Relationships between pharmacotherapy-induced metabolic changes and improved psychopathology in schizophrenia: data from a mirtazapine and first-generation antipsychotics combination trial

Int J Neuropsychopharmacol. 2013 Aug;16(7):1661-6. doi: 10.1017/S146114571200137X. Epub 2012 Dec 10.


Clinical efficacy and metabolic side-effects of antipsychotics seem to correlate with each other. In this study, interrelationship of similar metabolic effects of mirtazapine and its earlier reported desirable effects on psychopathology in first-generation antipsychotics (FGAs)-treated schizophrenia were explored. Symptomatic FGAs-treated patients with schizophrenia received a 6-wk double-blind treatment with add-on mirtazapine (n = 20) or placebo (n = 16), followed by a 6-wk open-label mirtazapine treatment. Mirtazapine (but not placebo) induced an increase in body weight and cholesterol levels. The latter was associated with a clinical improvement in all (sub)scales of the Positive and Negative Syndrome Scale [PANSS; an increase of cholesterol by 1 mmol/l predicted 7 points reduction on the PANSS total score (r = 0.85, p = 0.001)]. In schizophrenia, mirtazapine-induced weight gain and increase of total cholesterol are associated with the improved efficacy of mirtazapine-FGAs combination--a novel observation with possible clinical and theoretical implications.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Antidepressive Agents, Tricyclic / therapeutic use*
  • Antipsychotic Agents / adverse effects*
  • Antipsychotic Agents / therapeutic use
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Humans
  • Male
  • Metabolic Diseases / chemically induced*
  • Mianserin / analogs & derivatives*
  • Mianserin / therapeutic use
  • Mirtazapine
  • Psychiatric Status Rating Scales
  • Schizophrenia / drug therapy*
  • Statistics as Topic
  • Time Factors
  • Young Adult


  • Antidepressive Agents, Tricyclic
  • Antipsychotic Agents
  • Mianserin
  • Mirtazapine