title: Treatment of opiate-related sedation: utility of the cholinesterase inhibitors.
abstract: Daytime sedation is a common and potentially dose-limiting side effect of the opiate analgesics. The psychostimulants, such as methylphenidate, are frequently prescribed to treat this problem, but their use may be limited by side effects, such as weight loss, anxiety, or insomnia, or tolerance to their antisedative effects. Medications which enhance intracerebral cholinergic activity may offer an alternative treatment approach, since functional deficits of acetylcholine may, in part, account for the sedative and mind-dulling effects of opiates. Preliminary studies with donepezil, a centrally acting acetylcholinesterase (AChE) inhibitor approved for use in Alzheimer's disease, have suggested at least short-term benefit in treating opiate-related sedation. In a retrospective study, we reviewed the results of donepezil treatment in 40 patients, 37 of whom had cancer, which in most cases was in an advanced stage. All patients were receiving chronic opiate treatment, and the majority were on a stable opiate dose in the 2 weeks preceding the initiation of donepezil. The average opiate dose was 844 mg in oral morphine equivalents. Seventy-three percent of the patients experienced moderate or greater improvement on the Clinical Global Improvement Scale. Evaluations on the Epworth Sleepiness Scale (ESS; 0-24), visual analog sleepiness scale (VAS; 0-100), and average pain levels (0-100), before and after donepezil treatment, were obtained on 19 patients. Prior to donepezil, ESS, VAS, and pain scores were 18.5, 76.3, and 47.4. After an average of 21 days of donepezil treatment, scores were 9.5 (P < 0.001), 39.5 (P < 0.001), and 36.6 (P = 0.07), respectively. The mean total duration of treatment for patients was 54.4 days, with most patients stopping donepezil due to progression to a terminal state. Patients were generally started on 5 mg/ day, but 17 patients required higher doses to achieve or maintain efficacy, the average treatment dose being 9.13 mg/day. We concluded from this study that centrally acting AChE inhibitors are promising agents in the treatment of sedation,and perhaps of other neuropsychological side effects associated with the use of opiate analgesics.
authors.affiliation: Department of Supportive Care, Pain and Palliative Medicine, City of Hope National Medical Center, Duarte, California 91010, USA. nslatkin@coh.org
authors.forename: Neal E
authors.initials: NE
authors.lastname: Slatkin
authors.forename: Michelle
authors.initials: M
authors.lastname: Rhiner
mesh_terms: D000284:Administration, Oral; D000701:Analgesics, Opioid / Q000009:adverse effects* / Q000627:therapeutic use; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D000077265:Donepezil; D005221:Fatigue / Q000139:chemically induced* / Q000188:drug therapy; D005260:Female; D006801:Humans; D007189:Indans / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000188:drug therapy*; D010166:Palliative Care; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D011788:Quality of Life; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000701:Analgesics, Opioid; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil