Efficacy of mirtazapine add on therapy to haloperidol in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled study

The negative symptoms of schizophrenia remain a major clinical challenge. M irtazapine is an antidepressant with antagonist properties at 5-HT2A, 5-HT3 and alpha 2 receptors as well as indirect 5-HT1a agonist effects. Many of these pharmacological actions have clinical or preclinical evidence of effi cacy in schizophrenia. This study was a 6-week randomized placebo-controlle d trial of mirtzepine or placebo add on to haloperidol 5 mg in the treatmen t of 30 patients with DSM-IV schizophrenia. The primary finding of the tria l was a 42% reduction in Positive and Negative Syndrome Scale (PANSS) negat ive symptom scores in the mirtazapine group compared to placebo at the end of 6 weeks (mirtazapine 13.9, SD 1.56; placebo 23.9, SD 1.56; P = 0.000, F = 20.31, d.f. = 1). The PANNS total scores, Clinical Global Impression seve rity and improvement scales in addition showed superiority of mirtazapine o ver placebo. There was no difference between the groups on the Hamilton dep ression scale at endpoint, suggesting that the improvement in negative symp toms was not an artifact of mood improvement. These results suggest a poten tial role for mirtazapine in the negative symptoms of schizophrenia. (C) 20 01 Lippincott Williams & Wilkins.