SECOND OF 2 PARTS A practical approach to subtyping depression among your patients Improve outcomes by understanding the forms that depressive disorders can take epression—sad, empty, or irritable mood accompanied by somatic or cognitive changes—is not a homoge- Dneous condition. Recognizing subtypes of depressive illness can guide treatment and relieve your patient’s suf- fering. In this 2-part article [April and May 2014 issues], I summarize information about clinically distinct subtypes of depression, as they are recognized within diagnostic systems or as descriptors of treatment outcomes for particular sub- groups of patients. My focus is on practical considerations for assessing and managing depression. Because many forms of the disorder respond inadequately to initial antidepressant treatment, optimal “next-step” pharmacotherapy, after nonre- sponse or partial response, often hinges on clinical subtyping. JON KRAUSE/THE ISPOT.COM The second part of this article examines “situational,” treat- ment-resistant, melancholic, agitated, anxious, and atypical Joseph F. Goldberg, MD depression; depression occurring with a substance use disor- Clinical Professor of Psychiatry Icahn School of Medicine at Mount Sinai der; premenstrual dysphoric disorder; and seasonal affective New York, New York disorder. Treatments for these subtypes for which there is evi- Director, Affective Disorders Research Program dence, or a clinical rationale, are given in the Table, page 42. Silver Hill Hospital New Canaan, Connecticut ‘Situational’ depression In recent decades, the phenomenon of nonsyndromal depres- sion after a life stress has undergone many name changes but lit- tle conceptual revision: “situational,” “reactive,” and “neurotic” labels for depression that were used before DSM-III became “adjustment disorders” in DSM-IV-TR and then “stress Disclosure Dr. Goldberg has been a consultant to Avanir Pharmaceuticals and Merck; has served on the speakers’ bureau for AstraZeneca, Merck, Novartis, Sunovion Pharmaceuticals, Takeda-Lundbeck; and has received royalties from American Psychiatric Publishing and honoraria from Medscape Current Psychiatry and WebMD. Vol. 13, No. 5 41 Table Evidence- or rationale-based somatic therapy for select subtypes of depression Premenstrual Treatment Treatment-resistant Melancholic Agitated Anxious Atypical Seasonal dysphoric disorder Atypical OFCa √ √ √ No No data No data antipsychotics Adjunctive aripiprazolea datab a Subtyping Adjunctive quetiapine a depression Bupropion √ No data No data √ + open trials √ Inferior to SSRIs Deep brain √ No data No data No data No data No data No data stimulation Electroconvulsive √ √ √ (-) √ No data No data therapy prognostic factor Ketamine Preliminary No data No data No data No data No data No data Lamotrigine No data No data No data No data No data No data No data L-Methylfolate Adjunctive efficacy after SSRI No data No data No data No data No data No data Clinical Point non-response Lithium √ No data No data No data No data No data No data Stressful life Adjunct to antidepressants events more often MAOIs √ √ √ √ √ √ No data precede first or Mirtazapine √ √ √ √ No data No data No data early episodes N-Acetylcysteine No data No data No data No data No data No data No data Phototherapy No data No data No data No data No data √ Small effect, if any of depression Pramipexole Preliminary No data No data; No data No data No data No data than subsequent ill advised recurrences Psychostimulants Preliminary Preliminary No data; No data; No data No data No data ill-advised ill-advised Riluzole Preliminary No data No data No data No data No data No data Serotonin- √ √ √ √ Open trials Inconclusive No data norepinephrine reuptake inhibitors SSRIs √ TCAs might be √ √ √ √ √ superior Repetitive √ a (+) open trials No data (+) open trials No data No data No data transcranial magnetic stimulation Tricyclic √ √ √ √ Inferior to √ Not better than antidepressants SSRIs and placebo MAOIs Vagus nerve √ a No data No data No data No data No data No data stimulation Vortioxetine No data No data No data No data No data No data No data √ = traditional first-line intervention or recommended appropriate first-line intervention aAn FDA-approved indication; all other uses are off-label bThe effects of atypical antipsychotics on hypersomnia and hyperphagia associated with atypical depression are not well-established MAOIs: monoamine oxidase inhibitors; OFC: olanzapine-fluoxetine combination; SSRIs: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressant Discuss this article at www.facebook.com/ CurrentPsychiatry response syndromes” in DSM-5. These Paucity of guidance. There has been little names all connote presentations of depressed research to identify vulnerability variables mood after an environmental stressor, with- for adjustment disorders in the aftermath out either the full constellation of symptoms of particular stressors. Similarly, extensive that define major depression or the chronicity data are lacking on 1) the likely progression Current Psychiatry 42 May 2014 of dysthymic disorder. of such disorders to a syndromal form of depression can predispose to major depres- 1 Evidence- or rationale-based somatic therapy for select subtypes of depression sion or suicidal behaviors. Models of behavioral sensitization posit Premenstrual that stressful life events more often precede Treatment Treatment-resistant Melancholic Agitated Anxious Atypical Seasonal dysphoric disorder first or early episodes of depression than sub- Atypical OFCa √ √ √ No No data No data sequent recurrences.2 At the same time, non- antipsychotics Adjunctive aripiprazolea datab melancholic depressions that are preceded by Adjunctive quetiapinea “situational stresses” tend to recur in similar Bupropion √ No data No data √ + open trials √a Inferior to SSRIs fashion.3 Deep brain √ No data No data No data No data No data No data stimulation Electroconvulsive √ √ √ (-) √ No data No data Medical therapy of value? Psychotherapy therapy prognostic without medication—apart from occa- factor sional sedative−hypnotic drugs as needed Ketamine Preliminary No data No data No data No data No data No data for insomnia, anxiety, or distress—is con- Lamotrigine No data No data No data No data No data No data No data sidered the standard of care for treating an L-Methylfolate Adjunctive efficacy after SSRI No data No data No data No data No data No data adjustment disorder. No drug has demon- non-response strated superiority to placebo for alleviating Clinical Point Lithium √ No data No data No data No data No data No data symptoms of an adjustment disorder, but For treatment- Adjunct to antidepressants some clinicians nonetheless sometimes feel MAOIs √ √ √ √ √ √ No data compelled to “up-code” the diagnosis of an resistant depression, Mirtazapine √ √ √ √ No data No data No data adjustment disorder to the status of a major repetitive N-Acetylcysteine No data No data No data No data No data No data No data affective disorder, even when syndromal cri- transcranial Phototherapy No data No data No data No data No data √ Small effect, if any teria for major depressive disorder (MDD) or magnetic stimulation Pramipexole Preliminary No data No data; No data No data No data No data dysthymia are absent. ill advised appears to be Psychostimulants Preliminary Preliminary No data; No data; No data No data No data inferior to ECT ill-advised ill-advised Riluzole Preliminary No data No data No data No data No data No data Treatment-resistant depression Serotonin- √ √ √ √ Open trials Inconclusive No data Disease staging models for depression and norepinephrine other psychiatric disordersa make note that, reuptake inhibitors elsewhere in medicine, distinct clinical SSRIs √ TCAs might be √ √ √ √ √ entities often are identified based on their superior responsivity to treatment (eg, classifying Repetitive √ a (+) open trials No data (+) open trials No data No data No data infections as antibiotic-sensitive or -resis- transcranial magnetic tant). Within the study and management stimulation of mood disorders, “treatment resistance” Tricyclic √ √ √ √ Inferior to √ Not better than sometimes is a catch-all description of situ- antidepressants SSRIs and placebo ations in which past treatment 1) yielded MAOIs no improvement or partial improvement Vagus nerve √ a No data No data No data No data No data No data stimulation or 2) was marked by intolerance. Poor out- Vortioxetine No data No data No data No data No data No data No data comes due to past medication intolerance or √ = traditional first-line intervention or recommended appropriate first-line intervention an aborted trial often are commingled with aAn FDA-approved indication; all other uses are off-label cases of true lack of improvement after an b The effects of atypical antipsychotics on hypersomnia and hyperphagia associated with atypical depression are not well-established adequate treatment trial. MAOIs: monoamine oxidase inhibitors; OFC: olanzapine-fluoxetine combination; SSRIs: selective serotonin reuptake inhibitors; TCA: tricyclic antidepressant It is useful, therefore, to define terminology precisely when describing “treatment-resistant depression” and “treatment-refractory depres- sion.” True past nonresponse to appropriate depression or 2) protective factors against treatment often carries prognostic importance developing clinically significant depres- and bears on future treatment decisions. sion after a life stress. The extent to which Few interventions are FDA approved adjustment disorders