Lithium debunked for ALS

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder of motor neurons in the spinal cord, brainstem, and motor cortex, with ea median survival of 3-5 years.  At present, there is no cure for ALS, and the currently available treatments are of limited  efficacy.  Recently, a neuroprotective benefit of lithium carbonate was reported in animal models of ALS and in humans.  Specifically, it was reported that lithium increases survival and retards disease progression, thereby providing a potential ray of hope for the ALS patients.


Since the original studies, a number of large studies have been published refuting any benefits of lithium in ALS.  In this issue of JNNP, a group led by Prof van den Berg, apply the final nail to the notion that lithium may be efficacious in ALS.  Specifically, the authors assessed the efficacy of lithium carbonate in a double blind placebo controlled trial in a large cohort of ALS patients.  the primary outcome measures included survival, defined as death, tracheostomal ventilation or non-invasive ventilation for more than 16 h/day.  In addition, secondary outcome measures consisted of the revised ALS Functional Rating Scale and forced vital capacity.   The study failed to demonstrate any benefits of lithium on primary of secondary outcome measures in ALS.   Given the absence of any effects on survival of functional decline in ALS, this study has helped to resign lithium therapy in ALS to history.


Verstraete E, Veldink JH, Huisman MHB, et al. Lithium lacks effect on survival in amyotrophic lateral sclerosis: a phase IIb randomised sequential trial. Journal of Neurology, Neurosurgery & Psychiatry 2012;83:557-64.


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