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Antidepressant Medication and Weight Gain - written by Dr. Adam Klapperich

2/1/2021

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​“You might’ve noticed I’ve got a slight weight problem.  I went to this doctor.  Well, he told me I swallowed a lot of aggression…along with a lot of pizzas.”
 
You might recognize this quote from the 1981 movie Stripes. I sometimes think of Dewey Oxberger, played by John Candy, when prescribing psychotropic medications that can cause weight gain. We all know the second generation antipsychotics can lead to our patients swallowing a lot of pizzas. However, things are less clear regarding antidepressant medications. We know that risk of weight gain can be a major factor in a teen’s decision to start an antidepressant medication, and weight gain can lead to noncompliance. The aim of this article is to review the risk of weight gain with antidepressants commonly prescribed in the primary care setting.

Data points to a definite risk of mild weight gain with “long term” treatment with SSRI medication (meaning six months or more). This is less likely in treatment of six months or less. When weight gain does occur with short term SSRI treatment, the rates are comparable with placebo. This does not apply to Paroxetine (Paxil), which is more likely to cause weight gain than the other SSRIs in short or long term treatment.
In a 6-month placebo controlled trial (N=284) paroxetine showed significant weight gain (increase 7% or greater body weight) in 25.5% of patients. Sertraline (Zoloft) showed 4.2% significant weight gain and fluoxetine (Prozac), which showed 6.8%. Fluoxetine may show a transient weight loss in the initial phase of treatment.

There is limited data indicating citalopram (Celexa) and escitalopram (Lexapro) may cause higher rate of weight gain than sertraline and fluoxetine, though this is likely not significant.
Mirtazapine is well known to cause weight gain in the short and long term. Often this is prescribed to stimulate appetite. Weight gain is related to its histamine H1 and serotonin 2C receptor activity. Weight gain is often seen in the first four weeks of treatment.

As far as SNRI medication, Venlafaxine (Effexor) has been shown less likely than SSRI to cause weight gain. In a 52-week open-label study, duloxetine (Cymbalta) treated patients had a mean weight gain of 1.1 kg at endpoint. Duloxetine-treated patients experienced weight loss after short-term treatment, followed by modest weight gain on longer-term treatment.
​
Overall, antidepressants, aside from paroxetine and mirtazapine, and tricyclics, appear to have minimal large scale effects on body weight. Fluoxetine appears to be the SSRI least likely to cause weight gain. 
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