AMISULPRIDE VERSUS RISPERIDONE IN THE TREATMENT

Size: px
Start display at page:

Download "AMISULPRIDE VERSUS RISPERIDONE IN THE TREATMENT"

Transcription

1 AMISULPRIDE VERSUS RISPERIDONE IN THE TREATMENT OF SCHIZOPHRENIC PATIENTS: A DOUBLE-BLIND PILOT STUDY IN TAIWAN Tzung J. Hwang, 1 Shin-Min Lee, 2 Hsiao-Ju Sun, 3 Hsin-Nan Lin, 1 Shih-Jen Tsai, 4 Ying-Chiao Lee, 4 and Ying-Sheue Chen 4 Background and Purpose: The atypical antipsychotics, amisulpride and risperidone, have different receptor affinity characteristics. Although the relative efficacy of both drugs compared to conventional antipsychotics is well established, it remains unclear how the efficacy of amisulpride compares with risperidone. There have been no controlled studies comparing amisulpride to risperidone in Asian patients. The purpose of this study was to compare the efficacy and safety of amisulpride with that of risperidone in Taiwanese schizophrenic patients. Methods: Patients with productive positive symptoms (n = 48) were enrolled into this double-blind, randomized pilot study for 6 weeks. Patients received either amisulpride ( mg/day) or risperidone (4 8 mg/day). Positive and Negative Syndrome Scale (PANSS), Clinical Global Impression (CGI), Social and Occupational Functioning Assessment Scale (SOFAS), and patients subjective responses to treatment were assessed during the trial period. Adverse events were recorded at each follow-up visit. Results: At the end of the trial, the mean dosage was 630 ± 134 mg/day and 6.88 ± 1.54 mg/day for amisulpride and risperidone, respectively. There was no significant difference in the reduction of the PANSS total score (amisulpride versus risperidone -28.4, p = 0.999), the PANSS positive subscale score (amisulpride -6.8 versus risperidone -8.3, p = 0.467), the PANSS negative subscale score (amisulpride -5.6 versus risperidone -6.4, p = 0.999), or the CGI score between the two groups. The extrapyramidal symptom ratings, the improvement in the SOFAS (amisulpride 11.1 versus risperidone 10.0) and the subjective response (amisulpride 82% versus risperidone 83%) were comparable. No serious adverse events were recorded in either treatment group. There was a statistically significant body weight gain in the risperidone group. In contrast, there was a statistically, though not clinically, significant reduction of blood pressure and heart rate in the amisulpride group. Conclusions: This study suggests that amisulpride is as effective as risperidone in the treatment of patients with schizophrenia. Both drugs were well tolerated, but had different side effect profiles. Key words: Amisulpride; Risperidone; Schizophrenia; Double-blind study; Antipsychotic agents J Formos Med Assoc 2003;102:30-6 Amisulpride is a unique substituted benzamide with selective affinity to D 2 and D 3 receptors. Animal studies have shown that at low dose it blocks presynaptic dopamine autoreceptors and enhances dopamine release, whereas at high dose, it preferentially blocks postsynaptic dopaminergic receptors in the limbic region as compared to those of the striatum. 1,2 These findings are consistent with results of human clinical trials. Compared with conventional antipsychotics, amisulpride (400 to 800 mg/day) has been shown to have comparable efficacy for the treatment of positive symptoms, 3,4 better efficacy for the treatment of negative symptoms, and less propensity to induce extrapyramidal symptoms (EPS). 5,6 At lower dose (50 to 300 mg/day), amisulpride was shown to improve predominantly negative symptoms in patients with schizophrenia. 7 9 Thus, it bears the clinical features of so-called atypical antipsychotics, but with its own specific mechanism involving mainly dopaminergic receptors. Risperidone, a widely used atypical antipsychotic, is an antagonist at both dopaminergic D 2 and serotonergic 5HT 2 receptors. Compared with conventional antipsychotics, it has been shown to be equally effective in the treatment of positive symptoms, Department of Psychiatry, National Taiwan University Hospital, Taipei; 2 Department of General Psychiatry, Pali Psychiatric Center, Taipei county; 3 Department of Psychiatry, Taoyuan Psychiatric Center, Taoyuan county; 4 Department of Psychiatry, Veterans General Hospital-Taipei, Taipei, Taiwan. Received: 6 June 2002 Revised: 7 July 2002 Accepted: 1 October 2002 Reprint requests and correspondence to: Dr. Ying-Sheue Chen, Department of Psychiatry, Veterans General Hospital- Taipei, No. 201, Shih-Pai Road, Sec. 2, Taipei 11217, Taiwan. 30 J Formos Med Assoc 2003 Vol 102 No 1

2 Amisulpride Versus Risperidone in Schizophrenia more effective in the treatment of negative symptoms, 13 and less likely to induce EPS in patients with schizophrenia. 11,12 Although the efficacy of both amisulpride and risperidone has already been compared to conventional antipsychotics, it remains unclear how amisulpride compares with risperidone. To our knowledge, there has been only one study directly comparing amisulpride and risperidone, 14 and no such studies have been done in Asian patients with schizophrenia. The purpose of this study was to compare amisulpride to risperidone to evaluate their efficacy and safety in patients with schizophrenia in Taiwan. Methods Study design The study was designed as a double-blind, randomized, multicenter study comparing the efficacy and safety of amisulpride versus risperidone in schizophrenic patients. Patients were observed for a placebo run-in (washout) period of 3 to 6 days to evaluate their enrollment eligibility, and then were randomly allocated to receive either amisulpride or risperidone for 6 weeks. The study protocol was approved by the Joint Institutional Review Board, Taiwan. Patients Patients were recruited from 4 centers in northern Taiwan. The enrollment criteria required patients to be years old and to fulfill DSM IV 15 criteria for schizophrenia, with productive symptom [scoring 4 or above for at least 2 of the 7 positive symptoms in the Positive and Negative Symptom Scale (PANSS) and with a PANSS total score between 60 and 120] at the screening visit and day 0 (i.e. the day when patients took the first dose of trial drugs). Patients having the following conditions were excluded from the study: 1) history of allergy or hypersensitivity to risperidone, benzamides, procyclidine, or benzodiazepines; 2) significant neurological diseases such as stroke, Parkinson s disease or epilepsy; 3) significant organic brain syndrome; 4) history of severe medical diseases such as cardiovascular, respiratory, renal or liver disease; 5) pregnancy, lactation, or intention to become pregnant; 6) recent abuse of psychoactive drugs or alcohol; and 7) placebo responders, i.e. patients whose PANSS positive scores reduced by 40% or more during the placebo run-in period. Written informed consent was obtained from every patient prior to entry into the trial after explanation of the procedure and possible side effects. Efficacy, EPS, and other evaluations Efficacy and safety evaluations were done on days 0, 7, 14, 21, 28, and 42. The primary efficacy measure was the total score of the PANSS, which was assessed using a Chinese version of the PANSS (the PANSS- CH) with demonstrated reliability. 16 The secondary efficacy measures were: the subscale scores of the PANSS, the PANSS-derived BPRS (Brief Psychiatric Rating Scale) total scores, and the Clinical Global Impression (CGI) scores. 17 Other efficacy measures included the Social and Occupational Functioning Assessment Scale (SOFAS), 15 and a scale assessing patients subjective responses to treatment. EPS were evaluated with the Extrapyramidal Syndrome Rating Scale (ESRS). 18 All investigators participated in a oneday video training session of the rating procedures before the study started. The inter-rater reliability on PANSS was satisfactory ( for all items) after training. Study procedures At least 6 days prior to day 0, patients were assessed and screened by participating psychiatrists for eligibility according to the above-mentioned criteria. Medical history was taken, and physical and laboratory examinations were done, including hematology, blood chemistry, urinalysis, and electrocardiography (ECG). PANSS, PANSS-derived BPRS, and CGI scale ratings were evaluated. A patient s spontaneous complaints were recorded. Eligible patients were then admitted and entered a placebo run-in (washout) period for 3 to 6 days. Those receiving a depot injection were required to have a minimal washout period equivalent to the previous injection interval. After washout, on day 0, patients were randomly assigned to receive amisulpride ( mg/day) or risperidone (4 8 mg/day) for 6 weeks. Risperidone doses were titrated from 1 mg/day to 4 mg/day during the first 6 days to avoid acute adverse effects, while amisulpride remained at 400 mg/day. Subsequently, both drugs were titrated according to clinical response at the discretion of the investigators. In accordance with the double-blind nature of the study, both drugs were provided in identical sealed capsules. Psychopathology (PANSS, BPRS, CGI), ESRS, and physical examination were assessed, and patient s spontaneous complaints or clinical findings of adverse events were recorded on days 0, 7, 14, 21, 28, and 42. Adverse events were coded by the WHO-Adverse Reaction Terminology (WHO-ART) coding system and were tabulated by body system. Blood and urine examinations were performed on days 14 and 42. A follow-up ECG was performed on day 42. The SOFAS was used to evaluate the individual s level of social and occupational functioning on day 0 and day 42 J Formos Med Assoc 2003 Vol 102 No 1 31

