Mazindol in narcolepsy and idiopathic and symptomatic hypersomnia refractory to stimulants: A long-term chart review

ObjectiveMazindol is a tricyclic, anorectic, non-amphetamine stimulant used in narcolepsy and obesity since 1970. This study aimed to evaluate the long-term benefit/risk ratio in drug-resistant hypersomniacs and cataplexy sufferers.MethodsBy retrospective analysis of the patients’ files in the hospitals of Paris-Salpêtrière (n = 91), Montpellier (n = 40) and Lyon (n = 8), the benefit (Epworth Sleepiness Score (ESS), cataplexy frequency, authorization renewal) and tolerance (side-effects, vital signs, electrocardiogram and cardiac echography) of mazindol were assessed.ResultsThe 139 patients (45% men) aged 36 ± 15 years (range: 9–74) suffered narcolepsy (n = 94, 66% with cataplexy), idiopathic (n = 37) and symptomatic hypersomnia (n = 8) refractory to modafinil, methylphenidate and sodium oxybate. Under mazindol (3.4 ± 1.3 mg/day, 1–6 mg) for an average of 30 months, the ESS decreased from 17.7 ± 3.5 to 12.8 ± 5.1, with an average fall of −4.6 ± 4.7 (p < 0.0001) and the frequency of cataplexy fell from 4.6 ± 3.1 to 2 ± 2.8 episodes per week. The cataplexy was eliminated in 14.5% of patients, improved in 27.5%, and unchanged in 29% (missing data in 29%). The treatment was maintained long term in 83 (60%) patients, and stopped because of a lack of efficacy (22%) and/or secondary effects (9%). There was no pulmonary hypertension in the 45 patients who underwent a cardiac echography. The most common adverse effects were dry mouth (13%), palpitations (10%, including one with ventricular hyperexcitability), anorexia (6%), nervousness (6%) and headaches (6%).ConclusionMazindol has a long-term, favorable benefit/risk ratio in 60% of drug-resistant hypersomniacs, including a clear benefit on cataplexy.