title: Variability in the substance use disorder exclusion criterion in antidepressant efficacy trials.
abstract: Substance use disorders are the most commonly excluded psychiatric disorder in antidepressant efficacy trials (AETs). In a recent review of AETs we noticed variability in the definition of the substance use disorder exclusion criterion. In the present report we examined in greater detail the variability in defining the substance use disorder exclusion criterion, the potential impact of this variability on excluding patients from an AET, and whether the definition of the criterion has changed in the past 20 years.
  
  
  
  We identified 170 AETs published during the past 20 years and compared the studies published during the past 5 years (n=56) to the studies published during the 15 prior years (n=114).
  
  
  
  Substance abuse was more frequently used as an exclusion criterion than substance dependence. Six time frames have been used as the basis of exclusion, the most frequent being the past 12 months. The time frame had a greater impact on the number of patients who would be excluded than the abuse/dependence distinction. The definition of the substance use exclusion criterion was no different in the studies of the past 5 years compared to the prior 15 years.
  
  
  
  A limitation of the present analysis is that it was based on published placebo-controlled studies of antidepressants.
  
  
  
  Studies varied in whether abuse or dependence was the basis of exclusion, whether alcohol or illicit drugs or both were the basis of exclusion, and the time frame of the disorders' presence. We raise the question of whether the routine exclusion of patients with a substance use disorder should be reflected in a product's label.
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, 146 West River Street, Providence, RI 02904, United States. Electronic address: mzimmerman@lifespan.org.
authors.forename: Mark
authors.initials: M
authors.lastname: Zimmerman
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, 146 West River Street, Providence, RI 02904, United States.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Clark
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, 146 West River Street, Providence, RI 02904, United States.
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Multach
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, 146 West River Street, Providence, RI 02904, United States.
authors.forename: Emily
authors.initials: E
authors.lastname: Walsh
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, 146 West River Street, Providence, RI 02904, United States.
authors.forename: Lia K
authors.initials: LK
authors.lastname: Rosenstein
authors.affiliation: Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, 146 West River Street, Providence, RI 02904, United States.
authors.forename: Douglas
authors.initials: D
authors.lastname: Gazarian
mesh_terms: D000928:Antidepressive Agents / Q000627:therapeutic use*; D018849:Controlled Clinical Trials as Topic / Q000379:methods*; D003865:Major Depressive Disorder / Q000150:complications / Q000188:drug therapy; D006801:Humans; D018579:Patient Selection; D019966:Substance-Related Disorders / Q000150:complications / Q000175:diagnosis*; D009626:Terminology as Topic; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents
keywords: Alcohol use disorder; Antidepressant efficacy trials; Antidepressants; Drug use disorder; Exclusion criteria; External validity; Generalizability; Major depressive disorder; Substance use disorder