How to manage headache in patients undergoing lithium therapy?

Managing Headache in Lithium Therapy

For headache occurring as a side effect of lithium therapy, start with NSAIDs (ibuprofen 400-800 mg, naproxen sodium 275-550 mg, or aspirin 650-1000 mg) as first-line treatment, and if headaches become frequent or severe, consider whether lithium dose reduction or discontinuation is necessary after consulting with the prescribing psychiatrist. 1, 2

Understanding Lithium-Associated Headache

Headache is listed as an adverse reaction to lithium in the FDA labeling, occurring as part of the spectrum of side effects that may not be directly related to serum lithium levels 2. The key clinical challenge is distinguishing between:

• Simple lithium-induced headache - occurring as a direct medication side effect 2
• Early lithium toxicity - where headache may accompany other neurological symptoms like drowsiness, muscular weakness, giddiness, ataxia, or blurred vision 2
• Primary headache disorder - coincidentally occurring in a patient on lithium therapy

First-Line Acute Treatment Approach

NSAIDs as Primary Therapy

• Use standard NSAID dosing: ibuprofen 400-800 mg, naproxen sodium 275-550 mg, or aspirin 650-1000 mg for acute headache episodes 1
• These agents have demonstrated efficacy and favorable tolerability for migraine-type headaches 1
• For parenteral therapy in severe cases, ketorolac 30-60 mg IM/IV provides rapid onset with approximately six hours of duration 1

Combination Therapy for Enhanced Efficacy

• Consider aspirin plus acetaminophen plus caffeine when single-agent NSAIDs provide inadequate relief 1
• This combination provides synergistic analgesia and enhances absorption of analgesics 1

Escalation Strategy for Moderate-to-Severe Headache

When NSAIDs Fail Within 2 Hours

• Escalate to triptans (naratriptan, rizatriptan, sumatriptan, or zolmitriptan) for moderate-to-severe headache 1
• Oral triptans are appropriate for most patients, while subcutaneous or intranasal sumatriptan is particularly useful when nausea and vomiting are present 1
• Administer triptans early in the attack while headache remains mild for optimal efficacy 1

Managing Associated Symptoms

• Add antiemetics (metoclopramide 10 mg IV or prochlorperazine 10 mg IV) if nausea is present, as these provide synergistic analgesia beyond just treating nausea 1
• Select non-oral routes when significant nausea or vomiting accompanies the headache 1

Critical Monitoring and Safety Considerations

Rule Out Lithium Toxicity

• Check serum lithium level immediately if headache is accompanied by drowsiness, muscular weakness, lack of coordination, giddiness, ataxia, blurred vision, or tinnitus 2
• Toxic signs can occur at levels below 1.5 mEq/L in sensitive patients, though risk increases substantially above this threshold 2
• Serum lithium levels should not exceed 2 mEq/L during acute treatment phases 2

Assess for Medication-Overuse Headache

• Limit acute headache medications to no more than twice weekly to prevent medication-overuse headache, which results from frequent use and leads to increasing headache frequency 1
• If the patient requires acute treatment more than twice weekly, transition to preventive therapy rather than increasing frequency of acute medications 1

When to Consider Lithium Adjustment

Indications for Dose Reduction or Discontinuation

• Persistent headaches despite optimal acute treatment warrant discussion with the prescribing psychiatrist about lithium dose adjustment 2
• Headache accompanied by other adverse reactions (tremor, polyuria, mild thirst, nausea, general discomfort) that persist beyond initial therapy may indicate the need for temporary dose reduction or cessation 2
• The FDA labeling notes that transient side effects during the first few days usually subside with continued treatment or temporary dose reduction, but persistent symptoms warrant cessation 2

Coordinate with Psychiatric Care

• Do not discontinue lithium without psychiatric consultation, as abrupt cessation can precipitate mood episodes in patients with bipolar disorder
• Work collaboratively to balance headache management with maintenance of psychiatric stability

Treatments to Avoid

Opioids Should Be Last Resort

• Reserve opioids only for cases where other medications cannot be used, sedation is not a concern, and abuse risk has been addressed 1
• Opioids lead to dependency, rebound headaches, and eventual loss of efficacy, particularly problematic in patients requiring chronic lithium therapy 1
• If an opioid must be used, butorphanol nasal spray has better evidence than other opioid formulations 1

Preventive Therapy Consideration

When to Initiate Prevention

• Evaluate for preventive therapy if headaches occur more than 2 days per week or produce significant disability 1
• Preventive therapy reduces attack frequency and can restore responsiveness to acute treatments 1
• Efficacy requires 2-3 months for oral preventive agents to adequately assess 1

Important Clinical Pitfall

Do not allow patients to escalate the frequency of acute medication use in response to treatment failure, as this creates medication-overuse headache 1. Instead, optimize the acute treatment strategy (ensuring early administration, appropriate agent selection, adequate dosing) while simultaneously addressing whether lithium adjustment is needed and whether preventive therapy is indicated 1, 2.