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Poster #S230 NATURAL MEDICINES IN SCHIZOPHRENIA: A SYSTEMATIC REVIEW
Abstracts of the 4th Biennial Schizophrenia International Research Conference / Schizophrenia Research 153, Supplement 1 (2014) S1–S384
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 patients 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, benzodiazepines 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 consensus 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-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 unsatisfactory. 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, sarcosine, 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), pregnenolone (PREG), inositol, gamma-hydroxybutyrate (GHB) and des-tyrgamma-endorphin when added to antipsychotics. Omega-3 fatty acids without antipsychotics might be beneficial in the prevention of schizophrenia. In one large study, ayurvedic herbs seemed effective without antipsychotics. 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.
S173
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 investigating 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 schizophrenia. 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, occupational 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 significant 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 treatment 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-
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 patients 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, benzodiazepines 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 consensus 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-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 unsatisfactory. 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, sarcosine, 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), pregnenolone (PREG), inositol, gamma-hydroxybutyrate (GHB) and des-tyrgamma-endorphin when added to antipsychotics. Omega-3 fatty acids without antipsychotics might be beneficial in the prevention of schizophrenia. In one large study, ayurvedic herbs seemed effective without antipsychotics. 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.
S173
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 investigating 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 schizophrenia. 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, occupational 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 significant 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 treatment 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-