Mianserin or placebo as adjuncts to typical antipsychotics in resistant schizophrenia

The beneficial effect of atypical antipsychotic drugs (APDs) in treatment-resistant schizophrenia patients has been attributed, mostly, to their relatively high serotonergic (5-HT)2 to dopaminergic (D)2 receptor blockade ratio. We hypothesized that a combination of typical APDs (D2 antagonists) and mianserin, a potent 5-HT2 antagonist, might also exert superior efficacy in this population. Eighteen inpatients with treatment-resistant schizophrenia who had an acute psychotic exacerbation of the disorder received, in a double-blind design, 30 mg/day mianserin (n = 9) or placebo (n = 9) in conjunction with typical neuroleptics [haloperidol (n = 9) or perphenazine (n = 9)]. Clinical status was evaluated before, during, and at the end of 6 weeks of combined treatment with the Brief Psychiatric Rating Scale (BPRS), Scale for the Assessment of Positive Symptoms (SAPS), Scale for the Assessment of Negative Symptoms and Hamilton Rating Scale for Depression. The typical APD/mianserin group exhibited significantly greater improvement in total BPRS scores (17.6% versus 5.5%; P= 0.03) and a trend towards greater improvement in SAPS scores (35.3% versus 13.0%; P = 0.07). Our study indicates that patients with chronic treatment-resistant schizophrenia who have an acute psychotic exacerbation ('acute-on-chronic') may benefit from the addition of a potent 5-HT2 blocker, such as mianserin, to typical antipsychotics. Our findings may further emphasize the contribution of enhanced 5-HT2 blockade to the 'atypicality' of the atypical APDs and to their greater efficacy in alleviating symptoms of chronic treatment-resistant schizophrenia.