A pilot open label prospective study of memantine monotherapy in adults with ADHD

Abstract

Objectives. Available pharmacotherapies treat some adults with ADHD inadequately. A small literature suggests that glutamate modulation could have effects on ADHD. Methods. Memantine, an N‐methyl‐d‐aspartate (NMDA) receptor antagonist, was titrated to a maximum dose of 10 mg BID in 34 adult subjects aged 18–55 who met DSM-IV criteria for ADHD or ADHD NOS on structured interview. Twenty-eight subjects completed 12 weeks exposure. The Adult ADHD Investigator Symptom Report (AISRS), Clinical Global Impression (CGI), a neuropsychological battery sensitive to domains of executive function, and the CANTAB cognitive battery were administered. Paired t-tests compared treated and baseline scores. Results. At week 12, AISRS data showed reduction in total symptoms (–17.5, P < 0.001), inattentive symptoms (−10.6, P < 0.001), and hyperactive symptoms (–6.9, P < 0.01). A total of 44% of subjects had CGI ratings of much or very much improved. Cognitive performance improved in measures of attention, working memory, and other selected executive domains by weeks 6 and 12 (each P < 0.05); simple reaction time declined by week 12 (P < 0.05). There were no severe adverse events, but mild adverse events were common and six subjects discontinued due to adverse effects. Conclusions. Memantine was largely well-tolerated and associated with improvement in ADHD symptoms and neuropsychological performance. Randomized studies are indicated to confirm whether memantine is a novel therapy for ADHD across the lifespan.

Key words::

• ADHD
• adults
• memantine
• psychopharmacology
• cognition

Acknowledgements

Katherine B. O’Connor, BA, Massachusetts General Hospital, Pediatric Psychopharmacology Research Unit assisted by editing and formatting the text.

Statement of Interest

Dr Surman has received research support from Abbott, Alza, Cephalon, Eli Lilly, ElMinda the Hilda and Preston Davis Foundation, McNeil, Merck, New River, Nordic Naturals National Institutes of Health, Organon, Pfizer, Shire, and Takeda; has been a speaker for Janssen-Ortho, McNeil, Novartis, Shire, and MGH Academy/Reed Medical Education (which received funding from multiple pharmaceutical companies); and has been a consultant/advisor for McNeil, Shire, Somaxon and Takeda.

In the past 2 years, Dr Hammerness has received research funds or participated in CME activities/professional talks supported by the following pharmaceutical companies: Abbott, Eli Lilly, Forest, McNeil, Shire. Dr Hammerness has also received research funds from Elminda Ltd and has participated in speaker training and served on the advisory board for Shire. In the past 2 years, Dr Hammerness has participated, as an investigator, in research studies funded by the following pharmaceutical companies: Abbott, Bristol Myers Squibb, Cephalon, Eli Lilly, Glaxo-SmithKline, Johnson & Johnson, McNeil, Merck, New River, Organon, Pfizer, Shire, Takeda. Dr Hammerness has also received honoraria from Reed Medical Education (a logistics collaborator for the MGH Psychiatry Academy). Commercial entities supporting the MGH Psychiatry Academy are listed on the Academy's website, www.mghcme.org.

In the past, Robert Doyle Disclosure: Speaker's honoraria – Shire, Novartis, McNeil, Neuroeducational Institute, MGH Academy, and APA; Advisory Boards – Shire, Novartis.

Dr. Joseph Biederman is currently receiving research support from the following sources: Elminda, Janssen, McNeil, and Shire.

In 2011, Dr. Joseph Biederman gave a single unpaid talk for Juste Pharmaceutical Spain, received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course, and received an honorarium for presenting at an international scientific conference on ADHD. He also received an honorarium from Cambridge University Press for a chapter publication. Dr. Biederman received depart - mental royalties from a copyrighted rating scale used for ADHD diagnoses, paid by Eli Lilly, Shire and AstraZeneca; these royalties are paid to the Department of Psychiatry at MGH.

In 2010, Dr. Joseph Biederman received a speaker's fee from a single talk given at Fundaci n Dr.Manuel Camelo A.C. in Monterrey Mexico. Dr. Biederman provided single consultations for Shionogi Pharma Inc. and Cipher Pharmaceuticals Inc.; the honoraria for these consultations were paid to the Department of Psychiatry at the MGH. Dr. Biederman received honoraria from the MGH Psychiatry Academy for a tuition-funded CME course.

In previous years, Dr. Joseph Biederman received research support, consultation fees, or speaker's fees for/from the following additional sources: Abbott, Alza, AstraZeneca, Boston University, Bristol Myers Squibb, Celltech, Cephalon, Eli Lilly and Co., Esai, Fundacion Areces (Spain), Forest, Glaxo, Gliatech, Hastings Center, Janssen, McNeil, Medice Pharmaceuticals (Germany), Merck, MMC Pediatric, NARSAD, NIDA, New River, NICHD, NIMH, Novartis, Noven, Neurosearch, Organon, Otsuka, Pfizer, Pharmacia, Phase V Communications, Physicians Academy, The Prechter Foundation, Quantia Communications, Reed Exhibitions, Shire, the Spanish Child Psychiatry Association, The Stanley Foundation, UCB Pharma Inc., Veritas, and Wyeth.

Mr Carter Petty, Ms Nicole Chu, Ms Siena Nipolean, and Ms Dayna Yorks have nothing to disclose.

This work has been funded in part by the Pediatric Psychopharmacology Council.