CONTROLLED-STUDY OF THE TREATMENT OF RESIDUAL DEPRESSION WITH CLOMIPRAMINE VERSUS PLACEBO

The choice of a new treatment strategy for a patient suffering from residual depression in sometimes difficult; in reality, any change in the prescription involves a risk of losing any benefit, even partial, that has recently been obtained; consequently, can one be sure that a new antidepressant treatment will be beneficial ? To attempt to find the answer to this question, the Laboratoires Ciba-Geigy have conducted a controlled study versus placebo to evaluate the efficacy of clomipramine in residual depression which has been progressing for more than a year. 207 patients were pre-included in the 7-day wash-out phase and treated with placebo. During this period, a clinical examination and laboratory work-up made it possible to exclude patients with a curable cause of partial resistance to antidepressants (e.g., hypothyroidism) or who were << placebo-responders >>. After this run-in, 181 patients were included if they complied with the criteria characterizing a major depressive episode in partial remission (according to the DSM III-R), present for at least one year and treated throughout this period with at least two antidepressants at effective dosages. In addition, these patients had to have a score between 15 and 25 on the Montgomery and Asberg Depression Rating Scale (MADRS). The patients included were randomized into two groups, receiving either an clomipramine 75 tablet or a placebo tablet for two weeks; the dosage could be increased to two tablets as at D14 if necessary and maintained for the next six weeks. The only authorised concomitant treatments were tranquillizers (lorazepam or bromazepam) and/or non-barbiturate hypnotics (zopiclone or flunitrazepam). The efficacy analysis was conducted on 149 dossiers, 28 cases having been excluded (protocol violations or dropouts). Comparison of the clomipramine group (N = 78) and the placebo groupe (N = 71) shows: -a higher proportion of patients considered as cured (MADRS < 10) at the end of the 8 weeks of treatment with clomipramine (38 %) than after 8 weeks of placebo (25 %). However, the difference only revealed a tendency towards statistical significance (p < 0, 09); -a more favourable change in scores on the COVI anxiety scale with clomipramine (mean of 6 on D0 and 3.6 at the end of the study) than with placebo (mean score of 5.9 on D0 and 4.4 at the end of the study). The difference was statistically significant (p = 0.05); -on the CGI (Clinical Global Impression) scale, 58 % of patients were clearly or considerably improved with clomipramine versus 45 % with placebo (p = 0.04); -a greater improvement in the mean score in Weissman's social adaptation questionnaire with clomipramine than with placebo (p = 0.06). The safety study demonstrated a slightly higher frequency of the usual side effects of tricyclic antidepressants in the clomipramine group than in the placebo group. 55 % of the depressed patients treated with clomipramine reported at lest one adverse event versus 38 % in the placebo group (p = 0.024). This study therefore enables us to recommend clomipramine in the treatment of residual depression as its results prove that it induces a significant improvement in more that haff of the cases in patients who have been suffering fro this illness for more than a year. Moreover, this treatment effect appears more significant when signs and symptoms other than the symptoms of depression are evaluated, such as social adaptation or anxiety.