercise and medications 200mg), or exercise and medications (Blumenthal 1999). (Blumenthal 1999).

•• All groups had improved significantly by the end All groups had improved significantly by the end of the study, and there were no significant of the study, and there were no significant differences in response rates using standardized differences in response rates using standardized symptom rating scales assessing mood, selfsymptom rating scales assessing mood, self--esteem, negative thoughts, etc. esteem, negative thoughts, etc.


•• Patients taking Patients taking sertralinesertraline only improved faster only improved faster initially than the other two groups, but patients initially than the other two groups, but patients who exercised only had a lower 6who exercised only had a lower 6--month relapse month relapse rate. rate.

•• 60% of patients who exercised only experienced 60% of patients who exercised only experienced complete remission, versus 65% of patients complete remission, versus 65% of patients taking taking SertralineSertraline and 69% of patients who and 69% of patients who exercised and took a conventional exercised and took a conventional antidepressant.antidepressant.

•• Differences in these outcomes are not Differences in these outcomes are not significant. significant.

Treatment: depressionTreatment: depressiondietary modificationdietary modification

•• Foods rich in B vitamins are beneficial in Foods rich in B vitamins are beneficial in depressed mooddepressed mood

•• Observational trials show consistent Observational trials show consistent relationships between good nutrition and relationships between good nutrition and improved mood. improved mood.

•• Reducing or eliminating consumption of refined Reducing or eliminating consumption of refined sugar and caffeine significantly improves mood sugar and caffeine significantly improves mood in some depressed patients, but research in some depressed patients, but research findings are inconsistent (Christensen 1991). findings are inconsistent (Christensen 1991).


•• Foods rich in BFoods rich in B--vitamins, especially vitamins, especially folatefolate, , pyridoxine (Bpyridoxine (B--6), and methyl6), and methyl--cobalamincobalamin (B(B--12) 12) are especially beneficial. These vitamins work as are especially beneficial. These vitamins work as enzyme coenzyme co--factors, and facilitate the production factors, and facilitate the production of endogenous neurotransmitters including of endogenous neurotransmitters including serotonin, dopamine and norserotonin, dopamine and nor--epinephrine, epinephrine, whose deficiencies are hypothesized to be whose deficiencies are hypothesized to be associated with depressed mood. associated with depressed mood.

•• Foods rich in BFoods rich in B--vitamins include whole grains vitamins include whole grains and dark green leafy vegetables. and dark green leafy vegetables.


•• Diets high in OmegaDiets high in Omega--3 fatty acids are associated 3 fatty acids are associated with lower prevalence rates of depression with lower prevalence rates of depression

•• Food preferences influencing fatty acid consumption may Food preferences influencing fatty acid consumption may be directly related to different rates of depressed mood be directly related to different rates of depressed mood when industrialized countries are compared to more when industrialized countries are compared to more traditional cultures. traditional cultures.

•• Epidemiological surveys have demonstrated an inverse Epidemiological surveys have demonstrated an inverse correlation between risk of depressed mood and fish oil correlation between risk of depressed mood and fish oil consumption. Countries where fish is an important part consumption. Countries where fish is an important part of the average diet are characterized by significantly of the average diet are characterized by significantly lower rates of depressed mood and lower rates of depressed mood and suicidalitysuicidality ((HibbelnHibbeln, , 1998; 1998; TanskanenTanskanen 2001; Silvers 2002). 2001; Silvers 2002).


•• Negative findings from recent studies continue to Negative findings from recent studies continue to obscure the relationship between a highobscure the relationship between a high--fish diet fish diet and the risk of depressed mood.and the risk of depressed mood.

•• 452 men with histories of cardiovascular disease and 452 men with histories of cardiovascular disease and angina were randomized to a diet high in fatty fish (or angina were randomized to a diet high in fatty fish (or fish oil supplements) or “no fish advice” over a six month fish oil supplements) or “no fish advice” over a six month period (Ness 2003). period (Ness 2003).

•• At the end of the study period there were no significant At the end of the study period there were no significant group differences in new cases of anxious or depressed group differences in new cases of anxious or depressed mood, and in fact more patients in the highmood, and in fact more patients in the high--fish group fish group reported depressed mood or anxiety. reported depressed mood or anxiety.

•• Principle sources of omegaPrinciple sources of omega--3s include Salmon, Halibut, 3s include Salmon, Halibut, other deep sea fish, and flaxseed oil. other deep sea fish, and flaxseed oil.

OnOn--going research: depressiongoing research: depressionOmegaOmega--3 3 EFAsEFAs

•• OmegaOmega--3 fatty acids may accelerate 3 fatty acids may accelerate response to conventional antidepressantsresponse to conventional antidepressants

•• A NCCAMA NCCAM--sponsored doublesponsored double--blind controlled trial blind controlled trial will evaluate a possible synergistic antiwill evaluate a possible synergistic anti--depressant role of the Omegadepressant role of the Omega--3 fatty acid EPA 3 fatty acid EPA when combined with a conventional when combined with a conventional antidepressant. antidepressant.

•• All patients will take a conventional All patients will take a conventional antidepressant (antidepressant (CitalopramCitalopram), half will take EPA ), half will take EPA while half will take a placebowhile half will take a placebo

Treatment: depressionTreatment: depression55--HTPHTP•• 55--hydroxytryptophan (5hydroxytryptophan (5--HTP) in combination HTP) in combination

with conventional antidepressants is probably an with conventional antidepressants is probably an effective treatment in some cases of refractory effective treatment in some cases of refractory depressed mooddepressed mood

•• 55--HTP and LHTP and L--tryoptophantryoptophan are amino acid precursors of are amino acid precursors of serotonin. Both have been evaluated for their serotonin. Both have been evaluated for their antidepressant efficacy. antidepressant efficacy.

•• 55--HTP is generally preferred over LHTP is generally preferred over L--tryptophantryptophan because because it crosses the bloodit crosses the blood--brain barrier at a higher rate, is brain barrier at a higher rate, is converted converted convertedconverted into serotonin more efficiently than into serotonin more efficiently than LL--tryptophantryptophan, and has a more marked antidepressant , and has a more marked antidepressant effect. effect.

•• 55--HTP begins to have an antidepressant effect at doses HTP begins to have an antidepressant effect at doses between 100mg and 300mg/day. between 100mg and 300mg/day.

Treatment: depressionTreatment: depression55--HTPHTP•• More than 15 controlled studies have demonstrated More than 15 controlled studies have demonstrated

consistent positive effects of 5consistent positive effects of 5--HTP in moderate HTP in moderate depressed mood (depressed mood (BirdsallBirdsall 1998). However, most studies 1998). However, most studies on 5on 5--HTP in depressed mood are small and study design HTP in depressed mood are small and study design problems preclude definitive conclusions at present. problems preclude definitive conclusions at present.

•• A Cochrane review of 5A Cochrane review of 5--HTP and LHTP and L--tryptophantryptophan in in depressed mood identified 108 studies but analysis of depressed mood identified 108 studies but analysis of findings was limited to only two studies involving 64 findings was limited to only two studies involving 64 patients that met strict inclusion criteria (Shaw 2004). patients that met strict inclusion criteria (Shaw 2004). On the basis of those limited findings the Cochrane On the basis of those limited findings the Cochrane reviewers concluded that 5reviewers concluded that 5--HTP is HTP is probably more probably more effectiveeffective than placebo in depressed mood. than placebo in depressed mood.

Treatment: depressionTreatment: depression55--HTPHTP

•• 63 depressed patients randomized to 63 depressed patients randomized to fluvoxaminefluvoxamine 150mg or 5150mg or 5--HTP 300mg HTP 300mg experienced similar improvements in mood experienced similar improvements in mood ((PoldingerPoldinger et al. 1991). et al. 1991).

•• Case reports show that treatmentCase reports show that treatment--refractory refractory patients sometimes improve when 5patients sometimes improve when 5--HTP 300mg HTP 300mg is combined with is combined with CarbidopaCarbidopa, , tricyclictricyclicantidepressants, antidepressants, MAOIsMAOIs or or SSRIsSSRIs (van (van HieleHiele1980; 1980; NardiniNardini 1983; van 1983; van PraagPraag 1984; 1984; SargentSargent et et al. 1998; Kline & Sacks 1980; al. 1998; Kline & Sacks 1980; MendlewiczMendlewicz & & YoudimYoudim, 1980). , 1980).

Treatment: depressionTreatment: depression55--HTPHTP•• In an open study almost half of 100 patients who had In an open study almost half of 100 patients who had

been refractory to conventional antidepressants been refractory to conventional antidepressants responded to 5responded to 5--HTP (up to 600mg/day) in combination HTP (up to 600mg/day) in combination with with carbidopacarbidopa 150mg/day over a period of weeks to 150mg/day over a period of weeks to months (van months (van HieleHiele 1980). 1980).

•• Findings from another open trial suggest that 5Findings from another open trial suggest that 5--HTP HTP 300mg/d is more effective against Bipolar depression 300mg/d is more effective against Bipolar depression than than unipolarunipolar depressed mood (Fujiwara 1974). depressed mood (Fujiwara 1974).