3 Table 1. Demographic and baseline characteristics of the intent-to-treat population. Amisulpride (n = 22) Risperidone (n = 25) p value Male/female 9 /13 11 / Age [yr, mean (SD)] 36.3 (9.2) 34.1 (9.9) Schizophrenia subtype, no. (%) Paranoid 11 (50.0) 11 (44.0) Disorganized 5(22.7) 4 (16.0) Undifferentiated 6(27.3) 10 (40.0) Duration of illness [yr, mean (SD)] 13.3 (8.4) 13.4 (8.6) Body weight [kg, mean (SD)] 64.6 (14.4) 63.9 (13.2) (or at the time of premature withdrawal). Patients subjective responses were also assessed at day 7 and day 42, using a semi-structured interview by asking How does the medication agree with you? ; Did it make you feel calmer? ; Did it affect your thinking? ; and Do you think this would be the right medication for you?. Responses were rated on a seven-point (-3 to +3) euphoric/dysphoric scale. Concomitant medications were restricted unless clinically necessary. Statistical analysis The main analysis was carried out on the intent-totreat population using the Last Observation Carried Forward (LOCF) technique. Because of the limited sample size, non-parametric analyses were used. The main analysis was a Friedman two-way analysis of variance (treatment group and center) for between group analyses in efficacy parameters (PANSS, BPRS, CGI, SOFAS, subjective response) and safety parameters (ESRS, vital signs, body weight). Wilcoxon signed rank test was applied for within group analyses. Ordinal qualitative variables were examined using Cochran-Mantel-Haenszel test (with ridit transformation of the variables), with adjustment for center effect. Statistical significance was declared if the two-sided p value was less than All statistical analyses were performed using SAS statistical software. Results From October 01, 1999 to June 30, 2000, a total of 48 patients with schizophrenia were enrolled. There were 23 and 25 patients in the amisulpride and risperidone groups, respectively. One patient in the amisulpride group had multiple somatic complaints during the placebo run-in phase and withdrew himself from the trial at day 6; the patient was excluded for efficacy data analyses due to lack of any efficacy measure after active medication. Of the remaining 47 patients, two in the amisulpride group failed to complete the entire 6-week trial. In one this was due to adverse events; the other was found not to meet the washout criteria of abstinence for antipsychotic medication injection after inclusion. Demographic data of the two groups in the intentto-treat population are summarized in Table 1. There were no significant differences in baseline characteristics between the two groups. In the amisulpride group, the mean dose was unchanged after day 28 (630 ± 150 mg/day at day 28 and 630 ± 134 mg/day at day 42), while the mean dose was increased slightly after day 28 (6.56 ± 1.58 mg/day at day 28 and 6.88 ± 1.54 mg/day at day 42) in the risperidone group. Efficacy The PANSS total score and three subscores over the 6-week trial are shown in Table 2. At the end of the trial, there were significant changes in both groups, but no significant differences between the two groups in the PANSS total scores and the three subscores. The proportions of patients with more than 20% score reduction in the PANSS total scores were calculated, and no significant difference between the two groups was observed (68% with amisulpride versus 76% with risperidone, p = 0.745). Changes in the BPRS total scores and the CGI score are also shown in Table 2. Similarly, there were significant changes within each group, but no statistical differences between these two groups. When the categories of very much improved and much improved were grouped as a single responder category, there were no significant differences in the number and percentage of responders between the amisulpride and risperidone groups (41% versus 60%, respectively, p = 0.196). There was no significant difference in the scores of SOFAS between the two groups at the end of the trial (Table 2). The assessments of patients subjective response were also comparable. Approximately 75% of all patients expressed a positive subjective response to treatment after day 7. At day 42, 82% and 83% of patients expressed good subjective response in the amisulpride and risperidone groups, respectively. Safety During the trial period, no serious adverse events were recorded based on patients spontaneous 32 J Formos Med Assoc 2003 Vol 102 No 1

4 Table 2. Changes in PANSS, BPRS, CGI, and SOFAS scores of the intent-to-treat population. Amisulpride Versus Risperidone in Schizophrenia Amisulpride (n = 22) Risperidone (n = 25) p value Mean SD Mean SD PANSS Total score Day Day 42 minus Day PANSS positive subscale Day Day 42 minus Day PANSS negative subscale Day Day 42 minus Day PANSS general psychopathology Day Day 42 minus Day BPRS Day Day 42 minus Day CGI Day Day 42 minus Day SOFAS Day Day 42 minus Day PANSS = Positive and Negative Syndrome Scale; BPRS = Brief Psychiatric Rating Scale; CGI = Clinical Global Impression severity of illness; SOFAS = Social and Occupational Functioning Assessment Scale. reports or investigators examinations. The overall incidence of treatment-related adverse events was 65.2% (15/23) and 64.0% (16/25) for patients in the amisulpride and risperidone groups, respectively, and the difference was not statistically significant (p = 0.931). When the incidence of each adverse event was compared, none was shown to be significantly different between the 2 groups. The adverse events recorded in more than 5% of patients are listed in Table 3. The most frequent adverse events were insomnia (17.3%) and constipation (17.3%) in the amisulpride group, and akathisia (16%), tremo (12%), and constipation (12%) in the risperidone group. At the end of the trial, there were no significant between-group or within-group changes in the global assessment of parkinsonism, tardive dyskinesia, or total scores of BAS, except that the risperidone group had a significant within-group reduction in the global assessment of parkinsonism (day 0: 1.4 ± 1.0, day 42: 0.9 ± 0.8, p < 0.05). The number of patients using antiparkinsonian drugs, β-blockers, anxiolytics, and hypnotics was 7 (30.4%), 1 (4.3%), 6 (26.1%), and 16 (70%), respectively, in the amisulpride group; and 11 (44%), 4 (16%), 12 (48%), and 19 (76%), respectively, in the risperidone group. There were borderline to significant differences between the two groups in the use of antiparkinsonian drugs, β-blockers, and anxiolytics (Fisher s exact test: p = 0.06, 0.008, and 0.002, respectively). Regarding the vital signs, there were no significant differences between the 2 groups at the end of the trial (Table 4). The amisulpride group had significant within-group reduction (p < 0.01), while the risperidone group had borderline reduction (p < 0.07), in both supine systolic blood pressure (SBP) and diastolic blood pressure (DBP). The amisulpride group had significant within-group reduction (p < 0.04), while the risperidone group had a non-significant increase in supine heart rate (HR) [Table 4]. These changes in vital signs were judged as clinically insignificant. Mean body weight in the risperidone group was significantly increased at the end of the trial (Table 4), but there were no significant differences in this variable between the 2 groups. Three cases with normal baseline ECG had abnormal but clinically insignificant changes at the end of the study. Two cases were in the amisulpride Table 3. Treatment-emergent adverse events occurring in at least 5% of patients. Adverse event Amisulpride Risperidone n % n % Akathisia Muscle rigidity Tremor Dizziness Agitation Insomnia Constipation SGPT increase Palpitation Headache SGPT = serum glutamic pyruvic transaminase J Formos Med Assoc 2003 Vol 102 No 1 33

