1
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1S384 S173 dose of 12mg/day; however, for patients with rst episode of psychosis or drug naïve, it is recommended to initiate with lower dose of 6mg/day. The maximum targeting dose of Paliperidone ER for acutely exacerbated schizophrenia may be up to 18mg/day. 2. Switching strategies: If the pa- tients are non-compliant to previous antipsychotics, physicians may switch to Paliperidone ER with the recommended initial dose directly. For patients who are compliant with Multi-acting Receptor Targeted Antipsychotics (MARTA) antipsychotics previously, it is suggested to cross titrate from MARTA to Paliperidone ER to avoid withdrawal symptoms; especially for clozapine. 3. Concomitant medications: Concomitant oral benzodiazepines and short-acting injection (ex. Haloperidol injection and Lorazepam) are suggested for patients with agitation. Cognitive behavioral therapy, ben- zodiazepines and hypnotics are suggested for patients with insomnia. 4. Side effect management: The Paliperidone ER related EPS is not frequently noted; the preventative anticholinergic is considered only for patients sensitive to side effect. For patients noted with akathesia, propranolol or benzodiazepines are suggested. For patients with palpitation, propranolol is suggested. Discussion: Paliperidone ER has been launched in Taiwan since 2008. From recent studies and accumulating clinical experience, higher dose of Paliperidone ER is noted with better ecacy. This Taiwan expert consen- sus suggested the initial dose of Paliperidone ER for acutely exacerbated schizophrenia patient is at least 9mg/day in general, and the maximum targeting dose may be up to 18mg/day to achieve better clinical ecacy, and the side effects are generally fairly tolerable and manageable. Poster #S230 NATURAL MEDICINES IN SCHIZOPHRENIA: ASYSTEMATIC REVIEW Agna A. Bartels-Velthuis 1,2 , Rogier Hoenders 2 , Nina Vollbehr 2 , Richard Bruggeman 3 , Rikus Knegtering 4 , Joop de Jong 5 1 University Medical Center Groningen, University Center for Psychiatry; 2 Lentis Mental Health Organization; 3 University Medical Center Groningen; 4 Lentis Research, Lentis Center for Mental Health Care, Groningen; 5 University of Amsterdam Background: Despite progress in treatment options in the last century, the results of pharmacological treatment of schizophrenia are frequently un- satisfactory. Therefore some patients use natural medicines, although it is unclear whether natural medicines are effective and safe. We assessed the evidence for natural medicines with and without antipsychotics in treating symptoms or reducing side effects of antipsychotics in schizophrenia. Methods: A systematic review until April 2013. Only RCTs with a Jadad score of 3 or higher were included. Results: 105 RCTs were identied. Evidence was found for glycine, sar- cosine, NAC, some Chinese and ayurvedic herbs, ginkgo biloba, estradiol and vitamin B6 for improving symptoms of schizophrenia when added to antipsychotics (glycine not when added to clozapine). Inconclusive or no evidence was found for omega-3 fatty acids, D-serine, D-alanine, D-cycloserine, B vitamins, vitamin C, dehydroepiandrosteron (DHEA), preg- nenolone (PREG), inositol, gamma-hydroxybutyrate (GHB) and des-tyr- gamma-endorphin when added to antipsychotics. Omega-3 fatty acids without antipsychotics might be benecial in the prevention of schizophre- nia. In one large study, ayurvedic herbs seemed effective without an- tipsychotics. Other agents without antipsychotics (vitamin B3, vitamin C, sarcosine, glycine, Protilerin) were not effective or had only been tested in single or small trials. Ginkgo and vitamin B6 seemed to be effective in reducing side effects of antipsychotics (tardive dyskinesia and akathisia). The evidence for reducing side effects of antipsychotics by omega-3 fatty acids, melatonin and DHEA appeared to be inconclusive. All natural agents produced only mild or no side effects. Discussion: High-quality research on natural medicines for schizophrenia is scarce. However, there is emerging evidence for improved outcome for glycine, sarcosine, NAC, some Chinese and Ayurvedic herbs, ginkgo biloba, estradiol and vitamin B6, all with only mild or no side effects. Most study samples are small, the study periods are generally short, the studies only cover a modest