Can headaches be a side effect of starting a new medication?

Headaches as a Medication Side Effect

Yes, headaches are a well-documented side effect of many medications, and new-onset headaches after starting a medication strongly suggest a drug-induced etiology that requires evaluation and potential medication adjustment. 1, 2

Medications Most Commonly Causing Headaches

Stimulant Medications

• Stimulants are among the most frequent culprits for medication-induced headaches, including amphetamines (Vyvanse, Adderall), methylphenidate, and modafinil/armodafinil 1
• Headaches occur as a direct pharmacologic effect of increased norepinephrine and dopamine activity 1
• Dose-dependent relationship exists—higher doses correlate with increased headache frequency and severity 1

Antidepressants with Stimulant Properties

• Bupropion (Wellbutrin) can trigger or exacerbate headaches due to its norepinephrine-dopamine reuptake inhibition 1
• SSRIs commonly cause headaches during initial treatment, particularly fluoxetine, paroxetine, and sertraline 3

Other Common Offenders

• Efalizumab causes dose-related headache, fever, and nausea after initial dosing, which typically resolves after 3 weeks of continued treatment 3
• Phentermine frequently causes headaches as a common adverse effect, along with elevated blood pressure and insomnia 3
• Antiepileptic drugs like topiramate cause headaches in a subset of patients, though paradoxically it's also used for migraine prevention 1

Clinical Assessment Algorithm

Step 1: Establish Temporal Relationship

• Document exact timing of headache onset relative to medication initiation 4, 5
• New headaches appearing within days to weeks of starting medication strongly implicate that drug 1, 2
• Consider dose escalations—headaches may emerge when doses are increased 1

Step 2: Characterize Headache Features

• Medication-induced headaches are typically bilateral, constant, and of moderate severity 6, 7
• Distinguish from migraine features (unilateral, pulsating, severe, with nausea/photophobia) which suggest underlying primary headache disorder 1, 8
• Daily or near-daily headaches suggest medication effect rather than episodic primary headache 8, 6

Step 3: Identify High-Risk Medications

• Review all medications started or dose-adjusted in the 3 months prior to headache onset 4, 5
• Prioritize stimulants (amphetamines, modafinil), vasodilators, hormones, and medications affecting neurotransmitters 1, 4

Management Strategy

First-Line Approach: Medication Adjustment

• For non-essential medications causing headaches, discontinue the offending agent 2, 4
• For essential medications (e.g., antiepileptics, stimulants for ADHD), consider dose reduction first 2
• If headaches persist despite dose reduction, switch to alternative agent in same therapeutic class 2

Symptomatic Treatment During Adjustment Period

• NSAIDs (ibuprofen, naproxen) are first-line for moderate medication-induced headaches 2
• Acetaminophen combined with caffeine may provide relief for milder headaches 2
• Avoid opioids and butalbital-containing medications—these cause dependency and rebound headaches 2, 8

Critical Threshold to Prevent Medication Overuse Headache

• Limit acute headache treatments to <10 days per month for triptans and <15 days per month for NSAIDs 8, 6
• Using analgesics more than twice weekly risks developing medication overuse headache (MOH), a secondary chronic daily headache 8, 7

Common Pitfalls and How to Avoid Them

Pitfall 1: Missing Medication Overuse Headache

• If patient treats medication-induced headaches with frequent analgesics (>10-15 days/month), MOH develops on top of the original drug-induced headache 8, 6
• This creates a vicious cycle requiring both withdrawal of the causative medication AND the overused analgesic 8, 7
• Maintain headache diary to track analgesic frequency and prevent this complication 8

Pitfall 2: Confusing Withdrawal Headaches with Medication Side Effects

• Discontinuation of SSRIs (especially paroxetine, sertraline, fluvoxamine) causes withdrawal syndrome including headaches, dizziness, and nausea 3
• These withdrawal headaches appear 1-3 days after stopping medication, not during active treatment 3
• Taper SSRIs over at least 1 week to minimize withdrawal symptoms 3

Pitfall 3: Premature Abandonment of Essential Medications

• Some medication-induced headaches resolve spontaneously with continued treatment (e.g., efalizumab headaches resolve after 3 weeks) 3
• For essential medications, trial symptomatic treatment for 2-4 weeks before discontinuing 2
• Consult prescribing specialist about alternative options if headaches remain severe despite optimal management 2

Pitfall 4: Failing to Address Underlying Primary Headache Disorder

• Medication may unmask or exacerbate pre-existing migraine rather than causing de novo headaches 1, 8
• If headaches have migraine features (unilateral, pulsating, severe, with nausea), consider preventive therapy rather than just stopping the suspected medication 1, 8

When to Refer to Specialist

• Headaches persist >4 weeks after discontinuing suspected medication 2
• Headaches transform to chronic daily pattern (≥15 days/month) 8, 6
• Patient develops medication overuse headache requiring withdrawal management 8, 7
• Essential medication cannot be discontinued and headaches remain disabling despite symptomatic treatment 2