Does Wellbutrin XL Cause Weight Gain?

Daphne11 asked

My doctor just prescribed me Wellbutrin XL. I have been on several other antidepressants and have had issues with weight. Can you let me know, with Wellbutrin XL specifically, does it cause weight gain?

Answer

Wellbutrin XL (bupropion extended-release), an oral antidepressant, is more associated with weight loss than weight gain, although both have been reported.

The prescribing information for the drug lists the following incidence rates of weight gain and weight loss based on three large clinical trials:

• Weight gain of more than 5 pounds: 11% of clinical trial participants
• Weight loss of more than 5 pounds: 23% of clinical trial participants

Overall, studies discussing the side effects of Wellbutrin XL often state that weight gain on the drug is relatively rare, and if it does occur, is likely based on untreated/inadequately treated depression as depression is strongly associated with weight gain (although weight loss can certainly occur too).

In the next sections, I discuss Wellbutrin XL and its effects on weight in more detail.

What Is Wellbutrin XL?

Wellbutrin XL is an oral antidepressant containing the active ingredient bupropion in an extended-release dosage form. It typically is dosed once-daily.

It is unrelated to other antidepressants (such as SSRIs and SNRIs), both structurally and mechanistically.

It is thought to work mainly by inhibiting the neuronal reuptake of dopamine, but this effect may only happen at doses higher than what is needed to effectively treat depressive symptoms. It also appears to inhibit the reuptake of norepinephrine and has a mild CNS (central nervous system) stimulating effect.

Like all antidepressants, Wellbutrin takes a few weeks of therapy to begin having an effect. In general antidepressant activity is usually noticed within 1 to 3 weeks of starting therapy, but full effects may take up to 4 weeks.

In addition to its use as an antidepressant, it also is used for smoking cessation (Zyban) and seasonal affective disorder.

Weight Effects Of Wellbutrin XL

As stated at the outset, Wellbutrin is more likely to cause weight loss than weight gain.

The following is a chart summarizing the weight effects of Wellbutrin XL in clinical trial patients (from the prescribing information):

Below is a summary of this data:

• 11% of Wellbutrin XL patients had a weight gain of greater than 5 lbs. compared to 21% on placebo.
• 23% of Wellbutrin XL patients had a weight loss of greater than 5 lbs. compared to 11% on placebo;
  

It is important to point out that those taking placebo had a greater rate of weight gain than those taking Wellbutrin XL. This is likely due to depression being left untreated (which is associated with weight gain).

The prescribing information for Wellbutrin XL also gives us weight change data on another formulation of bupropion, Wellbutrin SR.

Wellbutrin SR is another extended-release version bupropion, but is generally dosed twice-daily (versus the once-daily dosing of Wellbutrin XL) and comes in different strengths.

The following is weight change data from clinical trials involving Wellbutrin SR:

Below is a summary of this data:

• 2-3 % of Wellbutrin XL patients had a weight gain of greater than 5 lbs. compared to 4% on placebo.
• 14-19 % of Wellbutrin XL patients had a weight loss of greater than 5 lbs. compared to 6% on placebo.

These results are clearly similar to the data for Wellbutrin XL listed above.

Why Does Wellbutrin Cause Weight Loss?

There are several theories as to why Wellbutrin causes weight loss.

First and foremost, it appears the effective treatment of depression is a major factor. Depression is often a cause of weight gain and obesity. Effectively treating it can help individuals return to a more healthy lifestyle and weight.

The fact that individuals in clinical trials who were given placebo gained weight more often than those given Wellbutrin may be strong evidence to the fact that effective treatment of depression can lead to weight loss.

Nevertheless, treatment of depression alone can't be the only factor since other antidepressants classes (e.g. SSRIs) so often cause an increase in weight.

The other likely reason for the weight loss effects of Wellbutrin is simply due to how it works.

Its reuptake inhibition of dopamine and norepinephrine give it a mild CNS stimulating effect, which is also associated with weight loss. In fact, other antidepressants that affect norepinephrine (like the SNRI class of antidepressants) are also associated with less weight gain than antidepressants that only work on serotonin (i.e. SSRIs).

Additionally, dopamine reuptake inhibition is associated with a decreased appetite.

How Does Wellbutrin Compare To Other Antidepressants?

Wellbutrin is associated with the least weight gain (often it is weight loss) among antidepressant drugs.

The classes of antidepressants that are most likely to cause weight gain include:

• SSRIs (Selective serotonin reuptake inhibitors)
• Mirtazapine
• Tricyclic antidepressants
• MAOIs

The guidelines for the Treatment of Patients With Major Depressive Disorder states this regarding SSRIs and weight gain:

Weight gain, at times substantial, occurs in some patients taking SSRIs. Patients who take paroxetine have a higher incidence of weight gain than those who take other SSRIs. Fluoxetine causes an initial reduction in weight, which tends to normalize with continued treatment.

It goes on to discuss weight gain associated with other classes, such as TCAs (tricyclic antidepressants):

Tricyclic antidepressants can cause weight gain, possibly through their histaminergic properties and/or blockade of 5-HT2 receptors . The degree of weight gain appears to vary by agent (e.g., greater weight gain with amitriptyline and less with desipramine), is often dose dependent, and is potentially reversible with cessation of TCA therapy.

The guidelines go on to suggest Wellbutrin in those that have (over)weight problems or have had issues in regard to weight with other antidepressants:

Patients typically experience minimal weight gain or even weight loss on bupropion [Wellbutrin], and for this reason it may be an appropriate antidepressant for patients who are overweight or obese.

However, just as Wellbutrin may be a good choice for the treatment of depression in those that are overweight, it may not be a good choice in individuals where weight loss and/or anorexia is a significant sign in their presentation of depression.