Weight gain with anti-depressants – is it real?

June 15, 2018, Dr Chee L Khoo

In primary care, we have to battle with the increasing incidence of obesity amongst our patients. We also have to battle with the patients with depression where anti-depressants are increasingly being prescribed. Obesity is associated with depression, which is particularly common in patients with severe obesity. Antidepressant treatment may also add on to our patients’ weight. The current high prevalence of antidepressant use could have potentially important public health impacts through the association with body weight gain, but the nature of this association is poorly understood.

Most of us would have seen the weight gain in patients on anti-depressants but yet data about the problem is scant. In a systematic review of 116 clinical trials and cohort studies (Serretti et al 2010), most did not provide data for more than 3 months of follow up. Fluoxetine seems to cause the least weight gain while mirtazapine and nortryptiline the most. In the few studies that had long follow up, weight gain after initiation of anti-depressants persisted several years.

A recent large population cohort study examined the records of >300,000 patients over 10 years. The UK Clinical Practice Research Datalink (CPRD) is one the largest databases of primary care electronic records with records from ~7% of UK general practices. From the records of >2 million patients between 2004 and 2014, data from patients older than 20 years who had 3 or more BMI measurements recorded were analysed.

Patient records were divided into patient years and patients were deemed to be exposed if one or more anti-depressants were prescribed in that year. The outcome was >5% gain in body weight. The anti-depressants examined included tricyclics antidepressants (TCA), monoamine oxidase inhibitors (MAOI) and selective serotonin reuptake inhibitors (SSRI).

Of the 294 719 participants selected, 53 100 (18%) were prescribed anti-depressants in the first year. Patients with higher BMI were more likely to be on anti-depressants. The presence of co-morbidities especially diabetes or strokes also increased the likelihood to be on anti-depressants.

Over the 10 year follow up, those participants not on anti-depressants, incidence of >5% weight gain was 8.1 per 100 person years. The incidence of >5% weight gain was 11.2 per 100 person years in those on anti-depressants. Irrespective of initial BMI category, there was a significant association between anti-depressants use and weight gain. Participants of normal weight showed an increased risk of transitioning to overweight or obesity, and overweight participants were more likely to become obese if they were treated with an antidepressant. Less than 12 months’ use of antidepressants did not appear to be associated with weight gain, but this might be an artefact from incomplete data recording.

Obesity and depression often co-exist and both are associated with physical morbidity and poorer health outcomes. The authors acknowledged that it might be the depression which leads to weight gain rather than the effects of the anti-depressants. However, both issues remain our problem in general practice when treating patients with depression.

From a population perspective, these results suggest that the widespread use of antidepressants might be an important factor contributing to increasing body weight. From a clinical perspective, this study reminds us of the need to incorporate weight management to the overall management of patients with depression particularly if antidepressant treatment is initiated. However, this is not always easy. The potential for weight gain may also be a consideration in the selection of individual antidepressant drugs.

Access abstract here.

Serretti A, Mandelli L. Antidepressants and body weight: a comprehensive review and meta-analysis. J Clin Psychiatry 2010;71:1259-72.