Non-conventional Treatment of Mood Disorders What the evidence suggests 21 st Annual DBSA Conference 15 October 2011 Non-conventional Treatment of Mood

Non-conventional Treatment of Non-conventional Treatment of Mood DisordersMood Disorders

What the evidence suggestsWhat the evidence suggests

2121stst Annual DBSA Conference Annual DBSA Conference15 October 201115 October 2011

James Lake, MDJames Lake, MD

Private Practice, MontereyPrivate Practice, Monterey

Chair, International Network of Integrative Mental Health Chair, International Network of Integrative Mental Health ((www.INIMH.org) )

http://www.inimh.org/

DisclosuresDisclosures

nonenone

Definitions Definitions ConventionalConventional treatmentstreatments—accepted —accepted in in

mainstream medicine (emphasis is on mainstream medicine (emphasis is on prescription drugs and psychotherapy)prescription drugs and psychotherapy)

CAMCAM (complementary and alternative) (complementary and alternative) treatments—not treatments—not currentlycurrently accepted in accepted in mainstream medicine (egs: herbs, other mainstream medicine (egs: herbs, other natural products, acupuncture, yoga)natural products, acupuncture, yoga)

Integrative treatmentsIntegrative treatments—combinations —combinations of of conventional and CAM treatmentsconventional and CAM treatments

CAM Rx trends in mental healthCAM Rx trends in mental health

Two thirds of patients hospitalized for a Two thirds of patients hospitalized for a mental health problem used a CAM therapy mental health problem used a CAM therapy within the past year (Elkins et al., 2005) within the past year (Elkins et al., 2005)

Few patients disclose CAM use to family Few patients disclose CAM use to family physician or psychiatrist resulting in physician or psychiatrist resulting in treatment failurestreatment failures, , delaysdelays and and safety issues safety issues (Eisenberg et al., 1998; Kessler et al., 2001)(Eisenberg et al., 1998; Kessler et al., 2001)

Integrative Rx—considerationsIntegrative Rx—considerations

Psychiatrists and CAM practitioners should be Psychiatrists and CAM practitioners should be familiar with evidence for CAM/integrative Rx familiar with evidence for CAM/integrative Rx choices to give choices to give appropriate, safe appropriate, safe adviceadvice

Most appropriate Rx determined byMost appropriate Rx determined by– sx type and severitysx type and severity

– co-morbid medical or psychiatric DOco-morbid medical or psychiatric DO

– previous conventional and CAM Rx and responseprevious conventional and CAM Rx and response

– Personal, cultural preferencesPersonal, cultural preferences

– cost and local availability cost and local availability

Integrative Rx—Basics Integrative Rx—Basics

When previous Rx not effective or no When previous Rx not effective or no previous similar episode, start with most previous similar episode, start with most validated Rx targeting core symptom(s)validated Rx targeting core symptom(s)

For severe sx always start Rx with first-line For severe sx always start Rx with first-line conventional medicationsconventional medications

For moderate sx consider evidence-based For moderate sx consider evidence-based use of adjunctive CAM Rxuse of adjunctive CAM Rx

When initial Rx ineffective consider When initial Rx ineffective consider conventional or CAM Rx with pt signed conventional or CAM Rx with pt signed informed consent of risks and benefitsinformed consent of risks and benefits

Alternative and Integrative Alternative and Integrative Treatments of Depressed MoodTreatments of Depressed Mood


Emerging context of CAM Rx for Emerging context of CAM Rx for depressed mooddepressed mood

CAM use greater among individuals CAM use greater among individuals diagnosed with diagnosed with anyany DSM-IV disorder DSM-IV disorder (Unutzer 2000)(Unutzer 2000)

Limited efficacy of conventional Rx in Limited efficacy of conventional Rx in severe depression; no benefit in moderate severe depression; no benefit in moderate depression (Kirsch 2008)depression (Kirsch 2008)

Two thirds of severely depressed Two thirds of severely depressed outpatients use CAM Rx outpatients use CAM Rx while taking while taking prescription medications (Kessler 2001) prescription medications (Kessler 2001)

CAM Rx in Depressed moodCAM Rx in Depressed mood

– Vitamins Vitamins – St. John’s wortSt. John’s wort– Omega-3 fatty acidsOmega-3 fatty acids– SAMeSAMe– Amino acidsAmino acids– DHEADHEA– Light therapyLight therapy– AcupunctureAcupuncture– ExerciseExercise

Folate, B-12, thiamin and DFolate, B-12, thiamin and D

In depressed moodIn depressed mood

FolateFolate

Studies of folate (1 to 5mg) in depressed Studies of folate (1 to 5mg) in depressed populations (elderly, concurrent alcohol populations (elderly, concurrent alcohol dependence, concurrent dementia) consistently dependence, concurrent dementia) consistently show significant improvement (show significant improvement (Guaraldi Guaraldi et al., et al., 1993; Di Palma et al., 1994; Glória et al., 1997; 1993; Di Palma et al., 1994; Glória et al., 1997; Passeri et al., 1993)Passeri et al., 1993)

Folate as add-on to antidepressant in folate Folate as add-on to antidepressant in folate deficient depressed patients (N = 24) showed deficient depressed patients (N = 24) showed more improvement than placebo (Godfrey et more improvement than placebo (Godfrey et al., 1990)al., 1990)

Folate—treatment issuesFolate—treatment issues Folate taken alone is probably beneficial Folate taken alone is probably beneficial More studies needed to confirm optimal More studies needed to confirm optimal

form and dosingform and dosing Adding to antidepressants is reasonable Adding to antidepressants is reasonable

when treating depressed folate deficient when treating depressed folate deficient patientspatients

Partial responders to antidepressants may Partial responders to antidepressants may benefit by adding folatebenefit by adding folate

Depressed individuals with normal folate Depressed individuals with normal folate levels may benefit from folate or levels may benefit from folate or methylfolatemethylfolate

B-12, thiaminB-12, thiamin Patients with higher BPatients with higher B1212 levels show more levels show more

robust response to antidepressants robust response to antidepressants (Hintikka 2003)(Hintikka 2003)

Oral BOral B1212 (800 μg/d) suggested as add-on (800 μg/d) suggested as add-on

Rx to antidepressantsRx to antidepressants Some report consistent improvements in Some report consistent improvements in

mood and energy with daily thiamin (50-mood and energy with daily thiamin (50-mg)mg)

Vitamin DVitamin D Literature review supports association between depressed mood Literature review supports association between depressed mood

and low vitamin D levels (Parker & Brotchie 2011) and low vitamin D levels (Parker & Brotchie 2011) however…however… Not clear whether deficiency is cause or effect of depressed moodNot clear whether deficiency is cause or effect of depressed mood Possible association with SAD not rigorously examinedPossible association with SAD not rigorously examined Insufficient research to support vitamin D augmentation with Insufficient research to support vitamin D augmentation with

antidepressantsantidepressants Bottom line: Bottom line: insufficient evidence for vitamin D supplementation in insufficient evidence for vitamin D supplementation in

depressed patients, but reasonable for depressed patients at risk depressed patients, but reasonable for depressed patients at risk of vitamin D insufficiency or where low vitamin D levels foundof vitamin D insufficiency or where low vitamin D levels found

St. John’s wortSt. John’s wort((Hypericum perforatumHypericum perforatum))


St. John’s WortSt. John’s Wort

Meta-analysis of controlled trials on SJW found Meta-analysis of controlled trials on SJW found serious design problems and inconsistent serious design problems and inconsistent outcomes (Linde et al., 2005)outcomes (Linde et al., 2005)

Two large well designed studies found no Two large well designed studies found no difference between SJW and placebo on difference between SJW and placebo on primary outcome measures in MDD (Shelton et primary outcome measures in MDD (Shelton et al., 2001; Hypericum Study Group, 2002)al., 2001; Hypericum Study Group, 2002)

However…However…another large trial found significant another large trial found significant difference between SJW and placebo in difference between SJW and placebo in mild-mild-moderate depression moderate depression (Lecrubier et al., 2002). (Lecrubier et al., 2002).