5 Table 4. Changes in vital signs and body weight measurement of the intent-to-treat population. group (non-specific ST-T changes and left ventricular hypertrophy criteria), and one in the risperidone group (sinus tachycardia). There were no cases with prolonged QTc (QTc > 500 ms) at the end of the trial in either group. Blood and urine examinations showed that there were no clinically significant changes in either group, and no patient was withdrawn from the study due to laboratory abnormalities. Discussion This double-blind pilot study showed that there were no significant differences in efficacy between amisulpride and risperidone in schizophrenic patients. Both drugs were effective in the treatment of positive and negative symptoms of schizophrenia, and all subjective responses and functional outcomes indicated that the drugs were comparable. The result is consistent with a previous report with a direct comparison design, 14 and other indirect comparison studies. 3,4,12,19 There was an initial significant decline in the total scores of the PANSS, BPRS, and CGI at Day 7 in both groups, and the decline continued till the end of the trial. However, it is interesting to note that the mean dose did not change after Day 28 in the amisulpride group, while there was mild dose escalation in the risperidone group. This implies that amisulpride 630 mg/day was clinically equivalent to risperidone mg/day in the 6-week trial. This estimate is close to that in the fixed-dose design of the study by Peuskens et al, in which amisulpride 800 mg/day was equivalent to risperidone 8 mg/day. 14 The finding is also consistent with a previous report that amisulpride mg/day is the most efficacious dose in the treatment of schizophrenia. 4 Previous studies showed a trend in favor of greater improvement in negative symptoms in the PANSS negative scale in patients receiving amisulpride, 6,14 but we did not find such a trend in this study. Possible relevant factors included differences in comparison Amisulpride (n = 22) Risperidone (n = 25) p value Mean SD Mean SD Systolic blood pressure Day Day 42 minus Day 0-7.6* Heart rate Day Day 42 minus Day 0-6.1* Body weight Day Day 42 minus Day * *p < 0.05 for the within-group comparison between day 0 and day 42; p values for the changes between groups at day 42. doses and concomitant medications, and a smaller sample size in our study. In the study of Peuskens et al, the dosages were relatively high (800 mg/day of amisulpride and 8 mg/day of risperidone), and the percentage of concomitant antiparkinsonian drugs was 30% in the amisulpride group and 23% in the risperidone group. In our study, the dosages were moderate, and the percentage of concomitant antiparkinsonian drugs in the amisulpride group (30%) was significantly lower than in the risperidone group (44%). Both drugs were well tolerated in this trial. There were no severe adverse events, a relatively low incidence of adverse events, and only rare withdrawal from the trial due to adverse events. Scores on different dimensions of EPS also did not increase significantly during the trial, indicating that neither amisulpride nor risperidone induced marked EPS at these dose ranges. This is consistent with previous experiences with these drugs. 6,20 There was a significant reduction in the rating of parkinsonism in the risperidone group at the end of the trial, which might be related to the dose employed, concomitant medications or the small sample size. In this trial, the risperidone group had significant body weight gain at the end of the study, which is commonly associated with the use of risperidone, 21,22 but not amisulpride. 5,22 There was no QTc prolongation or arrythmogenic effect for either drug, which is consistent with recent reviews. 23,24 Theoretically, amisulpride has a low autonomic neurocardiac risk due to its action at dopamine D 2 and D 3 receptors rather than at cholinergic or adrenergic receptors. 25,26 However, albeit judged to be clinically insignificant, there were statistically significant reductions of supine SBP, DBP and HR in the amisulpride group at the end of the trial. A large pooled analysis on safety profiles of amisulpride 27 showed that a trend towards a decrease in HR (defined as sitting or supine HR 50 beats/min and a decrease versus baseline 15 beats/min) occurred in 1% of amisulpride recipients, and a trend towards decreased 34 J Formos Med Assoc 2003 Vol 102 No 1

6 Amisulpride Versus Risperidone in Schizophrenia blood pressure (sitting or supine SBP 90 mm Hg and a decrease versus baseline of 20 mm Hg, or any sitting or supine DBP of 50 mm Hg and a decrease versus baseline of 15 mm Hg) in 7% of amisulpride recipients, 7% of risperidone recipients, 4% of haloperidol recipients, and 4% of placebo recipients. Therefore, our findings may be explained by the small sample size. But these cardiovascular findings in this group of relatively young patients deserve attention because they may imply a possible difference in racial response. Suspected evidence for racial differences was found in the required doses for antiparkinsonian drugs. In the European study by Peuskens et al, 14 antiparkinsonian medications were initiated in 30% of patients taking amisulpride 800 mg/day and 23% taking risperidone 8 mg/day. In our study, antiparkinsonian medications were initiated in 30% of patients taking amisulpride (mean dose 630 mg/day) and 44% taking risperidone (mean dose 6.88 mg/day). In both trials, antiparkinsonian medications were not to be initiated unless antipsychotic-induced extrapyramidal symptoms emerged. While receiving a lower mean dose of antipsychotics, the patients in our study showed greater need for antiparkinsonian medications, regardless of which antipsychotic agent they received. These findings suggest that there are racial differences in response to the atypical antipsychotics. This observation is supported by other studies which show that, although the condition is rare among Caucasians, as many as 20% of Chinese and Japanese are poor metabolizers via the cytochrome P450 enzymes. 28 Compared with Caucasian individuals, Chinese have been found to have 30% to 50% higher plasma levels of clozapine 29 and 10% to 50% higher levels of haloperidol. 30 Therefore, our results and some reports 31,32 suggest that caution should be used with atypical antipsychotic agents in view of the potential for racial and individual differences in drug response. Further large-scale studies with blood level measurement need to be done in order to produce more definitive conclusions regarding the clinical implications of these variations in atypical antipsychotic drug disposition. At present, vital signs should be monitored when amisulpride is prescribed, especially in the elderly. There are several limitations in this study. The sample size is not large enough for definitive conclusions to be reached based on this trial, and the trial duration is too short to evaluate long-term effects of the drugs. The absence of a placebo control group limits the findings regarding efficacy and safety, although inclusion of a placebo study arm was precluded because of ethical considerations. The value of the study is that it provides a direct comparison of atypical antipsychotics in an Asian population. Such studies are under-represented in the literature. ACKNOWLEDGMENTS: The project was supported by funding from the Fujisawa Taiwan and a grant NTUH 90s1004 to Dr. Hwang. We wish to thank the participating psychiatrists from the collaborative hospitals for data collection, and Dr. G. Bartzokis for advice on the paper. References 1. Perrault G, Depoortere R, Morel E, et al: Psychopharmacological profile of amisulpride: an antipsychotic drug with presynaptic D2/D3 dopamine receptor antagonist activity and limbic selectivity. J Pharmacol Exp Ther 1997;280: Schoemaker H, Claustre Y, Fage D, et al: Neurochemical characteristics of amisulpride, an atypical dopamine D2/D3 receptor antagonist with both presynaptic and limbic selectivity. J Pharmacol Exp Ther 1997;280: Moller HJ, Boyer P, Fleurot O, et al: Improvement of acute exacerbations of schizophrenia with amisulpride: a comparison with haloperidol. PROD-ASLP Study Group. Psychopharmacology (Berl) 1997;132: Puech A, Fleurot O, Rein W: Amisulpride, an atypical antipsychotic, in the treatment of acute episodes of schizophrenia: a dose-ranging study vs. haloperidol. The Amisulpride Study Group. Acta Psychiatr Scand 1998;98: Burns T, Bale R: Clinical advantages of amisulpride in the treatment of acute schizophrenia. J Int Med Res 2001;29: Leucht S, Pitschel-Walz G, Engel RR, et al: Amisulpride, an unusual atypical antipsychotic: a meta-analysis of randomized controlled trials. Am J Psychiatry 2002;159: Loo H, Poirier-Littre MF, Theron M, et al: Amisulpride versus placebo in the medium-term treatment of the negative symptoms of schizophrenia. Br J Psychiatry 1997;170: Boyer P, Lecrubier Y, Puech AJ, et al: Treatment of negative symptoms in schizophrenia with amisulpride. Br J Psychiatry 1995;166: Paillere-Martinot ML, Lecrubier Y, Martinot JL, et al: Improvement of some schizophrenic deficit symptoms with low doses of amisulpride. Am J Psychiatry 1995;152: McEvoy JP: Efficacy of risperidone on positive features of schizophrenia. J Clin Psychiatry 1994;55: Marder SR, Meibach RC: Risperidone in the treatment of schizophrenia. Am J Psychiatry 1994;151: Peuskens J: Risperidone in the treatment of patients with chronic schizophrenia: a multi-national, multi-centre, double-blind, parallel-group study versus haloperidol. Risperidone Study Group. Br J Psychiatry 1995;166:712-26; discussion J Formos Med Assoc 2003 Vol 102 No 1 35

