Abstract

Background: Antipsychotics are often prescribed for long-term periods, however, most evidence of their impact on body weight comes from short-term clinical trials. Particularly, impact associated with dosage has been barely studied. Aims: The aim of this study was to describe the short- and long-term change in body weight of people initiated on high or low doses of the three most commonly prescribed second-generation antipsychotics. Methods: Retrospective cohorts of individuals with a diagnosed psychotic disorder observed from 2005 to 2015 in the UK primary care. The exposure was the first prescription of olanzapine, quetiapine or risperidone. The main outcome was change in body weight four years before and four years after initiation of antipsychotic treatment, stratified on sex and ‘low’ or ‘high’ dose. Results: In total, 22,306 women and 16,559 men were observed. Olanzapine treatment was associated with the highest change in weight, with higher doses resulting in more weight gain. After 4 years, given a high dose of olanzapine (> 5 mg), women gained on average +6.1 kg; whereas given a low dose (⩽ 5 mg), they gained +4.4 kg. During the first six weeks of olanzapine treatment, they gained on average +3.2 kg on high dose and +1.9 kg on low dose. The trends were similar for men. Individuals prescribed risperidone and quetiapine experienced less weight gain in both the short- and long-term. Conclusions: Olanzapine treatment was associated with the highest increase in weight. Higher doses were associated with more weight gain. Doctors should prescribe the lowest effective dose to balance mental-health benefits, weight gain and other adverse effects.