St. John’s wort—treatment St. John’s wort—treatment issuesissues

Safety issues—induces liver enzymes lowering Safety issues—induces liver enzymes lowering blood levels of anti-HIV drugs, cancer drugs, blood levels of anti-HIV drugs, cancer drugs, anticoagulants, digoxin, OCPs and hormones anticoagulants, digoxin, OCPs and hormones (Roby et al., 2000; Mannel et al., 2004)(Roby et al., 2000; Mannel et al., 2004)

Reasonable for mild to moderate depression, Reasonable for mild to moderate depression, howeverhowever recent U.S. studies do recent U.S. studies do notnot show show efficacy over placeboefficacy over placebo

Drug interactions limit use and pose safety Drug interactions limit use and pose safety considerationsconsiderations

Essential fatty acidsEssential fatty acids


Omega-3s—general health benefitsOmega-3s—general health benefits

Fish, algae and flaxseed oilFish, algae and flaxseed oil Deficient in average American dietDeficient in average American diet Cardiovascular benefits—decrease risk of Cardiovascular benefits—decrease risk of

stroke and arrhythmias, reduce triglycerides, stroke and arrhythmias, reduce triglycerides, decrease atherosclerosis (Kris-Etherton 2003)decrease atherosclerosis (Kris-Etherton 2003)

AHA recommends fish twice weekly, and 1 AHA recommends fish twice weekly, and 1 g/day EPA + DHA for heart disease (Kris-g/day EPA + DHA for heart disease (Kris-Etherton 2003)Etherton 2003)

May reduce oxidative brain damage and slow May reduce oxidative brain damage and slow age-related cognitive decline (Cole 2005; age-related cognitive decline (Cole 2005; Morris 2005) Morris 2005)

Omega-3s in depressed moodOmega-3s in depressed mood

Meta-analyses show benefits in unipolar and Meta-analyses show benefits in unipolar and bipolar depression (Parker 2006; Freeman bipolar depression (Parker 2006; Freeman 2006; Lin and Su 2007)2006; Lin and Su 2007)

HoweverHowever…results difficult to interpret due to…results difficult to interpret due to– Inconsistent findingsInconsistent findings– Different study designsDifferent study designs

Stand-alone vs. add-on therapyStand-alone vs. add-on therapyEPA vs DHA vs both Omega-3sEPA vs DHA vs both Omega-3sVariability in dosingVariability in dosingVariability in study length Variability in study length

Omega-3s in depressed moodOmega-3s in depressed mood

DHA as monotherapy in depressed adults: DHA as monotherapy in depressed adults: no no benefit benefit over placebo (Marangell et al., 2003)over placebo (Marangell et al., 2003)

DHA/EPA monotherapy in depressed children: DHA/EPA monotherapy in depressed children: moderatemoderate benefitbenefit over placebo (Nemets et al., 2006)over placebo (Nemets et al., 2006)

DHA/EPA add-on to antidepressants: DHA/EPA add-on to antidepressants: no benefit no benefit over placebo (DHA dose over placebo (DHA dose higherhigher than EPA) (Grenyer than EPA) (Grenyer et al., 2007)et al., 2007)

EPA (1 g) alone vs Prozac (20 mg) vs EPA + EPA (1 g) alone vs Prozac (20 mg) vs EPA + Prozac: Prozac: similar efficacy similar efficacy with EPA and Prozac. with EPA and Prozac. Combined Rx superior to either (Jazayeri 2008) Combined Rx superior to either (Jazayeri 2008)

Omega-3s in depression—Omega-3s in depression—bottom linebottom line

Low-risk add-on therapy for depressed Low-risk add-on therapy for depressed patients with significant cardiovascular and patients with significant cardiovascular and health benefits endorsed by APA (Freeman health benefits endorsed by APA (Freeman 2006)2006)

Most findings support lower doses (1-2 Most findings support lower doses (1-2 gm/day)gm/day)

Add-on EPA or EPA/DHA probably most Add-on EPA or EPA/DHA probably most beneficial, less evidence for DHA alonebeneficial, less evidence for DHA alone

Stand-alone omega-3s in depression more Stand-alone omega-3s in depression more effective with EPA alone or EPA>DHAeffective with EPA alone or EPA>DHA

S-adenosyl-methionine S-adenosyl-methionine (SAMe)(SAMe)


SAMeSAMe

Equal efficacy of IV or oral SAMe and Equal efficacy of IV or oral SAMe and antidepressants with good tolerance antidepressants with good tolerance (Delle Chiaie 2002; Pancheri 2002) (Delle Chiaie 2002; Pancheri 2002)

