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. 2018 Apr 24;2018(4):CD008581. doi: 10.1002/14651858.CD008581.pub2

Kranzler 2006 arm B.

Methods Randomized, double‐blind, placebo‐controlled trial
Participants 139 depressed people with alcohol dependence (86 men and 53 women; age (mean ± SD): placebo = 42.9 ± 9.2 years; sertraline = 41.8 ± 9.4 years)
Inclusion criteria:
  • aged 21‐65 years

  • current DSM‐IV diagnoses of alcohol dependence and depression (modified: to meet DSM‐IV criteria for depression, except that symptoms could have occurred during a period of heavy alcohol use)

  • HRSD score ≤ 16 with cessation of heavy drinking


Exclusion criteria:
  • pregnant, nursing, or women of childbearing potential not using an effective method of contraception

  • clinically significant co‐occurring psychiatric or medical diagnoses

  • including dependence on any psychoactive substance other than alcohol or nicotine during the preceding year

  • current treatment with disulfiram, naltrexone, or psychotropic medication

  • serum aminotransferase levels or other measures of hepatic function > 250% of normal

  • significant suicidal risk


Participants with bipolar disorder were excluded.
Interventions Drugs:
  • sertraline (up to 200 mg/day; 70 participants)

  • placebo (69 participants)


Psychotherapy:
At each study visit, participants received supportive therapy delivered according to a manual developed specifically for study consisting of:
  • general support for abstinence;

  • promotion of compliance;

  • monitoring of medication adverse effects.


Scheduled duration of treatment: up to 10 weeks
Sites: 13 investigative sites in the USA
Setting: outpatients
Route of administration: orally
Starting dose: 50 mg/day
Pattern of dose reduction:
  • participants who achieved a satisfactory therapeutic response and who wished to continue treatment beyond the end of week 10 were continued double‐blind on the same medication they were taking at the end of week 10 for an additional 14‐week period;

  • participants who did not continue in the extension study were tapered off medication by reducing the daily dose by 1 capsule every 2 or 3 days until the medication was completely discontinued.

Outcomes Depression:
  • final HRSD score (obtained from a figure)

  • difference between baseline and final HRSD score

  • response


Alcohol dependence:
  • rate of abstinent days (obtained from a figure)


Dropout
Adverse effects
Notes Baseline characteristics of participants
Depression:
  • primary depression (rate of participants): 0%

  • duration: information not available

  • number of DSM‐IV criteria (mean ± SD): sertraline = 5.3 ± 1.3; placebo = 5.4 ± 1.1

  • HRSD score (mean ± SD): sertraline = 12.6 ± 2.8; placebo = 12.5 ± 2.9


Alcohol dependence:
  • number of DSM‐IV criteria (mean ± SD): sertraline = 4.6 ± 1.2; placebo = 4.5 ± 1.0

  • number of drinks per week (mean ± SD): sertraline = 54.4 ± 40.5; placebo = 46.8 ± 27.9

  • duration (mean ± SD): sertraline = 10.7 ± 8.1 years; placebo = 11.1 ± 8.5 years

  • being actively drinking: participants had to have drunk a mean of 18 drinks weekly for men or 14 drinks weekly for women and at least 1 heavy drinking day per week during the month before screening

  • length of abstinence: at least 4 days with no heavy drinking and no more than 16 days of abstinence


Other psychiatric comorbidity: participants with other mental disorders were excluded.
Other substance use disorders: participants with substance use disorders were excluded.
Other characteristics of study
Other pharmacological treatment offered: other pharmacological treatments were not allowed.
Funding source: study supported by Pfizer Pharmaceuticals. Manuscript preparation supported by NIH grant K24 AA13736.
Declarations of interest: information not available
Other information
In the original study, 328 participants were divided into the 2 groups on whether initially elevated HRSD score declined with cessation of heavy drinking:
  • HRSD score ≥ 17 (189 participants);

  • HRSD score ≤ 16 (139 participants).


In the present meta‐analysis, participants were divided into 2 substudies:

Both the substudies (Kranzler 2006 arm A; Kranzler 2006 arm B) were included in the 'Effects of interventions: Antidepressants versus placebo' comparison. Unfortunately, the original study did not report the adverse events for the single substudies.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Computer‐generated randomization schedule reported.
Allocation concealment (selection bias) Unclear risk The method of concealment was not described. Despite random assignment, participants who received placebo were older, reported more drinks per week during the pretreatment period, and had higher CGI depression scores at baseline.
Blinding of participants and personnel (performance bias) 
 All outcomes Unclear risk No information provided.
Blinding of outcome assessment (detection bias) objective Low risk No information on the blinding of outcome assessors.
Blinding of outcome assessment (detection bias) subjective Unclear risk No information on the blinding of outcome assessors.
Incomplete outcome data (attrition bias) 
 All outcomes Low risk All analyses used an intention‐to‐treat approach. Weekly comparisons including only participants for whom data were available from that visit, whereas end of study analyses used last observation carried forward analysis.
Selective reporting (reporting bias) Low risk All expected outcomes were reported. However, some of them were reported only as a % reduction (e.g. BDI score).