•• Rapid clinical improvement in depressed mood has been Rapid clinical improvement in depressed mood has been reported in patients treated by intravenous 5reported in patients treated by intravenous 5--HTP 25 to HTP 25 to 50mg who are already taking oral 50mg who are already taking oral MAOIsMAOIs (Kline and (Kline and Sacks 1980). Sacks 1980).

•• 55--HTP is moderately sedating, and doses greater than HTP is moderately sedating, and doses greater than 100mg are typically taken at bedtime. 100mg are typically taken at bedtime.

Treatment: depressionTreatment: depressionAcetylAcetyl--LL--carnitinecarnitine

•• AcetylAcetyl--LL--CarnitineCarnitine is probably beneficial when is probably beneficial when depression occurs with cognitive impairment depression occurs with cognitive impairment

•• AcetylAcetyl--LL--carnitinecarnitine (ALC) has been studied in placebo(ALC) has been studied in placebo--controlled doublecontrolled double--blind trials in severely depressed blind trials in severely depressed patients, elderly depressed patients, and depressed patients, elderly depressed patients, and depressed demented patients (demented patients (GarzyaGarzya 1990; Bella 1990). 1990; Bella 1990).

•• ALC has general ALC has general neuroprotectiveneuroprotective effects, and mediates effects, and mediates improved mood and possibly also reduction in the improved mood and possibly also reduction in the severity of cognitive impairments in normal aging, severity of cognitive impairments in normal aging, dementia or traumatic brain injury by enhancing dementia or traumatic brain injury by enhancing mitochondrial energy production and partially mitochondrial energy production and partially compensating for deficits in CNS cholinergic activity.compensating for deficits in CNS cholinergic activity.

Treatment: depressionTreatment: depressionAcetylAcetyl--LL--carnitinecarnitine•• Most studies conducted to date have evaluated Most studies conducted to date have evaluated

ALC in elderly depressed patients, and have ALC in elderly depressed patients, and have demonstrated a consistent antidepressant effect demonstrated a consistent antidepressant effect after about one month of treatment (after about one month of treatment (PettegrewPettegrew2000).2000).

•• In a two month placebo controlled study In a two month placebo controlled study demented depressed patients treated with ALC demented depressed patients treated with ALC 3g/day in divided doses experienced significantly 3g/day in divided doses experienced significantly greater improvements in mood and global greater improvements in mood and global functioning compared to patients taking a functioning compared to patients taking a placebo (Bella 1990).placebo (Bella 1990).

Treatment: depressionTreatment: depressionAcetylAcetyl--LL--carnitinecarnitine

•• In a doubleIn a double--blind placebo controlled study blind placebo controlled study almost half of elderly severely depressed almost half of elderly severely depressed patients (N=28) treated with ALC 500mg QID patients (N=28) treated with ALC 500mg QID experienced full remission, and previously experienced full remission, and previously elevated serum elevated serum cortisolcortisol levels normalized levels normalized ((GeceleGecele 1991). 1991).

•• In a small doubleIn a small double--blind crossblind cross--over study over study hospitalized elderly depressed patients ALC had hospitalized elderly depressed patients ALC had superior antidepressant efficacy compared to superior antidepressant efficacy compared to placebo, but placebo, but comorbidcomorbid anxiety symptoms did not anxiety symptoms did not improve (improve (TempestaTempesta 1987).1987).

Treatment: depressionTreatment: depressionDHEADHEA

•• DihydroepiandosteroneDihydroepiandosterone (DHEA) may be an (DHEA) may be an effective effective monotherapymonotherapy of moderate of moderate depressed mood, and should be considered depressed mood, and should be considered when depression occurs together with when depression occurs together with psychosis, anxiety or cognitive impairmentpsychosis, anxiety or cognitive impairment

•• The putative antidepressant mechanism of DHEA The putative antidepressant mechanism of DHEA remains unclear, but may involve androgen remains unclear, but may involve androgen receptors, estrogen receptors, or well defined receptors, estrogen receptors, or well defined neurotransmitter systems including serotonin, neurotransmitter systems including serotonin, GABA, NMDA and GABA, NMDA and norepinephrinenorepinephrine. .

Treatment: depressionTreatment: depressionDHEADHEA•• Physiological replacement doses of DHEA (Physiological replacement doses of DHEA (ieie, 30 to 90mg/day, a , 30 to 90mg/day, a

dose range corresponding to DHEA serum levels that are normal indose range corresponding to DHEA serum levels that are normal inpeople younger than age 40) probably improve mood in middlepeople younger than age 40) probably improve mood in middle--aged or elderly depressed patients (aged or elderly depressed patients (WolkowitzWolkowitz et al. 1997).et al. 1997).

•• In a small 6In a small 6--week study (N=22) DHEA administered in an escalating week study (N=22) DHEA administered in an escalating dose (30mg/day for two weeks followed by 30mg twice a day for dose (30mg/day for two weeks followed by 30mg twice a day for two weeks and 30mg three times daily for two weeks) resulted in two weeks and 30mg three times daily for two weeks) resulted in significant improvements in mood compared to placebo (significant improvements in mood compared to placebo (WolkowitzWolkowitzet al. 1999). et al. 1999).

•• Two thirds of patients in both groups continued on their Two thirds of patients in both groups continued on their conventional antidepressants, however 3 patients in the DHEA conventional antidepressants, however 3 patients in the DHEA group and 4 patients in the placebo group did not take medicatiogroup and 4 patients in the placebo group did not take medications ns during the study. during the study.

•• Depressed mood scores in half of patients in the DHEA group Depressed mood scores in half of patients in the DHEA group improved by 50% or more using standardized rating scales.improved by 50% or more using standardized rating scales.

Treatment: depressionTreatment: depressionDHEADHEA

•• A larger followA larger follow--up study suggests that up study suggests that higher doses are probably more effective higher doses are probably more effective when DHEA is used as a when DHEA is used as a monotherapymonotherapy. In . In a sixa six--week doubleweek double--blind randomized blind randomized placeboplacebo--controlled controlled, crosscontrolled controlled, cross--over over study (N=46) moderately depressed study (N=46) moderately depressed adults were randomized to DHEA adults were randomized to DHEA 90mg/day for three weeks followed by 90mg/day for three weeks followed by DHEA 450mg/day (150mg TID) for three DHEA 450mg/day (150mg TID) for three weeks versus placebo (Schmidt 2005). weeks versus placebo (Schmidt 2005).

Treatment: depressionTreatment: depressionDHEADHEA•• None of the patients used conventional antidepressants None of the patients used conventional antidepressants

concurrently with DHEA. concurrently with DHEA. •• A 50% or greater reduction in depressive symptoms was A 50% or greater reduction in depressive symptoms was

observed in the majority of patients in the DHEA group, observed in the majority of patients in the DHEA group, which also reported improvements in baseline sexual which also reported improvements in baseline sexual functioning. functioning.

•• Significantly, most patients who responded to DHEA Significantly, most patients who responded to DHEA remained asymptomatic at 12 months followremained asymptomatic at 12 months follow--up. up.

•• Further research is needed to replicate these findings, Further research is needed to replicate these findings, evaluate DHEA for severe depressed mood, and clarify evaluate DHEA for severe depressed mood, and clarify the mechanism for a synergistic or independent the mechanism for a synergistic or independent antidepressant effect of DHEA. antidepressant effect of DHEA.

Treatment: depressionTreatment: depressionYogaYoga•• Yoga is probably beneficial in both moderate and Yoga is probably beneficial in both moderate and

severe depressed moodsevere depressed mood•• Of the various mindOf the various mind--body disciplines used to obtain relief body disciplines used to obtain relief

from psychiatric symptoms, more studies have been from psychiatric symptoms, more studies have been done on Yoga than any other discipline (done on Yoga than any other discipline (ShannahoffShannahoff--KhalsaKhalsa 2004). 2004).

•• The mechanism of action of yogic breathing might be The mechanism of action of yogic breathing might be similar to similar to vagalvagal nerve stimulation (VNS) in that both nerve stimulation (VNS) in that both approaches involve modulation of the balance of approaches involve modulation of the balance of parasympathetic and sympathetic autonomic tone. parasympathetic and sympathetic autonomic tone.

•• Yogic breathing achieves desirable changes through a Yogic breathing achieves desirable changes through a variety of specific breathing exercises that differentially variety of specific breathing exercises that differentially affect the brain stem and limbic system while VNS relies affect the brain stem and limbic system while VNS relies on a weak electrical current to achieve desirable changes on a weak electrical current to achieve desirable changes in brain autonomic activity that mediate improved mood in brain autonomic activity that mediate improved mood or reduced anxiety. or reduced anxiety.

Treatment: depressionTreatment: depressionhighhigh--density negative ionsdensity negative ions•• Regular exposure to highRegular exposure to high--density negative ions is density negative ions is

beneficial in seasonal depressed moodbeneficial in seasonal depressed mood•• Research findings from doubleResearch findings from double--blind controlled trials blind controlled trials

suggest that regular daily exposure to highsuggest that regular daily exposure to high--density density negative ions is an effective treatment of depressed negative ions is an effective treatment of depressed mood when there is a seasonal pattern of occurrence, mood when there is a seasonal pattern of occurrence, and probably has comparable efficacy to bright light and probably has comparable efficacy to bright light exposure for this condition.exposure for this condition.

