Bupropion (Wellbutrin) Safety in Patients with History of Tardive Dyskinesia
Bupropion is safe to use in patients with a history of tardive dyskinesia (TD) and may actually be a preferred antidepressant choice in this population, as it does not block dopamine receptors and therefore does not cause or worsen TD.
Mechanism and Safety Profile
Bupropion is fundamentally different from the medications that cause TD:
TD is caused exclusively by dopamine receptor-blocking agents (DRBAs), primarily antipsychotics, which chronically block dopamine receptors in the nigrostriatal pathway 1, 2.
Bupropion does not block dopamine receptors; instead, it inhibits dopamine and norepinephrine reuptake, making it mechanistically incapable of causing or exacerbating TD 3.
The available guidelines on bupropion use make no mention of TD as a contraindication or precaution, noting only that it should be avoided in patients with seizure disorders and agitated patients 3.
Clinical Considerations for Use
When prescribing bupropion to patients with a history of TD:
Start with low doses (37.5 mg every morning) and titrate by 37.5 mg every 3 days up to a maximum of 150 mg twice daily 3.
Bupropion is activating and may cause rapid improvement in energy levels, making it particularly useful for patients with apathy or low energy 3.
Avoid in agitated patients and give the second dose before 3 p.m. to minimize insomnia risk 3.
Monitor for seizure risk, which is the primary safety concern with bupropion, not movement disorders 3.
Important Caveats
While bupropion itself is safe regarding TD:
Continue monitoring for TD progression if the patient remains on any dopamine-blocking agents, using the Abnormal Involuntary Movement Scale (AIMS) every 3-6 months 4, 5.
Avoid anticholinergic agents (like benztropine) if the patient has both TD and drug-induced parkinsonism, as anticholinergics can worsen TD 1.
Consider the underlying psychiatric condition: If the patient requires antipsychotic treatment for psychotic depression, bupropion alone will be insufficient, and concomitant antipsychotic medication will be necessary 3.
Preferred Antidepressant Strategy in TD Patients
Among antidepressants for patients with TD history:
Bupropion, SSRIs (sertraline, citalopram), and mirtazapine are all safe choices as none block dopamine receptors 3.
Avoid typical antipsychotics entirely in patients with TD history, as they carry up to 50% risk of TD in elderly patients after 2 years of continuous use 6.
If antipsychotic treatment is unavoidable, switch to atypical antipsychotics with lower D2 affinity 4, 5.