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Antidepressant Combination Strategies for Major Depressive Disorder

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Polypharmacy in Psychiatry Practice, Volume II

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Abstract

The majority of patients with major depressive disorder (MDD) fail to remit after initial antidepressant (AD) treatment trials. The results of the Treatment Alternatives to Relieve Depression (STAR*D) trial suggest that most MDD patients require a ‘next-step’ treatment, which include AD combination therapies, as well as various AD augmentation strategies. Antidepressant combination strategies are widely used by clinicians for the management of treatment-resistant depression (TRD). The aim of this chapter was to review current evidence on antidepressant combination strategies for TRD. There are limited evidences to guide even the most widely used combination strategies for TRD. This stands in marked contrast to several augmentation strategies for AD non-responders, including adjunctive ­lithium, thyroid hormone or atypical antipsychotics, for which there are stronger evidences from well designed randomized controlled trials to support efficacy. Recently, a few randomized trials have investigated the efficacy of different antidepressant combination strategies for MDD from treatment initiation. These trials provided discrepant results thus far. Potential clinical advantages of various combination strategies are also discussed (for example, avoidance of discontinuation-emergent symptoms). This chapter deals with pharmacological aspects of TRD and will not cover evidence-based psychotherapeutic and neuromodulatory (for example, electroconvulsive therapy) approaches for TRD. This chapter underscores the need for the design of adequately powered randomized controlled trials to provide a clearer evidence base for this widely employed clinical practice.

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Abbreviations

5-HT:

Serotonin

AD:

Antidepressant

ADHD:

Attention deficit hyperactivity disorder

EBM:

Evidence-based medicine

ECT:

Electroconvulsive therapy

HDRS:

Hamilton depression rating scale

MADRS:

Montgomery-Asberg Depression Rating Scale

MAOI:

Monoamine oxidase inhibitor

MDD:

Major depressive disorder

NRI:

Norepinephrine reuptake inhibitor

RCT:

Randomized controlled trial

SNRI:

Serotonin and norepinephrine reuptake inhibitor

SNRI:

Serotonin norepinephrine reuptake inhibitor

SSRI:

Selective serotonin reuptake inhibitors

STAR*D:

Sequenced Treatment Alternatives to Relieve Depression

TCA:

Tricyclic antidepressant

TRT:

Treatment-resistant depression

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Author information

Authors and Affiliations

  1. Department of Clinical Medicine and Psychiatry Research Group, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil

    André F. Carvalho M.D., Ph.D.

  2. Department of Physiology and Pharmacology, Faculty of Medicine, Federal University of Ceará, Fortaleza, CE, Brazil

    Danielle S. Macêdo Ph.D.

  3. Department of Psychiatry, Medical School, University of Ioaninna, Ioaninna, Greece

    Thomas N. Hyphantis M.D., Ph.D.

  4. Department of Psychiatry, University of Toronto, Toronto, ON, Canada

    Roger S. McIntyre M.D., FRCPC

  5. Mood Disorders Psychopharmacology Unit, University Health Network, Toronto, ON, Canada

    Roger S. McIntyre M.D., FRCPC

Authors
  1. André F. Carvalho M.D., Ph.D.
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  2. Danielle S. Macêdo Ph.D.
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  3. Thomas N. Hyphantis M.D., Ph.D.
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  4. Roger S. McIntyre M.D., FRCPC
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Corresponding author

Correspondence to André F. Carvalho M.D., Ph.D. .

Editor information

Editors and Affiliations

  1. Sha'ar Menashe Mental Health Center, Hadera, 38814, Israel

    Michael S. Ritsner

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Carvalho, A.F., Macêdo, D.S., Hyphantis, T.N., McIntyre, R.S. (2013). Antidepressant Combination Strategies for Major Depressive Disorder. In: Ritsner, M. (eds) Polypharmacy in Psychiatry Practice, Volume II. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-5799-8_10

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