Meta-analysis of controlled trials (total Meta-analysis of controlled trials (total patients=1,015)—no significant patients=1,015)—no significant differences in outcomes between differences in outcomes between SAMe and antidepressants (AHRQ SAMe and antidepressants (AHRQ Publication 2002; http://www.ahrq.gov) Publication 2002; http://www.ahrq.gov)

SAMe—treatment issuesSAMe—treatment issues

StabilityStability is issue—degrades rapidly is issue—degrades rapidly over several months on shelf. over several months on shelf. (Spillmann 1996)(Spillmann 1996)

Adverse effectsAdverse effects: insomnia, lack of : insomnia, lack of appetite, constipation, nausea, dry appetite, constipation, nausea, dry mouth, sweating, dizziness, and mouth, sweating, dizziness, and nervousness (Spillmann 1996) nervousness (Spillmann 1996)

Small % responders switch to mania Small % responders switch to mania (Carney 1987) (Carney 1987)

Amino acids and DHEAAmino acids and DHEA

Amino acids: L-tryptophan, 5-Amino acids: L-tryptophan, 5-HTP, tyrosine, Acetyl-L-carnitineHTP, tyrosine, Acetyl-L-carnitine

DHEA is a prohormoneDHEA is a prohormone

L-tryptophan and 5-HTPL-tryptophan and 5-HTP

L-tryp and 5-HTP both +/- effective but 5-L-tryp and 5-HTP both +/- effective but 5-HTP crosses blood-brain barrier at higher HTP crosses blood-brain barrier at higher rate, converted into serotonin more rate, converted into serotonin more efficiently, and greater antidepressant effectefficiently, and greater antidepressant effect

Antidepressant effect starts between 100mg Antidepressant effect starts between 100mg and 300mg/dayand 300mg/day

>15 controlled trials show consistent >15 controlled trials show consistent positive effects in moderate depressed positive effects in moderate depressed mood (Birdsall 1998)mood (Birdsall 1998)

5-HTP5-HTP

63 depressed patients randomized to 63 depressed patients randomized to fluvoxamine 150mg vs 5-HTP 300mg similar fluvoxamine 150mg vs 5-HTP 300mg similar improvements in mood (Poldinger 1991)improvements in mood (Poldinger 1991)

Case reports Rx-refractory pts improving Case reports Rx-refractory pts improving when 5-HTP 300mg combined with TCAs, when 5-HTP 300mg combined with TCAs, MAOIs or SSRIs; MAOIs or SSRIs; no serious side effects no serious side effects reported (van Praag 1984; Sargent 1998; reported (van Praag 1984; Sargent 1998; Kline 1980; Mendlewicz 1980)Kline 1980; Mendlewicz 1980)

L-tyrosineL-tyrosine

Obtained through diet or synthesized from Obtained through diet or synthesized from phenylalanine; essential precursor for phenylalanine; essential precursor for synthesis of epinephrine, norepinephrine and synthesis of epinephrine, norepinephrine and dopaminedopamine

Essential for synthesis of NGF and thyroxinEssential for synthesis of NGF and thyroxin Deficiency frequent in depressed mood (Grevet Deficiency frequent in depressed mood (Grevet

2002)2002) Beneficial doses 500-1500mg/dayBeneficial doses 500-1500mg/day Caution—high doses increase cancer risk Caution—high doses increase cancer risk

(Harvie 2002)(Harvie 2002)

Acetyl-L-carnitine (ALC)Acetyl-L-carnitine (ALC)

Neuroprotective, may reduce cognitive impairments Neuroprotective, may reduce cognitive impairments in normal aging, dementia, and traumatic brain in normal aging, dementia, and traumatic brain injuryinjury

Depressed demented patients taking 2-3gm/day Depressed demented patients taking 2-3gm/day reported greater improvements in mood and global reported greater improvements in mood and global functioning than placebo (Bella 1990)functioning than placebo (Bella 1990)

Severely depressed elderly patients taking 500-mg Severely depressed elderly patients taking 500-mg 4x/day achieved full remission (Gecele 1991)4x/day achieved full remission (Gecele 1991)

Few or no adverse effects; can be safely combined Few or no adverse effects; can be safely combined with antidepressantswith antidepressants

Dihydroepiandosterone (DHEA)Dihydroepiandosterone (DHEA) Pro-hormone. Mechanism involves serotonin, GABA, Pro-hormone. Mechanism involves serotonin, GABA,