7 13. Carman J, Peuskens J, Vangeneugden A: Risperidone in the treatment of negative symptoms of schizophrenia: a metaanalysis. Int Clin Psychopharmacol 1995;10: Peuskens J, Bech P, Moller HJ, et al: Amisulpride vs. risperidone in the treatment of acute exacerbations of schizophrenia. Amisulpride study group. Psychiatry Res 1999;88: American Psychiatric Association: Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatry Association, Cheng JJ, Ho H, Chang CJ, et al: Positive and Negative Syndrome Scale (PANSS): establishment and reliability study of a Mandarin Chinese language version. Chin Psychiatry 1996;10: Guy W: ECDEU Assessment Manual for Psychopharmacology: Publication ADM Rockville: US Department of Health, Education and Welfare, 1976: Chouinard G, Ross-Chouinard A, Annable L, et al: The Extrapyramidal Symptom Rating Scale. Can J Neurol Sci 1980;7: Chouinard G, Jones B, Remington G, et al: A Canadian multicenter placebo-controlled study of fixed doses of risperidone and haloperidol in the treatment of chronic schizophrenic patients. J Clin Psychopharmacol 1993;13: Leucht S, Pitschel-Walz G, Abraham D, et al: Efficacy and extrapyramidal side-effects of the new antipsychotics olanzapine, quetiapine, risperidone, and sertindole compared to conventional antipsychotics and placebo. A meta-analysis of randomized controlled trials. Schizophr Res 1999;35: Conley RR: Risperidone side effects. J Clin Psychiatry 2000;61: 20 3; discussion Taylor DM, McAskill R: Atypical antipsychotics and weight gain a systematic review. Acta Psychiatr Scand 2000;101: Wilton LV, Heeley EL, Pickering RM, et al: Comparative study of mortality rates and cardiac dysrhythmias in post-marketing surveillance studies of sertindole and two other atypical antipsychotic drugs, risperidone and olanzapine. J Psychopharmacol 2001;15: Glassman AH, Bigger JT, Jr.: Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death. Am J Psychiatry 2001;158: Agelink MW, Majewski T, Wurthmann C, et al: Effects of newer atypical antipsychotics on autonomic neurocardiac function: a comparison between amisulpride, olanzapine, sertindole, and clozapine. J Clin Psychopharmacol 2001;21: Curran MP, Perry CM: Amisulpride: a review of its use in the management of schizophrenia. Drugs 2001;61: Coulouvrat C, Dondey-Nouvel L: Safety of amisulpride (Solian): a review of 11 clinical studies. Int Clin Psychopharmacol 1999; 14: Lin KM, Poland RE: Ethnicity, culture, and psychopharmacology. In Bloom FE, Kupler DJ, eds. Psychopharmacology: the Fourth Generation of Progress. New York: Raven Press, 1995: Chang WH, Lin SK, Lane HY, et al: Clozapine dosages and plasma drug concentrations. J Formos Med Assoc 1997;96: Lane HY, Lin HN, Hwu HG, et al: Haloperidol plasma concentrations in Taiwanese psychiatric patients. J Formos Med Assoc 1995;94: Pedrosa Gil F, Grohmann R, Ruther E: Asymptomatic bradycardia associated with amisulpride. Pharmacopsychiatry 2001;34: Tracqui A, Mutter-Schmidt C, Kintz P, et al: Amisulpride poisoning: a report on two cases. Hum Exp Toxicol 1995; 14: J Formos Med Assoc 2003 Vol 102 No 1

Clinical Advantages of Amisulpride in the Treatment of Acute Schizophrenia

Clinical Advantages of Amisulpride in the Treatment of Acute Schizophrenia The Journal of International Medical Research 2001; 29: 451 466 Clinical Advantages of Amisulpride in the Treatment of Acute Schizophrenia T BURNS 1 AND R BALE 2 1 Department of Psychiatry; 2 Department

More information

Paliperidone: Clinical Protocol R076477SCH4012, CR Amendment INT-1

Paliperidone: Clinical Protocol R076477SCH4012, CR Amendment INT-1 Paliperidone: Clinical Protocol R076477SCH4012, CR013771 Amendment INT-1 A Randomized, Double-Blind, Placebo- and Active-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of a Fixed

More information

Trial No.: RIS-USA-102 Clinical phase: III

Trial No.: RIS-USA-102 Clinical phase: III SYNOPSIS Trial identification and protocol summary Company: Johnson & Johnson Pharmaceutical Research and Development, a division of Janssen Pharmaceutica, N.V. Finished product: Risperdal Active ingredient:

More information

Summary ID#7029. Clinical Study Summary: Study F1D-MC-HGKQ

Summary ID#7029. Clinical Study Summary: Study F1D-MC-HGKQ CT Registry ID# 7029 Page 1 Summary ID#7029 Clinical Study Summary: Study F1D-MC-HGKQ Clinical Study Report: Versus Divalproex and Placebo in the Treatment of Mild to Moderate Mania Associated with Bipolar

More information

(+)-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethyl]- 6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyridol[1,2-a]pyrimidin-4- one

(+)-3-[2-[4-(6-fluoro-1,2-benzisoxazol-3-yl)-1-piperidinyl]-ethyl]- 6,7,8,9-tetrahydro-9-hydroxy-2-methyl-4H-pyridol[1,2-a]pyrimidin-4- one SYNOPSIS Issue Date: 18 November 2008 Document No.: EDMS-PSDB-9006510:2.0 Name of Sponsor/Company Name of Finished Product Name of Active Ingredient(s) Ortho-McNeil Janssen Scientific Affairs, L.L.C. Paliperidone

More information

New Medications in Early Psychosis

New Medications in Early Psychosis New Medications in Early Psychosis Jean Starling Department of Psychological Medicine, the Children s Hospital at Westmead Department of Psychological Medicine and Department of Paediatrics and Child Health,

More information

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-INT-24 (FOR NATIONAL AUTHORITY USE ONLY)

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-INT-24 (FOR NATIONAL AUTHORITY USE ONLY) SYNOPSIS Protocol No.: RIS-INT-24 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: Risperidone in the treatment of behavioral disturbances in demented patients: an international, multicenter,

More information

Janssen-Cilag EMEA Medical Affairs a division of Janssen Pharmaceuticals N.V.

Janssen-Cilag EMEA Medical Affairs a division of Janssen Pharmaceuticals N.V. SYNOPSIS Issue Date: Final 22 July 2009 [Document No.: EDMS-PSDB-9245102] Name of Sponsor/Company Name of Finished Product Risperdal Consta Name of Active Ingredient(s) Protocol No.: RIS-BMN-3001 Janssen-Cilag

More information

INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER Volume: Page:

INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER Volume: Page: SYNOPSIS Protocol No.: CR004357 Title of Study: A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy and Safety of 50 and 100 mg eq. of Paliperidone Palmitate in Subjects With

More information

SYNOPSIS. Study Coordinator. Study centre(s)

SYNOPSIS. Study Coordinator. Study centre(s) Drug product: Seroquel Drug substance(s): Quetiapine Document No.: 1 Edition No.: 1 Study code: D1449C00005 Date: 02 January 2007 SYNOPSIS A Randomized, Parallel Group, Open Trial Examining the Safety,

More information

SYNOPSIS. ER OROS Paliperidone: Clinical Study Report R SCH-301

SYNOPSIS. ER OROS Paliperidone: Clinical Study Report R SCH-301 SYNOPSIS Protocol No.: R076477-SCH-301 Title of Study: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study With an Open-Label Extension Evaluating Extended Release OROS Paliperidone in

More information

Diagnosis and treatment of acute agitation and aggression in patients with schizophrenia and bipolar disorder: evidence for the efficacy of atypical

Diagnosis and treatment of acute agitation and aggression in patients with schizophrenia and bipolar disorder: evidence for the efficacy of atypical Diagnosis and treatment of acute agitation and aggression in patients with schizophrenia and bipolar disorder: evidence for the efficacy of atypical antipsychotics 1 Abstract Acute agitation and aggression

More information

SYNOPSIS (FOR NATIONAL AUTHORITY USE ONLY) INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER

SYNOPSIS (FOR NATIONAL AUTHORITY USE ONLY) INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER SYNOPSIS Protocol No.: RIS-USA-63 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: A randomized, double-blind, placebo controlled study of risperidone for treatment of behavioral disturbances

More information

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.

