Trivedi_edit.qxp 11/12/07 3:21 pm Page 17
Depression
Treatment Strategies and Tactics for Treatment-resistant Depression
a report by
Madhukar H Trivedi, MD and Ella J Daly, MB, MRC Psych
Mood Disorders Program, Department of Psychiatry, University of Texas Southwestern Medical Center, Dallas, Texas
Treatment-resistant depression (TRD)—depression that does not remit after longer a patient remains symptomatic, the lower the chances of a
one or more adequately delivered treatments
1,2
—is a major and increasing complete recovery.
20
Furthermore, the occurrence of both MDD and
public health burden due to its high prevalence, chronic and recurrent course, substance abuse, or other comorbidities, intensifies the degree of medical
substantial morbidity, and significant direct and indirect costs.
3–5
Treatment for and psychosocial impairment, resulting in significant suffering and
this condition needs to be aimed at effecting full remission (e.g. absence of degradation in global function.
symptoms) rather than response, since anything short of remission is likely to
result in relapse, recurrence, and future treatment resistance.
6–8
Tactics and Treatment Strategies for
Treatment-resistant Depression
The recent National Institute of Mental Health (NIMH)-funded Sequenced
Treatment Alternatives to Relieve Depression (STAR*D) study showed that Pharmacological Strategies
remission rates are modest even after two state-of-the-art, diligently Over time, many different strategies have been developed in an effort to
delivered treatment steps with the support of depression-care specialists.
9–11
overcome the problem of partial or non-response to treatment. These
Even following four steps, a large percentage of patients who do not include augmentation strategies, switching agents, combining
benefit remains.
8
antidepressants (two medications or medication and psychotherapy), and
dual-action agents.
Available treatment strategies, as currently implemented, are relatively
ineffective for patients in later stages of TRD, for example those who have In terms of sequential treatment approaches, as yet there are no
not achieved remission despite several adequately delivered treatments.
8,12–14
randomized studies suggesting the best specific treatment sequence, and
Specifically, current research on TRD fails to guide practicing physicians further studies are needed to evaluate the comparative efficacy and
about which treatment sequences are the most effective, with even greater tolerability of different approaches. Adaptive strategies to date rely
uncertainty about which specific treatment sequence is most effective for primarily on consensus-based, clinical decision-making rather than on
individual patients. Given that there is considerable response heterogeneity innovative study designs that address the identification of the best
among individuals, and insufficient understanding of who responds to what sequence for individual or groups of patients. Traditional approaches
treatment, the treatment process is often little more than trial and error until have considered each step in the sequence as a new trial, but we now
an appropriate treatment is found. There is a clear need for empirically know that each treatment step builds on the previous treatment, and
based information to identify effective treatments and use them earlier— that resistance to one step increases the chances of resistance to
thereby reducing the steps needed to achieve remission—and to determine
how to individualize and tailor treatment for a particular patient. The fact
that 60–70% of all patients with major depressive disorder (MDD) meet
Madhukar H Trivedi, MD, is Director of the Mood Disorders
Research Program and Clinic at the University of Texas
criteria for TRD underscores the need for systematic development of
Southwestern Medical Center, Dallas, Texas, where he holds
innovative treatments for TRD.
15–17
the Lydia Bryant Test Professorship in Psychiatric Research. Dr
Trivedi is an established efficacy and effectiveness researcher
in the treatment of depression, and has been a principal
Treatment-resistant Depression
investigator in multiple National Institute for Mental Health
Treatment-resistant depression is a common problem in the treatment of (NIMH) clinical trials.
MDD, yet little agreement exists about either the definition of TRD or
E: madhukar.trivedi@utsouthwestern.edu
evidence-based options for treatment. There is likely a continuum of
treatment resistance, with modest resistance referring to failure to fully
Ella J Daly, MD, MRC Psych, is an Assistant Professor of
respond to one adequate treatment trial, and greater resistance referring Psychiatry at the University of Texas Southwestern Medical
to failure to respond to two or more adequate treatment trials or one trial
Center, Dallas, Texas, where she works closely with Dr Trivedi in
the Mood Disorders Research Program and Clinic. Her area of
of augmentation.
11,18
interest is depression research, with a special interest in
comorbid medical disorders. Dr Daly completed her medical
Remission as the Goal of Treatment
training in Dublin, Ireland, and has been a member of the Royal
College of Psychiatry since 1997.
There is considerable evidence that, even with treatment, residual
symptoms often persist, leading to psychosocial dysfunction,
5–7,19
and the
© TOUCH BRIEFINGS 2007
17
Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52