Evid Based Mental Health: first published as 10.1136/ebmh.4.3.85 on 1 August 2001. Downloaded from

Review: galantamine improves most outcomes in Source of funding: US suspected Alzheimer’s disease National Institutes of Health. Olin J, Schneider L. Galantamine for Alzheimer’s disease. Cochrane Database Syst Rev. 2001;(2):CD001747 (latest version For correspondence: 01 Nov 2000). Dr J Olin, Adult and Geriatric Treatment and Prevention Interventions Branch, QUESTION: In elderly people with suspected Alzheimer’s disease (AD), does National Institute of galantamine improve clinical global ratings, cognition, behaviour, and activities of daily Mental Health, Room 7160, MSC 9635, living? 6001 Executive Boulevard, Bethesda, MD 20892-9635, USA. Fax +1 301 594 6784. Data sources and behaviour but also causes more adverse events than A modified version of Studies were identified by searching with the terms placebo. this abstract and galantamine and galanthamine in 14 databases and trial commentary appears in registers. The manufacturer of galantamine (Janssen) ACP Journal Club. was also contacted. Galantamine (Gala) v placebo for suspected Alzheimer’s disease* Study selection Scales assessed at Randomised, unconfounded, blinded, placebo control- 6 months Gala dose Gala Placebo RBI (95% CI) NNT (CI) led trials were selected if participants were elderly peo- CIBIC-plus 16 mg/day 68% 48% 42% (21 to 67) 6 (4 to 10) ple with suspected AD, if oral galantamine was studied, 24 mg/day 67%† 50%† 32% (20 to 47) 7 (5 to 10) and if outcomes were assessed using standardised 32 mg/day 51%† 37%† 35% (19 to 54) 8 (6 to 14) measurement tools (Clinician’s Interview Based Im- ADAS-cog 16 mg/day 36% 20% 82% (32 to 151) 6 (5 to 13) pression of Change plus Caregiver Input [CIBIC-plus], 24 mg/day 34%† 18%† 82% (3 to 151) 7 (5 to 13) Alzheimer’s Disease Assessment Scale Cognitive Sub- 32 mg/day 35% 15% 129% (52 to 248) 6 (4 to 10) scale [ADAS-cog], Alzheimer’s Disease Cooperative *CIBIC-plus=Clinician’s Interview Based Impression of Change plus Caregiver Input showing no change or Study Activities of Daily Living [ADCS-ADL] scale, improvement; ADAS-cog=Alzheimer’s Disease Assessment Scale-Cognitive Subscale >4 points improvement. Disability Assessment for Dementia [DAD] scale, and Other abbreviations defined in glossary; RBI, NNT, and CI calculated from data in article. †Weighted event rates (>1 study). Neuropsychiatric Inventory [NPI]).

Data extraction COMMENTARY Data were extracted on study quality, patient characteris- tics, drug dosage and duration, and outcomes. The meta-analysis by Olin and Schneider shows that galantamine has similar efficacy to tacrine, donepezil, and rivastigmine, the 3 acetylcholinesterase inhibitors (AChE-Is) cur- Main results rently marketed in the US for treatment of AD. Their comparable efficacy indicates that

touted unique properties, such as the allosteric modulation of nicotinic receptors with http://ebmh.bmj.com/ 6 trials met the inclusion criteria and had data suitable galantamine, confer no measurable added benefit. Clinicians, therefore, should select an for analysis. 6 trials evaluated CIBIC-plus. At 6 months, AChE-I based on adverse effect profile, patient tolerance, convenience of dosing, and galantamine in doses of 16, 24, and 32 mg/day showed cost. Although anecdotal reports show clinical improvement after switching non- improvements (table) but 8 mg/day did not. All 3 trials responders to a different AChE-I, no published data support this practice. evaluating ADAS-cog showed improvements of > 4 Functional dependency and behavioural disturbances, more than memory loss, con- points at 6 months with galantamine at doses 16, 24, tribute to caregiver stress and institutionalisation. Because of the uncertain clinical rel- and 32 mg/day (table) but not at 8 mg/day. 1 trial each evance of the ADAS-cog, recent clinical trials of AD treatments have incorporated evaluated ADCS-ADL and NPI scores: each showed instruments to assess their effect on activities of daily living and behavioural complica- tions.12 The slowing of decline in activities of daily living by galantamine and other

improvements with galantamine, 16 and 24 mg/day but on September 28, 2021 by guest. Protected copyright. not 8 mg/day. 1 trial evaluated DAD scores: galan- AChE-Is, as well as these agents’ potential to mitigate behavioural disturbances, repre- sent important reasons to recommend them for patients with AD. Although the major tamine, 32 mg/day but not 24 mg/day showed clinical trials have not included patients with advanced AD, long term, open label stud- improvements. Galantamine, at least in higher doses, ies suggest that AChE-Is may delay institutionalisation.3 increased the frequency of adverse events including Calvin H Hirsch, MD tremor, anorexia, vomiting, nausea, weight loss, head- University of California at Davis ache, abdominal pain, diarrhoea, dizziness, and agita- Sacramento, California, USA tion. More patients receiving galantamine stopped taking their medication because of adverse events. 1 Cummings JL. The Neuropsychiatric Inventory: assessing psychopathology in dementia patients. Neurology 1997;48:S10–6. Conclusion 2 Knopman D, Schneider L, Davis K, et al. Long-term tacrine (cognex) treatment: effects on nursing home placement and mortality, Tacrine Study Group. Neurology 1996;47:166–7. In patients with suspected Alzheimer’s disease, galan- 3 Gauthier S, Gelinas I, Gauthier L. Functional disability in Alzheimer’s disease. Int Psycho- tamine, in doses between 16 and 32 mg/day improves geriatr 1997;9:S163–5. global clinical status, cognition, activities of daily living,

Therapeutics www.ebmentalhealth.com EBMH Volume 4 August 2001 85