Copyright Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Original article 143 Ziprasidone and amisulpride effectively treat negative symptoms of schizophrenia: results of a 12-week, double-blind study Jean-Pierre Olié a, Edoardo Spina b, Stephen Murray c and

More information

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-AUS-5 (FOR NATIONAL AUTHORITY USE ONLY)

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-AUS-5 (FOR NATIONAL AUTHORITY USE ONLY) SYNOPSIS Protocol No.: RIS-AUS-5 Psychosis in Alzheimer s disease (PAD) analysis Title of Study: Risperidone in the treatment of behavioral and psychological symptoms in dementia: a multicenter, double-blind,

More information

Amisulpride in Addition to Clozapine: A Retrospective Study Indicates Improved Efficacy and Good Tolerability

Amisulpride in Addition to Clozapine: A Retrospective Study Indicates Improved Efficacy and Good Tolerability Reprinted from the German Journal of Psychiatry http://www.gjpsy.uni-goettingen.de ISSN 1433-1055 Amisulpride in Addition to Clozapine: A Retrospective Study Indicates Improved Efficacy and Good Tolerability

More information

Alternative Thresholds for Negative and Positive Symptoms in the CATIE Trial: Implications for Negative Symptom Clinical Trials

Alternative Thresholds for Negative and Positive Symptoms in the CATIE Trial: Implications for Negative Symptom Clinical Trials Alternative Thresholds for Negative and Positive Symptoms in the CATIE Trial: Implications for Negative Symptom Clinical Trials Eduardo Dunayevich, Chao-Yin Chen, Stephen Marder and Jonathan Rabinowitz

More information

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-USA-232 (FOR NATIONAL AUTHORITY USE ONLY)

SYNOPSIS. Risperidone-R064766: Clinical Study Report RIS-USA-232 (FOR NATIONAL AUTHORITY USE ONLY) SYNOPSIS Protocol No.: RIS-USA-232 Title of Study: Efficacy and Safety of a Flexible Dose of Risperidone Versus Placebo in the Treatment of Psychosis of Alzheimer's Disease Principal Investigator: M.D.

More information

2. SYNOPSIS Name of Sponsor/Company:

2. SYNOPSIS Name of Sponsor/Company: in patients with refractory partial seizures 14 Jun 2007 2. SYNOPSIS TITLE OF STUDY: Efficacy and safety of BIA 2-093 as adjunctive therapy for refractory partial seizures in a double-blind, randomized,

More information

Is Aristada (Aripiprazole Lauroxil) a Safe and Effective Treatment For Schizophrenia In Adult Patients?

Is Aristada (Aripiprazole Lauroxil) a Safe and Effective Treatment For Schizophrenia In Adult Patients? Philadelphia College of Osteopathic Medicine DigitalCommons@PCOM PCOM Physician Assistant Studies Student Scholarship Student Dissertations, Theses and Papers 12-2016 Is Aristada (Aripiprazole Lauroxil)

More information

PFIZER INC. THERAPEUTIC AREA AND FDA APPROVED INDICATIONS: See United States Package Insert (USPI)

PFIZER INC. THERAPEUTIC AREA AND FDA APPROVED INDICATIONS: See United States Package Insert (USPI) PFIZER INC. These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert. For publications based on this study, see associated bibliography.

More information

Study No.: Title: Rationale: Phase: Study Period: Study Design: Centers: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:

Study No.: Title: Rationale: Phase: Study Period: Study Design: Centers: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable: The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.

More information

PFIZER INC. Study Initiation Date and Primary Completion or Completion Dates: 11 November 1998 to 17 September 1999

PFIZER INC. Study Initiation Date and Primary Completion or Completion Dates: 11 November 1998 to 17 September 1999 PFIZER INC. These results are supplied for informational purposes only. Prescribing decisions should be made based on the approved package insert. For publications based on this study, see associated bibliography.

More information

Treatment of Schizophrenia

Treatment of Schizophrenia Treatment of Schizophrenia Conduct comprehensive assessment and use measurement-based care as found in the Principles of Practice (review pages 4-7). Most importantly assess social support system (housing,

More information

Appendix D: Included Studies adverse effects review

Appendix D: Included Studies adverse effects review DELIRIUM APPENDICES (Draft for Consultation) Appendix D: Included Studies adverse effects review Table D1: Studies directly comparing two antipsychotic agents in delirium Author Study design Setting Age

More information

Symptoms of schizophrenia are usually categorized as positive

Symptoms of schizophrenia are usually categorized as positive PHARMACOLOGY NOTES Ziprasidone mesylate (Geodon for injection): the first injectable atypical antipsychotic medication VALERIE SHEEHAN, PHARMD Symptoms of schizophrenia are usually categorized as positive

More information

Sponsor Novartis. Generic Drug Name. NA (not existing yet) Therapeutic Area of Trial Parkinson s Disease L-dopa induced dyskinesia

Sponsor Novartis. Generic Drug Name. NA (not existing yet) Therapeutic Area of Trial Parkinson s Disease L-dopa induced dyskinesia Page 1 Sponsor Novartis Generic Drug Name NA (not existing yet) Therapeutic Area of Trial Parkinson s Disease L-dopa induced dyskinesia Approved Indication Investigational. Study Number CA2206 Title A

More information

SYNOPSIS. Trial identification and protocol summary

SYNOPSIS. Trial identification and protocol summary SYNOPSIS Trial identification and protocol summary Company: JANSSEN PHARMACEUTICA N.V. Finished product: Risperdal Active ingredient: Risperidone (R64766) Title: The safety and efficacy of risperidone

More information

BRL /RSD-101C0D/1/CPMS-704. Report Synopsis

BRL /RSD-101C0D/1/CPMS-704. Report Synopsis Report Synopsis Study Title: A Randomized, Multicenter, 10-Week, Double-Blind, Placebo- Controlled, Flexible-Dose Study to Evaluate the Efficacy and Safety of Paroxetine in Children and Adolescents with

More information

) and serotonin Type 2 (5-HT 2A

) and serotonin Type 2 (5-HT 2A Latuda (lurasidone HCl) Fact Sheet Schizophrenia FREQUENTLY ASKED QUESTIONS What type of patient with schizophrenia is appropriate for LATUDA? LATUDA is an atypical antipsychotic agent indicated for the

More information

Pharmacotherapy of psychosis and schizophrenia in youth

Pharmacotherapy of psychosis and schizophrenia in youth Pharmacotherapy of psychosis and schizophrenia in youth Benedetto Vitiello Pavia, 2 December 2017 Disclosure Benedetto Vitiello, M.D. Professor of Child and Adolescent Neuropsychiatry University of Turin,

More information

SP.236 / ESG.SP236 Exploring Pharmacology Spring 2009

SP.236 / ESG.SP236 Exploring Pharmacology Spring 2009 MIT OpenCourseWare http://ocw.mit.edu SP.236 / ESG.SP236 Exploring Pharmacology Spring 2009 For information about citing these materials or our Terms of Use, visit: http://ocw.mit.edu/terms. Atypical (2

More information

Schizophrenia is a chronic, severe, and disabling brain

Schizophrenia is a chronic, severe, and disabling brain D 2 Receptor Occupancy During High- and Low- Dose Therapy with the Atypical Antipsychotic Amisulpride: A 123 I-Iodobenzamide SPECT Study Christian la Fougère, MD 1 ; Eva Meisenzahl, MD 2 ; Gisela Schmitt,

More information

Class Update: Oral Antipsychotics

Class Update: Oral Antipsychotics Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35 Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119

More information

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 30 November 2011

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 30 November 2011 The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 30 November 2011 List of medicines concerned: SECOND-GENERATION ORAL ANTIPSYCHOTICS SOLIAN 100 mg, 200 mg, 400 mg

More information

Technology appraisal guidance Published: 26 January 2011 nice.org.uk/guidance/ta213

Technology appraisal guidance Published: 26 January 2011 nice.org.uk/guidance/ta213 Aripiprazole for the treatment of schizophrenia in people aged 15 to 17 years Technology appraisal guidance Published: 26 January 2011 nice.org.uk/guidance/ta213 NICE 2018. All rights reserved. Subject

More information

Presented at the American Psychiatric Association Annual Meeting May 20 24, 2017 San Diego, CA.

