Maniform episode related to memantine therapy: unraveling of an unknown adverse side effect?

Introduction: Memantine, a type of N-methyl-D-aspartate (NMDA) antagonist, is a drug approved by Food and Drug Administration to the treatment of moderate-to-severe Alzheimer disease (AD). Glutamate has been hypothesized to be released in excess in AD, perhaps in part triggered by neurotoxic amyloid plaques and neurofibrillary tangles. Memantine reduces abnormal activation of glutamate neurotransmission and thus interferes with the pathophysiology of AD, improves cognitive function, and slows the rate of decline over time.
Methods: Case report description based on the consultation of the patient’s clinical records suggesting a new adverse side-effect associated with memantine taking. We performed a non-systematic review of the literature on the possible mechanisms that may be behind the development of this secondary effect and investigate the possible existence of other similar cases described in the literature.
Case Report: We present a case report of a 78-year-old female who developed maniform symptomatology after initiating memantine therapy. The symptomatology disappeared completely after the suspension of the drug, remaining psychopathologically stable at 12-months follow-up. This clinical report unravels a new possible adverse side effect of memantine, which is the triggering of maniform episodes.
Discussion: To the author´s knowledge there is only one more case report of a manic episode memantine-related published in the scientific literature, something that was not previously reported by the drug manufacturer. Memantine appears to have some antidepressant properties and a few mechanisms which might contribute to the antidepressant-like effect of memantine have been proposed. Thus, as with antidepressants, a hyperbolic response to the drug may have the adverse effect of triggering maniform states.
Conclusions: Memantine should be adequately prescribed and symptoms suggestive of mood elevation must be explored in patients taking this drug. We also highlight that memantine should be used with caution in combination with antidepressants, especially in patients with a history of maniform / manic episodes. Lastly, we underline the importance of the rational and correct use of psychopharmacological therapy, namely the discouragement of the off-label use of drugs, which exposes the patients to unnecessary risks.