•• 25 depressed patients with seasonal depressed mood 25 depressed patients with seasonal depressed mood were randomized to highwere randomized to high--density negative ions (2.7 X density negative ions (2.7 X 10(6) ions/cm3) versus low10(6) ions/cm3) versus low--density negative ions (1 X density negative ions (1 X 10(4) ions/cm3) using in10(4) ions/cm3) using in--home ion generators 30 home ion generators 30 minutes daily for three weeks (minutes daily for three weeks (TermanTerman 1995). 1995).

•• 58% of patients exposed to high58% of patients exposed to high--density negative ions density negative ions experienced significant improvements in mood on experienced significant improvements in mood on standardized rating scales compared to 15% of patients standardized rating scales compared to 15% of patients exposed to lowexposed to low--density negative ions. density negative ions.

Treatment: depressionTreatment: depressionacupunctureacupuncture•• Evaluating the clinical efficacy of Evaluating the clinical efficacy of

acupuncture in depressed mood poses acupuncture in depressed mood poses many methodological problems many methodological problems ((MacPhersonMacPherson 2004)2004)::–– heterogeneity in the severity and heterogeneity in the severity and comorbiditycomorbidity of of

mental, emotional or physical symptom patternsmental, emotional or physical symptom patterns–– concurrent uses of other conventional or nonconcurrent uses of other conventional or non--

conventional treatments in patients receiving conventional treatments in patients receiving acupunctureacupuncture

–– different Chinese medical diagnosesdifferent Chinese medical diagnoses–– the use of different acupuncture treatment protocols the use of different acupuncture treatment protocols

depending on the energetic formulation). depending on the energetic formulation).

Treatment: depressionTreatment: depressionacupunctureacupuncture

•• Acupuncture (including electroAcupuncture (including electro--acupuncture and computeracupuncture and computer--controlled controlled electroelectro--acupuncture) is probably beneficial acupuncture) is probably beneficial in moderate and severe depressed moodin moderate and severe depressed mood

•• Controlled studies and case reports suggest that Controlled studies and case reports suggest that acupuncture has beneficial effects on depressed acupuncture has beneficial effects on depressed mood, including conventional needle mood, including conventional needle acupuncture, electroacupuncture, electro--acupuncture (acupuncture (HechunHechun1990), and computer1990), and computer--controlled electrocontrolled electro--acupuncture (CCEA) (acupuncture (CCEA) (HechunHechun 1993).1993).

Treatment: depressionTreatment: depressionacupunctureacupuncture•• The evidence base for acupuncture treatments of The evidence base for acupuncture treatments of

depressed mood has been extensively reviewed (Flaws depressed mood has been extensively reviewed (Flaws and Lake 2000; and Lake 2000; SchnyerSchnyer 2001). 2001).

•• Findings of a doubleFindings of a double--blind shamblind sham--controlled study suggest controlled study suggest that traditional acupuncture (that traditional acupuncture (ieie, in the absence of , in the absence of electrical current) is an effective treatment of severely electrical current) is an effective treatment of severely depressed outpatients (Allen 1998). depressed outpatients (Allen 1998).

•• By the end of the 8By the end of the 8--week study 68% of 33 female week study 68% of 33 female outpatients being treated with an acupuncture protocol outpatients being treated with an acupuncture protocol directed at depressed mood had achieved full remission. directed at depressed mood had achieved full remission. Interestingly, depressed women patients who were not Interestingly, depressed women patients who were not receiving any treatment in the “waitreceiving any treatment in the “wait--list” group showed list” group showed equivalent improvement in mood. equivalent improvement in mood.

Treatment: depressionTreatment: depressionacupunctureacupuncture

•• In a large six week multiIn a large six week multi--center study 241 center study 241 depressed inpatients were randomized to receive depressed inpatients were randomized to receive electroelectro--acupuncture plus placebo or electroacupuncture plus placebo or electro--acupuncture plus acupuncture plus amitriptylineamitriptyline ((LuoLuo 1998).1998).

•• Both groups experienced equivalent Both groups experienced equivalent improvement in depressed mood. Factor analysis improvement in depressed mood. Factor analysis using the Hamilton Rating Scale for Depression using the Hamilton Rating Scale for Depression (HRSD) showed that electro(HRSD) showed that electro--acupuncture was acupuncture was superior to superior to amitriptylineamitriptyline when there was cowhen there was co--morbid anxiety.morbid anxiety.

OnOn--going research: depressiongoing research: depressionacupunctureacupuncture

•• An onAn on--going NCCAMgoing NCCAM--sponsored study is being conducted sponsored study is being conducted to further examine the reported efficacy of acupuncture to further examine the reported efficacy of acupuncture as a treatment of depressed mood. as a treatment of depressed mood.

•• 150 patients diagnosed with major depressive disorder 150 patients diagnosed with major depressive disorder will be randomized to acupuncture or a waitwill be randomized to acupuncture or a wait--list. list.

•• Patients receiving acupuncture will receive individualized Patients receiving acupuncture will receive individualized treatment based on energetic imbalances from the treatment based on energetic imbalances from the perspective of Chinese medical diagnosis. perspective of Chinese medical diagnosis.

•• PostPost--treatment followtreatment follow--up will last 18 months during up will last 18 months during which the investigators will study relationships between which the investigators will study relationships between beneficial energetic changes associated with beneficial energetic changes associated with acupuncture and clinical measures of improved mood acupuncture and clinical measures of improved mood used in conventional biomedicine.used in conventional biomedicine.

Treatment: depressionTreatment: depressionhighhigh--density negative ionsdensity negative ions

•• In a randomized controlled trial 158 patients In a randomized controlled trial 158 patients with seasonal depressed mood were randomly with seasonal depressed mood were randomly assigned to bright light exposure (10,000 assigned to bright light exposure (10,000 luxlux) at ) at different times of day versus highdifferent times of day versus high--density or density or lowlow--density negative ions for two weeks density negative ions for two weeks ((TermanTerman 1998).1998).

•• Patients exposed to highPatients exposed to high--density negative ions density negative ions or bright light experienced significant and or bright light experienced significant and equivalent improvements in mood. There was a equivalent improvements in mood. There was a differential beneficial effect of morning versus differential beneficial effect of morning versus evening bright light exposure. evening bright light exposure.

Treatment: depressionTreatment: depressionYogaYoga•• Like Yogic breathing techniques, the regular practice of Like Yogic breathing techniques, the regular practice of

various Yoga postures (various Yoga postures (asanasasanas) probably results in ) probably results in beneficial changes in the autonomic nervous system beneficial changes in the autonomic nervous system resulting in improved resulting in improved cardiorespiratorycardiorespiratory performance and performance and increased feelings of psychological wellincreased feelings of psychological well--being (being (HarinathHarinath2004). 2004).

•• Many styles of Yoga are probably beneficial in depressed Many styles of Yoga are probably beneficial in depressed mood. A particular style of yogic breathing called mood. A particular style of yogic breathing called SudarshanSudarshan KriyaKriya (SK) yoga has been extensively (SK) yoga has been extensively evaluated as a potential treatment of depressed mood evaluated as a potential treatment of depressed mood and other mental or emotional symptoms (and other mental or emotional symptoms (ShannahoffShannahoff--KhalsaKhalsa 1999). 1999).

•• Moderately depressed patients improved significantly by Moderately depressed patients improved significantly by the end of a 5the end of a 5--week yoga class (week yoga class (WooleryWoolery 2004). 2004).

Treatment: maniaTreatment: mania

•• EMPowerPlusEMPowerPlus ™, a unique nutrient formula, is ™, a unique nutrient formula, is probably an effective adjunctive or standprobably an effective adjunctive or stand--alone alone treatment of both depressive and manic treatment of both depressive and manic symptoms in Bipolar disordersymptoms in Bipolar disorder

•• The findings of two case series suggest that The findings of two case series suggest that EMPowerPlusEMPowerPlus ™, a nutrient formula containing 36 ™, a nutrient formula containing 36 separate constituents including separate constituents including chelatedchelated minerals, minerals, vitamins, and trace elements may significantly reduce vitamins, and trace elements may significantly reduce symptoms of mania, depressed mood and psychosis in symptoms of mania, depressed mood and psychosis in Bipolar patients when taken together with conventional Bipolar patients when taken together with conventional mood stabilizing medications (Popper 2001; Kaplan mood stabilizing medications (Popper 2001; Kaplan 2001). 2001).

Treatment: maniaTreatment: maniaEMPowerPlusEMPowerPlus™™•• Bipolar patients are genetically predisposed to develop Bipolar patients are genetically predisposed to develop

manic or depressive mood symptoms related to different manic or depressive mood symptoms related to different micronutrient deficiencies. The mechanism of action may micronutrient deficiencies. The mechanism of action may involve correction of ininvolve correction of in--born metabolic errors that born metabolic errors that predispose some individuals to become symptomatic predispose some individuals to become symptomatic when certain micronutrients are deficient in the diet when certain micronutrients are deficient in the diet (Kaplan 2001).(Kaplan 2001).

