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Double-blind comparison of milnacipran and imipramine in depressive patients
P Poster Presentations
48 by improvement in depressed mood throughout the treatment period. In addition, treatment with mirtazapine starts to differentiate from placebo as early as week 1.
I
P-4-9 1 Nefazodone vs. Sertraline in Outpatients with Major Depression: Focus on Efficacy, Tolerability, and Effects on Sexual Function and Satisfaction
R.K. Shrivastava, A. Feiger, Ari Kiev, P.G. Wisselink. Eastside Medical Center, New York, NY
Background: The efficacy, tolerability, and effects of nefazodone and sertraline on sexual function and satisfaction were compared in a multicenter, randomized, double-blind, parallel group study in outpatients with major depression. Method: One hundred sixty patients, 18 years of age or older, who met DSM-III-R criteria for single or recurrent nonpsychotic major depressive episode were randomized to six weeks of treatment with either nefazodone (100 to 600 mg daily) or sertraline (50 to 200 mg daily). Symptoms were assessed before and during treatment using the Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impressions (CGI) Improvement Scale, the CGI Severity of Illness Scale, and a sexual function questionnaire. Results: Of 143 patients evaluable for efficacy, 72 received senraline and 71 received nefazodone. The mean modal daily dose at endpoint was 148 mg for sertraline and 456 mg for nefazodone. Analysis of efficacy measures (HAM-D and CGI) showed consistent and comparable improvement in symptoms of depression for both treatment groups. Sertraline had negative effects on sexual function and satisfaction in both men and women in comparison to nefazodone. Safety assessments based on adverse effects, vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests revealed no serious adverse events or organ toxicity associated with nefazodone or sertraline administration. Conclusion: Nefazodone and sertraline are well-tolerated and there was no statistical difference in their antidepressant activity. Sertraline treatment has negativeeffects on sexual function and performancein both sexes, in comparison 10 nefazodone. These findings may have clinical implications when choosing antidepressant maintenance therapy.
I P-4-10 I Efficacy of Nefazodone Versus Placebo in a Double-Blind Trial of Depressed Inpatients J. Feighner I, M. Bennett I, D. Roberts 2, F. D' Amico 2, K. O'Brien 2. I FeighnerResearch Institute, San Diego, California; 2 Bristol-Myers Squibb, Wallingford, Connecticut
Nefazodone, a 5HT2 antagonist and 5HT reuptake inhibitor, downregulates 5HT2 receptors in the frontal cortex when given chronically (Taylor et el., 1995), Flexible doses of nefazodone (100-600 mg/d) and placebo (1- 6 tablets/d) were compared in 8J inpatients who met DSM-III-R criteria for nonpsychotic Major Depression and who required psychiatric hospitalization. The patients were melancholic (95%) and severely ill at baseline, The Hamilton Depression Rating Scale-l7-item (HAM-D-17) was over 29 and the eGI severity was over 4.9 (markedly ill). The sample was predominantly female (63%) with a mean age of38.7 years (range 19-71). The Last Observation Carried Forward data set was the primary data set for assessing drug efficacy, Results showed significant superiority (p < 0,01) of nefazodoneover placebo on the HAM-D-17 (mean change: -13.5 nefazodone, -6.1 placebo), the Clinical Global Impression Improvement score, physician'S opinion of much or very much improved (56% response rate in the nefazodone group and a 25% response rate in the placebo group). and the Montgomery Asberg Depression Rating Scale (mean change: -1 7.8 nefazodone, -7.7 placebo). Mean modal doses reached 500 mg with nefazodone and 5.4 tablets with placebo. Five placebo treated patients (13%) and 4 nefazodone treated patients (10%) discontinued for adverse experiences, while 19 (48%) in the placebo group and 12 (29%) in the nefazodone group discontinued for lack of effect. The results of this study demonstrate that nefazodone is effective in the treatment of severely depressed hospitalized patients.