Presented at the American Psychiatric Association Annual Meeting May 20 24, 2017 San Diego, CA. Original Presentations Key Words: amines, antipsychotic agents, double-blind method, mood disorders, psychopharmacology, psychotic disorders, schizophrenia, tardive dyskinesia, valbenazine Efficacy of

More information

Abbreviated Class Review: Long-Acting Injectable Antipsychotics

Abbreviated Class Review: Long-Acting Injectable Antipsychotics Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119

More information

Summary ID# Clinical Study Summary: Study B4Z-MC-LYBU

Summary ID# Clinical Study Summary: Study B4Z-MC-LYBU CT Registry ID#7065 Page 1 Summary ID# 7065 Clinical Study Summary: Study B4Z-MC-LYBU A Randomized, Double-Blind Comparison of Atomoxetine Hydrochloride Augmented with Either Extended-Release Methylphenidate

More information

JNJ AAA; paliperidone palmitate Clinical Study Report R SCH-4009

JNJ AAA; paliperidone palmitate Clinical Study Report R SCH-4009 SYNOPSIS Name of Sponsor/Company Name of Finished Product Name of Active Ingredient(s) Janssen Asia Pacific Medical Affairs, a Division of Johnson and Johnson Pte Ltd* INVEGA SUSTENNA * The legal entity

More information

Study Center(s): The study was conducted at 39 study sites in Japan.

Study Center(s): The study was conducted at 39 study sites in Japan. SYNOPSIS Issue Date: 20 NOVEMBER 2012 Name of Sponsor/Company Janssen Pharmaceutical K. K. Name of Finished Product CONCERTA Name of Active Ingredient(s) Methylphenidate HCl Protocol No.: JNS001-JPN-A01

More information

Clinical Study A Comparative Study between Olanzapine and Risperidone in the Management of Schizophrenia

Clinical Study A Comparative Study between Olanzapine and Risperidone in the Management of Schizophrenia Schizophrenia Research and Treatment, Article ID 307202, 5 pages http://dx.doi.org/10.1155/2014/307202 Clinical Study A Comparative Study between and in the Management of Schizophrenia Saeed Shoja Shafti

More information

Hearts and Minds An ECG Update. Tuesday 18 th November The Met Hotel, Leeds

Hearts and Minds An ECG Update. Tuesday 18 th November The Met Hotel, Leeds Hearts and Minds An ECG Update Tuesday 18 th November The Met Hotel, Leeds Ashleigh Bradley Specialist Clinical Pharmacist for Mental Health and Lithium Clinic Airedale NHS Foundation Trust Introduction

More information

APRIL 2008 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1. Harish Arora, Rajdeep Kaur Department of Psychiatry, G.G.S. Medical College, Faridkot, Punjab

APRIL 2008 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1. Harish Arora, Rajdeep Kaur Department of Psychiatry, G.G.S. Medical College, Faridkot, Punjab APRIL 2008 DELHI PSYCHIATRY JOURNAL Vol. 11 No.1 Original Article An Open Label Study on Amisulpride in Augmentation with Atypical Antipsychotics in Treatment Resistant Patients of Schizophrenia and Schizoaffective

More information

CIZOREST Tablets (Amisulpride)

CIZOREST Tablets (Amisulpride) Published on: 2 Dec 2015 CIZOREST Tablets (Amisulpride) Composition CIZOREST 50mg Tablets Each film-coated tablet contains: Amisulpride..50 mg CIZOREST 100mg Tablets Each film-coated tablet contains: Amisulpride..100

More information

RUNNING HEAD: Efficacy, Long Acting Injectable Antipsychotics and Schizophrenia 1

RUNNING HEAD: Efficacy, Long Acting Injectable Antipsychotics and Schizophrenia 1 RUNNING HEAD: Efficacy, Long Acting Injectable Antipsychotics and Schizophrenia 1 Efficacy of Long Acting Injectable Antipsychotics in Early Onset Schizophrenia Linda Pietras RN-BC Mercyhurst University

More information

An Open-Label, Effectiveness Study of Long-Term Quetiapine Treatment

An Open-Label, Effectiveness Study of Long-Term Quetiapine Treatment An Open-Label, Effectiveness Study of Long-Term Quetiapine Treatment Pierre Chue, FRCPC * Wahid Abouelnsar, MD Alain Gendron, PhD * Psychiatrist, University of Alberta Hospital, Edmonton, Alberta Psychiatrist,

More information

Abbreviated Class Review: Long-Acting Injectable Antipsychotics

Abbreviated Class Review: Long-Acting Injectable Antipsychotics Copyright 2012 Oregon State University. All Rights Reserved Drug Use Research & Management Program Oregon State University, 500 Summer Street NE, E35, Salem, Oregon 97301-1079 Phone 503-947-5220 Fax 503-947-1119

More information

Switching antipsychotics: Basing practice on pharmacology & pharmacokinetics

Switching antipsychotics: Basing practice on pharmacology & pharmacokinetics Switching antipsychotics: Basing practice on pharmacology & pharmacokinetics John Donoghue Liverpool L imagination est plus important que le savoir Albert Einstein Switching Antipsychotics: Objectives

More information

The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only.

The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. The clinical trial information provided in this public disclosure synopsis is supplied for informational purposes only. Please note that the results reported in any single trial may not reflect the overall

More information

Pharmaceutical form(s)/strength: 50, 100, 200, 400 mg tablets P-RMS:

Pharmaceutical form(s)/strength: 50, 100, 200, 400 mg tablets P-RMS: 0BCore Safety Profile Active substance: Amisulpride Pharmaceutical form(s)/strength: 50, 100, 200, 400 mg tablets P-RMS: IE/H/PSUR/0017/002 Date of FAR: 28.11.2012 Core Safety Profile [amisulpride] Formulations:

More information

Study No.: Title: Rationale: Phase: Study Period: Study Design: Centers Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:

Study No.: Title: Rationale: Phase: Study Period: Study Design: Centers Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable: The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.

More information

Minimising the Impact of Medication on Physical Health in Schizophrenia

Minimising the Impact of Medication on Physical Health in Schizophrenia Minimising the Impact of Medication on Physical Health in Schizophrenia John Donoghue Liverpool Imagination is more important than knowledge Albert Einstein LIFESTYLE Making choices TREATMENT Worse Psychopathology,

More information

Role of Clozapine in Treatment-Resistant Schizophrenia

Role of Clozapine in Treatment-Resistant Schizophrenia Disease Management and Treatment Strategies Elkis H, Meltzer HY (eds): Therapy-Resistant Schizophrenia. Adv Biol Psychiatry. Basel, Karger, 2010, vol 26, pp 114 128 Role of Clozapine in Treatment-Resistant

More information

Summary ID# Clinical Study Summary: Study B4Z-MC-LYCL

Summary ID# Clinical Study Summary: Study B4Z-MC-LYCL CT Registry ID#8226 Page 1 Summary ID# 8226. Clinical Study Summary: Study B4Z-MC-LYCL Guiding Dose Increases in Patients Incompletely Responsive to Usual Doses of Atomoxetine by Determining Plasma Atomoxetine

More information

Scottish Medicines Consortium

Scottish Medicines Consortium Scottish Medicines Consortium olanzapine 210mg, 300mg, 405mg powder and solvent for prolonged release suspension for injection (ZypAdhera ) No. (624/10) Eli Lilly and Company Limited 09 July 2010 The Scottish

More information

The Efficacy and Safety of Lower Doses of Aripiprazole for the Treatment of Patients with Acute Exacerbation of Schizophrenia

The Efficacy and Safety of Lower Doses of Aripiprazole for the Treatment of Patients with Acute Exacerbation of Schizophrenia The Efficacy and Safety of Lower Doses of for the Treatment of Patients with Acute Exacerbation of Schizophrenia By Andrew J. Cutler, MD, Ronald N. Marcus, MD, Sterling A. Hardy, MS, Amy O Donnell, MD,