•• Findings to date suggest that Findings to date suggest that EMPowerPlusEMPowerPlus™ is probably ™ is probably beneficial alone or in combination with conventional beneficial alone or in combination with conventional mood stabilizers.mood stabilizers.

•• Patients in the first series took 32 capsules of Patients in the first series took 32 capsules of EMPowerPlusEMPowerPlus™ daily in four divided doses. 11 patients ™ daily in four divided doses. 11 patients who completed the 6who completed the 6--month protocol were able to month protocol were able to reduce their conventional mood stabilizing medications reduce their conventional mood stabilizing medications by half while improving clinically according to by half while improving clinically according to standardized symptom rating scales. standardized symptom rating scales.

Treatment: maniaTreatment: maniaEMPowerPlusEMPowerPlus™™•• In another case series,In another case series, 13 out of 19 Bipolar patients who 13 out of 19 Bipolar patients who

continued to take continued to take EMPowerPlusEMPowerPlus™ reportedly remained ™ reportedly remained stable after discontinuing conventional mood stabilizing stable after discontinuing conventional mood stabilizing medications (Simmons 2003).medications (Simmons 2003).

•• Four patients stopped taking the nutrient formula Four patients stopped taking the nutrient formula because of gastrointestinal side effects including nausea because of gastrointestinal side effects including nausea and diarrhea. Three other patients resumed conventional and diarrhea. Three other patients resumed conventional mood stabilizers because of recurring manic symptoms mood stabilizers because of recurring manic symptoms while taking while taking EMPowerPlusEMPowerPlus ™. ™.

•• 11 of the 19 patients in the case series who elected to 11 of the 19 patients in the case series who elected to discontinue conventional mood stabilizers while discontinue conventional mood stabilizers while continuing continuing EMPowerPlusEMPowerPlus™ have remained stable for ™ have remained stable for more than one year. more than one year.

Treatment: maniaTreatment: maniaEMPowerPlusEMPowerPlus™™•• Two randomized placeboTwo randomized placebo--controlled doublecontrolled double--blind studies blind studies

are onare on--going at this time, one in Canada and one in the going at this time, one in Canada and one in the U.S. Bipolar patients enrolled in those studies will initially U.S. Bipolar patients enrolled in those studies will initially take 6 capsules three times a day, and further reduce take 6 capsules three times a day, and further reduce the dose to a maintenance regimen of 3 capsules three the dose to a maintenance regimen of 3 capsules three times a day after two months on the initial protocol.times a day after two months on the initial protocol.

•• OnOn--going trials will identify specific nutrients in the going trials will identify specific nutrients in the complex complex EMPowerPlusEMPowerPlus ™ formula that have the most ™ formula that have the most beneficial effects in Bipolar patients in order to simplify beneficial effects in Bipolar patients in order to simplify future treatment regimens and reduce adverse effects. future treatment regimens and reduce adverse effects.

•• More studies are needed to clarify whether a More studies are needed to clarify whether a micronutrient formula alone is sufficient to stabilize micronutrient formula alone is sufficient to stabilize Bipolar patients, and to determine possibly differing Bipolar patients, and to determine possibly differing micronutrient treatments that address different symptom micronutrient treatments that address different symptom severities.severities.

Treatment: maniaTreatment: maniaEMPowerPlusEMPowerPlus™ safety issues™ safety issues•• Significant micronutrientSignificant micronutrient--medication interactions have medication interactions have

been reported in patients taking been reported in patients taking EMPowerPlusEMPowerPlus™ with ™ with conventional mood stabilizers (Popper 2001). conventional mood stabilizers (Popper 2001).

•• Interactions with micronutrients reportedly Interactions with micronutrients reportedly potentiatepotentiatethe effects of mood stabilizers and necessitate gradual the effects of mood stabilizers and necessitate gradual reductions in doses as the nutrient formula is started. reductions in doses as the nutrient formula is started.

•• Researchers caution clinicians who are considering Researchers caution clinicians who are considering recommending recommending EMPowerPlusEMPowerPlus™ to proceed gradually ™ to proceed gradually while carefully monitoring for adverse effects when while carefully monitoring for adverse effects when transitioning Bipolar patients to the micronutrient transitioning Bipolar patients to the micronutrient formula in order to minimize the risk of toxicity.formula in order to minimize the risk of toxicity.

•• Lowering the doses of conventional mood stabilizing Lowering the doses of conventional mood stabilizing medications too rapidly after starting a patient on medications too rapidly after starting a patient on EMPowerPlusEMPowerPlus™ (or another nutrient formula) entails the ™ (or another nutrient formula) entails the risk of worsening symptoms, while maintaining risk of worsening symptoms, while maintaining conventional medications at their usual doses may result conventional medications at their usual doses may result in significant toxicity. in significant toxicity.

Treatment: maniaTreatment: maniabranchedbranched--chain amino acidschain amino acids•• A branchedA branched--chain amino acid drink resulting in chain amino acid drink resulting in

acute depletion of tyrosine and phenylalanine acute depletion of tyrosine and phenylalanine may reduce symptoms of acute mania may reduce symptoms of acute mania

•• Oral administration of certain branchOral administration of certain branch--chain amino acids chain amino acids may rapidly improve acute manic symptoms by may rapidly improve acute manic symptoms by interfering with the synthesis of the catecholamine interfering with the synthesis of the catecholamine neurotransmitters neurotransmitters norepinephrinenorepinephrine and dopamine (Barrett and dopamine (Barrett 2004). 2004).

•• A mixture of A mixture of bioavailablebioavailable amino acids excluding tyrosine amino acids excluding tyrosine and phenylalanine (the precursor of tyrosine) is believed and phenylalanine (the precursor of tyrosine) is believed to reduce brain dopamine in Bipolar patients, resulting in to reduce brain dopamine in Bipolar patients, resulting in diminished manic symptoms and improved overall diminished manic symptoms and improved overall cognitive functioning (cognitive functioning (GijsmanGijsman 2002). 2002).

Treatment: maniaTreatment: maniabranched chain amino acidsbranched chain amino acids•• Twenty adult inpatients diagnosed with mania were Twenty adult inpatients diagnosed with mania were

randomized to receive the tyrosinerandomized to receive the tyrosine--free mixture or free mixture or placebo four hours before methamphetamine (which placebo four hours before methamphetamine (which stimulates dopamine release) (stimulates dopamine release) (McTavishMcTavish 2001). 2001).

•• Significant improvements in objective and subjective Significant improvements in objective and subjective indicators of mania were noted in patients taking the indicators of mania were noted in patients taking the tyrosinetyrosine--free mixture of amino acids. free mixture of amino acids.

•• The researchers speculated that restricting tyrosine in The researchers speculated that restricting tyrosine in manic patients would result in diminished brain manic patients would result in diminished brain dopamine and attenuation of nondopamine and attenuation of non--stimulantstimulant--induced induced manic symptoms. manic symptoms.

Treatments: anxietyTreatments: anxietyLL--theaninetheanine

•• LL--theaninetheanine (gamma(gamma--ethylaminoethylamino--LL--glutamicglutamic acid) acid) is an effective treatment of moderate and severe is an effective treatment of moderate and severe anxiety and does not cause drowsinessanxiety and does not cause drowsiness

•• Green tea is used as a restorative in traditional Chinese Green tea is used as a restorative in traditional Chinese medicine and contains many bioactive constituents medicine and contains many bioactive constituents including the amino acid Lincluding the amino acid L--theaninetheanine. .

•• In recent years LIn recent years L--theaninetheanine has been extracted from has been extracted from Green tea, and is now widely used to treat anxiety Green tea, and is now widely used to treat anxiety symptoms and depressed mood in China, Japan and symptoms and depressed mood in China, Japan and other Asian countries. other Asian countries.

•• The calming effects of LThe calming effects of L--theaninetheanine are believed to are believed to compensate for the stimulating effects of caffeine in compensate for the stimulating effects of caffeine in Green tea (Green tea (KakudaKakuda 2000). 2000).

•• The antiThe anti--anxiety effect of Lanxiety effect of L--theaninetheanine is achieved through is achieved through enhanced alpha brain wave activity and increased enhanced alpha brain wave activity and increased synthesis of GABA (synthesis of GABA (JunejaJuneja 1999; 1999; KakudaKakuda 2000). 2000).

Treatments: anxietyTreatments: anxietyLL--theaninetheanine•• Increased GABA, in turn, increases brain levels of dopamine and Increased GABA, in turn, increases brain levels of dopamine and

reduces serotonin, resulting in general feelings of calm and welreduces serotonin, resulting in general feelings of calm and welll--being (Mason 2001). being (Mason 2001).

•• Changes in brain electrical activity measured by EEG are doseChanges in brain electrical activity measured by EEG are dose--dependent, and are similar to beneficial EEG changes observed independent, and are similar to beneficial EEG changes observed inmeditation, including increased alpha waves in the occipital andmeditation, including increased alpha waves in the occipital andparietal regions (Ito 1998). parietal regions (Ito 1998).

•• A calming effect is usually noted within 30 to 40 minutes after A calming effect is usually noted within 30 to 40 minutes after LL--theaninetheanine is taken at a dose of 50 to 200mg, and typically lasts 8 to is taken at a dose of 50 to 200mg, and typically lasts 8 to 10 hours. 10 hours.