IP-4-11 I A Double-Blind Comparison of MUnacipran and Imipramine in Depressive Patients
R. Matsubara, I. Onodera, K. Ito, F. Okada, Y. Asano. Hokkaido Clinical Psychopharmacological Research Association, Japan Milnacipran is a novel antidepressant drug, which cause neither downregulation of ,B-adrenergic receptors nor subsensitivity of adenylate cyclase system in spite of a potent inhibitor of both norepinephrine and serotonin uptake. In a multicenter double-blind study, we examined the antidepressant efficacy and tolerability of milnacipran compared to imipramine in the treatment of patients suffering from major depression and bipolar disorder, depressed, diagnosed by DSM-III-R criteria. One hundredand thirty-two patients were randomly assigned to treatment with daily doses of 50-150 mg of milnacipran or imipramine for 4 weeks according to fixed-flexible dosage schedule, and 127 patients were assessed with Hamilton Rating Scale for Depression, Clinical Psychopharmacological Research Group Depression Rating Scale for Doctor's Use and Clinical Global Impression weekly. In the final global improvement, the rates of moderate to marked improvement in milnacipran group and imipramine group were 58.1% and 56,3%, and there were no significant differences between two groups, whereas at week I milnacipran showed significantly greater improvement than imipramine; 38.7% and 18.8%, respectively, The rates of incidence of adverse events were 41.9% and 50,8% in milnacipran group and imipramine group, but orthostatic hypotension in milnacipran was significantly lower than in imipramine, and the numbers of anticholinergic symptoms such as dry mouth were 19 and 32 patients in milnacipran group and imipramine group, respectively. No clinically significant abnormalities in laboratory data were observed in both groups. Our study indicates that milnacipran is as effective and well tolerated as imipramine, furthermore milnacipran shows the early onset of clinical effect compared to imipramine.
IP-4-12!
Comparative Study of Moclobemide & Clomipramine in the Treatment of Mild Forms of Depression
M. Krsmanovic, C. Miljevic, M, Jasovic, C. Cmobaric, Institute of Psychiatry, Serbia, Yugoslavia Moclobemide was compared to clomipramine (I) with a view to evaluating its efficiency and tolerance in patients in which non-endogenous mild or moderate unipolar depression was diagnosed. The groups comprised patients of both sexes, 27 men and 38 women. The testing was open and lasted a total of four weeks. At the beginning as well as on the 7th, 14th, 21st and 28th days after the beginning of treatment the intensity of the depression, i.e. the success of treatment was assessed by Hamilton's rating scale for depression (21 item version). At the end of treatment, the mean average improvement in the moclobcmide group was 56,7% vs 60,I % in the clomipramine group, During treatment no significant undesired effects were observed in either group of patients, although their frequency was greater in those treated with clomipramine (83.3% vs 63.3%). Results show that moclobemide is an efficient antidepressant in the treatment of mild and moderateforms of unipolar depression. [I] Dierick M., Cauiez P., Franck G. et al.,: Moclobemideversus clomipramine in the treatment of depression: a double-blind multicentrestudy io Belgium. Acta Psychiatr, Scand. 1990: Suppl 360: 50-51
IP-4-13I Sulpiride Augmentation in Refractory Depression Z, Sjankovic, D. Zivkovic-Milovanovic, D. Bugarski-Kirola, A, Damjanovic, Institute f or Psychiatry, Pasterova 2, Belgrade, Yugoslavia Twelve major depressed subjects were included in an open trial of 4 weeks duration. They classified as partial or non responders to at least 4 weeks of monotherapy by cyclic antidepressants. All patients were added Sulpiride (mean dose =300 mg/day), Efficacy was measured using the HAMDI7 and the cm. Response to treatment was definedas a 50% drop or greater or ~ 12 in the HAMD 17 score and a cm of either very much improvedor moderately improved from the start of Sulpiride Augmentation.
