High Dose Olanzapine Results in Greatest Weight Gain Among Second Generation Antipsychotics

Olanzapine, especially in higher doses, is associated with the greatest weight gain in patients receiving commonly prescribed second-generation antipsychotics, according to results of a population-based cohort study published in the Journal of Psychopharmacology.

Researchers looked at the records of patients ≥18 years of age with a diagnosed psychotic disorder receiving primary care in the United Kingdom between 2005 and 2015. Patients were prescribed olanzapine, quetiapine, or risperidone and received at least 1 additional prescription of the same antipsychotic within a 3-month period. Researchers assessed change in body weight 4 years before and 4 years after starting antipsychotic treatment, stratified by sex and low or high dose.

Related Articles

The final cohort comprised 22,306 women and 16,559 men. In the short term (<6 weeks), men’s average weight increased by 3.4 kg and women’s average weight increased by 2.3 kg on olanzapine. In terms of dose, women receiving a high dose (>5 mg) gained an average 3.2 kg in the short term compared with 1.9 kg on a low dose (≤5 mg).

Weight gain slowed after the first 6 weeks. At ≤4 years, women receiving a low dose gained 4.4 kg, whereas those receiving a high dose gained an average of 6.1 kg. In contrast, men averaged similar weight gains for both high and low doses. Patients of either sex and with a lower weight before starting olanzapine treatment gained more weight in the short term.

Individuals prescribed risperidone and quetiapine experienced considerably less weight gain in both the short and long term in both men and women compared with those prescribed olanzapine. Most patients prescribed any antipsychotic did not lose the extra weight gained in the first 6 weeks. However, men receiving a low dose of quetiapine showed an average weight loss of 0.3 kg in the long term.

The investigators did not control for drugs prescribed to reduce weight gain or that could potentially affect weight, a potential limitation of the study. In addition, treatment duration and adherence may not have been captured fully.

The investigators concluded, “Doctors and patients may want to take the issue of a substantial weight gain into consideration when making decisions on initiation of antipsychotic treatments, and doctors should prescribe the lowest effective dose to balance mental health benefits, weight gain and other adverse effects.”


Bazo-Alvarez JC, Morris TP, Carpenter JR, Hayes JF, Petersen I. Effects of long-term antipsychotics treatment on body weight: a population-based cohort study [published online November 14, 2019]. J Psychopharmacol. doi:10.1177/0269881119885918