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Prophylactic effects of phenytoin in bipolar illness: A controlled study
P.1. Affective disorders and antidepressants
IP,1,0181 Prophylactic effects of phenytoin in bipolar illness: A controlled study ¥. Bersudsky, A. Mishory, J. Levine, M. Winokrur, R.H. Belmaker.
Ben Gurion University of the Negev, Beersheva, Israel Phenytoin, a classical anticonvulsant, shares the property of blockade of voltage activated sodium channels with antimanic anticonvulsants. We therefore planned a trim of phenytoin in acute mania. Thirty-nine patients entered a five week double-blind controlled trial of haloperidol plus phenytoin vs haloperidol plus placebo; thirty patients completed at least three weeks; twentyfive completed five weeks. Significantly more improvement was observed in those patients receiving phenytoin. We then planned a prophylactic study of phenytoin in bipolar disorder. Patients entered the study if they had been out of hospital for at least one month and had inadequate prophylaxis in the past on lithium, carbamazepine or valproate, and had at least one episode per year for the previous two years. Ongoing prophylactic treatment was not changed (lithium, carbamazepine, valproate or neuroleptic). Ratings (BPRS, YMS, HDS, GAS) were done by the clinical treating psychiatrist at baseline and once monthly thereafter. After six months patients were crossed over during a month of weekly visits with one drug (phenytoin or placebo) being reduced by 100 mg weekly and the other increased by 100 mg weekly. Twenty seven observation periods (six-month phases) were studied for 20 patients. Kaplan-Meier survival analysis showed highly significant benefits for phenytoin addition. Blockade of voltage-activated sodium channels may be a common therapeutic mechanism of many anticonvulsants in mania, and phenytoin may be a therapeutic option for some manic patients.
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Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder
D. Winkler, M. Willeit, R. Wolf, M. Stamenkovic, J. Tauscher, A. Konstantinidis, E. Pjrek, S.D. Schindler, C. Barnas, S. Kasper.
University of Vienna, Department of General Psychiatry, Vienna, Austria Objectives: The value of clonazepam (CNZP) as a long-term treatment in the prophylaxis of affective disorder is discussed controversially in the scientific literature [1, 2]. Altogether there are only a few reports about the use of this compound as a mood stabilizer, all of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate CNZP as a phase prophylactic medication in the different manifestations of affective disorder. Methods: We conducted a retrospective chart review in 34 outpatients, who had been treated with CNZP as a maintenance medication. 15 subjects were suffering from unipolar depression, 15 from bipolar disorder and 4 from schizoaffective disorder. CNZP was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients were treated for a mean duration of 1.5 years+7.5 months with CNZR We used a mirror-image design to evaluate the outcome. Statistical analysis was carried out with the Wilcoxon matched-pairs signed-ranks test. Results: In patients with unipolar depression treatment with CNZP led to a statistically significant reduction in affective
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episodes (z=-2.220, p=0.026). 4 patients with bipolar affective disorder remained phase-free during prophylaxis with CNZP. The remaining 11 patients relapsed quickly and did not show a reduction in phase density. Altogether neither manic/hypomanic phases (z=-0.114, p=0.909) nor depressive episodes (z=-l.501, p=0.133) were reduced in this group. Interestingly CNZP also reduced affective phases in our 4 schizoaffective patients on a trend level (z=-1.826, p=0.068). Conclusions: Our results indicate that patients with unipolar depression and schizoaffective disorder may benefit from a maintenance treatment with CNZE CNZP was ineffective as a phaseprophylactic treatment in subjects with bipolar affective disorder. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.