48 by improvement in depressed mood throughout the treatment period. In addition, treatment with mirtazapine starts to differentiate from placebo as early as week 1.
I
P-4-9 1 Nefazodone vs. Sertraline in Outpatients with Major Depression: Focus on Efficacy, Tolerability, and Effects on Sexual Function and Satisfaction
R.K. Shrivastava, A. Feiger, Ari Kiev, P.G. Wisselink. Eastside Medical Center, New York, NY
Background: The efficacy, tolerability, and effects of nefazodone and sertraline on sexual function and satisfaction were compared in a multicenter, randomized, double-blind, parallel group study in outpatients with major depression. Method: One hundred sixty patients, 18 years of age or older, who met DSM-III-R criteria for single or recurrent nonpsychotic major depressive episode were randomized to six weeks of treatment with either nefazodone (100 to 600 mg daily) or sertraline (50 to 200 mg daily). Symptoms were assessed before and during treatment using the Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impressions (CGI) Improvement Scale, the CGI Severity of Illness Scale, and a sexual function questionnaire. Results: Of 143 patients evaluable for efficacy, 72 received senraline and 71 received nefazodone. The mean modal daily dose at endpoint was 148 mg for sertraline and 456 mg for nefazodone. Analysis of efficacy measures (HAM-D and CGI) showed consistent and comparable improvement in symptoms of depression for both treatment groups. Sertraline had negative effects on sexual function and satisfaction in both men and women in comparison to nefazodone. Safety assessments based on adverse effects, vital sign measurements, electrocardiograms, physical examinations, and clinical laboratory tests revealed no serious adverse events or organ toxicity associated with nefazodone or sertraline administration. Conclusion: Nefazodone and sertraline are well-tolerated and there was no statistical difference in their antidepressant activity. Sertraline treatment has negativeeffects on sexual function and performancein both sexes, in comparison 10 nefazodone. These findings may have clinical implications when choosing antidepressant maintenance therapy.
I P-4-10 I Efficacy of Nefazodone Versus Placebo in a Double-Blind Trial of Depressed Inpatients J. Feighner I, M. Bennett I, D. Roberts 2, F. D' Amico 2, K. O'Brien 2. I FeighnerResearch Institute, San Diego, California; 2 Bristol-Myers Squibb, Wallingford, Connecticut
Nefazodone, a 5HT2 antagonist and 5HT reuptake inhibitor, downregulates 5HT2 receptors in the frontal cortex when given chronically (Taylor et el., 1995), Flexible doses of nefazodone (100-600 mg/d) and placebo (1- 6 tablets/d) were compared in 8J inpatients who met DSM-III-R criteria for nonpsychotic Major Depression and who required psychiatric hospitalization. The patients were melancholic (95%) and severely ill at baseline, The Hamilton Depression Rating Scale-l7-item (HAM-D-17) was over 29 and the eGI severity was over 4.9 (markedly ill). The sample was predominantly female (63%) with a mean age of38.7 years (range 19-71). The Last Observation Carried Forward data set was the primary data set for assessing drug efficacy, Results showed significant superiority (p < 0,01) of nefazodoneover placebo on the HAM-D-17 (mean change: -13.5 nefazodone, -6.1 placebo), the Clinical Global Impression Improvement score, physician'S opinion of much or very much improved (56% response rate in the nefazodone group and a 25% response rate in the placebo group). and the Montgomery Asberg Depression Rating Scale (mean change: -1 7.8 nefazodone, -7.7 placebo). Mean modal doses reached 500 mg with nefazodone and 5.4 tablets with placebo. Five placebo treated patients (13%) and 4 nefazodone treated patients (10%) discontinued for adverse experiences, while 19 (48%) in the placebo group and 12 (29%) in the nefazodone group discontinued for lack of effect. The results of this study demonstrate that nefazodone is effective in the treatment of severely depressed hospitalized patients.
