Review and meta-analysis of add-on tranylcypromine with antipsychotic drugs for the treatment of schizophrenia with predominant negative symptoms: a restoration of evidence.

BACKGROUND Treatment using add-on antidepressants with antipsychotic drugs in negative symptoms of schizophrenia has been reviewed recently in comprehensive meta-analyses. Tranylcypromine (TCP), an irreversible monoamine oxidase (MAO)-A/B inhibitor applied in treatment resistant depression, was not included because of strict requirements for quality of study design. To get a clear picture of available evidence for this resource in the treatment of schizophrenia, we conducted a review and meta-analysis of add-on TCP in the treatment of predominant negative symptoms of schizophrenia (negative schizophrenia). METHODS Seven controlled studies of add-on TCP in schizophrenia with predominant negative symptoms were found in a search of multiple databases. A subset of four studies of the prospective and parallel comparison of add-on TCP with antipsychotic drugs vs. antipsychotic drug monotherapy and meeting minimum quality criteria formed the primary meta-analysis. The effect size was calculated as the natural logarithm of the odds ratio (logOR) of responders and non-responders. RESULTS In the primary meta-analysis, a pooled logOR =1.092 with 95%CI 0.410-1.774 (I2 = 43.4%, moderate heterogeneity) was calculated according to a fixed effect model. Heterogeneity was reduced for three double-blind studies of add-on TCP with trifluoperazine (TFP) vs. TFP-monotherapy and resulted a pooled logOR =0.916 with 95%CI 0.216-1.616 (I2 negative, no heterogeneity). A significant logOR =1.558 with 95%CI 0.340-2.776 was found for TCP/TFP compared to placebo in one study. In a meta-analysis of extrapyramidal adverse effects, studies were very heterogeneous and revealed no significant differences between treatments. The risk of exacerbation of positive symptoms with add-on TCP was found to be very low for a duration of treatment of 12 to 16 weeks. No cases of hypertensive crisis were reported. The main methodical limitations were insufficient description of randomization or matching of patients without randomization. The main clinical limitation is a gap of data for add-on TCP with second generation antipsychotics. CONCLUSION New studies are needed for add-on TCP with antipsychotic drugs in schizophrenia with predominant negative symptoms. Trials of this treatment may be possible in rare and selected cases. The therapeutic effect of add-on TCP may be explained by a strong dopaminergic activity.