Moclobemide, imipramine and placebo in the treatment of major depression Versiani M, Nardi AE, Mundim FD, Alves A, Schmid-Burgk W. Moclobemide, imipramine and placebo in the treatment of major depression. Acta Psychatr Scand 1990: Suppl 360: 57-58.
M. Versiani', A. E. Nardi', F. 0. Mundim', A. A i m Z , W. Schmid-Burgka
Moclobemide was compared with imipramine and placebo in the treatment of major depressive episodes in 75 outpatients. The dosage of moclobemide (25 patients) was 300 mg daily for the first 5 days, after which it could be increased to 600 mg. Imipramine (25 patients) was given in a dosage starting with 33 mg and gradually increased to 100 mg/ day in the first 5 days, after which it could be further increased; 25 patients received placebo. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression, the overall assessment of efficacy and the Zung Self-rating Scale, and clearly superior to placebo; there were no significant differences between the 2 active drugs. Moclobemide was better tolerated than imipramine, and was almost comparable to placebo in this respect.
'Prograrna de Ansiedade e Depressao, lnstituto de Psiquiatria da Universidade Federal do Rio de Janeiro, Rio de Janeiro, 'Department of International Clinical Research, Produtos Roche Quimicos e Farmaceuticos, SAo Paulo, Brazil, 3F. HoffmannLa Roche, Bask, Switzerland
This study (part of the South American multicentre trial) was designed to compare the reversible, preferential type A monoamine oxidase inhibitor moclobemide with placebo and with the tricyclic antidepressant imipramine in the treatment of outpatients suffering from major depressive episodes. Material and methods
Patients were diagnosed according to the Structured Clinical Interview for DSM-111-R (1, 2). Inclusion criteria were a diagnosis of major depression (DSM-111-R) and a minimum score of 17 points on the Hamilton Rating Scale for Depression (HRSD, 21-item version). The study was performed as a randomized, comparative, prospective double-blind study with 3 parallel groups. The foreseen treatment duration was 6 weeks and assessments were performed at baseline and on treatment days 3, 7, 14, 21, 28 and 42. Assessments at baseline comprised a thorough psychiatric history and physical examination, including electrocardiogram and a panel of laboratory parameters (red and white blood cell count, blood chemistry and urine analysis) as well as HRSD and the Zung Self-rating Scale. The assessments during treatment comprised HRSD, the Zung scale, vital parameters and recorded adverse events. At end of the study, clinical global impressions were performed together with physical
Key words: major depressive episode; treatment; double-blind comparison; moclobemide; irnipramine; placebo M. Nrsiani, Programa de Ansiedade e Depressao, lnstituto de Psiquiatria da Universidade Federal do Rio de Janeiro, Av. Copacabana, 1133 Sala 1303, 22070 Rio de Janeiro, Brazil
examination, electrocardiogram and the laboratory panel. Treatment was started with 300 mg of moclobemide (3 capsules of 100 mg), 33 mg of imipramine (1 active capsule plus 2 placebo capsules) and 3 placebo capsules. During days 1-5 the moclobemide dose was kept constant, whereas the imipramine dose was increased to 100 mg/day. After day 5, the dose was increased to a maximum of 6 capsules/day, i.e. 600 mg moclobemide, 200 mg imipramine or placebo. Results
Seventy-five patients were included in the trial and equally allocated to one of the 3 treatments. There 40
1r I
Moclobemide 629lmipraminen Placebo
-
"
before
3
7 14 21 Treatment day
28
42
Fig. I. HRSD total score.
57
were no relevant differences between the groups for sex ratio, age, diagnosis, and duration and severity of the depressive syndrome. In all groups women predominated by 2 :1. Five patients on moclobemide, 3 on imipramine and 3 in the placebo group stopped treatment prematurely. Poor tolerance was the reason for 1 case each in the moclobemide and the imipramine group, refusal the reason for another case in the imipramine group and insufficient efficacy was the reason in the remaining cases. The mean daily doses at both day 7 and day 42 of the treatment period were: 600 mg/day for moclobemide, 200 mg/day for imipramine and 6 capsules/day for placebo, corresponding to the maximum doses allowed by the protocol. The HRSD outcome in the 3 treatment groups is shown in Fig. 1. The efficacy of both active drugs, as measured by HRSD, overall assessment of efficacy and the Zung Self-rating Scale, was satisfactory and comparable and both were clearly superior to placebo. There was no significant difference between moclobemide and imipramine. Moclobemide was better tolerated than imipramine according to the global assessment of tolerance; 24 moclobemide patients, 21 imipramine patients and 24 placebo patients received a tolerance
58
rating of very good or good. The tolerance rating good (equivalent to no side effects) was given more frequently in the moclobemide (n = 10) group than in the imipramine (n = 5 ) group. The tolerance ratings for moclobemide were similar to those of placebo. This overall assessment is supported by the frequency of side effects, which were more frequent with imipramine and were rated as severe in the imipramine group only. Conclusion
Moclobemide has comparable efficacy to imipramine in the treatment of major depressive disorder (unipolar, single or recurrent with or without melancholia, nonpsychotic). Both moclobemide and imipramine are superior to placebo in the treatment of these patients. Moclobemide produces far fewer side effects than imipramine, and is almost comparable to placebo -with regard to tolerance. Reference 1. SPITZERRL, WILLIAMS JBW. Revised diagnostic criteria
and a new structured interview for diagnoses. J Psychiatr Res 1988: 22 (suppl. 1): 55-85. 2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd edn, revised. Washington, DC: APA, 1987.
