Posted by Iansf on September 14, 2003, at 18:09:17
THE SYNERGY TIMES
Dr. Chittaranjan Andrade=================================================================
Sept 12, 2003; Vol 3, No 118
SELEGILINE PATCH FOR MAJOR DEPRESSION?
JD Amsterdam (2003) investigated the antidepressant efficacy of the selegiline transdermal system in a large, 16-center clinical
trial conducted in the USA. The sample comprised 301 outpatients, aged 16-65 (mean, 42.3) years, with DSM-IV major depressive disorder. The sample was 64% female. No patient had significant Axis I or Axis II comorbidity, a history of recent substance abuse, or significant medical illness. The severity of depression was, on average, in the mild to moderate range.After a 1-week, single-blind placebo run-in period to eliminate placebo responders, the subjects were randomized to receive selegiline (20 mg per 20 sq cm; n=149) or placebo patch (n=152) daily for 8 weeks under double-blind conditions. While no dietary restrictions were placed upon the subjects, a number of psychotropic, sympathomimetic, antihistaminic, and other
medications were prohibited because of the risk of drug interactions with an irreversible MAOI.The two groups were similar at baseline on all important variables. Dropouts accounted for 27.5% of the selegiline group and 27.0% of the placebo group. Adverse events accounted for dropouts in 6.7% of the selegiline group and 5.3% of the placebo group. Most of the other dropouts were due to loss to follow-up.
IMPORTANT FINDINGS WERE:
1. The attenuation of depression scores was narrowly but significantly greater with selegiline from week 4 onwards, but only on the Montgomery-Asberg Depression Rating Scale (MADRS); on almost all other specific and global measures, selegiline was no better than placebo at any time point.2. Significantly more patients responded to selegiline than to placebo; the response rates, however, were low (33.1% vs 20.8%, respectively). In this context, response was defined as at least
50% attenuation of MADRS scores at the 8-week endpoint. The response rate did not differ significantly between the two groups when other definitions of response were employed.3. Adverse events were, overall, commoner with selegiline (62.4%) than with placebo (50.0%); however, patch application site reactions were the only individual adverse event which significantly differentiated the groups (incidence, 31.5% vs
15.1%, respectively).4. No patient had hypertensive crises or any adverse effect the risk of which is high with the classical MAOI.
CONCLUSIONS
The 20 mg per 20 sq cm per day transdermal selegiline delivery system causes application site reactions but is otherwise well-tolerated; however, it does not appear to have satisfactory
antidepressant efficacy by this route and at this dose.COMMENTS
1. It is curious that a study of this size was published by a single author. It is also curious that the response rates were low; in most studies of this nature, the placebo response rate, itself, is in the 40-50% range.2. An earlier study (Bodkin and Amsterdam, 2002) reported more encouraging results with the selegiline transdermal delivery system; the reason for the relative failure of the present study is unclear.
REFERENCES
Amsterdam JD. A double-blind, placebo-controlled trial of the safety and efficacy of selegiline transdermal system without dietary restrictions in patients with major depressive disorder. J Clin Psychiatry 2003; 64: 208-214.Bodkin JA, Amsterdam JD. Transdermal selegiline in major depression: a double-blind, placebo- controlled, parallel-group study in outpatients. Am J Psychiatry 2002; 159: 1869-1875.
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