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Moclobemide in treatment-resistant depression
328 excessive dreaming and nightmares in two patients, exacerbation of anxiety in one patient. There were no cases of 'cheese" reaction or any significant elevation of blood pressure in our sample (Chen, 1992). The efficacy index (EI) derived by dividing therapeutic effect score by side effect score proved to be much higher for the patients on Auririx than for those on imipramine. This is obviously due to the much more dramatic mainly autonomous side effects related to the classical drug.
Conclusions (l) Moclobemide (Aurorix) is a sate and effective antidepressant drug. (2) Moclobemide is very well tolerated and devoid of the side effects not only of tricyclic antidepressants, but also of earlier MAOIs. (3) Moclobemide is a valuable drug in some patients with concomitant somatic diseases such as glaucoma and ischemic heart disease. (4) In some patients the onset and fading of therapeutic effect is very rapid which may make it a fast, suitable drug for rapid cycling patients.
References Bakish, D., Bradwyn, J., Nair, N. McClure, J. and Remit, R. (1992) A comparison of moclobemide, amitriptyline and placebo in depression A Canadian multicenter study. Psychopharmacology 106, $98 SI01. Chen, D.T. (1992) Safety of moclobemide in clinical use. Clin. Neuropharmacol. 15, Suppl. I, 428 429.
Moclobemide in treatment-resistant depression
M. D ~ b k o w s k a a n d J.K. R y b a k o w s k i
Department q/ Psychiatry. Medical Academy, 85-863 Bvdgoszcz. Poland Key words: Moclobemide; Depression, treatment-resistant Moclobemide is the first specific and reversible inhibitor of MAO-A (RIMA) which to date is available on the market. Efficacy of the drug has been demonstrated in various degrees and types of depression (Baumhackl et al., 1989: Lecrubier and Guelfi, 1990). In this study, moclobemide was given to a group of depressive inpatients, mainly resistant to treatment with tricyclic and tetracyclic antidepressants (imipramine, amitriptyline, clomipramine, doxepine, mianserin, trazodone). Patients were treated for 6 weeks with a daily dose of 450 600 mg moclobemide. Thirty patients (five male, 25 female) aged 31 74 (mean 47 years) were studied. They were diagnosed as unipolar (26 cases) and bipolar (four cases) affective disorder. The duration of the illness ranged from 1 to 19 (mean 8) years and the duration of" the last depressive episode ranged from 1 to 18 (mean 6) months. The intensity of depression, assessed according to the 17-item Hamilton Depression Rating Scale (HDRS), was 26+6. In 26 patients, a dexamethasone suppression test (DST) was performed. A total of 15 (50%) of the patients responded to moclobemide treatment. Good antidepressant response (reduction in HDRS > 50%) was obtained in seven patients (23%) and moderate response (reduction of 30 50%) in eight patients (27%). Fifteen patients (50%) did not show any or only slight improvement according to HDRS. Table 1 summarizes the clinical and DST data in patients with good and moderate response (group I) vs. the remaining ones (group II). Step-wise linear regression showed a negative correlation between the degree of antidepressant response and the initial intensity of depression as measured with HDRS and a positive correlation with male sex. Other clinical factors and DST did not show a correlation with the treatment outcome. The tolerability of moclobemide was excellent (no side effects) in eight patients. In 18 patients, mild symptoms, mostly insomnia and headaches, were observed. In four patients, moclobemide was discontinued after 10 30 days of treatment on account of increasing anxiety and restlessness (two patients), emerging hypertension (one patient) and transient hemiparesis (one patient). The latter two patients had a concomitant somatic condition (diabetes, cardiomyopathy).
329
Table 1.
Gender M/F Diagnosis (UP/BP) Age (years) Duration of illness (years) Last episode (months) Baseline HDS DST (path/norm) Baseline cortisol 17-h postdex, cortisol 24-h postdex, cortisol
Group 1 (n 15)
Group 11 (n-15)
5/10 13/2 49 _+13 8_+6 7 _+5 25 + 4 6/8 ( n - 14) 13.2 _+8.6 5.8 + 8.9 4.(1+ 5.6
0/15 l 3/2 45 _+7 7_+5 6_+4 27 + 7 5/7 ( n - 12) 9.6 _+4.2 3.4 i 4.2 2.8 + 4.4
The results of this study may suggest a possible usefulness of moclobemide in treatment-resistant depression. References
Baumhackl, U., Biziere, K.. Fischbach, R. et al. (1989) Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM-III): an Austrian double-blind multicentre study. Br. J. Psychiatry 155 (Suppl. 6), 78 83. Lecrubier, Y. and Guelfi, J.D. (1990) Efficacy of reversible inhibitors of monoamine oxidase-A in various forms of depression. Acta Psychiatr. Scand. 82 (Suppl. 360), 18 23.
