Update on Mood Disorders: Implications for Practice

May 20, 2016

How generalizable are the results of depression treatment studies? Which factors predict readmission and length of stay in inpatients with mood disorders?


How generalizable are the results of depression treatment studies? Which factors predict readmission and length of stay in inpatients with mood disorders? These questions were recently addressed in presentations at APA 2016.

Exclusion criteria in treatment trials of bipolar depression

Mark Zimmerman, MD, Professor of Psychiatry at Brown Medical School, and his colleagues have studied the limitations exclusion criteria have placed on the generalizability of drug efficacy trials. They first published findings on studies of MDD more than 15 years ago, with an update in 2015.1,2 The update examined 170 MDD efficacy trials published in English; these studies comprised mostly outpatients and spanned the years 1995 to 2014.

[[{"type":"media","view_mode":"media_crop","fid":"38391","attributes":{"alt":"","class":"media-image","id":"media_crop_9582353741986","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"%7BMCIID%7D","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","title":" ","typeof":"foaf:Image"}}]]The hypothesis was that studies would become more generalizable with fewer exclusions over time. Unfortunately, the investigators found the opposite to be the case. The frequency of exclusion criteria is increasing across the board: most commonly, threshold severity, significant suicidality, comorbid psychiatric diagnoses, and length of mood episodes.

The researchers repeated the analysis for studies of bipolar disorder. They found the following exclusion criteria in more than 50% of studies: severity cutoff (100%), substance abuse/dependence (77.3%), significant suicidality (81.6%), other Axis I conditions (50%), and prolonged length of episode (63.6%).

The investigators concluded that there are more similarities than differences among exclusion criteria in efficacy studies of MDD and bipolar disorder. Exceptions are that MDD studies are more likely to exclude psychotic features and bipolar studies more often exclude violence and episodes of long duration.

Implications for practice

Every psychiatrist must determine the extent to which new research applies to particular patients. Even when patients meet criteria for a mood disorder, clinicians must ask themselves whether they would qualify for the trials that led the FDA to approve the various medication options.

Predictors of length of stay and readmission in inpatients with mood disorders

John W. Goethe, MD, discussed data from his research group at the Burlingame Center in Hartford, Connecticut. He noted that readmission (RA) and length of stay (LOS) are particularly important in mood disorders and that researchers have questioned whether differences exist between MDD and bipolar disorder in these 2 areas.

Dr Goethe and his colleagues studied whether RA and LOS were affected by 6 variables:

  • psychotic features
  • borderline personality disorder
  • PTSD
  • alcohol abuse
  • other drug abuse
  • being on more than 2 psychotropics at discharge

Included were all inpatient discharges between 2000 and 2013 that involved patients age 17 or older with a diagnosis of MDD or bipolar disorder. The sample size was 12,563, and two-thirds of participants had a diagnosis of MDD.

Readmission was examined at the 1-, 3-, 6-, and 12-month marks. Extended LOS was defined as more than 9 days, which represented the top quartile of patients.

RA rates did not vary significantly between MDD and bipolar disorder. Psychotic features increased RA at the 1-month mark only for MDD (11.6% to 7.7%). Borderline personality disorder was more likely to lead to readmission in MDD at all times but not in bipolar disorder.

Patients discharged on more than 2 psychotropics had higher RA rates for both diagnoses at all time points. PTSD and alcohol/drug abuse were not associated with an increased RA rate.

RA was more likely if previous LOS exceeded 9 days. RA rates were similar in males and females, and age was not a significant factor. This finding runs counter to previous studies in which RA risk was increased in females and patients over age 70. The overall RA rate for MDD at 12 months was 23%, which is similar to the rates in previous studies.

Extended LOS was more common in patients with bipolar disorder than in those with MDD (30.6% vs 22.8%). Patients with psychosis and those taking more than 2 psychotropics had longer LOS for both diagnoses.

Strengths of the study include a large sample size of real-world patients who received treatment as usual. Multiple factors were studied simultaneously, and there were multiple time points.

Limitations included studying only inpatients, a single site, no control for prescribing practices (eg, hospital formulary), and prescription data that were available only at discharge and not at follow-up.

Implications for practice

Hopefully, studies such as this will lead to better allocation of resources in the attempt to reduce hospital RA and extended LOS.


Dr Williams is Assistant Professor of Psychiatry and Health Behavior and Medical Director of the Inpatient Service at the Medical College of Georgia, Georgia Regents University, in Augusta, Georgia.


1. Zimmerman M, Chelminski I, Posternak MA. Exclusion criteria used in antidepressant efficacy trials: consistency across studies and representativeness of samples included. J Nerv Ment Dis. 2004;192:87-94.
2. Zimmerman M, Clark HL, Multach MD, et al. Have treatment studies of depression become even less generalizable? A review of the inclusion and exclusion criteria used in placebo-controlled antidepressant efficacy trials published during the past 20 years. Mayo Clin Proc. 2015;90:1180-1186.