Nefazodone for chronic daily headache prophylaxis: an open-label study

Area of Science:

• Neurology
• Pharmacology

Background:

• Nefazodone, a 5-HT2 antagonist, has a unique mechanism of action relevant to headache pathophysiology.
• Chronic daily headache may involve 5-HT2 receptor up-regulation, similar to other migraine treatments.
• Nefazodone's antidepressant efficacy and safety are established, but its headache prophylaxis role is untested.

Purpose of the Study:

• To evaluate nefazodone's effectiveness for chronic daily headache prophylaxis.
• To assess the tolerability and safety of nefazodone in this patient population.
• To explore nefazodone's impact on quality of life and comorbid mood symptoms.

Main Methods:

• An open-label, two-center study involving 52 patients with chronic daily headache (≥15 days/month).
• A 4-week baseline followed by 12 weeks of nefazodone treatment (median 300 mg/day).
• Primary outcome measures included headache diary parameters and validated scales for depression and anxiety.

Main Results:

• Significant reductions in headache intensity, duration, frequency, and impairment were observed (P<.00001).
• 71% of completers showed ≥50% reduction in headache index; 59% had ≥75% improvement.
• Improvements noted in quality of life, mood, and sexual function; significant benefits for patients with depression/anxiety.

Conclusions:

• Nefazodone shows preliminary efficacy for chronic daily headache prophylaxis.
• The drug was safe and well-tolerated, with improved sexual function reported.
• Nefazodone may be particularly advantageous for patients with comorbid depression and anxiety.