Major Depressive Disorder: Understanding the Significance of Residual Symptoms and Balancing Efficacy with Tolerability

Effective treatment with antidepressants is currently limited by factors that affect treatment compliance, including delay in onset of therapeutic effects and, often, intolerable side-effects. Recent data suggest that use of antidepressant combinations with different mechanisms of action may be a better first-line strategy prior to augmentation with other drug classes. The rationale for this approach is that combining multiple pharmacological actions affecting multiple monoamine targets produces greater efficacy. The latest data on multimodal therapies indicate shorter onset of therapeutic effects and improved tolerability. By modulating multiple receptors and neurotransmitter systems, it is hoped that these new agents may also treat some of the associated symptoms of major depressive disorder, such as anxiety and cognitive dysfunction.


Primary care physicians, Psychiatrists and other healthcare clinicians responsible for the care of patients with Major Depressive Disorder.


Upon completion of this activity, participants will be able to:

  1. Recognize the complexity and persistence of the symptoms of Major Depressive Disorder (MDD), particularly the significance of residual symptoms.
  2. Apply the knowledge surrounding neurotransmitter modulation into the selection of treatment options
  3. Examine the specific factors that contribute to patient adherence on MDD, particularly the role of tolerability.
  4. Evaluate current and emerging strategies for MDD to individualize care for patients.


Larry Culpepper, MD, MPH
Department of Family Medicine
Boston University School of Medicine
Boston Medical Center
Boston, MA

Philip R. Muskin, MD
Department of Psychiatry
Columbia University Medical Center
New York, New York

Stephen M. Stahl, MD
Department of Psychiatry
University of California San Diego,San Diego, California
Neuroscience Education Insitute,Carlsbad California
Department of Psychiatry
University of Cambridge,
Cambridge, United Kingdom


Disclosure of Conflicts of Interest

According to the disclosure policy of The University of Cincinnati College of Medicine, faculty, editors, managers, and other individuals who are in a position to control content are required to disclose any relevant financial relationships with the commercial companies related to this activity. All relevant relationships that are identified are reviewed for potential conflicts of interest. If a conflict of interest is identified, it is the responsibility of The University of Cincinnati College of Medicine to initiate a mechanism to resolve the conflict(s). The existence of these interests or relationships is not viewed as implying bias or decreasing the value of the presentation. All educational materials are reviewed for fair balance, scientific objectivity of studies reported, and levels of evidence.

The following faculty has reported real or apparent conflicts of interest that have been resolved:


Relationship Identified With:

Larry Culpepper, MD, MPH

an advisor for AstraZeneca, Forest Labs, Jazz Pharmaceuticals, Lundbeck A/S, Merck, Shire PLC, Sunovion Pharmaceuticals Inc., Takeda Pharmaceuticals Inc.

Philip R. Muskin, MD

has nothing to disclose


Stephen M. Stahl, MD, PhD, 


a consultant for Acadia, Biomarin, En Vivo, Forum, Jazz Pharmaceuticals, Orexigen, Otsuka, Pam Labs, Servier, Shire, Sprout, Taisho, Takeda Pharmaceuticals and Trius. He is an advisory board member for: Biomarin, En Vivo, Forum, GenoMind, Lundbeck, Otsuka, RCT Logic and Shire. He is on the speakers’ Bureau of Forum, Takeda, Servier and Sunovion UK and received research grant from Alkermes, Clintara, Eli Lilly, Forest, Forum, GenoMind, JayMac, Jazz, Merck, Novartis, Otsuka, Pam Labs, Pfizer, Servier, Shire, Sprout, Sunovion, Sunovion UK, Takeda, Teva and Tonix.

Planners, Managers, Reviewers:Susan Tyler, MEd, CMP, CHCP,Rick Ricer, MD, Deborah Cole, Program Coordinator, Otto Ratz, MD, Christina Culbert, MSc, hereby state that they or their spouse/life partner do not have any financial relationships to products or devices with any commercial interest related to the content of this activity of any amount during the past 12 months. 

Accreditation Statement 

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of The University of Cincinnati and CORE Medical Education, LLC. The University of Cincinnati is accredited by the ACCME to provide continuing medical education for physicians.

Credit Designation Statement

The University of Cincinnati designates this enduring material for a maximum of 3.0 AMA PRA Category 1 CreditsTM.  Physicians should claim only the credit commensurate with the extent of their participation in the activity. 


This CME activity was developed through the joint providership of The University of Cincinnati and CORE Medical Education, LLC.

Financial Support

This CME activity is supported by an educational grant from Mylan Pharmaceuticals, Inc.

Disclosure of Unlabeled Use

This educational activity may contain discussion of published and/or investigational uses of agents that are not indicated by the FDA. Neither The University of Cincinnati College of Medicine nor CORE Medical Education, LLC, recommend the use of any agent outside of the labeled indications. The opinions expressed in the educational activity are those of the faculty and do not necessarily represent the views of The University of Cincinnati College of Medicine or CORE Medical Education. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications, and warnings.

Review Process

The entire faculty discussed the content at a peer-review planning session; the chair reviewed the activity for accuracy and fair balance, and a member of the External CME Advisory Board, who is without conflict of interest, reviewed the activity to determine whether the material is evidence-based, objective and demonstrated fair balance.


This Supplement is derived from a planning teleconference series which was held between October 22, 2014 and January 22, 2015 and was independently developed by The University of Cincinnati College of Medicine and CORE Medical Education LLC, pursuant to an educational grant from Mylan Pharmaceuticals, Inc. The opinions expressed herein are those of the faculty and do not necessarily reflect the opinions of the CME provider and publisher, or the commercial supporter.


Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient management. Any procedures, medications, or other courses of diagnosis or treatment discussed or suggested in this activity should not be used by clinicians without evaluation of their patient’s conditions and possible contraindications on dangers in use, review of any applicable manufacturer’s product information, and comparison with recommendations of other authorities.


For all CME inquiries or special needs, please contact

Course summary
Available credit: 
  • 3.00 AMA PRA Category 1 Credit(s)™
  • 3.00 Non-physician
Course opens: 
Course expires: 

Available Credit

  • 3.00 AMA PRA Category 1 Credit(s)™
  • 3.00 Non-physician
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