NMDA, other neurotransmittersNMDA, other neurotransmitters 30mg 2x/day 50% reduction in sx severity (most 30mg 2x/day 50% reduction in sx severity (most

remained on antidepressants)remained on antidepressants) Moderately depressed adults given 90-mg 3 wks Moderately depressed adults given 90-mg 3 wks

followed by 150-mg 3x/day 3 wks reported 50% sx followed by 150-mg 3x/day 3 wks reported 50% sx reduction, improved sexual fx (Schmidt 2005)reduction, improved sexual fx (Schmidt 2005)

Depressed HIV positive patients taking 200 to 500 Depressed HIV positive patients taking 200 to 500 mg/day reported significant improvements in mood and mg/day reported significant improvements in mood and fatigue (Rabkin 2000)fatigue (Rabkin 2000)

..

Light exposure therapyLight exposure therapy


Bright light exposure therapyBright light exposure therapy

Systematic review—all published studies on Systematic review—all published studies on bright light exposure for non-seasonal bright light exposure for non-seasonal depression found “modest…promising anti-depression found “modest…promising anti-depressive efficacy, especially when depressive efficacy, especially when administered during the first week of administered during the first week of treatment, in the morning, and as an treatment, in the morning, and as an adjunctive treatment to sleep deprivation adjunctive treatment to sleep deprivation responders (Tuuainen 2004).”responders (Tuuainen 2004).”

Bright light exposure therapyBright light exposure therapy

More recent reviews report mixed findingsMore recent reviews report mixed findings Comparable efficacy of bright light and Comparable efficacy of bright light and

antidepressants for SAD and non-antidepressants for SAD and non-seasonal depressed moodseasonal depressed mood

Ineffective alone but mayIneffective alone but may improve improve response when combined with response when combined with antidepressant in antidepressant in non-seasonalnon-seasonal depression (Golden 2005; Even 2008)depression (Golden 2005; Even 2008)

Light exposure—treatment issuesLight exposure—treatment issues

Mechanism unclear—full-spectrum bright light Mechanism unclear—full-spectrum bright light probablyprobably modulates CNS melatonin, serotonin modulates CNS melatonin, serotonin and dopamine (Neumeister 2004).and dopamine (Neumeister 2004).

Safe effective alternative to antidepressants in Safe effective alternative to antidepressants in pregnant depressed women (Epperson 2004)pregnant depressed women (Epperson 2004)

Uncommon side effects: jitteriness, headaches Uncommon side effects: jitteriness, headaches (10%), mild nausea (16%) (Terman 2005) (10%), mild nausea (16%) (Terman 2005)

Sporadic cases of hypomania reported Sporadic cases of hypomania reported (Epperson et al., 2004; Terman 2005)(Epperson et al., 2004; Terman 2005)

AcupunctureAcupuncture


AcupunctureAcupuncture Efficacy difficult to evaluate due to:Efficacy difficult to evaluate due to:

– Differences in study designsDifferences in study designs– Concurrent use of other conventional or CAM RxConcurrent use of other conventional or CAM Rx– Different Chinese vs Western medical diagnosesDifferent Chinese vs Western medical diagnoses– Use of different acupuncture protocolsUse of different acupuncture protocols

Most systematic reviews included Most systematic reviews included onlyonly English English language studies (Mukaino 2005; Smith and Hay, language studies (Mukaino 2005; Smith and Hay, 2005; Leo and Ligot, 2007) 2005; Leo and Ligot, 2007)

Acupuncture—research and Rx Acupuncture—research and Rx issuesissues

No significant clinical differences between No significant clinical differences between manual acupuncture and electro-manual acupuncture and electro-acupuncture and sham or waitlist. acupuncture and sham or waitlist.

Insufficient data to conclude differences in Insufficient data to conclude differences in efficacy of acupuncture vs antidepressantsefficacy of acupuncture vs antidepressants

Uncommon adverse effects: bruising, Uncommon adverse effects: bruising, fatigue, nausea. Rare serious risks: HIV, fatigue, nausea. Rare serious risks: HIV, hepatitis B and C (Vincent 2001) hepatitis B and C (Vincent 2001)

Research and treatment issuesResearch and treatment issues

No agreement on standardized sham No agreement on standardized sham acupunctureacupuncture

Possible beneficial effects from stimulating Possible beneficial effects from stimulating specific acu-points used as specific acu-points used as sham pointssham points