References [1] Aronson TA, Shukla S, Hirschowitz J (1989) Clonapezam treatment of five lithium-refractory patients with bipolar disorder. Am J Psychiatry 146:77-80 [2] Sachs GS (1990) Use of clonazepam for bipolar affective disorder. J Clin Psychiatry 51(suppl 5):31-34
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Pharmacological treatment pattern of mania in a natural setting: A retrospective chart review 1997-1999
M. Letmaier, D. Schreinzer, N. Thierry, R. Wolf, S. Kasper.
University of Vienna, Department of General Psychiatry, Vienna, Austria The present retrospective chart analysis documents the treatment practice of inpatients, suffering from acute manic or hypomanic episodes, at the Department of General Psychiatry, University of Vienna in the time from 1997 to 1999.90 episodes of consecutive admitted patients with acute mania (n=77) or hypomania (n=13) were included in a retrospective chart analysis (70 patients; 36 women, 34 men). The treatment strategies during the first 14 days after admission and the medication on discharge were evaluated. Furthermore, sociodemographic data and Clinical Global Impression (CGI) scores were analysed. The mean age of the patients at admission was 44.34-14.5 years. The hospitalization lasted on average 42.2+23.3 days. During the first 14 days the most frequently prescribed neuroleptics/antipsychotics were chlorprothixene, haloperidol and prothipendyl, while atypical antipsychotics like clozapine, olanzapine and risperidone were used rarely. From the group of mood stabilizers lithium was more often prescribed than valproic acid. Clonazepam, diazepam and lorazepam were the most commonly prescribed tranquilizers/hypnotics. The most frequently prescribed neuroleptics/antipsychotics on discharge were prothipendyl, thioridazine and halperidol. Lithium was used predominant as mood stabilizing agent on discharge and from the group of tranquilizers/hypnotics clonazepam, lorazepam and zolpidem were most frequently prescribed. The CGI-score at admission was 6.4--0.8 and at discharge 3.94-0.9. The results of our retrospective chart analysis reflects that international guidelines have not as yet been included in daily practice in the time from 1997 to 1999, with regard to the usage pattern of typical neuroleptics versus atypical antipsychotics.
IP,1,0181 Prophylactic effects of phenytoin in bipolar illness: A controlled study ¥. Bersudsky, A. Mishory, J. Levine, M. Winokrur, R.H. Belmaker.
Ben Gurion University of the Negev, Beersheva, Israel Phenytoin, a classical anticonvulsant, shares the property of blockade of voltage activated sodium channels with antimanic anticonvulsants. We therefore planned a trim of phenytoin in acute mania. Thirty-nine patients entered a five week double-blind controlled trial of haloperidol plus phenytoin vs haloperidol plus placebo; thirty patients completed at least three weeks; twentyfive completed five weeks. Significantly more improvement was observed in those patients receiving phenytoin. We then planned a prophylactic study of phenytoin in bipolar disorder. Patients entered the study if they had been out of hospital for at least one month and had inadequate prophylaxis in the past on lithium, carbamazepine or valproate, and had at least one episode per year for the previous two years. Ongoing prophylactic treatment was not changed (lithium, carbamazepine, valproate or neuroleptic). Ratings (BPRS, YMS, HDS, GAS) were done by the clinical treating psychiatrist at baseline and once monthly thereafter. After six months patients were crossed over during a month of weekly visits with one drug (phenytoin or placebo) being reduced by 100 mg weekly and the other increased by 100 mg weekly. Twenty seven observation periods (six-month phases) were studied for 20 patients. Kaplan-Meier survival analysis showed highly significant benefits for phenytoin addition. Blockade of voltage-activated sodium channels may be a common therapeutic mechanism of many anticonvulsants in mania, and phenytoin may be a therapeutic option for some manic patients.
•
Clonazepam in the long-term treatment of patients with unipolar depression, bipolar and schizoaffective disorder
D. Winkler, M. Willeit, R. Wolf, M. Stamenkovic, J. Tauscher, A. Konstantinidis, E. Pjrek, S.D. Schindler, C. Barnas, S. Kasper.