More information

Sponsor. Novartis Pharmaceuticals Corporation Generic Drug Name. Agomelatine Therapeutic Area of Trial. Major depressive disorder Approved Indication

Sponsor. Novartis Pharmaceuticals Corporation Generic Drug Name. Agomelatine Therapeutic Area of Trial. Major depressive disorder Approved Indication Clinical Trial Results Database Page 1 Sponsor Novartis Pharmaceuticals Corporation Generic Drug Name Therapeutic Area of Trial Major depressive disorder Approved Indication Investigational drug Study

More information

Cocaine is a Major Risk Factor for Antipsychotic Induced Akathisia, Parkinsonism and Dyskinesia By Arija Maat, Annemarie Fouwels, Lieuwe de Haan

Cocaine is a Major Risk Factor for Antipsychotic Induced Akathisia, Parkinsonism and Dyskinesia By Arija Maat, Annemarie Fouwels, Lieuwe de Haan PB-41-3-2008-De haan.qxp 09-09-2008 15:45 Page 5 ORIGINAL RESEARCH Key Words: cannabis, cocaine, drug abuse, extrapyramidal side effects, neuroleptics, antipsychotics Cocaine is a Major Risk Factor for

More information

How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials

How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials ORIGINAL ARTICLE How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials S Leucht 1, D Arbter 1, RR Engel 2, W Kissling 1 and JM Davis 3 (2009) 14, 429 447

More information

Summary ID# Clinical Study Summary: Study B4Z-JE-LYBC

Summary ID# Clinical Study Summary: Study B4Z-JE-LYBC CT Registry ID# 5285 Page 1 Summary ID# 5285 Clinical Study Summary: Study B4Z-JE-LYBC A Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Comparison of Fixed-Dose Ranges of Hydrochloride

More information

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 18 February 2009

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 18 February 2009 The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 18 February 2009 ABILIFY 5 mg tablets, pack of 28 (CIP: 364 069-7) ABILIFY 10 mg tablets, pack of 28 (CIP: 364 073-4)

More information

CLINICAL STUDY REPORT SYNOPSIS

CLINICAL STUDY REPORT SYNOPSIS CLINICAL STUDY REPORT SYNOPSIS Document No.: EDMS-PSDB-6511694:4.0 Name of Sponsor/Company Johnson & Johnson Pharmaceutical Research & Development Name of Finished Product Name of Active Ingredient Protocol

More information

SiGMA/ MMHSCT GUIDELINES FOR ANTIPSYCHOTIC DRUG TREATMENT OF SCHIZOPHRENIA. [compatible with NICE guidance]

SiGMA/ MMHSCT GUIDELINES FOR ANTIPSYCHOTIC DRUG TREATMENT OF SCHIZOPHRENIA. [compatible with NICE guidance] SiGMA/ MMHSCT GUIDELINES FOR ANTIPSYCHOTIC DRUG TREATMENT OF SCHIZOPHRENIA [compatible with NICE guidance] Medicines Management Committee August 2002 For review August 2003 Rationale The SiGMA algorithm

More information

SYNOPSIS INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER (FOR NATIONAL AUTHORITY USE ONLY) Volume: Page:

SYNOPSIS INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER (FOR NATIONAL AUTHORITY USE ONLY) Volume: Page: SYNOPSIS Risperdal Risperidone (R064766) Protocol No.: RIS-USA-150 Part 1 INDIVIDUAL STUDY TABLE REFERRING TO PART OF THE DOSSIER AUTHORITY USE ONLY) Title of Study: A Double-Blind, Placebo-Controlled

More information

2.0 Synopsis. ABT-711 M Clinical Study Report R&D/06/054. (For National Authority Use Only) Referring to Part of Dossier: Volume: Page:

2.0 Synopsis. ABT-711 M Clinical Study Report R&D/06/054. (For National Authority Use Only) Referring to Part of Dossier: Volume: Page: 2.0 Synopsis Abbott Laboratories Name of Study Drug: Depakote ER Name of Active Ingredient: Divalproex Sodium Individual Study Table Referring to Part of Dossier: Volume: Page: (For National Authority

More information

SYNOPSIS. Trial No.: RIS-USA-70 Clinical phase: III. JRF, Clinical Research Report RIS-USA-70, 16 October, 1998 N Trial period: Start: 20 Nov 95

SYNOPSIS. Trial No.: RIS-USA-70 Clinical phase: III. JRF, Clinical Research Report RIS-USA-70, 16 October, 1998 N Trial period: Start: 20 Nov 95 SYNOPSIS Trial identification and protocol summary Company: Janssen Research Foundation Finished product: RISPERDAL Active ingredient: Risperidone (R064,766) Title: An open-label, long-term study of risperidone

More information

Antipsychotics. Something Old, Something New, Something Used to Treat the Blues

Antipsychotics. Something Old, Something New, Something Used to Treat the Blues Antipsychotics Something Old, Something New, Something Used to Treat the Blues Objectives To provide an overview of the key differences between first and second generation agents To an overview the newer

More information

Antipsychotic Medications

Antipsychotic Medications TRAIL: Team Review of EVIDENCE REVIEW & RECOMMENDATIONS FOR LTC Behavioural and psychological symptoms of dementia (BPSD) refer to the non-cognitive symptoms of disturbed perception, thought content, mood

More information

Double-Blind Comparison of Olanzapine versus Clozapine in Schizophrenic Patients Clinically Eligible for Treatment with Clozapine

Double-Blind Comparison of Olanzapine versus Clozapine in Schizophrenic Patients Clinically Eligible for Treatment with Clozapine Double-Blind Comparison of Olanzapine versus Clozapine in Schizophrenic Patients Clinically Eligible for Treatment with Clozapine Gary D. Tollefson, Martin A. Birkett, Gerilyn M. Kiesler, Andrew J. Wood,

More information

Chapter 161 Antipsychotics

Chapter 161 Antipsychotics Chapter 161 Antipsychotics Episode Overview Extrapyramidal syndromes are a common complication of antipsychotic medications. First line treatment is benztropine or diphenhydramine. Lorazepam is used in

More information

Method. NeuRA Paliperidone August 2016

Method. NeuRA Paliperidone August 2016 Introduction Second generation antipsychotics (sometimes referred to as atypical antipsychotics) are a newer class of antipsychotic medication than first generation typical antipsychotics. Second generation

More information

Supplementary Online Content

Supplementary Online Content Supplementary Online Content Subotnik KL, Casaus LR, Ventura J, et al. Long-acting injectable risperidone for relapse prevention and control of breakthrough symptoms after a recent first episode of schizophrenia:

More information

Study No.: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable:

Study No.: Title: Rationale: Phase: Study Period: Study Design: Centres: Indication: Treatment: Objectives: Primary Outcome/Efficacy Variable: The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.

More information

Method. NeuRA First versus second generation antipsychotics August 2016

Method. NeuRA First versus second generation antipsychotics August 2016 Introduction First generation typical are an older class of antipsychotic than second generation atypical. First generation are used primarily to treat positive symptoms including the experiences of perceptual

More information

Treatment of Children and Adolescents with Schizophrenia

Treatment of Children and Adolescents with Schizophrenia Treatment of Children and Adolescents with Schizophrenia The evidence base pertaining to the pharmacotherapy of schizophrenia in children and adolescents (C&A) is tiny compared to what is available for

More information

AMISULPRIDE. THERAPEUTICS Brands Solian see index for additional brand names. Generic? No

AMISULPRIDE. THERAPEUTICS Brands Solian see index for additional brand names. Generic? No AMISULPRIDE THERAPEUTICS Brands Solian see index for additional brand names Generic? No Class Neuroscience-based Nomenclature: dopamine receptor antagonist (D-RAn) Atypical antipsychotic (benzamide; possibly

More information

Recent Advances in the Antipsychotic Treatment of People with schizophrenia. Robert W. Buchanan, M.D.

Recent Advances in the Antipsychotic Treatment of People with schizophrenia. Robert W. Buchanan, M.D. Recent Advances in the Antipsychotic Treatment of People with schizophrenia Robert W. Buchanan, M.D. Antipsychotic medications are the primary class of drugs used in the pharmacological treatment of schizophrenia.

