What is the relationship between Bupropion (Wellbutrin) and hypomania?

From the Guidelines

Wellbutrin (bupropion) can potentially trigger hypomania in some individuals, particularly those with bipolar disorder or a predisposition to mood disorders. If you're taking Wellbutrin and experience symptoms of hypomania—such as decreased need for sleep, racing thoughts, increased energy, rapid speech, impulsivity, or grandiose thinking—contact your healthcare provider immediately. The typical dose range for Wellbutrin is 150-450 mg daily, with the medication often started at a lower dose (150 mg) and gradually increased to minimize side effects. For patients with known bipolar disorder, Wellbutrin is generally prescribed with caution and often alongside a mood stabilizer like lithium, valproate, or lamotrigine to prevent mood elevation. The risk of hypomania with Wellbutrin is related to its mechanism of action as a norepinephrine-dopamine reuptake inhibitor, which increases these neurotransmitters in the brain and can potentially accelerate thought processes and energy levels. Regular monitoring for mood changes is essential when starting Wellbutrin or adjusting the dose, especially during the first few weeks of treatment, as recommended by the American College of Physicians 1. Some key points to consider when taking Wellbutrin include:

• Monitoring for adverse effects, such as nausea, vomiting, and sexual dysfunction, which are common with second-generation antidepressants 1
• Being aware of the potential for increased risk of suicidality, particularly in the first 1-2 months of treatment 1
• Discussing adverse event profiles with your healthcare provider before selecting a medication 1

From the FDA Drug Label

Instruct patients, their families, and/or their caregivers to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down.

Bupropion, the active ingredient in WELLBUTRIN, may be associated with an increased risk of hypomania, especially early during treatment and when the dose is adjusted. Patients should be monitored for the emergence of hypomania and other unusual changes in behavior.

• Key points:
  • Bupropion may increase the risk of hypomania.
  • Patients should be monitored for hypomania and other unusual changes in behavior.
  • The risk of hypomania may be higher early during treatment and when the dose is adjusted. 2

From the Research

Welbutrin and Hypomania

• Welbutrin, also known as bupropion, is a selective norepinephrine and dopamine reuptake inhibitor used in the treatment of depression and nicotine addiction 3.
• Compared to other antidepressants, bupropion has a relatively lower risk of triggering a shift to hypomania or mania in bipolar depression treatment 3, 4, 5.
• However, case reports have shown that bupropion can still induce manic shifts in some patients with bipolar depression, particularly when used as an adjunct to mood stabilizer treatment 3.
• A study found that the rate of threshold switches to full-duration hypomania and mania was lower in patients treated with bupropion compared to venlafaxine and sertraline 4.
• Another study reported that bupropion was effective in treating severe bipolar depression with a low risk of inducing switches to hypomania or mania, especially when used at a daily dose not exceeding 450 mg 5.

Risk of Hypomania

• The risk of switch in mood polarity to hypomania or mania in patients with bipolar depression during acute and continuation trials of bupropion as an adjunct to mood stabilizers is relatively low compared to other antidepressants 4.
• However, the risk of threshold switches to full-duration hypomania and mania was found to be higher in patients with bipolar I disorder compared to those with bipolar II disorder 4.
• Bupropion has been suggested as a first-line antidepressant in the treatment of severe bipolar depression due to its efficacy and relatively low risk of inducing hypomania or mania 5.

Treatment of Bipolar Disorder

• Bipolar disorder is characterized by recurrent episodes of depression and mania or hypomania, and its treatment typically involves mood stabilizers, antipsychotic agents, and antidepressants 6.
• First-line therapy for bipolar disorder includes mood stabilizers such as lithium, anticonvulsants such as valproate and lamotrigine, and atypical antipsychotic drugs such as quetiapine, aripiprazole, and olanzapine 6, 7.
• The treatment of mixed mania/hypomania is challenging due to the necessity to treat both manic/hypomanic and depressive symptoms concurrently, and high-potency antipsychotics and antidepressants can potentially deteriorate symptoms of the opposite polarity 7.