•• Moderate anxiety symptoms often improve with a regimen of 200mg Moderate anxiety symptoms often improve with a regimen of 200mg once or twice daily. More severe anxiety symptoms may require once or twice daily. More severe anxiety symptoms may require doses up to 600mg to 800mg daily taken in increments of 100mg todoses up to 600mg to 800mg daily taken in increments of 100mg to200mg spaced over the day. 200mg spaced over the day.

•• Unlike benzodiazepines and other conventional antiUnlike benzodiazepines and other conventional anti--anxiety anxiety treatments, Ltreatments, L--theaninetheanine does not result in increased drowsiness, does not result in increased drowsiness, slowed reflexes or impaired concentration. There is no risk of slowed reflexes or impaired concentration. There is no risk of developing tolerance or dependence, and there have been no developing tolerance or dependence, and there have been no reports of serious adverse side effects or interactions with othreports of serious adverse side effects or interactions with other er natural products or synthetic drugs. natural products or synthetic drugs.

Treatment: anxietyTreatment: anxietyVR graded exposure therapyVR graded exposure therapy

•• VRGET is an effective treatment of many anxiety VRGET is an effective treatment of many anxiety symptom patterns including specific phobias, symptom patterns including specific phobias, generalized anxiety, panic disorder with generalized anxiety, panic disorder with agoraphobia (agoraphobia (VincelliVincelli 2000) and post2000) and post--traumatic traumatic stress disorder (Riva 2001). stress disorder (Riva 2001).

•• In a controlled study VRGET and conventional In a controlled study VRGET and conventional cognitivecognitive--behavioral therapy were equally behavioral therapy were equally effective in the treatment of panic disorder with effective in the treatment of panic disorder with agoraphobia, however patients who underwent agoraphobia, however patients who underwent VRGET required 33% fewer sessions (VRGET required 33% fewer sessions (VincelliVincelli2003). 2003).

Treatment: anxietyTreatment: anxietyVR exposure therapyVR exposure therapy

•• Case reports and controlled studies have Case reports and controlled studies have demonstrated the effectiveness of VRGET in demonstrated the effectiveness of VRGET in many specific phobias including fear of flying many specific phobias including fear of flying ((RothbaumRothbaum 2000; 2000; WiederholdWiederhold 2002), fear of 2002), fear of heights, fear of small animals, fear of driving, heights, fear of small animals, fear of driving, and others (and others (RothbaumRothbaum 1999; 1999; GlantzGlantz 1996).1996).

•• In one controlled study 65% of anxious adults In one controlled study 65% of anxious adults (N=45) diagnosed with a specific anxiety (N=45) diagnosed with a specific anxiety disorder according to DSMdisorder according to DSM--IV criteria reported IV criteria reported significant reductions in 4 of 5 anxiety measures significant reductions in 4 of 5 anxiety measures ((MaltbyMaltby 2002).2002).

Treatment: anxietyTreatment: anxietyVR exposure therapyVR exposure therapy•• VRGET is as effective as conventional exposure VRGET is as effective as conventional exposure

therapy for fear of flying, and is more costtherapy for fear of flying, and is more cost--effective because both patient and therapist effective because both patient and therapist avoid significant time commitments and the avoid significant time commitments and the need to use airplanes (need to use airplanes (RothbaumRothbaum 1999; 1999; RothbaumRothbaum 2000). 2000).

•• In a pilot study individuals who overcame fear of In a pilot study individuals who overcame fear of flying using VRGET combined with biofeedback flying using VRGET combined with biofeedback (including respirations, GSR and heart rate) (including respirations, GSR and heart rate) were able to fly without the use of conventional were able to fly without the use of conventional medications or alcohol 3 months after treatment medications or alcohol 3 months after treatment ended (ended (WiederholdWiederhold 2002). 2002).

Treatment: anxietyTreatment: anxietyVR exposure therapyVR exposure therapy

•• VRGET is also beneficial for VRGET is also beneficial for traumatized patients who have been traumatized patients who have been diagnosed with PTSD. A virtual diagnosed with PTSD. A virtual environment that simulates the environment that simulates the devastation that took place following devastation that took place following the September 11, 2001 attacks of the September 11, 2001 attacks of the World Trade Towers has been the World Trade Towers has been successfully used to treat individuals successfully used to treat individuals who suffered from severe PTSD who suffered from severe PTSD following the attacks (following the attacks (DifedeDifede 2002).2002).

Treatment: anxietyTreatment: anxietyVR exposure therapyVR exposure therapy——safety issuessafety issues

•• Fewer than 4% of individuals experience transient Fewer than 4% of individuals experience transient symptoms of disorientation, nausea, dizziness, headache symptoms of disorientation, nausea, dizziness, headache and blurred vision when in a virtual environment. and blurred vision when in a virtual environment.

•• “Simulator sleepiness” is a feeling of generalized fatigue “Simulator sleepiness” is a feeling of generalized fatigue that occurs infrequently. Intense sensory stimulation that occurs infrequently. Intense sensory stimulation during VRGET can trigger migraine headaches, seizures, during VRGET can trigger migraine headaches, seizures, or gait abnormalities in individuals who have these or gait abnormalities in individuals who have these medical problems. medical problems.

•• VRGET is therefore contraVRGET is therefore contra--indicated in these indicated in these populations. Anxious patients who are actively abusing populations. Anxious patients who are actively abusing alcohol or narcotics should not use VRGET. alcohol or narcotics should not use VRGET.

Treatment: anxietyTreatment: anxietyVR exposure therapyVR exposure therapy——safety safety

•• Patients who have disorders of the Patients who have disorders of the vestibular system should be advised to not vestibular system should be advised to not use VRGET. use VRGET.

•• Psychotic patients should not use VRGET Psychotic patients should not use VRGET because immersion in a virtual because immersion in a virtual environment can exacerbate delusions and environment can exacerbate delusions and potentially worsen realitypotentially worsen reality--testing testing ((WiederholdWiederhold 2005). 2005).

Treatment: anxietyTreatment: anxietyEEG biofeedbackEEG biofeedback•• EMG, GSR and EEG biofeedback training reduces EMG, GSR and EEG biofeedback training reduces

symptoms of generalized anxietysymptoms of generalized anxiety•• Biofeedback has nonBiofeedback has non--specific beneficial effects on many specific beneficial effects on many

anxiety symptoms. EMG, thermal and EEG biofeedback anxiety symptoms. EMG, thermal and EEG biofeedback training are efficacious treatments of generalized anxiety training are efficacious treatments of generalized anxiety (Hurley 1992; (Hurley 1992; WenckWenck 1996; 1996; VanathyVanathy 1998).1998).

•• Biofeedback is probably equivalent to relaxation Biofeedback is probably equivalent to relaxation techniques (techniques (ScandrettScandrett 1986; 1986; RoomeRoome 1985) for the 1985) for the management of generalized anxiety in both adults and management of generalized anxiety in both adults and children. children.

•• Chronically anxious patients trained in EEG or EMG Chronically anxious patients trained in EEG or EMG biofeedback achieve symptom reduction similar to those biofeedback achieve symptom reduction similar to those taking conventional antitaking conventional anti--anxiety medications (Rice 1993; anxiety medications (Rice 1993; SarkarSarkar 1999). 1999).

Treatment: anxietyTreatment: anxietybiofeedbackbiofeedback

•• GSR biofeedback in combination with a relaxation GSR biofeedback in combination with a relaxation technique improves anxiety more than relaxation alone technique improves anxiety more than relaxation alone ((FehringFehring 1983). 1983).

•• The residual benefits of EEG biofeedback for anxious The residual benefits of EEG biofeedback for anxious patients have not been clearly established. One study patients have not been clearly established. One study evaluated two EEG biofeedback machines on patients evaluated two EEG biofeedback machines on patients complaining of anxiety and “burnout” in an addiction complaining of anxiety and “burnout” in an addiction treatment center (treatment center (OssebaardOssebaard 2000). 2000).

•• Although patients experienced immediate reductions in Although patients experienced immediate reductions in state anxiety during biofeedback training, longstate anxiety during biofeedback training, long--term term effects on “burnout” were not maintained following effects on “burnout” were not maintained following discontinuation of treatment.discontinuation of treatment.

Treatment: anxietyTreatment: anxiety55--HTPHTP

•• 55--HTP may be as effective as conventional medications for HTP may be as effective as conventional medications for generalized anxietygeneralized anxiety

•• LL--tryptophantryptophan and 5and 5--HTP are widely used nonHTP are widely used non--conventional conventional treatments of generalized anxiety, but to date few rigorously treatments of generalized anxiety, but to date few rigorously conducted studies have examined their efficacy. conducted studies have examined their efficacy.

•• Both amino acids are essential precursors for serotonin synthesiBoth amino acids are essential precursors for serotonin synthesis, a s, a neurotransmitter that has a central role in the regulation of moneurotransmitter that has a central role in the regulation of mood od and anxiety. and anxiety.

•• There is a more extensive research literature on 5There is a more extensive research literature on 5--HTP for anxiety HTP for anxiety compared to Lcompared to L--tryptophantryptophan. .