More information

( delirium ) 15%- ( extrapyramidal syndrome ) risperidone olanzapine ( extrapyramidal side effect ) olanzapine ( Delirium Rating Scale, DRS )

( delirium ) 15%- ( extrapyramidal syndrome ) risperidone olanzapine ( extrapyramidal side effect ) olanzapine ( Delirium Rating Scale, DRS ) 2005 6 48-52 Olanzapine 30% ( delirium 5%- Haloperidol ( extrapyramidal syndrome risperidone ( extrapyramidal side effect ( Delirium Rating Scale, DRS ( Delirium ( Olanzapine ( Delirium Rating Scale, DRS

More information

Cariprazine is a newly approved

Cariprazine is a newly approved Cariprazine for schizophrenia and bipolar I disorder Gregory Mattingly, MD, and Richard Anderson, MD, PhD Cariprazine is a newly approved (September 2015) dopamine D3/D2 receptor partial agonist with higher

More information

Lurasidone: A New Antipsychotic For Schizophrenia. Objectives. Introduction. Pharmacology/Pharmacokinetics. Mechanism of Action. Mechanism of Action

Lurasidone: A New Antipsychotic For Schizophrenia. Objectives. Introduction. Pharmacology/Pharmacokinetics. Mechanism of Action. Mechanism of Action Lurasidone: A New Antipsychotic For Schizophrenia Theodore Pikoulas, PharmD PGY2 Psychiatric Pharmacy Resident Louis Stokes Cleveland VAMC Objectives Review the pharmacology and the pharmacokinetics Identify

More information

Psychosis and Agitation in Dementia

Psychosis and Agitation in Dementia Psychosis and Agitation in Dementia Dilip V. Jeste, MD Estelle & Edgar Levi Chair in Aging, Director, Stein Institute for Research on Aging, Distinguished Professor of Psychiatry & Neurosciences, University

More information

droxidopa (Northera )

droxidopa (Northera ) Applies to all products administered or underwritten by Blue Cross and Blue Shield of Louisiana and its subsidiary, HMO Louisiana, Inc.(collectively referred to as the Company ), unless otherwise provided

More information

Schizophrenia Pharmacology UNIVERSITY OF HAWAI I HILO PRE -NURSING PROGRAM

Schizophrenia Pharmacology UNIVERSITY OF HAWAI I HILO PRE -NURSING PROGRAM Schizophrenia Pharmacology UNIVERSITY OF HAWAI I HILO PRE -NURSING PROGRAM NURS 203 GENERAL PHARMACOLOGY DANITA NARCISO PHARM D Learning Objectives Understand the result of dopamine binding to D2 receptors

More information

Resubmission. Scottish Medicines Consortium

Resubmission. Scottish Medicines Consortium Scottish Medicines Consortium Resubmission aripiprazole 5mg, 10mg, 15mg, 0mg tablets; 10mg, 15mg orodispersible tablets; 1mg/mL oral solution (Abilify ) No. (498/08) Bristol-Myers Squibb Pharmaceuticals

More information

Handout for the Neuroscience Education Institute (NEI) online activity: First-Episode Schizophrenia: Setting the Stage for Successful Outcomes

Handout for the Neuroscience Education Institute (NEI) online activity: First-Episode Schizophrenia: Setting the Stage for Successful Outcomes Handout for the Neuroscience Education Institute (NEI) online activity: First-Episode Schizophrenia: Setting the Stage for Successful Outcomes Learning Objectives Initiate low-dose antipsychotic medication

More information

Is Lurasidone more safe and effective in the treatment ofschizoaffective disorder and schizophrenia than other commonanti-psychotic medications?

Is Lurasidone more safe and effective in the treatment ofschizoaffective disorder and schizophrenia than other commonanti-psychotic medications? Philadelphia College of Osteopathic Medicine DigitalCommons@PCOM PCOM Physician Assistant Studies Student Scholarship Student Dissertations, Theses and Papers 2015 Is Lurasidone more safe and effective

More information

This was a randomized, double-blind, placebo-controlled, fixed-dose, parallel-group study.

This was a randomized, double-blind, placebo-controlled, fixed-dose, parallel-group study. The study listed may include approved and non-approved uses, formulations or treatment regimens. The results reported in any single study may not reflect the overall results obtained on studies of a product.

More information

BRL /RSD-101C0F/1/CPMS-716. Report Synopsis

BRL /RSD-101C0F/1/CPMS-716. Report Synopsis Report Synopsis Study Title: A Multicenter, Open-label, Six-Month Extension Study to Assess the Long-Term Safety of Paroxetine in Children and Adolescents with Major Depressive Disorder (MDD) or Obsessive-Compulsive

More information

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 1 February 2012

The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION. 1 February 2012 The legally binding text is the original French version TRANSPARENCY COMMITTEE OPINION 1 February 2012 XEPLION 25 mg, prolonged-release suspension for injection 1 pre-filled polycycloolefin syringe with

More information

New Medicines Committee Briefing November 2011

New Medicines Committee Briefing November 2011 New Medicines Committee Briefing November 2011 Paliperidone long-acting injection (Xeplion ) for schizophrenia Paliperidone palmitate long-acting injection (Xeplion ) is to be reviewed for use within:

More information

THIOTHIXENE. THERAPEUTICS Brands Navane see index for additional brand names. Generic? Yes

THIOTHIXENE. THERAPEUTICS Brands Navane see index for additional brand names. Generic? Yes THIOTHIXENE THERAPEUTICS Brands Navane see index for additional brand names Generic? Yes Class Conventional antipsychotic (neuroleptic, thioxanthene, dopamine 2 antagonist) Commonly Prescribed for (bold

More information

Dosing & Administration

Dosing & Administration Dosing & Administration REAL LIFE. REAL RESULTS. INDICATION INVEGA SUSTENNA (paliperidone palmitate) is indicated for the treatment of: Schizophrenia. Schizoaffective disorder as monotherapy and as an

More information

Source of effectiveness data The effectiveness evidence was derived from published studies and from experts' opinions.

Source of effectiveness data The effectiveness evidence was derived from published studies and from experts' opinions. Analisis coste-efectividad de olanzapina frente a haloperidol en el tratamiento de la esquizofrenia en Espana [Cost effectiveness analysis of olanzapine versus haloperidol in the treatment of schizophrenia

More information

Primary Endpoint The primary endpoint is overall survival, measured as the time in weeks from randomization to date of death due to any cause.

Primary Endpoint The primary endpoint is overall survival, measured as the time in weeks from randomization to date of death due to any cause. CASE STUDY Randomized, Double-Blind, Phase III Trial of NES-822 plus AMO-1002 vs. AMO-1002 alone as first-line therapy in patients with advanced pancreatic cancer This is a multicenter, randomized Phase

More information

BRL /RSD-101RLL/1/CPMS-716. Report Synopsis

BRL /RSD-101RLL/1/CPMS-716. Report Synopsis Report Synopsis Study Title: A Multicenter, Open-label, Six-Month Extension Study to Assess the Long-term Safety of Paroxetine in Children and Adolescents with Major Depressive Disorder (MDD) or Obsessive-Compulsive

More information

Clinical Trial Synopsis TL-OPI-518, NCT#

Clinical Trial Synopsis TL-OPI-518, NCT# Clinical Trial Synopsis, NCT# 00225264 Title of Study: A Double-Blind, Randomized, Comparator-Controlled Study in Subjects With Type 2 Diabetes Mellitus Comparing the Effects of Pioglitazone HCl vs Glimepiride

More information

Supplementary Online Content

Supplementary Online Content Supplementary Online Content Lam RW, Levitt AJ, Levitan RD, et al. Efficacy of bright light treatment, fluoxetine, and the combination in patients with nonseasonal major depressive disorder: a randomized

More information

Allergan Not Applicable AGN A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Multiple Dose, Parallel

Allergan Not Applicable AGN A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Multiple Dose, Parallel Peripheral Neuropathy Design, Dose Ranging Study of the Safety and Efficacy of AGN 203818 in Patients with Painful Diabetic 203818-004. A Multi-Center, Double-Blind, Randomized, Placebo-Controlled, Multiple

More information