The Role of Memantine in the Treatment of Psychiatric Disorders Other Than the Dementias

Abstract

Memantine, a non-competitive NMDA receptor antagonist approved for Alzheimer's disease with a good safety profile, is increasingly being studied in a variety of non-dementia psychiatric disorders. We aimed to critically review relevant literature on the use of the drug in such disorders. We performed a PubMed search of the effects of memantine in animal models of psychiatric disorders and its effects in human studies of specific psychiatric disorders. The bulk of the data relates to the effects of memantine in major depressive disorder and schizophrenia, although more recent studies have provided data on the use of the drug in bipolar disorder as an add-on. Despite interesting preclinical data, results in major depression are not encouraging. Animal studies investigating the possible usefulness of memantine in schizophrenia are controversial; however, interesting findings were obtained in open studies of schizophrenia, but negative placebo-controlled, double-blind studies cast doubt on their validity. The effects of memantine in anxiety disorders have been poorly investigated, but data indicate that the use of the drug in obsessive-compulsive disorder and post-traumatic stress disorder holds promise, while findings relating to generalized anxiety disorder are rather disappointing. Results in eating disorders, catatonia, impulse control disorders (pathological gambling), substance and alcohol abuse/dependence, and attention-deficit hyperactivity disorder are inconclusive. In most psychiatric non-Alzheimer's disease conditions, the clinical data fail to support the usefulness of memantine as monotherapy or add-on treatment However, recent preclinical and clinical findings suggest that add-on memantine may show antimanic and mood-stabilizing effects in treatment-resistant bipolar disorder.

Failure of memantine to “reverse” quinpirole-induced hypomotility

“…On the contrary, memantine fails to stimulate the locomotor response to quinpirole, suggesting that, at variance with antidepressant treatments, it does not sensitize D2 receptors. This observation provides further support to our hypothesis [30,31,42] that the effect observed in the FST is a "false positive" and is in keeping with the failure of clinical studies to demonstrate an acute antidepressant action of memantine in depressed subjects [2129] .…”

Acetylcholinesterase inhibitors and memantine in bipolar disorder: A systematic review and best evidence synthesis of the efficacy and safety for multiple disease dimensions

“…However, our results indicate that conflicting evidence is available about memantine for manic symptoms, while further studies are needed for depression, psychosis and cognition. These results from randomized controlled trials are in contrast with previous reviews (Sani et al, 2012;Serra et al, 2014c) and several case reports about memantine in BD, which each suggested efficacy of memantine in BD (De Chiara et al; Serra et al, 2013Serra et al, , 2014aSerra et al, , 2014b. However, the uncontrolled and isolated nature of these reports is at best hypothesisgenerating.…”

“…However, the uncontrolled and isolated nature of these reports is at best hypothesisgenerating. Furthermore, since all studies focused on short-or medium-term treatment, we were unable to evaluate the effect of AchI or memantine on relapse prevention, for which only case reports (Sani et al, 2012;Serra et al, 2014c) and one mirror image study (Serra et al, 2015) exist, underscoring the need for additional controlled studies. Additionally, we could not include a 3-year naturalistic trial suggesting memantine's efficacy for manic symptoms, since it included patients underwent ECT, which we chose to exclude from the evaluated studies (Serra et al, 2015).…”

Memantine in the management of affective recurrences of bipolar disorders after the discontinuation of long-term lithium treatment: three case histories

“…We have recently provided clinical observations strongly suggesting that memantine, a noncompetitive N-methyl D-aspartate receptor antagonist, has a clinically relevant antimanic and a sustained mood-stabilizing effect in treatmentresistant bipolar disorder with excellent safety and tolerability [Koukopoulos et al 2010[Koukopoulos et al , 2012Sani et al 2012;Serra et al 2013]. …”