Which Antidepressant Does Not Cause Weight Gain?

Any antidepressant that does not cause weight gain may be best for people who are weight-conscious and weight gain could add to the symptoms of anxiety.

Antidepressants may cause weight gain in one person and weight loss in another. The effect of the antidepressant on weight is also affected by multiple factors including dietary habits, inactivity, concomitant medications, and illnesses that might cause weight gain.

The specific medication and treatment duration will determine the effect of SSRIs on weight. Short-term treatment for two to three months with antidepressants is usually not associated with weight gain. However, short-term therapy is not recommended for most patients.

Weight gain may occur if antidepressants are used for prolonged periods. It is unclear if this is a side effect of the antidepressant medicine or a result of recovery from depression resulting in the reversal of weight loss associated with depression.

Evidence suggests that Bupropion (Welbutrin) and Fluoxetine (Prozac) are the least associated with weight gain while paroxetine (Seroxat) is associated with the most weight gain. These weight effects were reported in studies that lasted between 6 and 30 months.

Effect of Fluoxetine (Prozac) on Weight:

Fluoxetine can lead to weight changes of small amounts, ranging from a loss in body weight of 0.2% at baseline up to an increase of 0.9 percent.

A randomized trial showed a mean weight gain of 3.0 kg (6.6 lb) for fluoxetine, compared to 3.2 kg (7.0 lb) for placebo [Ref].

The slight weight gain was attributed to a change in appetite and improvement in well-being and diet.

In one study, the mean change in body weight with fluoxetine was observed as follows:

• Percentage of patients who had an increase in weight of 7% or more at treatment completion [Ref]:
  • At 26 weeks:
    • Fluoxetine group: 5.4%
    • Placebo group: 16%
  • At 38 weeks:
    • Fluoxetine group: 18.3%
    • Placebo group: 22.2%
  • At 50 weeks:
    • Fluoxetine group: 25.4%
    • Placebo group: 26.7%

• Percentage of weight change in the fluoxetine group compared to placebo at treatment completion:
  • At 26 weeks:
    • Fluoxetine group: 1.4%
    • Placebo group: 3.2%
  • At 38 weeks:
    • Fluoxetine group: 3.1%
    • Placebo group: 4.2%
  • At 50 weeks:
    • Fluoxetine group: 4.3%
    • Placebo group: 5.3%

Another study reported a weight loss of 3 to 6 kgs and a reduction in BMI of 1 to 2% with fluoxetine [Ref]

Effect of Citalopram on Weight:

Citalopram (Celexa) can lead to weight changes that range from zero to a 2.5 percent increase in baseline body weight.

Citalopram, venlafaxine, and Sertraline are considered to cause less weight gain compared to other antidepressant medications. Citalopram, in one study, resulted in a weight gain of 6.9 kgs [Ref].

Fluvoxamine (Luvox) effect on weight:

Fluvoxamine like other SSRIs has been associated with some degree of weight gain, although, not greater than most SSRIs. It has been found in studies to cause a weight gain of 2.6 percent of the baseline body weight.

One study evaluated its role in obese individuals with depression. Fluvoxamine use resulted in more weight loss than placebo at the end of the treatment period, although statistically, the results were not significant. Nevertheless, it did not cause weight gain as predicted with the use of an antidepressant SSRI [Ref].

Another study evaluated the role of fluvoxamine in patients with social anxiety disorder. Fluvoxamine did not result in significant weight gain or sexual dysfunction as measured by the ASEX score [Ref].

Paroxetine (Seroxat) Side effect: Weight Gain

Paroxetine is a potent antidepressant that is especially indicated for the treatment of depression with symptoms of anxiety.

Paroxetine, however, causes more weight gain, sexual dysfunction, sedation, constipation, and discontinuation syndrome than other antidepressant medications [Ref].

Weight gain was observed in 6 percent of patients ranging from 1.6 to 3.6% of the baseline body weight.

Paroxetine caused a weight gain of 3.6% from baseline compared to a slight weight gain with sertraline and weight loss with fluoxetine.

The rates of significant weight gain, defined as weight gain exceeding 7% of the baseline body weight, occurred in 25.5% of the paroxetine group compared with 6.8% in patients who received fluoxetine, and 4.2% of patients who received sertraline [Ref].

Sertraline (Zoloft) Side effect: Weight Gain

Sertraline is relatively weight-neutral. It can lead to weight gain ranging from 1.0 – 1.6 percent of your baseline body weight.

A randomized trial showed a mean weight gain of 1.5 kg (3.3 lb) for sertraline, compared to 1.8 kg (4.0 lb) for placebo [Ref].

Sertraline was compared to Agomelatine in one study. Both drugs resulted in significant improvement in depression scores.

Sertraline use was associated with dyslipidemia while agomelatine resulted in deranged liver enzymes. Change in BMI and waist circumference before and after treatment is given in the chart below [Ref]:

Vortioxetine (Brintellix) effect on body weight:

Vortioxetine is available under the brand names Brintellix and Trintellix. It is a serotonin modulator and is used in patients with refractory depression.

In one trial, vortioxetine was compared with sertraline in patients with depression and comorbid diabetes mellitus.

Vortioxetine significantly improved all the metabolic parameters including improvement in the glycated hemoglobin and change in weight.

A mean weight loss of 2.4 kgs occurred in the vortioxetine group compared to a mean weight gain of 2.3 kgs in the sertraline group.

Similarly, waist circumference was reduced by a mean of 3.3 cm in the vortioxetine group vs 0.1 cm in the sertraline group.

Vilazodone (Viibryd) effect on body weight:

Vilazodone is another serotonin modulator that is available under the brand name Viibryd. It is a novel antidepressant and data is limited.

However, vilazodone when compared to sertraline resulted in weight loss and had significantly fewer sexual side effects [Ref].

Bupropion causes weight loss:

Bupropion is the only antidepressant associated with significant weight loss. It is the only antidepressant that has been FDA-approved for weight loss.

However, the formulation that has been FDA-approved for weight loss is a combination of bupropion and Naltrexone. It is marketed by the brand name “Contrave“.

Bupropion monotherapy, in one 8-week trial, resulted in a weight loss of greater than 5 lb (2.27 kgs) in 14% and 19% of patients treated with Bupropion SR 300 mg and 400 mg per day compared to 6% in the placebo-treated patients.

A weight loss of greater than 10lb (4.54 kgs) occurred in 2% and 6% of the patients treated with bupropion SR 300 mg and 400 mg per day compared to 2% of the patients treated with placebo.

Final words:

The major depressive disorder has been the subject of many studies. It is unclear whether weight changes caused by SSRIs are different for different demographic profiles, such as age and sex.

A review found that weight gain during treatment with SSRIs may be due to remission of major depression, improved appetite, increased carbohydrate craving, and changes in serotonin 2C receptor activity [Ref].

Conversely, weight loss during acute SSRI treatment may be related to poor appetite at the beginning of treatment.

Among the antidepressants, paroxetine causes the greatest weight gain while bupropion is associated with significant weight loss.

Lastly, the novel serotonin modulators are effective in the treatment of depression and have fewer side effects, especially those related to body weight and sexual side effects.