Awards Nomination 20+ Million Readerbase
Walsh Medical Media
Google Scholar citation report
Citations : 654

Advances in Pharmacoepidemiology and Drug Safety received 654 citations as per Google Scholar report

Flyer image
Advances in Pharmacoepidemiology and Drug Safety peer review process verified at publons
Flyer image
Indexed In
  • Open J Gate
  • Genamics JournalSeek
  • Academic Keys
  • JournalTOCs
  • RefSeek
  • Hamdard University
  • EBSCO A-Z
  • SWB online catalog
  • Publons
  • Geneva Foundation for Medical Education and Research
  • Euro Pub
  • Google Scholar
View More
Useful Links
Share This Page
Journal Flyer
Flyer image
Open Access Journals
View More

Review Article - (2022) Volume 11, Issue 2

A Systematic Review of Off-Label Use of Memantine for Neuropsychiatric Disorders Other than Dementia
Rochaknaveen S. Bains1*, Manvir Kaur2, Raman Marwaha1, Kanwal Naveen Bains3, Rajesh Mehta1 and Garima Garg1
 
1Department of Psychiatry, Metro Health Medical Center/Case Western Reserve University, Cleveland, Ohio, United States
2Department of Pharmaceutical and Environmental Health Sciences, College of Pharmacy and Health Sciences, Texas Southern University, 3100 Cleburne St, Houston, Texas, United States
3Department of Surgery, Brigham and Women's Hospital, Boston, Massachusetts, United States
 
*Correspondence: Rochaknaveen S. Bains, Department of Psychiatry, Metro Health Medical Center/Case Western Reserve University, Cleveland, Ohio, United States, Email:

Received: 28-Jan-2022, Manuscript No. PDS-22-15560; Editor assigned: 31-Jan-2022, Pre QC No. PDS-22-15560 (PQ); Reviewed: 15-Feb-2022, QC No. PDS-22-15560; Revised: 22-Feb-2022, Manuscript No. PDS-22-15560 (R); Published: 01-Mar-2022, DOI: 10.35248/2167-1052.22.11.263

Abstract

We provide a review on detailed literature review on the off-label use of memantine for neuropsychiatric disorders other than dementia focusing primarily on the use and efficacy of memantine. We performed a search on PubMed, Medline, EMBASE, Google Scholar, Ovid Medline, Psyc INFO, CENTRAL, consultant 360 and reviewed reference sections of selected papers. We also drew data from reflections and clinical experiences of expert mental health practitioners.

Keywords

Memantine; Neuropsychiatric disorders; Bipolar disorder; Treatment

Introduction

Memantine is N-methyl-d-aspartate receptor antagonist that is quite effective in the treatment of Alzheimer’s disease. It is used to slow the neurotoxicity which is thought to be involved in Alzheimer’s disease and other neurodegenerative diseases. Memantine blocks the NMDA-receptor subtype of glutamate receptors preventing the over-activation of glutamine receptors while allowing the normal activity. Its blocking effects antagonize an overactive glutaminergic system in the Central Nervous System (CNS) which is thought to be involved in the neurotoxicity seen in Alzheimer disease [1]. Memantine use has been proposed for many psychiatric conditions like schizophrenia, bipolar disorder, Major Depressive Disorder (MDD), adult Attention Deficit Hypersensitivity Disorder (ADHD), Obsessive Compulsive Disorder (OCD) and autism spectrum disorder, although there is limited data available, but more research need to be conducted.

Memantine is used in various neuropsychiatric conditions and growing evidence show that memantine might be effective in management and prevention of various psychiatric conditions.

We will discuss memantine use in following psychiatric disorders individually.

Mementine Use in Bipolar Disorder

Growing evidence have shown that memantine have been used at preventing recurrences of both phases of bipolar disorder and in reducing the manic-like symptomatology associated with several neurological and psychiatric conditions [2-4]. Memantine as a monotherapy also has been reported to show beneficial effects in a few individual patients with bipolar disorder, including after discontinuation of lithium treatment [5,6]. Finally, it has been recently reported that memantine improves cognitive dysfunctions and increases hippocampal volume in euthymic bipolar patients [7].

Memantine Use in Schizophrenia

Schizophrenia is chronic psychiatric illness which is managed by many psychotropics. Although first line treatment in schizophrenia is antipsychotics but there is some evidence for the use of memantine for psychosis. Memantine treats both the positive symptoms like hallucinations, delusions, psychosis as well as the negative symptoms like withdrawal, flat affect, lack of pleasure as these negative symptoms are the mainly responsible for withdrawal from the society and lack of motivation which further worsens the outcome of the patient [8]. One studied case found that adding memantine to risperidone therapy significantly decreased the degree of negative symptoms. There was also a case study in which a patient was seen improving after 6 weeks on memantine 10 mg/day and was rated 96 on the SANS scale (Scale for the Assessment of Negative Symptoms), 3 in SAPS (Scale for the Assessment of Positive Symptoms), 3 in MMSE (Mini-Mental State Examination), and 2 in CDSS (Calgary Depression for Schizophrenia Scale). Following a dose increase to 20 mg/day, the typical dose for Alzheimer’s disease, he was rated SANS 76, SAPS 1, MMSE 26, and CDSS 1. Two months later, SANS had dropped to 70 and MMSE was 27, with SAPS and CDSS remaining the same [9]. There were no additional adverse effects noted. This increased level of glutamate release in schizophrenia may be caused by NMDA receptor hypoactivity. For this reason, reversing this by NMDA receptor antagonist could represent a promising strategy to treating schizophrenia symptoms [10].

