Khachen Kongpakwattana1, Ratree Sawangjit2, Itthipol Tawankanjanachot3, J Simon Bell4, Sarah N Hilmer5, Nathorn Chaiyakunapruk1,6,7,8. 1. School of Pharmacy, Monash University Malaysia, Selangor, Malaysia. 2. Clinical Trials and Evidence Base Syntheses Research Unit (CTEBs RU), Department of Clinical Pharmacy, Faculty of Pharmacy, Mahasarakham University, Mahasarakham, Thailand. 3. Department of Psychiatry, King Chulalongkorn Memorial Hospital, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. 4. Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Australia. 5. Kolling Institute of Medical Research, Royal North Shore Hospital and University of Sydney, St Leonards, NSW, Australia. 6. Center of Pharmaceutical Outcomes Research (CPOR), Department of Pharmacy Practice, Faculty of Pharmaceutical Sciences, Naresuan University, Phitsanulok, Thailand. 7. Asian Centre for Evidence Synthesis in Population, Implementation and Clinical Outcomes (PICO), Health and Well-being Cluster, Global Asia in the 21st Century (GA21) Platform, Monash University Malaysia, Bandar Sunway, Selangor, Malaysia. 8. School of Pharmacy, University of Wisconsin, Madison, USA.
Abstract
AIMS: To determine the most efficacious and acceptable treatments of agitation in dementia. METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks. RESULTS: Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses. CONCLUSIONS: Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.
AIMS: To determine the most efficacious and acceptable treatments of agitation in dementia. METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL and clinicaltrials.gov were searched up to 7 February 2017. Two independent reviewers selected randomized controlled trials (RCTs) of treatments to alleviate agitation in people with all-types dementia. Data were extracted using standardized forms and study quality was assessed using the revised Cochrane Risk of Bias Tool for RCTs. Data were pooled using meta-analysis. The primary outcome, efficacy, was 8-week response rates defined as a 50% reduction in baseline agitation score. The secondary outcome was treatment acceptability defined as treatment continuation for 8 weeks. RESULTS: Thirty-six RCTs comprising 5585 participants (30.9% male; mean ± standard deviation age, 81.8 ± 4.9 years) were included. Dextromethorphan/quinidine [odds ratio (OR) 3.04; 95% confidence interval (CI), 1.63-5.66], risperidone (OR 1.96; 95% CI, 1.49-2.59) and selective serotonin reuptake inhibitors as a class (OR 1.61; 95% CI, 1.02-2.53) were found to be significantly more efficacious than placebo. Haloperidol appeared less efficacious than nearly all comparators. Most treatments had noninferior treatment continuation compared to placebo, except oxcarbazepine, which was inferior. Findings were supported by subgroup and sensitivity analyses. CONCLUSIONS:Risperidone, serotonin reuptake inhibitors as a class and dextromethorphan/quinidine demonstrated evidence of efficacy for agitation in dementia, although findings for dextromethorphan/quinidine were based on a single RCT. Our findings do not support prescribing haloperidol due to lack of efficacy, or oxcarbazepine due to lack of acceptability. The decision to prescribe should be based on comprehensive consideration of the benefits and risks, including those not evaluated in this meta-analysis.
Authors: A P Porsteinsson; P N Tariot; R Erb; C Cox; E Smith; L Jakimovich; J Noviasky; N Kowalski; C J Holt; C Irvine Journal: Am J Geriatr Psychiatry Date: 2001 Impact factor: 4.105
Authors: Victor I Reus; Laura J Fochtmann; A Evan Eyler; Donald M Hilty; Marcela Horvitz-Lennon; Michael D Jibson; Oscar L Lopez; Jane Mahoney; Jagoda Pasic; Zaldy S Tan; Cheryl D Wills; Richard Rhoads; Joel Yager Journal: Am J Psychiatry Date: 2016-05-01 Impact factor: 18.112
Authors: Pierre N Tariot; Lon Schneider; Ira R Katz; Jacobo E Mintzer; Jamie Street; Margaret Copenhaver; Celeste Williams-Hughes Journal: Am J Geriatr Psychiatry Date: 2006-08-11 Impact factor: 4.105
Authors: J S Street; W S Clark; K S Gannon; J L Cummings; F P Bymaster; R N Tamura; S J Mitan; D L Kadam; T M Sanger; P D Feldman; G D Tollefson; A Breier Journal: Arch Gen Psychiatry Date: 2000-10
Authors: Henry Brodaty; David Ames; John Snowdon; Michael Woodward; Jeff Kirwan; Roger Clarnette; Emma Lee; Ben Lyons; Fred Grossman Journal: J Clin Psychiatry Date: 2003-02 Impact factor: 4.384
Authors: Dallas P Seitz; Sudeep S Gill; Nathan Herrmann; Sarah Brisbin; Mark J Rapoport; Jenna Rines; Kimberley Wilson; Ken Le Clair; David K Conn Journal: Int Psychogeriatr Date: 2012-10-19 Impact factor: 3.878
Authors: Stephen Ph Alexander; Eamonn Kelly; Neil V Marrion; John A Peters; Elena Faccenda; Simon D Harding; Adam J Pawson; Joanna L Sharman; Christopher Southan; O Peter Buneman; John A Cidlowski; Arthur Christopoulos; Anthony P Davenport; Doriano Fabbro; Michael Spedding; Jörg Striessnig; Jamie A Davies Journal: Br J Pharmacol Date: 2017-12 Impact factor: 8.739
Authors: Sujita W Narayan; Sallie-Anne Pearson; Melisa Litchfield; David G Le Couteur; Nicholas Buckley; Andrew J McLachlan; Helga Zoega Journal: Br J Clin Pharmacol Date: 2019-07-07 Impact factor: 4.335
Authors: K S Frederiksen; C Cooper; G B Frisoni; L Frölich; J Georges; M G Kramberger; C Nilsson; P Passmore; L Mantoan Ritter; D Religa; R Schmidt; E Stefanova; A Verdelho; M Vandenbulcke; B Winblad; G Waldemar Journal: Eur J Neurol Date: 2020-07-26 Impact factor: 6.089
Authors: Claudia Carrarini; Mirella Russo; Fedele Dono; Filomena Barbone; Marianna G Rispoli; Laura Ferri; Martina Di Pietro; Anna Digiovanni; Paola Ajdinaj; Rino Speranza; Alberto Granzotto; Valerio Frazzini; Astrid Thomas; Andrea Pilotto; Alessandro Padovani; Marco Onofrj; Stefano L Sensi; Laura Bonanni Journal: Front Neurol Date: 2021-04-16 Impact factor: 4.003
Authors: Sube Banerjee; Juliet High; Susan Stirling; Lee Shepstone; Ann Marie Swart; Tanya Telling; Catherine Henderson; Clive Ballard; Peter Bentham; Alistair Burns; Nicolas Farina; Chris Fox; Paul Francis; Robert Howard; Martin Knapp; Iracema Leroi; Gill Livingston; Ramin Nilforooshan; Shirley Nurock; John O'Brien; Annabel Price; Alan J Thomas; Naji Tabet Journal: Lancet Date: 2021-10-23 Impact factor: 79.321
Authors: Giovanni Ostuzzi; Chiara Gastaldon; Davide Papola; Andrea Fagiolini; Serdar Dursun; David Taylor; Christoph U Correll; Corrado Barbui Journal: Ther Adv Psychopharmacol Date: 2020-07-20