Bupropion for Anxiety Treatment
Bupropion can be used to treat anxiety symptoms that occur in the context of major depressive disorder, but it is not a first-line agent for primary anxiety disorders and shows modest inferiority to SSRIs when treating anxious depression.
Evidence for Anxiolytic Effects in Depression
Bupropion demonstrates comparable efficacy to SSRIs in reducing anxiety symptoms when treating major depressive disorder overall, but with important nuances:
In patients with high baseline anxiety (anxious depression), SSRIs show a modest advantage over bupropion, with response rates of 65.4% versus 59.4% respectively (p=0.03), translating to a number-needed-to-treat of 17 patients to obtain one additional responder 1
In patients with moderate to low anxiety levels, there is no significant difference in efficacy between bupropion and SSRIs for treating anxiety symptoms 1
A large meta-analysis of 2,890 patients found no overall difference in anxiolytic efficacy between bupropion and SSRIs when treating anxiety symptoms in major depressive disorder, with comparable improvements in Hamilton Anxiety Scale scores (-8.8 vs -9.1, p=0.177) 2
A recent 2023 naturalistic study using propensity matching found no difference in anxiety outcomes between SSRI and bupropion groups over 12 weeks of treatment, directly challenging the clinical belief that bupropion exacerbates anxiety 3
Clinical Context and Mechanism
The American Academy of Family Physicians recommends bupropion as an activating antidepressant that improves energy levels and reduces apathy through its effects on dopamine and norepinephrine reuptake 4. This mechanism differs fundamentally from SSRIs' serotonergic action.
Bupropion is particularly effective for symptoms of apathy and lack of energy in depression, with beneficial effects on dopamine levels 5
One older study showed that 300 mg/day of bupropion reduced anxiety symptoms in hospitalized depressed patients 6
Case reports demonstrate successful use of bupropion in patients complaining of anxiety as a symptom of MDD, resulting in remission 7
When to Consider Bupropion for Anxiety
Bupropion is an appropriate choice for anxiety when it occurs as part of a depressive syndrome, particularly in these scenarios:
Patients with depression and comorbid anxiety who also have prominent apathy, fatigue, or low energy 5, 4
Patients requiring an activating antidepressant who cannot tolerate SSRIs 4
As augmentation therapy with other agents (such as mirtazapine) when targeting multiple symptom domains including anxiety 4
Patients with depression and anxiety who are also trying to quit smoking or reduce alcohol intake 8
Critical Precautions
Bupropion should be avoided in patients with:
History of seizure disorders, as it lowers the seizure threshold 5, 4
Conditions predisposing to seizures including anorexia or bulimia nervosa, or abrupt discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 8
Concurrent MAOI use or within 14 days of discontinuing MAOIs 5
Uncontrolled hypertension (blood pressure monitoring is essential, especially at treatment initiation) 8, 5
Dosing Considerations
The second daily dose should be taken before 3 PM to minimize insomnia risk 5, 4
Maximum dose is 150 mg twice daily for immediate release formulation 4
In renal impairment (moderate to severe), reduce total daily dose to 150 mg/day 5
In hepatic impairment (moderate to severe), do not exceed 150 mg total daily dose 5
Evaluate response after 12 weeks of treatment 5
Common Pitfall
The longstanding clinical belief that bupropion worsens anxiety is not supported by the most recent high-quality evidence 3. However, for patients presenting with anxious depression (high baseline anxiety), SSRIs remain marginally superior 1. The key is distinguishing between primary anxiety disorders (where bupropion is not indicated) versus anxiety symptoms occurring within major depressive disorder (where bupropion is effective, especially when energy and motivation are also impaired).