part of the world’s population and most results need replication. Poster #S231 TREATMENT OF VIOLENT DISSOCIAL PERSONALITY DISORDER PATIENTS WITH CLOZAPINE REQUIRES LOWER DOSE AND THERAPEUTIC LEVELS THAN IN SCHIZOPHRENIA Darcy Brown 1,2 , Fintan Larkin 3 , Samrat Sengupta 3 , Jose Romero 3 , Callum Ross 3 , Morris Vinestock 3 , Mrigendra Das 3,4 1 Aberdeen University, Medical School; 2 Broadmoor Hospital, West London Mental Health NHS Trust; 3 Broadmoor Hospital; 4 West London Mental Health NHS Trust Background: Clozapine is effective in treatment- resistant schizophrenia and in reducing aggression and violence in these patients. Studies investi- gating clozapine treatment in schizophrenia and have recommended that to minimise relapse rates, the maintenance dose of clozapine should yield a plasma serum level of at least 350 ng/ml. There is emerging evidence to support its use of clozapine in personality disorders. A number of small studies have shown the benet of clozapine in borderline personality disorder reporting it’s effectiveness in reducing self-harm, aggression and improving overall clinical severity. A further study reports effectiveness in borderline personality disorder using low-dose clozapine. We report a case-series of 6 patients with primary dissocial personality disorder (DPD), treated with clozapine to determine it’s ecacy and the dose required for therapeutic response in comparison to the existing literature in schizophre- nia. The patients did not have co-morbid schizophrenia. All patients had signicant history of violence, and were deemed to pose a level of risk that they were detained in a high secure hospital. Methods: Clozapine plasma serum levels were measured after patients were established on an effective clozapine dose. To assess treatment ecacy, Clinical Global Impression (CGI) scores were formulated retrospectively on case note review and the treating psychiatrist reported improvement in specic symptom domains of cognitive-perceptual, impulsive-behaviour dyscontrol and affective dysregulation. Records were reviewed for violent incidents, aggression and positive factors of engagement with staff, occu- pational and psychological therapy. Metabolic parameters before and after clozapine were assessed, and side-effects noted Results: All 6 patients showed improvement in CGI on low-dose clozapine and benet was demonstrated in all symptom domains. There was a signi- cant reduction in violent incidents in ve of the six patients. The remaining patient did not have incidents before or after clozapine treatment, but reported reduction in frequency and severity of violent thoughts. The risk of violence toward others was reduced for all patients after clozapine treat- ment and three of the six patients progressed to lower dependency wards. These positive results were achieved on lower doses than are traditionally used to treat schizophrenia. The mean dose of clozapine used was only 208 mg (Range 100-325mg) and the duration of clozapine was at least 12 weeks (Range 12-67 weeks, median 26 weeks). Five of six patients had clozapine serum plasma levels below 300 ng/ml, the remaining patient’s level was 350 ng/ml. Discussion: We found that clozapine treatment in our 6 patients with DPD led to a reduction in illness severity and reduction in levels of violence. This was achieved in 5 of the 6 patients with low-dose clozapine and lower recommended therapeutic plasma level than is traditionally used in reference to schizophrenia treatment. To our knowledge this is the rst account of clozapine being effective in primary DPD. The reasons for the effectiveness of lower doses of clozapine in these patients can be because of differing pharmacodynamics and target-symptoms compared to that in schizophrenia, and require further investigation. This may be particularly relevant because a proportion of patients with DPD also have co-morbid schizophrenia spectrum disorders. Poster #S232 EFFICACY OF SECOND- VERSUS FIRST-GENERATION ANTIPSYCHOTIC DRUGS FOR TREATMENT-RESISTANT SCHIZOPHRENIA: ASYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS Markus Dold , Stefan Leucht Technical University Munich, Department of Psychiatry and Psychotherapy Background: Treatment resistance to antipsychotic drugs is a critical issue in the management of schizophrenia. Despite adequate antipsychotic phar-