•• In a doubleIn a double--blind study, 58% of generally anxious patients (N=79) blind study, 58% of generally anxious patients (N=79) randomized to Lrandomized to L--tryptophantryptophan 3g/day reported significantly greater 3g/day reported significantly greater reductions in baseline anxiety compared to placebo (reductions in baseline anxiety compared to placebo (ZangZang 1991). 1991).

•• Animal studies and human clinical trials provide evidence that 5Animal studies and human clinical trials provide evidence that 5--HTP HTP has consistent antihas consistent anti--anxiety effects (anxiety effects (SoderpalmSoderpalm 1990; Kahn et al. 1990; Kahn et al. 1987). 1987).

Treatment: anxietyTreatment: anxiety55--HTPHTP•• 55--HTP may inhibit panic attacks induced by HTP may inhibit panic attacks induced by

carbon dioxide (carbon dioxide (SchruersSchruers 2000).2000). Patients Patients randomized to 5randomized to 5--HTP with HTP with carbidobacarbidoba (a drug (a drug that inhibits the enzyme that breaks down 5that inhibits the enzyme that breaks down 5--HTP in the peripheral blood supply, thus HTP in the peripheral blood supply, thus increasing the amount of 5increasing the amount of 5--HTP that crosses the HTP that crosses the bloodblood--brain barrier) reported significant brain barrier) reported significant reductions in anxiety that were comparable to reductions in anxiety that were comparable to clomipramineclomipramine, a conventional anti, a conventional anti--anxiety anxiety medication. medication.

•• Patients taking a placebo did not improve (Kahn Patients taking a placebo did not improve (Kahn 1987). 51987). 5--HTP may be safely combined with HTP may be safely combined with conventional anticonventional anti--anxiety drugs with monitoring anxiety drugs with monitoring for adverse effects related to excessive brain for adverse effects related to excessive brain serotonin, including insomnia, agitation and serotonin, including insomnia, agitation and nervousness.nervousness.

Treatment: anxietyTreatment: anxiety55--HTPHTP•• The risk of adverse effects is minimized when 5The risk of adverse effects is minimized when 5--

HTP is started at doses of 25mg/day and HTP is started at doses of 25mg/day and gradually increased over several weeks to a daily gradually increased over several weeks to a daily regimen that is well tolerated and produces regimen that is well tolerated and produces beneficial antibeneficial anti--anxiety effects. anxiety effects.

•• 55--HTP 50mg to 100mg three times a day is well HTP 50mg to 100mg three times a day is well tolerated without excessive daytime sedation, tolerated without excessive daytime sedation, and is effective approach for many chronically and is effective approach for many chronically anxious patients when used alone or in anxious patients when used alone or in combination with combination with SSRIsSSRIs or other conventional or other conventional antianti--anxiety drugs. anxiety drugs.

•• Gradually titrating a bedtime dose of 5Gradually titrating a bedtime dose of 5--HTP to HTP to 200 to 400mg often reduces daytime anxiety 200 to 400mg often reduces daytime anxiety and improves the quality of sleep in chronically and improves the quality of sleep in chronically anxious patients who complain of insomnia.anxious patients who complain of insomnia.

Treatment: anxietyTreatment: anxietyacupunctureacupuncture

•• Acupuncture and electroAcupuncture and electro--acupuncture probably acupuncture probably reduce symptoms of generalized anxietyreduce symptoms of generalized anxiety

•• Acupuncture and acupressure are widely used to treat Acupuncture and acupressure are widely used to treat anxiety. Extensive case reports from the Chinese medical anxiety. Extensive case reports from the Chinese medical literature suggest that different acupuncture protocols literature suggest that different acupuncture protocols are beneficial in the management of anxiety symptom are beneficial in the management of anxiety symptom pattern that resemble generalized anxiety and panic pattern that resemble generalized anxiety and panic attacks (Flaws and Lake 2001). attacks (Flaws and Lake 2001).

•• Only a few small prospective controlled studies support Only a few small prospective controlled studies support the use of these traditional energy therapies, and most the use of these traditional energy therapies, and most studies on the anxietystudies on the anxiety--reducing effects of acupuncture reducing effects of acupuncture examine the general benefits of acupuncture on several examine the general benefits of acupuncture on several mental and emotional symptoms, including anxiety. mental and emotional symptoms, including anxiety.

Treatment: anxietyTreatment: anxietyacupunctureacupuncture

•• A narrative review of controlled studies, A narrative review of controlled studies, outcomes studies and published case outcomes studies and published case reports on acupuncture as a treatment of reports on acupuncture as a treatment of anxiety and depressed mood was recently anxiety and depressed mood was recently published by the British Acupuncture published by the British Acupuncture Council. (British Acupuncture Council Council. (British Acupuncture Council 2002). Sham2002). Sham--controlled studies yielded controlled studies yielded consistent improvements in anxiety using consistent improvements in anxiety using both regular acupuncture and electroboth regular acupuncture and electro--acupuncture. acupuncture.

Treatment: anxietyTreatment: anxietyReikiReiki

•• Regular Reiki treatments may reduce symptoms Regular Reiki treatments may reduce symptoms of anxiety associated with chronic pain or of anxiety associated with chronic pain or depressed mooddepressed mood

•• The findings of two studies suggest that regular Reiki The findings of two studies suggest that regular Reiki treatments reduce the severity of anxiety symptoms in treatments reduce the severity of anxiety symptoms in individuals who are chronically stressed (individuals who are chronically stressed (HeidtHeidt 1981; 1981; Kramer 1990). Kramer 1990).

•• Patients with mixed anxious depressed mood Patients with mixed anxious depressed mood experienced significant relief following weekly treatments experienced significant relief following weekly treatments with contact or nonwith contact or non--contact Reiki (Shore 2004). contact Reiki (Shore 2004).

•• Reiki treatments may improve state anxiety in chronic Reiki treatments may improve state anxiety in chronic pain patients. 120 chronically ill patients were pain patients. 120 chronically ill patients were randomized to receive Reiki, sham Reiki, progressive randomized to receive Reiki, sham Reiki, progressive muscle relaxation and no treatment (muscle relaxation and no treatment (DressenDressen 1998). 1998).

Treatment: anxietyTreatment: anxietyReikiReiki

•• Improvements in state anxiety (and pain) Improvements in state anxiety (and pain) in patients receiving Reiki were in patients receiving Reiki were significantly greater than the other three significantly greater than the other three groups. groups.

•• Significance of findings limited by absence Significance of findings limited by absence of control for possible differences in the of control for possible differences in the use of anxiety reducing medications use of anxiety reducing medications between the active treatment groups and between the active treatment groups and the control groups.the control groups.

Treatment: psychosisTreatment: psychosisAyurvedicAyurvedic herbal formulasherbal formulas

•• BrahmyadiyogaBrahmyadiyoga, an , an AyurvedicAyurvedic compound herbal compound herbal medicine, holds significant promise for the medicine, holds significant promise for the management of psychosismanagement of psychosis

•• BrahmyadiyogaBrahmyadiyoga is a compound herbal formula used in is a compound herbal formula used in AyurvedicAyurvedic medicine for the treatment of symptom medicine for the treatment of symptom patterns that resemble schizophrenia. The formula patterns that resemble schizophrenia. The formula includes six herbs including includes six herbs including RauwolfiaRauwolfia serpentinaserpentina from from which which reserpinereserpine was isolated in the early 20th century was isolated in the early 20th century and shown to have significant antipsychotic efficacy. and shown to have significant antipsychotic efficacy.

•• ReserpineReserpine is seldom used to treat schizophrenia in is seldom used to treat schizophrenia in Western countries today because of concerns over Western countries today because of concerns over reports of severe depressed mood. reports of severe depressed mood.

Treatment: psychosisTreatment: psychosisAyurvedicAyurvedic herbal formulasherbal formulas•• In a twoIn a two--month doublemonth double--blind placebo controlled study, blind placebo controlled study,

108 chronically psychotic patients were randomized to 108 chronically psychotic patients were randomized to BrahmyadiyogaBrahmyadiyoga 88--12g in four divided doses, 12g in four divided doses, ValarianValarian 88--12 g in four divided doses, chlorpromazine 20012 g in four divided doses, chlorpromazine 200--300mg/day and placebo (300mg/day and placebo (MahalMahal 1976). 1976).

•• Patients treated with Patients treated with BrahmyadiyogaBrahmyadiyoga (but not Valerian) (but not Valerian) and chlorpromazine reported significant and comparable and chlorpromazine reported significant and comparable improvements in symptom severity. No significant improvements in symptom severity. No significant adverse effects were reported in the group taking adverse effects were reported in the group taking BrahmyadiyogaBrahmyadiyoga. .

•• A subsequent study confirmed the antipsychotic efficacy A subsequent study confirmed the antipsychotic efficacy of of BrahmyadiyogaBrahmyadiyoga ((RamuRamu 1992). 1992).

•• Preliminary research findings suggest that another Preliminary research findings suggest that another compound herbal formula, compound herbal formula, MentatMentat ™, may reduce ™, may reduce negative psychotic symptoms (negative psychotic symptoms (DasDas 1989). 1989).