IP-4-11 I A Double-Blind Comparison of MUnacipran and Imipramine in Depressive Patients
R. Matsubara, I. Onodera, K. Ito, F. Okada, Y. Asano. Hokkaido Clinical Psychopharmacological Research Association, Japan Milnacipran is a novel antidepressant drug, which cause neither downregulation of ,B-adrenergic receptors nor subsensitivity of adenylate cyclase system in spite of a potent inhibitor of both norepinephrine and serotonin uptake. In a multicenter double-blind study, we examined the antidepressant efficacy and tolerability of milnacipran compared to imipramine in the treatment of patients suffering from major depression and bipolar disorder, depressed, diagnosed by DSM-III-R criteria. One hundredand thirty-two patients were randomly assigned to treatment with daily doses of 50-150 mg of milnacipran or imipramine for 4 weeks according to fixed-flexible dosage schedule, and 127 patients were assessed with Hamilton Rating Scale for Depression, Clinical Psychopharmacological Research Group Depression Rating Scale for Doctor's Use and Clinical Global Impression weekly. In the final global improvement, the rates of moderate to marked improvement in milnacipran group and imipramine group were 58.1% and 56,3%, and there were no significant differences between two groups, whereas at week I milnacipran showed significantly greater improvement than imipramine; 38.7% and 18.8%, respectively, The rates of incidence of adverse events were 41.9% and 50,8% in milnacipran group and imipramine group, but orthostatic hypotension in milnacipran was significantly lower than in imipramine, and the numbers of anticholinergic symptoms such as dry mouth were 19 and 32 patients in milnacipran group and imipramine group, respectively. No clinically significant abnormalities in laboratory data were observed in both groups. Our study indicates that milnacipran is as effective and well tolerated as imipramine, furthermore milnacipran shows the early onset of clinical effect compared to imipramine.
IP-4-12!
Comparative Study of Moclobemide & Clomipramine in the Treatment of Mild Forms of Depression
M. Krsmanovic, C. Miljevic, M, Jasovic, C. Cmobaric, Institute of Psychiatry, Serbia, Yugoslavia Moclobemide was compared to clomipramine (I) with a view to evaluating its efficiency and tolerance in patients in which non-endogenous mild or moderate unipolar depression was diagnosed. The groups comprised patients of both sexes, 27 men and 38 women. The testing was open and lasted a total of four weeks. At the beginning as well as on the 7th, 14th, 21st and 28th days after the beginning of treatment the intensity of the depression, i.e. the success of treatment was assessed by Hamilton's rating scale for depression (21 item version). At the end of treatment, the mean average improvement in the moclobcmide group was 56,7% vs 60,I % in the clomipramine group, During treatment no significant undesired effects were observed in either group of patients, although their frequency was greater in those treated with clomipramine (83.3% vs 63.3%). Results show that moclobemide is an efficient antidepressant in the treatment of mild and moderateforms of unipolar depression. [I] Dierick M., Cauiez P., Franck G. et al.,: Moclobemideversus clomipramine in the treatment of depression: a double-blind multicentrestudy io Belgium. Acta Psychiatr, Scand. 1990: Suppl 360: 50-51
IP-4-13I Sulpiride Augmentation in Refractory Depression Z, Sjankovic, D. Zivkovic-Milovanovic, D. Bugarski-Kirola, A, Damjanovic, Institute f or Psychiatry, Pasterova 2, Belgrade, Yugoslavia Twelve major depressed subjects were included in an open trial of 4 weeks duration. They classified as partial or non responders to at least 4 weeks of monotherapy by cyclic antidepressants. All patients were added Sulpiride (mean dose =300 mg/day), Efficacy was measured using the HAMDI7 and the cm. Response to treatment was definedas a 50% drop or greater or ~ 12 in the HAMD 17 score and a cm of either very much improvedor moderately improved from the start of Sulpiride Augmentation.