title: Prevalence of subthreshold hypomania and impact on internal validity of RCTs for major depressive disorder: results from a national epidemiological sample.
abstract: BACKGROUND
  Growing evidence supports the validity of distinguishing major depressive disorder (MDD) plus a lifetime history of subthreshold hypomania (D(m)) from pure MDD in psychiatric classifications. The present study sought to estimate the proportion of individuals with D(m) that would have been included in RCTs for MDD using typical eligibility criteria, and examine the potential impact of including these participants on internal validity.
  
  
  METHODS
  Data were derived from the 2001-2002 National Epidemiological Survey on Alcohol and Related Conditions (NESARC), a national representative sample of 43,093 adults of the United States population. We examined the proportion of participants with a current diagnosis of pure MDD and D(m) that would have been eligible in clinical trials for MDD with a traditional set of eligibility criteria, and compared it with that of participants with bipolar 2 disorder if the same set of eligibility criteria was applied. We considered 4 models including different definitions of subthreshold hypomania.
  
  
  RESULTS
  We found that more than 7 out of ten participants with pure MDD and with D(m) would have been excluded by at least one classical eligibility criterion. Prevalence rate of individuals with D(m) in RCTs for MDD with traditional eligibility criteria would have ranged from 7.98% to 22.59%. Overall exclusion rate of individuals with MDD plus at least 4 lifetime concomitant hypomanic probes significantly differ from those with pure MDD, whereas it was not significantly different in those with at least 2 lifetime concomitant hypomanic probes compared to those with bipolar 2 disorder.
  
  
  CONCLUSIONS
  The current design of clinical trials for MDD may suffer from impaired external validity and potential impaired internal validity, due to the inclusion of a substantial proportion of individuals with subthreshold hypomania presenting with similar pattern of exclusion rates to those with bipolar 2 disorder, possibly resulting in a selection bias.
authors: Assistance Publique-Hôpitaux de Paris (AP-HP), Hôpital Corentin-Celton, Service de Psychiatrie, Issy-les-Moulineaux, France. nico.hoertel@yahoo.fr
authors: Nicolas
authors: N
authors: Hoertel
authors: Yann
authors: Y
authors: Le Strat
authors: Frédéric
authors: F
authors: Limosin
authors: Caroline
authors: C
authors: Dubertret
authors: Philip
authors: P
authors: Gorwood
mesh_terms: D000293:Adolescent; D000328:Adult; D001714:Bipolar Disorder / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology; D002986:Clinical Trials as Topic; D003865:Major Depressive Disorder / Q000175:diagnosis* / Q000453:epidemiology* / Q000523:psychology; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D006801:Humans; D015995:Prevalence; D011569:Psychiatric Status Rating Scales; D016032:Randomized Controlled Trials as Topic / Q000592:standards* / Q000706:statistics & numerical data; D014481:United States / Q000453:epidemiology; D055815:Young Adult