•• AyurvedicAyurvedic herbal medicines should be used only under herbal medicines should be used only under the supervision of a qualified the supervision of a qualified AyurvedicAyurvedic physician.physician.

Treatment: psychosisTreatment: psychosisOmegaOmega--3 fatty acids3 fatty acids

•• Supplementation with OmegaSupplementation with Omega--3 fatty acids may 3 fatty acids may improve both positive and negative psychotic improve both positive and negative psychotic symptomssymptoms

•• Findings from case reports (Findings from case reports (PuriPuri 2002; Su 2001) suggest 2002; Su 2001) suggest that Omegathat Omega--3 fatty acids improve psychotic symptoms. 3 fatty acids improve psychotic symptoms.

•• In a small open study (In a small open study (ArvindakshanArvindakshan 2003b) chronically 2003b) chronically psychotic patients experienced significant clinical psychotic patients experienced significant clinical improvements when treated with Omegaimprovements when treated with Omega--3s (EPA and 3s (EPA and DHA) 300mg and antioxidant vitamins twice daily over a DHA) 300mg and antioxidant vitamins twice daily over a four month period. Sustained improvements in psychotic four month period. Sustained improvements in psychotic symptoms were reported throughout the trial. symptoms were reported throughout the trial.

•• A small doubleA small double--blind study (blind study (PeetPeet 1997) demonstrated 1997) demonstrated sustained improvement in both positive and negative sustained improvement in both positive and negative psychotic symptoms in chronically psychotic patients psychotic symptoms in chronically psychotic patients treated with Omegatreated with Omega--3 fatty acids, with or without 3 fatty acids, with or without conventional antipsychotic medications.conventional antipsychotic medications.


•• In a more recent and larger study (In a more recent and larger study (PeetPeet 2002) 2002) 115 treatment115 treatment--refractory schizophrenics were refractory schizophrenics were randomized to receive 1, 2 or 4g/day of EPA or randomized to receive 1, 2 or 4g/day of EPA or placebo together with their conventional placebo together with their conventional antipsychotic medications. antipsychotic medications.

•• Only patients taking Only patients taking ClozapineClozapine (but not other (but not other antipsychoticsantipsychotics) experienced improvements ) experienced improvements greater than those observed in the group taking greater than those observed in the group taking EPA. Clinical improvements were observed in all EPA. Clinical improvements were observed in all EPAEPA--treated groups taking treated groups taking ClozapineClozapine, but the , but the group receiving 2g/day benefited most. group receiving 2g/day benefited most.


•• Another doubleAnother double--blind placeboblind placebo--controlled study revealed controlled study revealed no differences in response between an Omegano differences in response between an Omega--3 fatty 3 fatty acid, acid, ecosapentanoicecosapentanoic acid (EPA) (3gm/day), and placebo acid (EPA) (3gm/day), and placebo over a 4 month period in a group of 87 chronically over a 4 month period in a group of 87 chronically psychotic patients taking conventional psychotic patients taking conventional antipsychoticsantipsychoticsconcurrently (Fenton 2001).concurrently (Fenton 2001).

•• In contrast to earlier studies, patients in the Fenton In contrast to earlier studies, patients in the Fenton study were treated for residual psychotic symptoms, but study were treated for residual psychotic symptoms, but did not receive Omegadid not receive Omega--3 fatty acids while in the early 3 fatty acids while in the early acute phase of illnessacute phase of illness. .

•• Significantly, the results of a similar study (Significantly, the results of a similar study (EmsleyEmsley 2002) 2002) using ethylusing ethyl--EPA instead of EPA concluded that EPA was EPA instead of EPA concluded that EPA was an effective augmentation treatment.an effective augmentation treatment.

Treatment: psychosisTreatment: psychosisDHEADHEA•• DHEA may be an effective adjunctive treatment DHEA may be an effective adjunctive treatment

especially for especially for negativenegative psychotic symptomspsychotic symptoms•• The sulfated form of DHEAThe sulfated form of DHEA——DHEADHEA--SS——is the most is the most

abundant steroid in the body. DHEA is an important abundant steroid in the body. DHEA is an important neuroactiveneuroactive steroid because it acts as an antagonist to steroid because it acts as an antagonist to the GABA receptor complex, thus modulating neuronal the GABA receptor complex, thus modulating neuronal excitability (Howard 1992). excitability (Howard 1992).

•• Possible mechanism of action include increased Possible mechanism of action include increased dopamine release in the frontal cortex and enhanced dopamine release in the frontal cortex and enhanced activity of NMDA and sigma receptors (activity of NMDA and sigma receptors (MajewskaMajewska 1987; 1987; Maurice 2001). Maurice 2001).

•• In a sixIn a six--week randomized placeboweek randomized placebo--controlled study thirty controlled study thirty schizophrenic inpatients treated with DHEA 100mg/day schizophrenic inpatients treated with DHEA 100mg/day in addition to their regular antipsychotic medications in addition to their regular antipsychotic medications experienced significant improvements in negative experienced significant improvements in negative psychotic symptoms including reduced apathy and social psychotic symptoms including reduced apathy and social withdrawal. withdrawal.

Treatment: psychosisTreatment: psychosisDHEADHEA•• Patients taking DHEA report marked Patients taking DHEA report marked

improvement in depressed mood and anxiety improvement in depressed mood and anxiety ((StrousStrous 2003). 2003).

•• There were no significant changes in positive There were no significant changes in positive psychotic symptoms including auditory psychotic symptoms including auditory hallucinations and delusions. hallucinations and delusions.

•• Findings of another small doubleFindings of another small double--blind study blind study (N=30) suggest that DHEA augmentation (N=30) suggest that DHEA augmentation (100mg/day for six weeks) of conventional (100mg/day for six weeks) of conventional antipsychotic medications, is well tolerated, antipsychotic medications, is well tolerated, significantly reduces negative symptoms, and significantly reduces negative symptoms, and may be especially effective in women (may be especially effective in women (StrousStrous2005).2005).

Treatment: psychosisTreatment: psychosisglycineglycine•• Adding Adding glycineglycine to conventional to conventional antipsychoticsantipsychotics

may improve negative symptoms may improve negative symptoms •• Some cases of chronic psychosis may be related to Some cases of chronic psychosis may be related to

abnormal low activity of the excitatory neurotransmitter abnormal low activity of the excitatory neurotransmitter glutamate or glutamate or dysregulationdysregulation of NMDA receptors to which of NMDA receptors to which glutamate binds. glutamate binds.

•• NMDA receptors function best when both glutamate and NMDA receptors function best when both glutamate and glycineglycine bind to them, increasing their excitatory activity bind to them, increasing their excitatory activity ((IshimaruIshimaru 1997). 1997).

•• Provisional evidence is consistent with the hypothesis Provisional evidence is consistent with the hypothesis that atypical that atypical antipsychoticsantipsychotics increase brain glutamate. increase brain glutamate.

Treatment: psychosisTreatment: psychosisglycineglycine•• In one small open series, 11 patients switched from a In one small open series, 11 patients switched from a

firstfirst--generation antipsychotic to a newer atypical agent generation antipsychotic to a newer atypical agent were found to have significantly higher brain glutamate were found to have significantly higher brain glutamate concentrations (Goff 2001).concentrations (Goff 2001).

•• Increased glutamate correlated with significant Increased glutamate correlated with significant improvements in negative psychotic symptoms including improvements in negative psychotic symptoms including reduced social withdrawal and apathy. reduced social withdrawal and apathy.

•• A small open trial resulted in beneficial effects of A small open trial resulted in beneficial effects of glycineglycineat doses up to 60g/day (at doses up to 60g/day (LeidermanLeiderman 1996). 1996).

•• In a six week doubleIn a six week double--blind crossblind cross--over study 22 over study 22 treatmenttreatment--resistant schizophrenics were randomized to resistant schizophrenics were randomized to glycineglycine 0.8g/kg versus placebo in addition to their 0.8g/kg versus placebo in addition to their conventional antipsychotic medication (conventional antipsychotic medication (HerescoHeresco--Levy Levy 1999). 1999).

Treatment: psychosisTreatment: psychosisglycineglycine

•• Negative symptoms and global functioning decreased by Negative symptoms and global functioning decreased by 20 to 30% with 20 to 30% with glycineglycine augmentation (up to 60g/day) augmentation (up to 60g/day) compared to conventional treatment alone, and compared to conventional treatment alone, and glycineglycinewas well tolerated at therapeutic doses. was well tolerated at therapeutic doses.

•• Case reports suggest that Case reports suggest that glycineglycine supplementation may supplementation may improve mood and overall cognitive functioning in some improve mood and overall cognitive functioning in some chronic schizophrenics (chronic schizophrenics (HerescoHeresco--Levy 1996; Levy 1996; ZylbermanZylberman1994). 1994).

•• GlycineGlycine has few adverse effects however there are case has few adverse effects however there are case reports of acute psychosis in some chronically psychotic reports of acute psychosis in some chronically psychotic patients treated with large doses. patients treated with large doses.