University of Vienna, Department of General Psychiatry, Vienna, Austria Objectives: The value of clonazepam (CNZP) as a long-term treatment in the prophylaxis of affective disorder is discussed controversially in the scientific literature [1, 2]. Altogether there are only a few reports about the use of this compound as a mood stabilizer, all of them describing patients suffering from bipolar affective disorder. The aim of this investigation was to evaluate CNZP as a phase prophylactic medication in the different manifestations of affective disorder. Methods: We conducted a retrospective chart review in 34 outpatients, who had been treated with CNZP as a maintenance medication. 15 subjects were suffering from unipolar depression, 15 from bipolar disorder and 4 from schizoaffective disorder. CNZP was either given as monotherapy, or as in the case of lithium non-responders, as adjunctive therapy. Patients were treated for a mean duration of 1.5 years+7.5 months with CNZR We used a mirror-image design to evaluate the outcome. Statistical analysis was carried out with the Wilcoxon matched-pairs signed-ranks test. Results: In patients with unipolar depression treatment with CNZP led to a statistically significant reduction in affective
S179
episodes (z=-2.220, p=0.026). 4 patients with bipolar affective disorder remained phase-free during prophylaxis with CNZP. The remaining 11 patients relapsed quickly and did not show a reduction in phase density. Altogether neither manic/hypomanic phases (z=-0.114, p=0.909) nor depressive episodes (z=-l.501, p=0.133) were reduced in this group. Interestingly CNZP also reduced affective phases in our 4 schizoaffective patients on a trend level (z=-1.826, p=0.068). Conclusions: Our results indicate that patients with unipolar depression and schizoaffective disorder may benefit from a maintenance treatment with CNZE CNZP was ineffective as a phaseprophylactic treatment in subjects with bipolar affective disorder. Due to methodological limitations our results need to be replicated in controlled double-blind randomized clinical trials.
References [1] Aronson TA, Shukla S, Hirschowitz J (1989) Clonapezam treatment of five lithium-refractory patients with bipolar disorder. Am J Psychiatry 146:77-80 [2] Sachs GS (1990) Use of clonazepam for bipolar affective disorder. J Clin Psychiatry 51(suppl 5):31-34
•
Pharmacological treatment pattern of mania in a natural setting: A retrospective chart review 1997-1999
M. Letmaier, D. Schreinzer, N. Thierry, R. Wolf, S. Kasper.
University of Vienna, Department of General Psychiatry, Vienna, Austria The present retrospective chart analysis documents the treatment practice of inpatients, suffering from acute manic or hypomanic episodes, at the Department of General Psychiatry, University of Vienna in the time from 1997 to 1999.90 episodes of consecutive admitted patients with acute mania (n=77) or hypomania (n=13) were included in a retrospective chart analysis (70 patients; 36 women, 34 men). The treatment strategies during the first 14 days after admission and the medication on discharge were evaluated. Furthermore, sociodemographic data and Clinical Global Impression (CGI) scores were analysed. The mean age of the patients at admission was 44.34-14.5 years. The hospitalization lasted on average 42.2+23.3 days. During the first 14 days the most frequently prescribed neuroleptics/antipsychotics were chlorprothixene, haloperidol and prothipendyl, while atypical antipsychotics like clozapine, olanzapine and risperidone were used rarely. From the group of mood stabilizers lithium was more often prescribed than valproic acid. Clonazepam, diazepam and lorazepam were the most commonly prescribed tranquilizers/hypnotics. The most frequently prescribed neuroleptics/antipsychotics on discharge were prothipendyl, thioridazine and halperidol. Lithium was used predominant as mood stabilizing agent on discharge and from the group of tranquilizers/hypnotics clonazepam, lorazepam and zolpidem were most frequently prescribed. The CGI-score at admission was 6.4--0.8 and at discharge 3.94-0.9. The results of our retrospective chart analysis reflects that international guidelines have not as yet been included in daily practice in the time from 1997 to 1999, with regard to the usage pattern of typical neuroleptics versus atypical antipsychotics.