A review comparing the safety and tolerability of memantine with the acetylcholinesterase inhibitors

Abstract

Objective: Alzheimer's disease (AD) is prevalent among elderly people, who often have comorbid conditions, and may be prescribed multiple medications. Drug safety and tolerability is paramount in maximising efficacy and optimising patient and carer quality of life, as patients are vulnerable to adverse events (AEs) and/or compliance difficulties. The two principal categories of drug used in the treatment of AD are the acetylcholinesterase inhibitors (AChEIs) and the NMDA-receptor antagonist, memantine. This paper reviews the most recent safety data for memantine in comparison with the AChEIs. Design: Review of most recent safety/tolerability data for memantine and AChEIs, derived from metaanalyses, pooled analyses, European SPCs and EMEA publications. Results: Memantine was found to have a favourable tolerability profile when used as monotherapy or in combination with other agents. AChEIs were found to be fairly well tolerated. All treatments commonly or very commonly produce dizziness and/or headache. AChEIs are associated with many more types of AEs than memantine, particularly in the gastrointestinal category. Agitation is a less common AE when comparing memantine treatment to placebo, but just as common when comparing AChEI treatment to placebo. Withdrawals in memantine-treated groups are comparable to placebo, and more common in AChEI-treated groups compared to placebo. Overall, drug-drug interactions, contraindications and warnings were fewer for memantine than AChEIs. Conclusions: In both the clinical and naturalistic setting, memantine displays a safety and tolerability profile that is favourable and distinct from that of AChEIs. Safety and tolerability profiles should be given careful consideration when selecting treatment for AD patients.

Memantine: New prospective in bipolar disorder treatment

“…Its pharmacological profile is well known and has been extensively described [8][9][10][11][12][13][14][15][16] .…”

Memantine: A New Mood Stabilizer for Treatment-Resistant Bipolar Disorders

“…A recent review (Jones, 2010) of the most recent safety/tolerability data for memantine (derived from meta-analyses, pooled analyses, European SPCs, and EMEA publications) confirmed that memantine has a favorable tolerability profile when used in monotherapy or in combination with other agents. Moreover, results of studies of a total treatment period of up to two years show that memantine is safe and tolerated, with an adverse event profile almost indistinguable from that of placebo.…”

“…Although its actual efficacy on the AD patient's quality of life has proven to be moderate (Emre et al, 2008;Kaduszkiewicz & Hoffmann, 2008), several pre-marketing and postmarketing studies have demonstrated the excellent safety and tolerability profile of the drug (Farlow & Phillips, 2008;Jones, 2010).…”

The Urgent Need of New Mood-Stabilizers: The Promising Results of Memantine

“…Anticonvulsants have been shown to be of limited efficacy both as a monotherapy and in combination with lithium [1,[3][4][5][6][7] and the mood stabilizing effect of atypical antipsychotics has been severely questioned [8,9]. Thus, the research and development of more effective moodstabilizers for the prophylaxis of bipolar patients resistant to lithium, is an urgent challenge of modern psychopharmacology.Indeed, even with currently available treatments, patients with BD remain unwell in 50% of their time, with about 75% of this time spent in depression [6].We have recently suggested that blockade of NMDA receptors by memantine, a drug with excellent safety and tolerability profile [10], could result in an antimanic and mood-stabilizing effect in treatmentresistant BD patients [11,12].Our group found suggestive evidence of the mood-stabilizing effect of memantine when added to stable, ongoing but inadequately effective standard treatments in 40 BD patients in two 6 and 12-month clinical trials [13,14].Memantine as a monotherapy also has been reported to show beneficial effects in few individual BD patients, including after discontinuation of lithium treatment [15][16][17][18].Finally, we reported the results of a three-year naturalistic study of adding memantine to 30 treatment-resistant bipolar patients [19]. In this trial, memantine achieves clinically meaningful long-term benefits, for both depressive and mania-like (mania, hypomania) morbidity, in outpatients who had proved resistant to standard treatments for more than 3 years, until memantine (20-30 mg/day) was added to otherwise stable regimens for another 3 years, during which patients improved progressively.…”

“…We have recently suggested that blockade of NMDA receptors by memantine, a drug with excellent safety and tolerability profile [10], could result in an antimanic and mood-stabilizing effect in treatmentresistant BD patients [11,12].…”