•• The clinical use of The clinical use of glycineglycine is complicated by the fact that is complicated by the fact that it is impractical for many chronically psychotic patients to it is impractical for many chronically psychotic patients to take large doses of take large doses of glycineglycine (or any nutritional (or any nutritional supplement) that can potentially ameliorate their supplement) that can potentially ameliorate their symptoms.symptoms.

OnOn--going research: psychosisgoing research: psychosis----glycineglycine

•• GlycineGlycine may improve negative and positive symptoms when may improve negative and positive symptoms when combined with combined with ClozapineClozapine

•• Previous research has established that high doses of Previous research has established that high doses of glycineglycine result result in significant improvements in negative psychotic symptoms in significant improvements in negative psychotic symptoms (above).(above).

•• DD--cycloserinecycloserine may improve negative psychotic symptoms when used may improve negative psychotic symptoms when used in conjunction with conventional in conjunction with conventional antipsychoticsantipsychotics, but may exacerbate , but may exacerbate psychotic symptoms when used concurrently with psychotic symptoms when used concurrently with ClozapineClozapine. .

•• GlycineGlycine and and ClozapineClozapine may have a shared mechanism of action may have a shared mechanism of action involving modulation of the NMDA complex.involving modulation of the NMDA complex.

•• This NCCAMThis NCCAM--sponsored study will determine whether there is a sponsored study will determine whether there is a significant synergistic effect when significant synergistic effect when glycineglycine is taken together with is taken together with ClozapineClozapine. .

•• Researchers will also evaluate DResearchers will also evaluate D--cycloserinecycloserine to determine a possible to determine a possible worsening effect when used with worsening effect when used with ClozapineClozapine. .

Treatment: psychosisTreatment: psychosisspiritual support group and yogaspiritual support group and yoga•• Yogic breathing combined with spiritually Yogic breathing combined with spiritually

oriented group psychotherapy improves overall oriented group psychotherapy improves overall functioning in chronic schizophrenicsfunctioning in chronic schizophrenics

•• Complex relationships exist between religious or spiritual Complex relationships exist between religious or spiritual beliefs and practices and psychotic symptoms. beliefs and practices and psychotic symptoms.

•• Individuals who have a history of schizophrenia or Individuals who have a history of schizophrenia or another chronic psychotic illness and are stable or have another chronic psychotic illness and are stable or have well controlled residual symptoms may benefit from well controlled residual symptoms may benefit from social support that comes with involvement in organized social support that comes with involvement in organized religion. religion.

•• A spiritual orientation can provide encouragement, social A spiritual orientation can provide encouragement, social support and valuable insights to people who struggle support and valuable insights to people who struggle daily with schizophrenia (Sullivan 1993). daily with schizophrenia (Sullivan 1993).

•• Innovative efforts to build support groups for chronic Innovative efforts to build support groups for chronic schizophrenics around spiritual themes and mindschizophrenics around spiritual themes and mind--body body practices have identified important benefits of this practices have identified important benefits of this approach (approach (SagemanSageman 2004).2004).

Treatment: psychosisTreatment: psychosisspiritual support group and Yogaspiritual support group and Yoga

•• Individuals who participated in the support Individuals who participated in the support group reported significant improvements in group reported significant improvements in general selfgeneral self--esteem and increased hopefulness esteem and increased hopefulness together with a deeper sense of connection with together with a deeper sense of connection with their peers and communities. their peers and communities.

•• Group prayer, reading passages from various Group prayer, reading passages from various spiritual traditions, and Yogic breathing practices spiritual traditions, and Yogic breathing practices are valuable components of the group process. are valuable components of the group process. SudarshanSudarshan KriyaKriya yoga is especially effective in yoga is especially effective in reducing anxiety and improving mental clarity reducing anxiety and improving mental clarity (Brown 2002). (Brown 2002).

Treatment: psychosisTreatment: psychosisspiritual support groupsspiritual support groups•• The researchers felt that schizophrenic patients The researchers felt that schizophrenic patients

who attended spiritually oriented support groups who attended spiritually oriented support groups improved more than patients in more improved more than patients in more conventional support groups. conventional support groups.

•• Significant clinical benefits of regular spiritually Significant clinical benefits of regular spiritually oriented groups include improved range of oriented groups include improved range of affect, enhanced feelings of subjective wellaffect, enhanced feelings of subjective well--being, improved cognitive functioning during being, improved cognitive functioning during groups, deeper experiences of interpersonal groups, deeper experiences of interpersonal bonding with other group members, and bonding with other group members, and enhanced capacity for empathy.enhanced capacity for empathy.

Treatment: psychosisTreatment: psychosislaser acupuncturelaser acupuncture•• Daily laser acupuncture treatments may improve global Daily laser acupuncture treatments may improve global

functioning in schizophrenicsfunctioning in schizophrenics•• The use of laser light to stimulate specific acupuncture points The use of laser light to stimulate specific acupuncture points

reportedly results in significant clinical improvements in patiereportedly results in significant clinical improvements in patients nts diagnosed with schizophrenia based on standardized symptom diagnosed with schizophrenia based on standardized symptom rating scales. rating scales.

•• Researchers at the Institute of Mental Health, Beijing College oResearchers at the Institute of Mental Health, Beijing College of f Medicine, have developed a protocol that uses laser light of difMedicine, have developed a protocol that uses laser light of different ferent wavelengths to stimulate the wavelengths to stimulate the ermenermen acupointacupoint in schizophrenics in schizophrenics (Liu (Liu 1986).1986).

•• The protocol is based on daily 10 minute sessions , excluding The protocol is based on daily 10 minute sessions , excluding Sundays, and reportedly reduces the severity of auditory Sundays, and reportedly reduces the severity of auditory hallucinations and other positive psychotic symptoms. In a singlhallucinations and other positive psychotic symptoms. In a singlee--blind study 15 schizophrenic patients with a 5 year or shorter hblind study 15 schizophrenic patients with a 5 year or shorter history istory of active symptoms were randomly assigned to receive laser of active symptoms were randomly assigned to receive laser acupointacupoint therapy with a 25mW versus a 5.9mW laser for a total therapy with a 25mW versus a 5.9mW laser for a total number of 30 consecutive daily treatments (number of 30 consecutive daily treatments (JiaJia 1987). 1987).

Treatment: psychosisTreatment: psychosislaser acupuncturelaser acupuncture•• Patients did not know the specifications of the Patients did not know the specifications of the

laser used. Conventional antipsychotic drugs laser used. Conventional antipsychotic drugs were not taken throughout the 30 day trial.were not taken throughout the 30 day trial.

•• Protocols using both lasers reportedly resulted in Protocols using both lasers reportedly resulted in significant and equivalent clinical improvement significant and equivalent clinical improvement by blind physician raters on the Brief Psychiatric by blind physician raters on the Brief Psychiatric Rating Scale (BPRS), the CGI, and other Rating Scale (BPRS), the CGI, and other standardized symptom rating instruments. No standardized symptom rating instruments. No significant betweensignificant between--group differences were group differences were observed. observed.

•• Changes in blood chemistries or adverse physical Changes in blood chemistries or adverse physical or psychological effects of laser or psychological effects of laser acupointacupointtreatment in this population have not been treatment in this population have not been reported.reported.

Treatment: psychosisTreatment: psychosislaser acupuncturelaser acupuncture•• A subsequent controlled study on 33 individuals A subsequent controlled study on 33 individuals

diagnosed with schizophrenia concluded that diagnosed with schizophrenia concluded that laser acupuncture following the above protocol laser acupuncture following the above protocol and daily chlorpromazine were equally effective and daily chlorpromazine were equally effective as measured by standardized rating scales of as measured by standardized rating scales of positive and negative psychotic symptoms positive and negative psychotic symptoms (Zhang 1991). (Zhang 1991).

•• Larger studies including a shamLarger studies including a sham--laser treatment laser treatment arm, a sham acupuncture protocol, and doublearm, a sham acupuncture protocol, and double--blinding are needed to confirm the significance blinding are needed to confirm the significance of these findings.of these findings.

Closing remarksClosing remarks

•• Many nonMany non--conventional assessment and conventional assessment and treatment approaches are supported by strong treatment approaches are supported by strong research evidenceresearch evidence

•• Emerging assessment approaches may improve Emerging assessment approaches may improve the diagnostic accuracy or specificitythe diagnostic accuracy or specificity

•• Emerging treatments used alone or in Emerging treatments used alone or in combination with conventional approaches may combination with conventional approaches may improve outcomes, costimprove outcomes, cost--effectiveness, and effectiveness, and safetysafety

Forthcoming publicationsForthcoming publications

•• A Clinical Manual of Complementary and A Clinical Manual of Complementary and Alternative Treatments in Mental HealthAlternative Treatments in Mental Health, , eds. Lake and Spiegel, American Psychiatric eds. Lake and Spiegel, American Psychiatric Press, Inc., expected publication date March, Press, Inc., expected publication date March, 2006.2006.

•• A Textbook of Integrative Mental Health A Textbook of Integrative Mental Health Care: Foundations and Clinical Methods,Care: Foundations and Clinical Methods,Lake, Lake, ThiemeThieme Medical Publishers, expected Medical Publishers, expected publication date March 2006publication date March 2006

Citations for: Evidence-based uses of non-conventional

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