Significant differences in type of Significant differences in type of acupuncture, duration, frequency and acupuncture, duration, frequency and number of sessions limit analysis of pooled number of sessions limit analysis of pooled treatment outcomes from different study treatment outcomes from different study designs designs

ExerciseExercise


ExerciseExercise

Treatment studies consistently show benefit Treatment studies consistently show benefit of aerobic exercise (Dunn 2005; Penninx of aerobic exercise (Dunn 2005; Penninx 2002; Mather 2002; Herman 2002)2002; Mather 2002; Herman 2002)

Some studies show mood benefits of Some studies show mood benefits of resistance training (Singh 2005; Singh 2001)resistance training (Singh 2005; Singh 2001)

Beneficial effects of exercise on mood may Beneficial effects of exercise on mood may be sustained over time (Babyak 2000)be sustained over time (Babyak 2000)

Long-term longitudinal studies neededLong-term longitudinal studies needed

Alternative and Integrative Alternative and Integrative Treatments of Bipolar DisorderTreatments of Bipolar Disorder


Conventional Rx—limitationsConventional Rx—limitations

50% of BD pts discontinue Rx 50% of BD pts discontinue Rx because of AEs: tremor, weight because of AEs: tremor, weight gain, elevated liver enzymes (Fleck gain, elevated liver enzymes (Fleck et al., 2005) et al., 2005)

High relapse rate in BD pts on High relapse rate in BD pts on maintenance mood stabilizers maintenance mood stabilizers (Boschert 2004)(Boschert 2004)

CAM use in Bipolar DisorderCAM use in Bipolar Disorder

High % BD pts use CAM together High % BD pts use CAM together with prescription Rx (Andreescu with prescription Rx (Andreescu 2008)2008)

Weak evidence for Weak evidence for mostmost CAM Rx CAM Rx (Ernst 2003; Dennehy 2004)(Ernst 2003; Dennehy 2004)

BD pts may be at high risk for AEs BD pts may be at high risk for AEs due to concurrent use of conventional due to concurrent use of conventional Rx (Vazquez 2002; Izzo 2004)Rx (Vazquez 2002; Izzo 2004)

Non-conventional RxNon-conventional Rx

ExerciseExercise Omega-3 EFAsOmega-3 EFAs N-acetyl-cysteineN-acetyl-cysteine Adjunctive folate in acute maniaAdjunctive folate in acute mania Adding choline to lithiumAdding choline to lithium Trace lithiumTrace lithium Proprietary nutrient formulaProprietary nutrient formula St. John’s wort plus bright light in SADSt. John’s wort plus bright light in SAD AcupunctureAcupuncture

ExerciseExercise

Adjunctive (plus medication) exercise may Adjunctive (plus medication) exercise may increase in brain-derived neurotrophic factor increase in brain-derived neurotrophic factor stimulating increased neurogenesis (Sylvia stimulating increased neurogenesis (Sylvia et al. 2009)et al. 2009)

But…But…BD pts who exercise BD pts who exercise probablyprobably have have healthier lifestyles than non-exercisers healthier lifestyles than non-exercisers (causality difficult to establish) (causality difficult to establish)

Large prospective trials needed to Large prospective trials needed to determine effect sizedetermine effect size

Omega-3 fatty acidsOmega-3 fatty acids

4-mo PCRT (N=30) BD pts treated with 4-mo PCRT (N=30) BD pts treated with Omega-3s (9.6gm/d) vs placebo while Omega-3s (9.6gm/d) vs placebo while continuing mood stabilizers (Stoll 1999)continuing mood stabilizers (Stoll 1999)

Omega-3 group remained in remission Omega-3 group remained in remission significantly longer than placebosignificantly longer than placebo

Pts taking Omega-3 fatty acids only Pts taking Omega-3 fatty acids only remained in remission significantly longer remained in remission significantly longer than placebo than placebo groupgroup

Review findings—omega-3s in Review findings—omega-3s in Bipolar DisorderBipolar Disorder

5 studies met inclusion criteria however uneven 5 studies met inclusion criteria however uneven quality (Montgomery & Richardson 2008)quality (Montgomery & Richardson 2008)

One study (N= 75) adequate quality/size for One study (N= 75) adequate quality/size for analysis—small benefit of omega-3s over analysis—small benefit of omega-3s over placebo for depressive phase placebo for depressive phase not manianot mania