Memantine Use in Major Depressive Disorder (MDD)

MDD is chronic illness which causes significant impairment in both physical and social functioning. Despite the availability of a wide range of antidepressant drugs, a proportion of patients with major depression fail to respond to first-line antidepressant treatment, despite of trying adequate dosage and duration. Recent studies suggest that the glutamatergic system may play a role in the pathophysiology and treatment of depression. Memantine and other agents which reduce glutamatergic neurotransmission may represent a novel class of antidepressants. Thus, there is a clear need to develop novel and improved therapeutics for unipolar and bipolar depression. Some studies have shown glutamatergic system may play a role in the pathophysiology and treatment of depression and those agents which more directly reduce glutamatergic neurotransmission may represent a novel class of antidepressants like Memantine as it has ant glutamatergic output via openchannel block of the NMDA receptor-associated ion channel and neuroprotective properties which helps in the patients of depression [11].

Memantine Use in Attention Deficit Hyperactivity Disorder (ADHD)

Memantine is usually given along with stimulants for the patients with ADHD and some studies have shown memantine could amplify the effects of stimulants when given in a combined state [12]. As the receptors of the major excitatory neurotransmitter in the mammalian Central Nervous System (CNS), glutamate receptors (GluRs) are strongly linked to normal brain functioning and pathological processes. Extensive investigations have been made about the structure, function, and regulation of GluR family, describing evidences that support the disruption of these mechanisms in mental disorders, including ADHD [13]. Whether ADHD is a hyper or hypoglutamatergic condition is not clear. Treatment with a glutamatergic agonist was inconclusive but an eight-week, openlabel, dose finding trial with memantine in 16 children, 6-12 years of age, diagnosed with ADHD (combined type), using a dose of 10 mg/day in eight children and 20 mg/day in the other eight children, reported a dose dependent benefit in both the inattention and the hyperactivity/impulsivity domains. The response was minimal at 10 mg/day and significantly better on the 20 mg/day dosage [14-16].

Memantine Use in Obsessive Compulsive Disorder (OCD)

Obsessive-compulsive disorder can be quite challenging sometimes and can often be refractory in some cases. Primary treatment of OCD is SSRI and psychotherapy but recently memantine is also shown to treat refractory cases of OCD [17]. Memantine, which is an N-methyl-D-aspartate (NMDA) antagonist, is also found to be a good agent as an augmentation therapy for OCD. The frontostriatal circuits implicated in compulsivity and impulsivity are notable for their relatively rich glutamatergic receptor density. Moreover, glutamate modulates the metabolism and function of the frontostriatal circuits. Glutaminergic projections to and from the various frontal subregions (orbitofrontal cortex, infralimbic cortex, and prelimbic cortex) to the striatum play a key role in the regulation of various compulsive behaviors in humans including the feeling of loss of control (OCD), repetitive motor behaviors (stereotypy in autistic spectrum disorder) and a maladaptive habitual pattern (addiction). Neuroimaging studies have confirmed that glutamatergic projections between the various frontal subregions and the striatum play a key role in the regulation of compulsive behaviors in humans. Compulsivity has been associated with increased glutamatergic activity in the striatum and the anterior cingulate cortex in clinical magnetic resonance spectroscopy studies [18]. Glutamate a major excitatory neurotransmitter is thought to play a major role in pathophysiology of anxiety. As memantine inhibits NMDA glutamate receptors activity thereby decreases glutamate levels in brain. So, studies like these have shown that memantine is good choice as add on therapy along with SSRI and SNRI without any major side effects like weight gain and sexual problems and addiction like sedatives.

Memantine Use in Autism Spectrum Disorder

Autism Spectrum Disorder (ASD) refers to a pervasive developmental disorder with severe impairment of social interaction and communicational skills as well as manifestations of stereotyped behaviors, interests, and activities [19-21]. Aman et al. evaluating the safety and efficacy of memantine in autistic children, found that based on Social Responsiveness Scale, no significant difference between groups in the primary efficacy outcome of caregiver/parent ratings, was observed; however, it was improved at week 12 in both groups compared to preintervention [22]. Another study evaluating the efficacy of memantine on children and adults with idiopathic autistic disorder and incubatory growth disorder based on Clinical Global Impressions-Improvement Subscale (CG-I); found a significant improvement in 23% of cases and a moderate improvement in 47% of cases and the maximum improvement was observed in language and social behaviors as well [23]. Furthermore, although all studies mentioned here are in agreement with the current study regarding the effectiveness of memantine in social interactions, communication, and repetitive and stereotyped behaviors of the children, the scales of calculation and evaluation of the improvement differ [24].

Conclusion

Memantine has demonstrated some beneficial effects in some psychiatric disorders but the evidence is too limited at present and further research needs to be conducted. Thus, current use remains off-label until further validation of efficacy comes from blinded, randomized, placebo-controlled studies. Memantine has shown some significant beneficial effects as an add-on therapy especially in OCD and in the manic phase of BD but more rigorous clinical trials are needed to confirm this result.

REFERENCES

Citation: Bains RS, Kaur M, Marwaha R, Bains KN, Mehta R, Garg G (2022) A Systematic Review of Off-Label Use of Memantine for Neuropsychiatric Disorders Other than Dementia. Adv Pharmacoepidemiol Drug Saf. 11:263.

Copyright: © 2022 Bains RS et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.