Wellbutrin in Bipolar Disorder: Risks and Benefits

Wellbutrin — also known by its generic name, bupropion — is an antidepressant that's sometimes used to treat depression in bipolar disorder. Bupropion's manufacturer sells the drug under a third name, as well: Zyban, a drug marketed to help people quit smoking.

The medication is available in immediate release (75 and 100 mg tablets) and sustained release (100 and 150 mg) formulas (sold as Wellbutrin SR®).

It's not clear why Wellbutrin works to reduce depressive symptoms. Chemically, it's not related to any other major antidepressant. However, studies show it does work, and it may have some advantages over other antidepressants for treating depression in people with bipolar disorder.

Wellbutrin in Bipolar Disorder

Antidepressants, including Wellbutrin, are widely used in bipolar disorder, even though there's not very much evidence for their safety and usefulness. Few well-designed, long-term medical studies have been performed, and it's not clear exactly how antidepressants may interact with the mood stabilizers commonly prescribed for those with bipolar disorder.

One 10-week study did show Wellbutrin helped about half of the people with bipolar disorder who were treated with the drug while also taking mood stabilizers.

When prescribing antidepressants for their bipolar patients, psychiatrists mainly are concerned about "mood switching," which is when a depressive mood suddenly switches to mania, hypomania or a mixed state.

There is some evidence that Wellbutrin may have lower rates of "manic switch" when compared with other forms of antidepressants, such as older tricyclic antidepressants and norepinephrine-serotonin reuptake inhibitors (SNRIs). About 10% of patients in the 10-week study saw a significant increase in their manic symptoms, compared to about 29% for those taking an SNRI.

Mood switching seems to occur more often in people with bipolar I who take antidepressants. Therefore, experts recommend that bipolar I patients only be prescribed antidepressants in conjunction with mood stabilizing medications.

Starting Wellbutrin: General Guidelines

Your doctor most likely will want to start you on Wellbutrin or Zyban at a lower dose and then increase your dosage, due to the risk of side effects.

When you first begin taking Wellbutrin, your initial dosage should be no more than 150 mg/day. This may be increased to no more than 300 mg/day on the fourth day when used as a stop-smoking aid, and eventually to 400 mg (sustained release) or 450 mg (immediate release) when used to treat depression.

At doses of 400-450 mg/day your risk of seizures triples, although it's still very, very small: four in every 1,000 people experience seizures from Wellbutrin at a dose this high. Patients who experience agitation, restlessness or insomnia should remain on a lower dose longer and/or increase the dosage more gradually. It may take one to four weeks for patients taking bupropion to feel the full benefits.

Most common side effects of the drug include headache, dry mouth, nausea, and insomnia.

Although many antidepressants seem to cause or contribute to weight gain, Wellbutrin/Zyban is considered "weight neutral," and more people report losing weight than gaining weight while taking the medication.

Cautions on Wellbutrin/Zyban

Here are some things you should watch out for when taking this medication:

  • A small percentage of people experienced anorexia while taking bupropion, so patients with a history of anorexia nervosa or bulimia, or with a history of seizures, should not take this medication. In fact, some sources recommend that Bupropion not be taken by anyone who cannot afford to lose more than 5% of current body weight.
  • If you're taking an MAOI antidepressant, you should wait at least two weeks following your last dose of that medication to start Wellbutrin/Zyban.
  • Bupropion isn't known to be dangerous during pregnancy or nursing, but of course, your obstetrician and pediatrician should know all medications you are taking at all times.
  • If you miss a dose, SKIP IT. The risk of seizure is dose dependent, and doubling up is more likely to cause a seizure.
  • Never take both Wellbutrin AND Zyban. All you'd be doing is increasing the dosage to a possibly dangerous level.
  • The use — especially excessive use — of alcohol increases the risk of seizure while taking bupropion.
  • Care should be taken when combining Wellbutrin or Zyban with the anticonvulsant medications phenytoin (brand name Dilantin), carbamazepine (brand name Tegretol) (which is commonly used to treat bipolar disorder), or phenobarbital, or with the ulcer medication cimetidine (brand name Tagamet).


National Alliance on Mental Illness. Bupropion (Wellbutrin) fact sheet. 

Pacchiarotti I et al. The International Society for Bipolar Disorders (ISBD) task force report on antidepressant use in bipolar disorders. American Journal of Psychiatry. 2013 Nov;170(11):1249-62.

Post RM et al. Mood switch in bipolar depression: comparison of adjunctive venlafaxine, bupropion, and sertraline. British Journal of Psychiatry. Jul 2006, 189 (2) 124-131.