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World J Psychiatr. Dec 22, 2014; 4(4): 80-90
Published online Dec 22, 2014. doi: 10.5498/wjp.v4.i4.80
Memantine: New prospective in bipolar disorder treatment
Giulia Serra, Francesca Demontis, Francesca Serra, Lavinia De Chiara, Andrea Spoto, Paolo Girardi, Giulio Vidotto, Gino Serra
Giulia Serra, Department of Psychiatry, Harvard Medical School, Boston, MA 02115, United States
Giulia Serra, International Consortium for Bipolar Disorder Research, McLean Hospital, Belmont, MA 02478, United States
Giulia Serra, Lavinia De Chiara, Paolo Girardi, NESMOS Department, Sant’Andrea Hospital, Sapienza University, 00185 Rome, Italy
Giulia Serra, Lavinia De Chiara, Paolo Girardi, Centro Lucio Bini Mood Disorder Center, 00193 Rome, Italy
Francesca Demontis, Gino Serra, Department of Biomedical Sciences, University of Sassari, 07100 Sassari, Italy
Francesca Serra, Andrea Spoto, Giulio Vidotto, Department of General Psychology, University of Padua, 35122 Padova, Italy
Author contributions: All authors contributed to this work.
Supported by In part Research Fellowship from the Sapienza Foundation, Rome (to Giulia S) and by Fondazione Banco di Sardegna, Italy (to Gino S)
Conflict-of-interest: Dr. Gino Serra has applied for a patent for the use of memantine to treat bipolar disorder. No other author or immediate family member has current financial relationships with commercial entities that might represent or appear to represent potential conflicts of interest with the material presented here.
Open-Access: This article is an open-access article which selected by an in-house editor and fully peer-reviewed by external reviewers. It distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Gino Serra, MD, Department of Biomedical Science, University of Sassari, Viale San Pietro 43/b, 07100 Sassari, Italy. dsfserra@uniss.it
Telephone: +39-32-90092278 Fax: +39-07-9228715
Received: September 28, 2014
Peer-review started: September 29, 2014
First decision: November 3, 2014
Revised: November 23, 2014
Accepted: December 3, 2014
Article in press: December 10, 2014
Published online: December 22, 2014
Processing time: 86 Days and 0.6 Hours
Abstract

We review preclinical and clinical evidences strongly suggesting that memantine, an old drug currently approved for Alzheimer’s dementia, is an effective treatment for acute mania and for the prevention of manic/hypomanic and depressive recurrences of manic-depressive illness. Lithium remains the first line for the treatment and prophylaxis of bipolar disorders, but currently available treatment alternatives for lithium resistant patients are of limited and/or questionable efficacy. Thus, research and development of more effective mood stabilizer drugs is a leading challenge for modern psychopharmacology. We have demonstrated that 21 d administration of imipramine causes a behavioural syndrome similar to a cycle of bipolar disorder, i.e., a mania followed by a depression, in rats. Indeed, such treatment causes a behavioural supersensitivity to dopamine D2 receptor agonists associated with an increase sexual activity and aggressivity (mania). The dopamine receptor sensitization is followed, after imipramine discontinuation, by an opposite phenomenon (dopamine receptor desensitization) and an increased immobility time (depression) in the forced swimming test of depression. Memantine blocks the development of the supersensitivity and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action (at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in manic-like symptoms occurring in psychiatric disorders other than bipolar. Limitations: A randomized controlled clinical trial is needed to confirm our naturalistic observations. Conclusion: We believe that this review presents enough pharmacological and clinical information to consider the administration of memantine in the treatment of bipolar disorders that no respond to standard mood stabilizers.

Keywords: Memantine; Bipolar disorder; Depression; Mood stabilizer; Manic symptoms

Core tip: Memantine, blocks the development of the supersensitivity of dopamine receptors caused by antidepressants and the ensuing desensitization associated with the depressive like behavior. On the basis of these observations we have suggested the use of memantine in the treatment of mania and in the prophylaxis of bipolar disorders. To test this hypothesis we performed several naturalistic studies that showed an acute antimanic effect and a long-lasting and progressive mood-stabilizing action (at least 3 years), without clinically relevant side effects. To confirm the observations of our naturalistic trials we are now performing a randomized controlled clinical trial. Finally we described the studies reporting the efficacy of memantine in manic-like symptoms occurring in psychiatric disorders other than bipolar.