Can Bupropion (Wellbutrin) exacerbate weight gain associated with Selective Serotonin Reuptake Inhibitors (SSRIs)?

From the Guidelines

Wellbutrin can actually help counteract the weight gain side effects commonly associated with SSRIs. Unlike many antidepressants, Wellbutrin is generally weight-neutral or may even promote modest weight loss in some patients, as noted in a study published in Gastroenterology in 2017 1. When added to SSRI therapy, Wellbutrin often serves as a helpful adjunct that may offset weight gain tendencies. This combination approach works because Wellbutrin primarily affects dopamine and norepinephrine rather than serotonin.

Some key points to consider when using Wellbutrin to counteract weight gain from SSRIs include:

• Typical Wellbutrin dosing ranges from 150-450mg daily, usually in the XL (once-daily) or SR (twice-daily) formulations, as seen in various clinical trials 1.
• Patients should start at lower doses (usually 150mg) and gradually increase if needed to minimize side effects like anxiety, insomnia, or seizure risk.
• This combination therapy should always be monitored by a healthcare provider as it can increase the risk of side effects such as increased blood pressure, anxiety, or rarely, serotonin syndrome.
• The weight-balancing effect occurs because Wellbutrin's stimulating properties can slightly increase metabolism and potentially reduce appetite, counteracting the metabolic changes that SSRIs sometimes cause, as discussed in the context of treating obesity and weight management 1.

It's essential to weigh the benefits and risks of this combination therapy, considering the individual patient's circumstances and medical history. As noted in the study, bupropion is the only antidepressant that has been shown to consistently promote weight loss 1, making it a valuable option for patients experiencing weight gain due to SSRI use.

From the FDA Drug Label

Table 5: Incidence of Weight Gain or Weight Loss (≥5 lbs) in MDD Trials Using Bupropion HCl Sustained-Release Weight Change Bupropion HCl Sustained- Release 300 mg/day (n=339) Bupropion HCl Sustained- Release 400 mg/day (n=112) Placebo (n=347) Gained >5 lbs 3% 2% 4% Lost >5 lbs 14% 19% 6% Table 6: Incidence of Weight Gain or Weight Loss (≥5 lbs) in SAD Trials Using Bupropion HCl Extended-Release Weight Change Bupropion HCl Extended-Release 150 to 300 mg/day (n=537) Placebo (n=511) Gained >5 lbs 11% 21% Lost >5 lbs 23% 11%

Weight Effects of Bupropion: Bupropion is associated with a lower incidence of weight gain compared to placebo.

• In MDD trials, 3-4% of patients on bupropion gained >5 lbs, compared to 4% on placebo.
• In SAD trials, 11% of patients on bupropion gained >5 lbs, compared to 21% on placebo. Augmenting Weight Gain Side Effects of SSRIs: Based on the available data, bupropion is unlikely to augment weight gain side effects of SSRIs, as it is associated with a lower incidence of weight gain compared to placebo. However, the FDA label does not directly address the interaction between bupropion and SSRIs on weight gain. 2

From the Research

Weight Gain Side Effects of SSRIs and Augmentation with Wellbutrin

• SSRIs have been associated with weight gain, with some studies suggesting that high SSRI users gain more weight than non-users 3.
• The weight gain effect of SSRIs is thought to be due to the role of histamine and serotonin off-target appetite-promoting pathways 4.
• Bupropion, also known as Wellbutrin, has been shown to have a weight-loss effect, particularly in the acute phase of treatment 5.
• As an antidepressant, bupropion has been found to be effective as a sole agent or in combination with other antidepressants, including SSRIs 6.
• The use of bupropion as an augmenting agent with SSRIs may help mitigate the weight gain side effects associated with SSRIs, given its weight-loss properties 6.
• However, it is essential to consider individual variations in response to antidepressants and their effects on body weight, as well as other factors such as lifestyle and diet 3, 7.

Mechanism of Action and Weight Effects

• Bupropion's unique pharmacology, inhibiting the reuptake of noradrenaline and dopamine, may provide pharmacological augmentation to SSRIs 6.
• The weight effects of antidepressants, including SSRIs and bupropion, can vary greatly depending on individual characteristics and treatment duration 5.
• Switching to or adding a low-risk antidepressant, such as bupropion, may be considered if significant weight gain occurs with SSRI use 7.

Clinical Implications

• The selection of antidepressants should take into account the potential weight effects, particularly for patients at risk of obesity or related medical illnesses 4, 5.
• Clinicians should consider the evidence on the weight effects of different antidepressants, including bupropion, when making treatment decisions 6.
• Non-pharmacological interventions, such as lifestyle modifications, should also be considered in the management of weight gain associated with antidepressant use 7.