Moelobemide versus fluoxetine for a major depressive episode
C. Reynaer( ~, M. Parent b, J. Mirel c, P.
J a n n e ~ a n d L. H a a z e n d
"University Department of Psvehiatrt', B-5530 Mont-Godinne, Belgium, h Psychiatric Hospital, Henri-Chapelle, Belgium, 'Psychog~,riat)'ie Hospital, Montigny, Belgium and dN. V. R~)eheS.A., Brussels, Belgium Key words." Depression; Anti-depressant drugs; Moclobemide; Fluoxetine Both reversible inhibitors of monoamine oxidase of the type A (RIMA) and selective serotonin re-uptake inhibitors (SSRI) have been demonstrated to be safer and to be better tolerated than classical antidepressant drugs while exhibiting comparable efficacy, thereby representing a step forward in the treatment of depression. This study was designed to compare two representatives of these new classes of antidepressant drugs, moclobemide (M) and fluoxetine (F), in terms of efficacy, safety and tolerability at clinically representative dosages in depressed patients. In a double-blind randomized multicenter study of 6 weeks' duration, a fixed-flexible dosage of M (300 or 600 mg/day) or F (20 or 40 rag/day) was administered tbr the treatment of 65 in- and 34 outpatients with a major depressive episode (DSMIIIR). After a placebo run-in phase of 4 7 days, control visits were foreseen on days 10 (D10), 21 (D21) and 42 (D42). Starting with the lowest dosage, this could be doubled from D22 on in case of insufficient efficacy and good tolerability. No dietary restrictions were imposed. The 17-item Hamilton Depression Rating Scale (HDRS) and a 7-grade Clinical Global Impression (CGI) scale were used to evaluate efficacy, while safety was evaluated using an adverse effects list, by measuring vital signs and by performing a standard laboratory examination at baseline and on D42. At study end, an overall efficacy and safety assessment was performed by investigator and patient. At baseline, no statistical differences were found in patient characteristics or medical condition between both study groups, the mean total HDRS scores being 25.4 ± 4.9 (M) and 24.1 ± 5.3 (F). In both groups there was a highly significant (P<0.001, MANOVA) decrease in mean total HDRS score during treatment. Nineteen patients (M 12: F = 7) did not complete the 6-week study period. The study dosage was doubled in 30% (M) and 27% (F) of the patients respectively from D22 on. No statistically significant differences were found between the two treatment groups regarding efficacy or safety, during or
Conclusions (l) Moclobemide (Aurorix) is a sate and effective antidepressant drug. (2) Moclobemide is very well tolerated and devoid of the side effects not only of tricyclic antidepressants, but also of earlier MAOIs. (3) Moclobemide is a valuable drug in some patients with concomitant somatic diseases such as glaucoma and ischemic heart disease. (4) In some patients the onset and fading of therapeutic effect is very rapid which may make it a fast, suitable drug for rapid cycling patients.
References Bakish, D., Bradwyn, J., Nair, N. McClure, J. and Remit, R. (1992) A comparison of moclobemide, amitriptyline and placebo in depression A Canadian multicenter study. Psychopharmacology 106, $98 SI01. Chen, D.T. (1992) Safety of moclobemide in clinical use. Clin. Neuropharmacol. 15, Suppl. I, 428 429.
Moclobemide in treatment-resistant depression
M. D ~ b k o w s k a a n d J.K. R y b a k o w s k i
Department q/ Psychiatry. Medical Academy, 85-863 Bvdgoszcz. Poland Key words: Moclobemide; Depression, treatment-resistant Moclobemide is the first specific and reversible inhibitor of MAO-A (RIMA) which to date is available on the market. Efficacy of the drug has been demonstrated in various degrees and types of depression (Baumhackl et al., 1989: Lecrubier and Guelfi, 1990). In this study, moclobemide was given to a group of depressive inpatients, mainly resistant to treatment with tricyclic and tetracyclic antidepressants (imipramine, amitriptyline, clomipramine, doxepine, mianserin, trazodone). Patients were treated for 6 weeks with a daily dose of 450 600 mg moclobemide. Thirty patients (five male, 25 female) aged 31 74 (mean 47 years) were studied. They were diagnosed as unipolar (26 cases) and bipolar (four cases) affective disorder. The duration of the illness ranged from 1 to 19 (mean 8) years and the duration of" the last depressive episode ranged from 1 to 18 (mean 6) months. The intensity of depression, assessed according to the 17-item Hamilton Depression Rating Scale (HDRS), was 26+6. In 26 patients, a dexamethasone suppression test (DST) was performed. A total of 15 (50%) of the patients responded to moclobemide treatment. Good antidepressant response (reduction in HDRS > 50%) was obtained in seven patients (23%) and moderate response (reduction of 30 50%) in eight patients (27%). Fifteen patients (50%) did not show any or only slight improvement according to HDRS. Table 1 summarizes the clinical and DST data in patients with good and moderate response (group I) vs. the remaining ones (group II). Step-wise linear regression showed a negative correlation between the degree of antidepressant response and the initial intensity of depression as measured with HDRS and a positive correlation with male sex. Other clinical factors and DST did not show a correlation with the treatment outcome. The tolerability of moclobemide was excellent (no side effects) in eight patients. In 18 patients, mild symptoms, mostly insomnia and headaches, were observed. In four patients, moclobemide was discontinued after 10 30 days of treatment on account of increasing anxiety and restlessness (two patients), emerging hypertension (one patient) and transient hemiparesis (one patient). The latter two patients had a concomitant somatic condition (diabetes, cardiomyopathy).
