Is the new neck‑to‑forehead headache in a 65‑year‑old woman after increasing bupropion from 150 mg to 300 mg likely a dose‑related adverse effect, and should the bupropion be discontinued?

Bupropion-Related Headache: Dose-Dependent Adverse Effect Requiring Immediate Dose Reduction

The new neck-to-forehead headache after increasing bupropion from 150 mg to 300 mg is a dose-related adverse effect, and you should immediately reduce the dose back to 150 mg daily rather than discontinue entirely, given her ongoing depression and anxiety.

Evidence for Dose-Related Headache

Headache is one of the most common neurological adverse effects of bupropion, occurring frequently enough to be listed among the primary side effects across multiple authoritative sources 1, 2, 3. The temporal relationship—headaches beginning specifically after the dose escalation from 150 mg to 300 mg—strongly suggests a dose-dependent reaction 1, 4.

In controlled trials, headache occurred significantly with bupropion SR at 300 mg/day, alongside insomnia and dry mouth 3. The 300 mg dose produces higher plasma concentrations and greater noradrenergic/dopaminergic activity, which can trigger headaches through increased sympathetic tone 1, 5.

Immediate Management Algorithm

Step 1: Reduce dose immediately

• Decrease bupropion SR back to 150 mg once daily (the dose she tolerated without headaches) 1, 6
• Do not discontinue abruptly, as this may worsen her depression and anxiety 1

Step 2: Monitor response over 7–10 days

• Headaches should resolve within 3–5 days at the lower dose if they are truly dose-related 3, 5
• Continue monitoring her depression and anxiety symptoms 1

Step 3: Reassess at 6–8 weeks

• If depression and anxiety remain inadequately controlled on 150 mg after 6–8 weeks, consider augmentation with an SSRI (such as sertraline 50–100 mg or escitalopram 10 mg) rather than increasing bupropion again 1
• Augmenting bupropion with an SSRI addresses both noradrenergic/dopaminergic and serotonergic pathways and has superior efficacy compared to other strategies 1

Why Not Discontinue Entirely?

Stopping bupropion completely would leave her untreated depression and high anxiety unaddressed 1. She tolerated 150 mg without headaches, indicating she can benefit from bupropion at that dose 6. The 150 mg dose has demonstrated antidepressant efficacy comparable to 300 mg in some patients, particularly when given adequate time (6–8 weeks) 6.

Critical Safety Screening

Before continuing any dose of bupropion, verify she does not have absolute contraindications 1, 2:

• Seizure history or predisposing conditions (prior head trauma, brain tumor, stroke) 1, 2
• Eating disorders (bulimia or anorexia nervosa) 1, 2
• Uncontrolled hypertension (check blood pressure now, as bupropion can elevate BP) 1, 2
• Recent discontinuation of alcohol, benzodiazepines, or antiepileptic drugs 1, 2
• Current MAOI use or within 14 days of stopping an MAOI 1, 2

Monitoring Parameters Going Forward

• Blood pressure and heart rate at each visit, especially in the first 12 weeks, as bupropion can cause elevations 1, 2
• Suicidal ideation and behavioral changes weekly for the first month, as the risk is highest in the first 1–2 months of antidepressant therapy 1
• Headache severity and frequency to confirm resolution at the lower dose 2, 3

Alternative Explanation to Rule Out

While the temporal relationship strongly suggests bupropion-induced headache, also consider:

• New-onset hypertension from bupropion (measure BP immediately) 1, 2
• Tension-type headache from uncontrolled anxiety (though the neck-to-forehead pattern and timing after dose increase favor drug effect) 7

Common Pitfall to Avoid

Do not mistake early activation or anxiety for treatment failure. Bupropion has activating properties that can transiently increase anxiety in the first 1–2 weeks, but this often resolves with continued treatment 1, 5. However, the headache pattern described is a distinct adverse effect requiring dose adjustment, not a transient activation symptom 2, 3.