CONCLUSIONS: CONCLUSIONS: Findings must be regarded Findings must be regarded with caution with caution due to limited data. Acute need for due to limited data. Acute need for well-designed adequately powered PCRTswell-designed adequately powered PCRTs

Omega-3 fatty acids—safety Omega-3 fatty acids—safety issuesissues

Case report of hypomania induced by Case report of hypomania induced by high doses of omega-3s (Kinrys 2000)high doses of omega-3s (Kinrys 2000)

Rare cases of increased bleeding Rare cases of increased bleeding times, but times, but notnot increased bleeding risk increased bleeding risk in pts taking aspirin or anti-coagulants in pts taking aspirin or anti-coagulants

Omega-3s should be regarded as Omega-3s should be regarded as viable adjuvant Rx of mania and bipolar viable adjuvant Rx of mania and bipolar illnessillness

N-acetyl cysteine (NAC)N-acetyl cysteine (NAC) Amino acid with strong anti-oxidant properties used to Amino acid with strong anti-oxidant properties used to

treat inflammatory disorders (Dodd, Dean et al. 2008)treat inflammatory disorders (Dodd, Dean et al. 2008) May reduce symptoms of depressed mood but not May reduce symptoms of depressed mood but not

mania in stable bipolar patients when combined with mania in stable bipolar patients when combined with mood stabilizersmood stabilizers

24-week PCRT (N=75) stable BD patients taking NAC 24-week PCRT (N=75) stable BD patients taking NAC (1g/d) vs placebo with mood stabilizer showed (1g/d) vs placebo with mood stabilizer showed significant improvements in depression (Berk et al significant improvements in depression (Berk et al 2008). 2008).

Non-significant improvements in maniaNon-significant improvements in mania

Folate + Valproic acid in acute Folate + Valproic acid in acute maniamania

3 week DBPCT (N=88) BD I manic 3 week DBPCT (N=88) BD I manic patients randomized to folic acid patients randomized to folic acid (3mg) + valproate vs placebo + (3mg) + valproate vs placebo + valproate (Behzadi et al. 2009)valproate (Behzadi et al. 2009)

Statistically significant difference in Statistically significant difference in YMRS at 3 weeks suggesting folate YMRS at 3 weeks suggesting folate effective adjuvant to valproate in acute effective adjuvant to valproate in acute maniamania

Adding choline to lithiumAdding choline to lithium

Choline is required for biosynthesis of Choline is required for biosynthesis of acetylcholine (Ach); low Ach levels are acetylcholine (Ach); low Ach levels are known cause of mania (Leiva 1990).known cause of mania (Leiva 1990).

Case study of Rx-refractory rapid-Case study of Rx-refractory rapid-cycling BD pts taking lithium—four of cycling BD pts taking lithium—four of six responded to addition of 2,000-six responded to addition of 2,000-7,200 mg/day free choline (Stoll 1996) 7,200 mg/day free choline (Stoll 1996)

Need large DB prospective studiesNeed large DB prospective studies

Adding choline to lithiumAdding choline to lithium

Small PCRT found Small PCRT found phosphatidylcholine 15gm to phosphatidylcholine 15gm to 30gm/day reduces severity of both 30gm/day reduces severity of both mania and depressed mood in BD mania and depressed mood in BD pts (Stoll 1996)pts (Stoll 1996)

Sx recurred when Rx discontinuedSx recurred when Rx discontinued

Trace lithium supplementationTrace lithium supplementation

Small open study suggests BD I pts Small open study suggests BD I pts with mania or depressed mood improve with mania or depressed mood improve with low doses (50 micrograms/meal) with low doses (50 micrograms/meal) of a natural lithium preparation (Fierro of a natural lithium preparation (Fierro 1988)1988)

Responders had undetectable post-Rx Responders had undetectable post-Rx serum Li+ levelsserum Li+ levels

Need large PCRTs to replicate findingsNeed large PCRTs to replicate findings

Proprietary nutrient formulaProprietary nutrient formula

Proprietary nutrient formula containing 36 Proprietary nutrient formula containing 36 separate constituents may reduce manic sx separate constituents may reduce manic sx when taken with conventional mood when taken with conventional mood stabilizers (Popper 2001; Kaplan 2001). stabilizers (Popper 2001; Kaplan 2001).

