Krymchantowski AV et al. – Authors conclude that combination therapy (of TPM and NTP) is effective in patients with incomplete benefit using these agents in monotherapy.

• The objective of the study is to conduct a randomized controlled trial testing whether combination therapy of topiramate and nortriptyline is useful in patients who had less than 50% decrease in headache frequency with the use of the single agents.
• Patients with episodic migraine were enrolled if they had less than 50% reduction in headache frequency after 8 weeks of using topiramate (TPM) (100 mg/day) or nortriptyline (NTP) (30 mg/day).
• They were randomized (blinded fashion) to have placebo added to their regimen, or to receive the second medication (combination therapy).
• Primary endpoint was decrease in number of headache days at 6 weeks, relative to baseline, comparing both groups.
• Secondary endpoint was proportion of patients with at least 50% reduction in headache frequency at 6 weeks relative to baseline.

• A total of 38 patients were randomized to receive combination therapy, while 30 continued on monotherapy (with placebo) (six drop outs in the combination group and three for each single drug group).
• For the primary endpoint, mean and standard deviation (SD) of reduction in headache frequency were 4.6 (1.9) for those in polytherapy, relative to 3.5 (2.3) for those in monotherapy.
• Differences were significant (p < 0.05].
• Similarly, 78.3% of patients randomized to receive polytherapy had at least 50% headache reduction, as compared to 37% in monotherapy (p < 0.04).