title: What happens when people discontinue taking medications? Lessons from COMBINE.
abstract: OBJECTIVE
  We use intensive longitudinal data methods to illuminate processes affecting patients' drinking in relation to the discontinuation of medications within an alcohol treatment study. Although previous work has focused on broad measures of medication adherence, we focus on dynamic changes in drinking both before and after patients discontinue.
  
  
  METHODS
  We conducted secondary data analyses using the COMBINE (Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence) study, focused on participants who discontinued medications prior to the planned end of treatment. Using an interrupted time-series analysis, we analysed drinking in the weeks before and after discontinuation and also studied outcomes at the end of the COMBINE follow-up.
  
  
  METHODS
  Unites States of America.
  
  
  METHODS
  We describe the subsample of COMBINE participants who discontinued medications (n = 450), and compare them with those who were medication-adherent (n = 559) and with those who discontinued but had substantial missing data (n = 217).
  
  
  METHODS
  The primary outcomes were percentage of days abstinent (PDA) and percentage of heavy drinking days (PHDD). Medication adherence data were used to approximate the date of discontinuation.
  
  
  RESULTS
  For many patients, an increase in drinking began weeks before discontinuation (PDA: F(1,4803) = 19.07, P < 0.001; PHDD: F(1,4804) = 8.58, P = 0.003) then escalated at discontinuation (PDA: F(1,446) = 5.05, P = 0.025; PHDD: F(1,446) = 4.52, P = 0.034). Among other effects, the amount of change was moderated by the reason for discontinuation (e.g. adverse event; PDA: F(2,4803) = 3.85, P = 0.021; PHDD: F(2,4804) = 5.36, P = 0.005) and also whether it occurred in the first or second half of treatment (PDA: F(1,4803) = 5.23, P = 0.022; PHDD: F(1,4804) = 8.79, P = 0.003).
  
  
  CONCLUSIONS
  A patient's decision to stop taking medications during alcohol treatment appears to take place during a weeks-long process of disengagement from treatment. Patients who discontinue medications early in treatment or without medical consultation appear to drink more frequently and more heavily.
authors.affiliation: Decision Sciences Institute, Pacific Institute for Research and Evaluation, Pawtucket, RI, USA.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Stout
authors.forename: Jordan M
authors.initials: JM
authors.lastname: Braciszewski
authors.forename: Meenakshi Sabina
authors.initials: MS
authors.lastname: Subbaraman
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.forename: Stephanie S
authors.initials: SS
authors.lastname: O'Malley
authors.forename: Daniel
authors.initials: D
authors.lastname: Falk
mesh_terms: D000077443:Acamprosate; D000328:Adult; D000427:Alcohol Deterrents / Q000008:administration & dosage*; D000428:Alcohol Drinking / Q000453:epidemiology*; D000437:Alcoholism / Q000453:epidemiology* / Q000534:rehabilitation*; D001521:Behavior Therapy; D003131:Combined Modality Therapy; D003430:Cross-Sectional Studies; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000008:administration & dosage*; D010352:Patient Dropouts / Q000706:statistics & numerical data; D012008:Recurrence; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016903:Drug Monitoring
chemical_list: D000427:Alcohol Deterrents; D013654:Taurine; D009271:Naltrexone; D000077443:Acamprosate
keywords: Alcohol treatment outcome; clinical intervention; imputation; medication compliance; medication study; missing data; research methods; statistics
references.citation: Addict Behav. 2013 May;38(5):2119-27
references.pmid: 23435273
references.citation: Alcohol Clin Exp Res. 2003 Jul;27(7):1107-22
references.pmid: 12878917
references.citation: Alcohol Clin Exp Res. 2013 Dec;37(12):2152-60
references.pmid: 23889334
references.citation: Addiction. 2004 Nov;99(11):1382-92
references.pmid: 15500591
references.citation: J Addict Dis. 2000;19(1):71-83
references.pmid: 10772604
references.citation: Alcohol Clin Exp Res. 1996 Feb;20(1):16-20
references.pmid: 8651447
references.citation: Epidemiol Rev. 2002;24(1):26-38
references.pmid: 12119853
references.citation: Alcohol Clin Exp Res. 2008 Sep;32(9):1661-9
references.pmid: 18616687
references.citation: J Subst Abuse Treat. 2010 Oct;39(3):218-26
references.pmid: 20627222
references.citation: JAMA. 2006 May 3;295(17):2003-17
references.pmid: 16670409
references.citation: Psychopharmacology (Berl). 1996 Nov;128(2):206-15
references.pmid: 8956382
references.citation: Addiction. 2002 Aug;97(8):1041-53
references.pmid: 12144607
references.citation: Alcohol Clin Exp Res. 2003 Jul;27(7):1123-31
references.pmid: 12878918
references.citation: Neuropsychopharmacology. 2012 Jan;37(2):402-11
references.pmid: 21900883
references.citation: Alcohol Clin Exp Res. 2008 Jul;32(7):1299-308
references.pmid: 18540910
references.citation: Subst Abuse Treat Prev Policy. 2009 Feb 18;4:2
references.pmid: 19226454
references.citation: J Stud Alcohol Drugs. 2011 Nov;72(6):1012-8
references.pmid: 22051215
references.citation: Alcohol Alcohol. 2013 Nov-Dec;48(6):712-9
references.pmid: 23955872