Proposed mechanism: correction of Proposed mechanism: correction of metabolic errors that predispose individuals metabolic errors that predispose individuals to become symptomatic when micronutrient to become symptomatic when micronutrient dietary deficiencies (Kaplan 2001). dietary deficiencies (Kaplan 2001).


First series took 32 capsules daily in First series took 32 capsules daily in four divided doses over 6 mos. 11 pts four divided doses over 6 mos. 11 pts reduced mood stabilizers by half while reduced mood stabilizers by half while improving clinicallyimproving clinically

Second seriesSecond series 13 out of 19 BD pts 13 out of 19 BD pts remained stable after discontinuing remained stable after discontinuing mood stabilizers (Simmons 2003)mood stabilizers (Simmons 2003)


Two PCRTs on-going in U.S. and Two PCRTs on-going in U.S. and Canada to determine most efficacious Canada to determine most efficacious nutrients, simplify Rx and minimize AE nutrients, simplify Rx and minimize AE riskrisk

Protocol starts with 6 capsules TID Protocol starts with 6 capsules TID then 3 capsules TID after two monthsthen 3 capsules TID after two months

Proprietary multi-ingredient formulaProprietary multi-ingredient formula—safety concerns—safety concerns

Micronutrient-medication interactions require Micronutrient-medication interactions require gradual dose reductions (Popper 2001)gradual dose reductions (Popper 2001)

Lowering mood stabilizer doses too rapidly Lowering mood stabilizer doses too rapidly risks worsening while keeping medications risks worsening while keeping medications at therapeutic doses may cause toxicity at therapeutic doses may cause toxicity

Large prospective studies needed to Large prospective studies needed to clarify whether formula is beneficial and clarify whether formula is beneficial and safe alone or as augmentation therapysafe alone or as augmentation therapy

AcupunctureAcupuncture

2 12-wk sham-controlled randomized trials on 2 12-wk sham-controlled randomized trials on adjunctive acupuncture adjunctive to mood adjunctive acupuncture adjunctive to mood stabilizers for sx of depression (N=26) and stabilizers for sx of depression (N=26) and hypomania (N=20) in outpts dx;d BD I & II hypomania (N=20) in outpts dx;d BD I & II (Dennegy et al. 2009)(Dennegy et al. 2009)

Rx-arm received treatment at specific Rx-arm received treatment at specific acupoints addressing target sx. Sham group acupoints addressing target sx. Sham group received non-specific acupuncture Rxreceived non-specific acupuncture Rx

RESULTS: RESULTS: all patients improved; greater all patients improved; greater improvement with targeted Rx for both phasesimprovement with targeted Rx for both phases

Few transient negative side effects and no Few transient negative side effects and no attrition related to acupunctureattrition related to acupuncture

International Network of Integrative International Network of Integrative Mental Health www.INIMH.orgMental Health www.INIMH.org

Advance a global vision for an integrated whole person Advance a global vision for an integrated whole person approach to mental health care through education, approach to mental health care through education, research, networking and advocacyresearch, networking and advocacy

Create community and opportunities for nurturing personal Create community and opportunities for nurturing personal and professional connectionsand professional connections

Promote evidence-based conventional and CAM therapies Promote evidence-based conventional and CAM therapies for the betterment of mental healthcarefor the betterment of mental healthcare

Educate, support and inspire mental health professionals Educate, support and inspire mental health professionals and trainees at all career levels in all world regions and trainees at all career levels in all world regions

Facilitate collaborative efforts between researchers and Facilitate collaborative efforts between researchers and cliniciansclinicians

General resourcesGeneral resources

My website: My website: www.IntegrativeMentalHealth.net

Textbook of Integrative Mental Health Textbook of Integrative Mental Health Care,Care, Lake, Thieme Medical Publishers, Lake, Thieme Medical Publishers, September, 2006September, 2006

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., January, 2007Press, Inc., January, 2007

Integrative Mental Health Care: A Integrative Mental Health Care: A Therapist’s HandbookTherapist’s Handbook, Lake, Norton, 2009, Lake, Norton, 2009

http://www.integrativementalhealth.net/

Documents

Non-conventional Treatment of Mood Disorders What the evidence suggests 21 st Annual DBSA Conference 15 October 2011 Non-conventional Treatment of Mood