Do sub-syndromal manic symptoms influence outcome in treatment resistant depression in adolescents? A latent class analysis from the TORDIA study

Abstract

Background: To identify distinct depressive symptom trajectories in the TORDIA study and determine their correlates.

Methods: Latent Class Growth Analysis (LCGA) using the Children's Depression Rating Scale-Revised (CDRS-R) through 72 weeks from intake.

Results: 3 classes were identified: (1) little change in symptomatic status ("NO"), comprising 24.9% of participants, with a 72-week remission rate of 25.3%; (2) slow, steady improvement ("SLOW"), comprising 47.9% of participants, with a remission rate of 60.0%, and (3) rapid symptom response ("GO"), comprising 27.2% of participants, with a remission rate of 85.7%. Higher baseline CDRS-R (p<0.001) and poorer functioning (p=0.03) were the strongest discriminators between NO and GO. Higher baseline CDRS (p<0.001) and scores on the Mania Rating Scale (MRS) (p=0.01) were the strongest discriminators between SLOW and GO. Other variables differentiating GO from both NO and from SLOW, were better baseline functioning, lower hopelessness, and lower family conflict. Both NO and SLOW showed increases on the MRS over time compared to GO (ps ≤ 0.04), and increasing MRS was strongly associated with lack of remission by 72 weeks (p=0.02).

Limitations: High rate of open treatment by the end of the follow-up period creates difficulty in drawing clear inferences about the long-term impact of initial randomization.

Conclusion: Along with depressive severity, sub-syndromal manic symptoms, at baseline, and over time emerged as important predictors and correlates of poor outcome in this sample. Further research is needed on the treatment of severe depression, and on the assessment and management of sub-syndromal manic symptoms in treatment resistant depression.

Trial registration: ClinicalTrials.gov NCT00018902.

Conflict of interest statement

Conflict of Interest

Dr. Maalouf is on the Speaker's Bureau of Eli Lilly and participated in a meeting sponsored by Hikma pharmaceuticals.

Dr. Emslie has received research support from Biobehavioral Diagnostics, Eli Lilly, Forest Laboratories, GlaxoSmithKline, and Somerset. He has served as a consultant for Biobehavioral Diagnostics, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Pfizer, and Wyeth Pharmaceuticals.

Dr. Wagner receives honoraria from Physicians Postgraduate Press, CMP Medica, Contemporary Forums, Quantia Communications, American Psychiatric Association, American Academy of Child and Adolescent Psychiatry, CME LLC.

Dr. Asarnow reports receiving unrestricted research support from Phillip Morris and consulting on cognitive-behavior therapy and depression quality improvement.

Dr. Keller is currently a professor of Psychiatry and Human Behavior at Brown University School of Medicine, has been a consultant and received honoraria from CENEREX, Medtronic, Sierra Neuropharmaceuticals, and has received grant funding from Pfizer.

Dr. Birmaher is currently employed by the University of Pittsburgh and the University of Pittsburgh Medical Center/Western Psychiatric Institute and Clinic; has received research funding from the National Institute of Mental Health; is a consultant for Schering Plough; and has received royalties from Random House, Inc. (New Hope for Children and Teens with Bipolar Disorder) and Lippincott Williams & Wilkins (Treating Child and Adolescent Depression).

Dr. Brent is currently employed by the University of Pittsburgh, School of Medicine and the University of Pittsburgh Medical Center, Western Psychiatric Institute and Clinic; has received research support from the National Institute of Mental Health; receives royalties from Guilford Press; and serves as UpToDate Psychiatry Editor.

Drs. Vitiello, Clarke, Spirito, Ryan, Shamseddeen, Iyengar, Ms. Mayes, and Ms. Porta report no potential conflicts of interest.

Copyright © 2011. Published by Elsevier B.V.

Figures

Fig.1

CDRS-R Trajectories in TORDIA: “No”, “SLOW” and “GO” Classes.

Fig.2

Kaplan Meir Survival Curve by Class: Time to Remission

Fig 3

Mean Mania Rating Scale (MRS) by Class Over Time Class: chi2(2)=10.25, p=0.006 , Class*week: chi2(2)=14.15, p

Fig 4

Number of Endorsed Manic Symptoms by Class Over Time The mixed effects regression model of number of items endorsed on the MRS showed a class effect (p=0.003) and a logtime*class interaction (p=