Herbert Harris, MD, PhD Validus Pharmaceuticals, Parsippany, New Jersey Bruce Corser, MD

Safety and Tolerability of the MAO Inhibitor Isocarboxazid (Marplan) in the prophylactic treatment of migraine* • Herbert Harris, MD, PhD • Validus Pharmaceuticals, Parsippany, New Jersey • Bruce Corser, MD • Community Research, Cincinnati, Ohio • Richard A Guarino, MD • Oxford Pharmaceutical Services, Totowa, New Jersey * Study funded by Validus Pharmaceuticals

Migraine prophylaxis • antiepileptic agents • topiramate and divalproex • beta-adrenergic blockers • propranolol and timolol. • methysergide (withdrawn) • antidepressants • tricyclic antidepressants

Objective The purpose of this open-label pilot study was to evaluate the safety and tolerability of the MAOI Isocarboxazid (Marplan) in the prophylactic treatment of migraine.

Methods • Male and female subjects 18-60 years of age • Diagnosis of migraine according to IHS criteria • 3-12 HAs per month for the 3 months prior to screening • Isocarboxazid (Marplan) treatment was initiated at 20mg per day and increased as tolerated to a maximum dose of 60mg per day • Treatment covered three months • Concomitant use of tryptans, NSAIDs antidepressants and other commonly used anti-migraine agents was prohibited • The primary efficacy measure was within-subject change from baseline in migraine frequency.

Study Population

Demographics

Safety and Tolerability

Discontinuations due to AEs

Maximum Tolerated Dose

IsocarboxazidDoses in Study

Other Treatment Emergent AEs

Efficacy

Average Migraine Frequency (Completers)

Responders

Observed Cases and LOCF

Conclusions • The tolerability of Isocarboxazid (Marplan) in this study was similar to that reported in depression trials • Insomnia, irritability, and sexual dysfunction were the most common adverse events • Five subjects (31%) withdrew due to adverse events • No serious adverse events were reported • In this small open-label study, Isocarboxazid (Marplan) showed very robust clinical efficacy in the prophylactic treatment of migraine attacks • Isocarboxazid offers a mechanistically novel approach to migraine prophylaxis that warrants further investigation.

Herbert Harris, MD, PhD Validus Pharmaceuticals, Parsippany, New Jersey Bruce Corser, MD

Herbert Harris, MD, PhD Validus Pharmaceuticals, Parsippany, New Jersey Bruce Corser, MD

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