Poster #S230 NATURAL MEDICINES IN SCHIZOPHRENIA: A SYSTEMATIC REVIEW

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Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384 S173

dose of 12mg/day; however, for patients with first episode of psychosis

or drug naïve, it is recommended to initiate with lower dose of 6mg/day.

The maximum targeting dose of Paliperidone ER for acutely exacerbated

schizophrenia may be up to 18mg/day. 2. Switching strategies: If the pa-

tients are non-compliant to previous antipsychotics, physicians may switch

to Paliperidone ER with the recommended initial dose directly. For patients

who are compliant with Multi-acting Receptor Targeted Antipsychotics

(MARTA) antipsychotics previously, it is suggested to cross titrate from

MARTA to Paliperidone ER to avoid withdrawal symptoms; especially for

clozapine. 3. Concomitant medications: Concomitant oral benzodiazepines

and short-acting injection (ex. Haloperidol injection and Lorazepam) are

suggested for patients with agitation. Cognitive behavioral therapy, ben-

zodiazepines and hypnotics are suggested for patients with insomnia. 4.

Side effect management: The Paliperidone ER related EPS is not frequently

noted; the preventative anticholinergic is considered only for patients

sensitive to side effect. For patients noted with akathesia, propranolol or

benzodiazepines are suggested. For patients with palpitation, propranolol

is suggested.

Discussion: Paliperidone ER has been launched in Taiwan since 2008.

From recent studies and accumulating clinical experience, higher dose of

Paliperidone ER is noted with better efficacy. This Taiwan expert consen-

sus suggested the initial dose of Paliperidone ER for acutely exacerbated

schizophrenia patient is at least 9mg/day in general, and the maximum

targeting dose may be up to 18mg/day to achieve better clinical efficacy,

and the side effects are generally fairly tolerable and manageable.

Poster #S230

NATURAL MEDICINES IN SCHIZOPHRENIA: A SYSTEMATIC REVIEW

Agna A. Bartels-Velthuis1,2, Rogier Hoenders2, Nina Vollbehr2,

Richard Bruggeman3, Rikus Knegtering4, Joop de Jong5

1University Medical Center Groningen, University Center for Psychiatry;2Lentis Mental Health Organization; 3University Medical Center Groningen;4Lentis Research, Lentis Center for Mental Health Care, Groningen; 5University

of Amsterdam

Background: Despite progress in treatment options in the last century, the

results of pharmacological treatment of schizophrenia are frequently un-

satisfactory. Therefore some patients use natural medicines, although it is

unclear whether natural medicines are effective and safe. We assessed the

evidence for natural medicines with and without antipsychotics in treating

symptoms or reducing side effects of antipsychotics in schizophrenia.

Methods: A systematic review until April 2013. Only RCTs with a Jadad

score of 3 or higher were included.

Results: 105 RCTs were identified. Evidence was found for glycine, sar-

cosine, NAC, some Chinese and ayurvedic herbs, ginkgo biloba, estradiol

and vitamin B6 for improving symptoms of schizophrenia when added

to antipsychotics (glycine not when added to clozapine). Inconclusive

or no evidence was found for omega-3 fatty acids, D-serine, D-alanine,

D-cycloserine, B vitamins, vitamin C, dehydroepiandrosteron (DHEA), preg-

nenolone (PREG), inositol, gamma-hydroxybutyrate (GHB) and des-tyr-

gamma-endorphin when added to antipsychotics. Omega-3 fatty acids

without antipsychotics might be beneficial in the prevention of schizophre-

nia. In one large study, ayurvedic herbs seemed effective without an-

tipsychotics. Other agents without antipsychotics (vitamin B3, vitamin C,

sarcosine, glycine, Protilerin) were not effective or had only been tested

in single or small trials. Ginkgo and vitamin B6 seemed to be effective in

reducing side effects of antipsychotics (tardive dyskinesia and akathisia).

The evidence for reducing side effects of antipsychotics by omega-3 fatty

acids, melatonin and DHEA appeared to be inconclusive. All natural agents

produced only mild or no side effects.

Discussion: High-quality research on natural medicines for schizophrenia

is scarce. However, there is emerging evidence for improved outcome for

glycine, sarcosine, NAC, some Chinese and Ayurvedic herbs, ginkgo biloba,

estradiol and vitamin B6, all with only mild or no side effects. Most study

samples are small, the study periods are generally short, the studies only

cover a modest part of the world’s population and most results need

replication.

