Antipsychotic Efficacy of the Antidepressant Trimipramine: A Randomized, Double-blind Comparison with the Phenothiazine Perazine

Background: The tricyclic antidepressant trimipramine exhibits several features (e.g., dopaminergic effect, molecular structure similar to a neuroleptic, receptor-binding profile similar to clozapine) that suggest its potential as an antipsychotic medication. The aim of the study was to investigate the antipsychotic potential of trimipramine in a controlled clinical trial comparing its antipsychotic efficacy with that of a neuroleptic. Method: In a German multi-center, randomized, double-blind trial, the antipsychotic efficacy of trimipramine was compared with that of the phenothiazine neuroleptic perazine, using the Brief Psychiatric Rating Scale (BPRS), the Positive and Negative Syndrome Scale (PANSS), and Clinical Global Impressions (CGI). Antidepressant efficacy of both agents was measured by use of the Bech-Rafaelsen Melancholia Scale (BRMES). Ninety-five patients with acute schizophrenia (DSM-III-R) and a BPRS total score > 40 at baseline were treated with either 300-400 mg trimipramine or 450-600 mg perazine for 5 weeks. Results: Therapeutic equivalence of both treatments (in the dosages used) could not be demonstrated (change in BPRS total score, per-protocol [PP] analysis, one-sided equivalence testing). However, intention-to-treat (ITT) as well as PP analysis showed a statistically significant decrease in the BPRS total scores in both treatment groups (PP: trimipramine, 56.5 ± 9.8 to 44.1 ± 17.9; perazine, 56.4 ± 10.8 to 37.9 ± 12.9). Significant decreases in all BPRS and PANSS subscores as well as CG1 results and response rate support the antipsychotic efficacy of trimipramine. The BRMES total scores significantly decreased in both treatment groups without showing a significant difference between the two agents. Trimipramine was better tolerated than perazine and did not elicit extrapyramidal symptoms. Conclusion: Trimipramine failed to exhibit therapeutic equivalence to perazine in the dosages used. However, there was evidence of a substantial antipsychotic effect of trimipramine. It may be a useful medication if depressive symptoms in psychotic patients require antidepressant treatment or if other antipsychotics cannot be administered.