title: The Psychiatric Inclusion and Exclusion Criteria in Placebo-Controlled Monotherapy Trials of Bipolar Depression: An Analysis of Studies of the Past 20 Years.
abstract: Concerns about the generalizability of pharmacotherapy efficacy trials to "real-world" patients have been raised for more than 40 years. Almost all of this literature has focused on treatment studies of major depressive disorder (MDD).
  
  
  
  The aim of the study was to review the psychiatric inclusion and exclusion criteria used in placebo-controlled trials that assessed the efficacy of medications for bipolar depression (bipolar disorder efficacy trials [BDETs]) and compare the criteria used in BDETs with those used in efficacy trials of antidepressants to treat MDD (antidepressant efficacy trials [AETs]).
  
  
  
  We searched the MEDLINE, Embase, and PsycINFO databases for articles published from January 1995 through December 2014. We identified 170 placebo-controlled AETs and 22 BDETs published during these 20 years. Two of the authors independently reviewed each article and completed a pre-specified information extraction form listing the psychiatric inclusion and exclusion criteria used in the study.
  
  
  
  Six inclusion/exclusion criteria were used in at least half of the BDETs: minimum severity on a depression symptom severity scale, significant suicidal ideation, diagnosis of alcohol or drug use disorder, presence of a comorbid nondepressive, nonsubstance use Axis I disorder, current episode of depression being too long, and absence of current manic symptoms. BDETs were significantly less likely than AETs to exclude patients with a history of psychotic features/disorders, borderline personality disorder, and post-traumatic stress disorder and more likely to exclude individuals who scored too low on the first item of the Hamilton Depression Rating Scale. Nearly two-thirds of the BDETs placed an upper limit on the duration of the current depressive episode, three times higher than the rate in the AETs. There was no difference on other variables between the AETs and BDETs.
  
  
  
  Similar to treatment studies of nonbipolar MDD, the treatment studies of bipolar depression frequently excluded patients with comorbid psychiatric and substance use disorders and insufficient severity of depressive symptoms as rated on standardized scales. These findings indicate that concerns about the generalizability of data from trials of recently approved medications for the treatment of bipolar depression are as relevant as the concerns that have been raised about studies of antidepressants for nonbipolar depression.
authors.affiliation: Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA. mzimmerman@lifespan.org.|Department of Psychiatry and Human Behavior, Brown Medical School, Rhode Island Hospital, 146 West River Street, Providence, RI, 02904, USA. mzimmerman@lifespan.org.
authors.forename: Mark
authors.initials: M
authors.lastname: Zimmerman
authors.affiliation: Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Carolina Guzman
authors.initials: CG
authors.lastname: Holst
authors.affiliation: Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Heather L
authors.initials: HL
authors.lastname: Clark
authors.affiliation: Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Matthew
authors.initials: M
authors.lastname: Multach
authors.affiliation: Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Emily
authors.initials: E
authors.lastname: Walsh
authors.affiliation: Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Lia K
authors.initials: LK
authors.lastname: Rosenstein
authors.affiliation: Department of Psychiatry, Rhode Island Hospital, Providence, RI, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Gazarian
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D001714:Bipolar Disorder / Q000188:drug therapy*; D015897:Comorbidity; D018849:Controlled Clinical Trials as Topic; D003863:Depression / Q000188:drug therapy*; D003865:Major Depressive Disorder / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D011569:Psychiatric Status Rating Scales; D013313:Stress Disorders, Post-Traumatic / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000928:Antidepressive Agents