329
Table 1.
Gender M/F Diagnosis (UP/BP) Age (years) Duration of illness (years) Last episode (months) Baseline HDS DST (path/norm) Baseline cortisol 17-h postdex, cortisol 24-h postdex, cortisol
Group 1 (n 15)
Group 11 (n-15)
5/10 13/2 49 _+13 8_+6 7 _+5 25 + 4 6/8 ( n - 14) 13.2 _+8.6 5.8 + 8.9 4.(1+ 5.6
0/15 l 3/2 45 _+7 7_+5 6_+4 27 + 7 5/7 ( n - 12) 9.6 _+4.2 3.4 i 4.2 2.8 + 4.4
The results of this study may suggest a possible usefulness of moclobemide in treatment-resistant depression. References
Baumhackl, U., Biziere, K.. Fischbach, R. et al. (1989) Efficacy and tolerability of moclobemide compared with imipramine in depressive disorder (DSM-III): an Austrian double-blind multicentre study. Br. J. Psychiatry 155 (Suppl. 6), 78 83. Lecrubier, Y. and Guelfi, J.D. (1990) Efficacy of reversible inhibitors of monoamine oxidase-A in various forms of depression. Acta Psychiatr. Scand. 82 (Suppl. 360), 18 23.
Moelobemide versus fluoxetine for a major depressive episode
C. Reynaer( ~, M. Parent b, J. Mirel c, P.
J a n n e ~ a n d L. H a a z e n d
"University Department of Psvehiatrt', B-5530 Mont-Godinne, Belgium, h Psychiatric Hospital, Henri-Chapelle, Belgium, 'Psychog~,riat)'ie Hospital, Montigny, Belgium and dN. V. R~)eheS.A., Brussels, Belgium Key words." Depression; Anti-depressant drugs; Moclobemide; Fluoxetine Both reversible inhibitors of monoamine oxidase of the type A (RIMA) and selective serotonin re-uptake inhibitors (SSRI) have been demonstrated to be safer and to be better tolerated than classical antidepressant drugs while exhibiting comparable efficacy, thereby representing a step forward in the treatment of depression. This study was designed to compare two representatives of these new classes of antidepressant drugs, moclobemide (M) and fluoxetine (F), in terms of efficacy, safety and tolerability at clinically representative dosages in depressed patients. In a double-blind randomized multicenter study of 6 weeks' duration, a fixed-flexible dosage of M (300 or 600 mg/day) or F (20 or 40 rag/day) was administered tbr the treatment of 65 in- and 34 outpatients with a major depressive episode (DSMIIIR). After a placebo run-in phase of 4 7 days, control visits were foreseen on days 10 (D10), 21 (D21) and 42 (D42). Starting with the lowest dosage, this could be doubled from D22 on in case of insufficient efficacy and good tolerability. No dietary restrictions were imposed. The 17-item Hamilton Depression Rating Scale (HDRS) and a 7-grade Clinical Global Impression (CGI) scale were used to evaluate efficacy, while safety was evaluated using an adverse effects list, by measuring vital signs and by performing a standard laboratory examination at baseline and on D42. At study end, an overall efficacy and safety assessment was performed by investigator and patient. At baseline, no statistical differences were found in patient characteristics or medical condition between both study groups, the mean total HDRS scores being 25.4 ± 4.9 (M) and 24.1 ± 5.3 (F). In both groups there was a highly significant (P<0.001, MANOVA) decrease in mean total HDRS score during treatment. Nineteen patients (M 12: F = 7) did not complete the 6-week study period. The study dosage was doubled in 30% (M) and 27% (F) of the patients respectively from D22 on. No statistically significant differences were found between the two treatment groups regarding efficacy or safety, during or