Poster #S231

TREATMENT OF VIOLENT DISSOCIAL PERSONALITY DISORDER PATIENTS

WITH CLOZAPINE REQUIRES LOWER DOSE AND THERAPEUTIC LEVELS

THAN IN SCHIZOPHRENIA

Darcy Brown1,2, Fintan Larkin3, Samrat Sengupta3, Jose Romero3,

Callum Ross3, Morris Vinestock3, Mrigendra Das3,4

1Aberdeen University, Medical School; 2Broadmoor Hospital, West London

Mental Health NHS Trust; 3Broadmoor Hospital; 4West London Mental Health

NHS Trust

Background: Clozapine is effective in treatment- resistant schizophrenia

and in reducing aggression and violence in these patients. Studies investi-

gating clozapine treatment in schizophrenia and have recommended that

to minimise relapse rates, the maintenance dose of clozapine should yield

a plasma serum level of at least 350 ng/ml. There is emerging evidence

to support its use of clozapine in personality disorders. A number of

small studies have shown the benefit of clozapine in borderline personality

disorder reporting it’s effectiveness in reducing self-harm, aggression and

improving overall clinical severity. A further study reports effectiveness

in borderline personality disorder using low-dose clozapine. We report a

case-series of 6 patients with primary dissocial personality disorder (DPD),

treated with clozapine to determine it’s efficacy and the dose required for

therapeutic response in comparison to the existing literature in schizophre-

nia. The patients did not have co-morbid schizophrenia. All patients had

significant history of violence, and were deemed to pose a level of risk that

they were detained in a high secure hospital.

Methods: Clozapine plasma serum levels were measured after patients were

established on an effective clozapine dose. To assess treatment efficacy,

Clinical Global Impression (CGI) scores were formulated retrospectively

on case note review and the treating psychiatrist reported improvement

in specific symptom domains of cognitive-perceptual, impulsive-behaviour

dyscontrol and affective dysregulation. Records were reviewed for violent

incidents, aggression and positive factors of engagement with staff, occu-

pational and psychological therapy. Metabolic parameters before and after

clozapine were assessed, and side-effects noted

Results: All 6 patients showed improvement in CGI on low-dose clozapine

and benefit was demonstrated in all symptom domains. There was a signifi-

cant reduction in violent incidents in five of the six patients. The remaining

patient did not have incidents before or after clozapine treatment, but

reported reduction in frequency and severity of violent thoughts. The risk

of violence toward others was reduced for all patients after clozapine treat-

ment and three of the six patients progressed to lower dependency wards.

These positive results were achieved on lower doses than are traditionally

used to treat schizophrenia. The mean dose of clozapine used was only 208

mg (Range 100-325mg) and the duration of clozapine was at least 12 weeks

(Range 12-67 weeks, median 26 weeks). Five of six patients had clozapine

serum plasma levels below 300 ng/ml, the remaining patient’s level was

350 ng/ml.

Discussion: We found that clozapine treatment in our 6 patients with DPD

led to a reduction in illness severity and reduction in levels of violence.

This was achieved in 5 of the 6 patients with low-dose clozapine and

lower recommended therapeutic plasma level than is traditionally used in

reference to schizophrenia treatment. To our knowledge this is the first

account of clozapine being effective in primary DPD. The reasons for the

effectiveness of lower doses of clozapine in these patients can be because

of differing pharmacodynamics and target-symptoms compared to that in

schizophrenia, and require further investigation. This may be particularly

relevant because a proportion of patients with DPD also have co-morbid

schizophrenia spectrum disorders.

Poster #S232

EFFICACY OF SECOND- VERSUS FIRST-GENERATION ANTIPSYCHOTIC

DRUGS FOR TREATMENT-RESISTANT SCHIZOPHRENIA: A SYSTEMATIC

REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Markus Dold, Stefan Leucht

Technical University Munich, Department of Psychiatry and Psychotherapy

Background: Treatment resistance to antipsychotic drugs is a critical issue

in the management of schizophrenia. Despite adequate antipsychotic phar-