Is my bupropion (Wellbutrin) causing symptoms due to high norepinephrine and dopamine activity?

Bupropion and Norepinephrine/Dopamine-Related Symptoms

Direct Answer

Yes, bupropion can cause symptoms related to its norepinephrine and dopamine activity, including cardiovascular effects (tachycardia, elevated blood pressure), neurological effects (tremor, insomnia, headache, dizziness), and gastrointestinal symptoms (dry mouth, nausea). 1, 2

Mechanism of Action

Bupropion works through dual inhibition of norepinephrine and dopamine reuptake with no clinically significant serotonergic effects. 3 The drug's mechanism is mediated by noradrenergic and/or dopaminergic pathways, making it fundamentally different from SSRIs. 2, 4

• Research demonstrates that bupropion selectively inhibits norepinephrine cells in the locus coeruleus at lower doses than those affecting dopamine cells, suggesting the noradrenergic mechanism may be primary. 5
• The active metabolite hydroxybupropion (formed via CYP2B6) contributes significantly to clinical effects, with plasma concentrations approximately 7 times higher than the parent drug at steady state. 2

Common Side Effects Related to Norepinephrine/Dopamine Activity

Cardiovascular Effects

• Tachycardia and elevated blood pressure are common cardiovascular manifestations of increased norepinephrine activity. 1
• Blood pressure and heart rate should be monitored periodically, especially during the first 12 weeks of treatment. 1
• The FDA label reports sinus tachycardia and ECG changes including conduction disturbances or arrhythmias in overdose situations. 2

Neurological Effects

• Insomnia, headache, dizziness, and tremor are among the most frequently reported neurological side effects. 1
• Nervousness and insomnia are particularly common manifestations of increased noradrenergic activity. 4
• These symptoms reflect the drug's stimulant-like properties from dopamine and norepinephrine reuptake inhibition. 3

Gastrointestinal Effects

• Dry mouth (xerostomia) is one of the most common side effects, occurring due to anticholinergic properties that reduce saliva production. 6
• Nausea, constipation, and vomiting are also common, though nausea appears slightly less common than with SSRIs. 1, 4
• Dry mouth can create a globus pharyngeus sensation (feeling of something stuck in the throat) due to reduced saliva and altered swallowing mechanics. 6

Serious Adverse Effects

Seizure Risk

• Bupropion carries a dose-dependent seizure risk of approximately 0.1% (1/1000 patients) at doses up to 300 mg daily. 7, 1
• Risk factors include prior seizure history, structural brain lesions, alcohol abuse, eating disorders, and medications that lower seizure threshold. 1
• Multiple uncontrolled seizures have been reported in overdose situations. 2

Other Serious Effects

• Hallucinations, loss of consciousness, mental status changes, clonus, myoclonus, and hyperreflexia can occur, particularly in overdose. 2
• Fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, and respiratory failure have been reported mainly in multiple drug overdoses. 2

Management Strategies

Symptom Management

• Increase water intake throughout the day to manage dry mouth and throat discomfort. 6
• Take medication with plenty of water to reduce throat irritation. 6
• If symptoms are severe or persistent, dosage adjustment should be considered. 6

When to Seek Medical Attention

• Seek prompt evaluation if experiencing severe or persistent symptoms, difficulty swallowing (dysphagia), or signs of cardiovascular instability. 6
• Monitor for emergence of seizure activity, especially if risk factors are present. 1

Important Contraindications

Bupropion should be avoided entirely in patients with:

• History of seizure disorders or epilepsy (significant risk of reduced seizure threshold). 7
• Current or previous bulimia or anorexia nervosa (higher seizure risk). 7
• Uncontrolled hypertension (may increase blood pressure). 7
• Concurrent MAOI use (risk of hypertensive crisis). 7, 1

Clinical Context

While these norepinephrine and dopamine-related effects can be bothersome, bupropion offers distinct advantages over SSRIs, including significantly lower rates of sexual dysfunction and less weight gain. 8, 3 The benefits for depression or smoking cessation should be weighed against these side effects. 6