M. Versiani', A. E. Nardi', F. 0. Mundim', A. A i m Z , W. Schmid-Burgka
Moclobemide was compared with imipramine and placebo in the treatment of major depressive episodes in 75 outpatients. The dosage of moclobemide (25 patients) was 300 mg daily for the first 5 days, after which it could be increased to 600 mg. Imipramine (25 patients) was given in a dosage starting with 33 mg and gradually increased to 100 mg/ day in the first 5 days, after which it could be further increased; 25 patients received placebo. Both drugs were equally effective as measured by the Hamilton Rating Scale for Depression, the overall assessment of efficacy and the Zung Self-rating Scale, and clearly superior to placebo; there were no significant differences between the 2 active drugs. Moclobemide was better tolerated than imipramine, and was almost comparable to placebo in this respect.
'Prograrna de Ansiedade e Depressao, lnstituto de Psiquiatria da Universidade Federal do Rio de Janeiro, Rio de Janeiro, 'Department of International Clinical Research, Produtos Roche Quimicos e Farmaceuticos, SAo Paulo, Brazil, 3F. HoffmannLa Roche, Bask, Switzerland
This study (part of the South American multicentre trial) was designed to compare the reversible, preferential type A monoamine oxidase inhibitor moclobemide with placebo and with the tricyclic antidepressant imipramine in the treatment of outpatients suffering from major depressive episodes. Material and methods
Patients were diagnosed according to the Structured Clinical Interview for DSM-111-R (1, 2). Inclusion criteria were a diagnosis of major depression (DSM-111-R) and a minimum score of 17 points on the Hamilton Rating Scale for Depression (HRSD, 21-item version). The study was performed as a randomized, comparative, prospective double-blind study with 3 parallel groups. The foreseen treatment duration was 6 weeks and assessments were performed at baseline and on treatment days 3, 7, 14, 21, 28 and 42. Assessments at baseline comprised a thorough psychiatric history and physical examination, including electrocardiogram and a panel of laboratory parameters (red and white blood cell count, blood chemistry and urine analysis) as well as HRSD and the Zung Self-rating Scale. The assessments during treatment comprised HRSD, the Zung scale, vital parameters and recorded adverse events. At end of the study, clinical global impressions were performed together with physical
Key words: major depressive episode; treatment; double-blind comparison; moclobemide; irnipramine; placebo M. Nrsiani, Programa de Ansiedade e Depressao, lnstituto de Psiquiatria da Universidade Federal do Rio de Janeiro, Av. Copacabana, 1133 Sala 1303, 22070 Rio de Janeiro, Brazil
examination, electrocardiogram and the laboratory panel. Treatment was started with 300 mg of moclobemide (3 capsules of 100 mg), 33 mg of imipramine (1 active capsule plus 2 placebo capsules) and 3 placebo capsules. During days 1-5 the moclobemide dose was kept constant, whereas the imipramine dose was increased to 100 mg/day. After day 5, the dose was increased to a maximum of 6 capsules/day, i.e. 600 mg moclobemide, 200 mg imipramine or placebo. Results
Seventy-five patients were included in the trial and equally allocated to one of the 3 treatments. There 40
1r I
Moclobemide 629lmipraminen Placebo
-
"
before
3
7 14 21 Treatment day
28
42
Fig. I. HRSD total score.
57
were no relevant differences between the groups for sex ratio, age, diagnosis, and duration and severity of the depressive syndrome. In all groups women predominated by 2 :1. Five patients on moclobemide, 3 on imipramine and 3 in the placebo group stopped treatment prematurely. Poor tolerance was the reason for 1 case each in the moclobemide and the imipramine group, refusal the reason for another case in the imipramine group and insufficient efficacy was the reason in the remaining cases. The mean daily doses at both day 7 and day 42 of the treatment period were: 600 mg/day for moclobemide, 200 mg/day for imipramine and 6 capsules/day for placebo, corresponding to the maximum doses allowed by the protocol. The HRSD outcome in the 3 treatment groups is shown in Fig. 1. The efficacy of both active drugs, as measured by HRSD, overall assessment of efficacy and the Zung Self-rating Scale, was satisfactory and comparable and both were clearly superior to placebo. There was no significant difference between moclobemide and imipramine. Moclobemide was better tolerated than imipramine according to the global assessment of tolerance; 24 moclobemide patients, 21 imipramine patients and 24 placebo patients received a tolerance
58
rating of very good or good. The tolerance rating good (equivalent to no side effects) was given more frequently in the moclobemide (n = 10) group than in the imipramine (n = 5 ) group. The tolerance ratings for moclobemide were similar to those of placebo. This overall assessment is supported by the frequency of side effects, which were more frequent with imipramine and were rated as severe in the imipramine group only. Conclusion
Moclobemide has comparable efficacy to imipramine in the treatment of major depressive disorder (unipolar, single or recurrent with or without melancholia, nonpsychotic). Both moclobemide and imipramine are superior to placebo in the treatment of these patients. Moclobemide produces far fewer side effects than imipramine, and is almost comparable to placebo -with regard to tolerance. Reference 1. SPITZERRL, WILLIAMS JBW. Revised diagnostic criteria
and a new structured interview for diagnoses. J Psychiatr Res 1988: 22 (suppl. 1): 55-85. 2. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 3rd edn, revised. Washington, DC: APA, 1987.
