The first of 2 parts: A practical approach to subtyping depression among your patients

In dysthymic and minor-depressive middle-age and older adult men who have a low serum level of testosterone, hormone replacement was shown to be superior to placebo in several randomized trials.¹¹ Studies of adjunctive atypical antipsy­chotics for dysthymic disorder are scarce; a Cochrane review identified controlled data only with amisulpride (not approved for use in the United States), which yielded a modest therapeutic effect.¹²

Polarity
In recent years, depression in bipolar dis­order (BD) has been contrasted with uni­polar MDD based on a difference in:
• duration (briefer in BD)
• severity (worse in BD)
• risk of suicide (higher)
• comorbidity (more extensive)
• family history (often present for BD and highly recurrent depression)
• treatment outcome (generally less favorable).

DSM-5 has at least somewhat blurred the distinctions in polarity by way of the new construct of “major depression with mixed features” (see the discussion of MDD above), identifiable even when a person has never had a full manic or hypo­manic episode.

No randomized trials have been con­ducted to identify the best treatments for such presentations, which has invited ex­trapolation from the literature in regard to bipolar mixed episodes, and suggesting that 1) some mood stabilizers (eg, divalproex) might have value and 2) antidepres­sants might exacerbate manic symptoms.

Perhaps most noteworthy in regard to treating bipolar depression is the unresolved, but hotly debated, contro­versy over whether and, if so, when, an antidepressant is inappropriate (based on concerns about possible induction or exac­erbation of manic symptoms). In addition, nearly all of the large, randomized con­trolled trials of antidepressants for bipolar depression have shown that they offer no advantage over placebo.

Some authors argue that a lack of re­sponse to antidepressants might, itself, be a “soft” indicator of “bipolarity.” However, nonresponse to antidepressants should prompt a wider assessment of features other than polarity—including psychosis, anxiety, substance abuse, a personality disorder, psychiatric adverse effects from concomitant medications, medical comor­ bidity, adequacy of trials of medical ther­apy, and potential non-adherence to such trials—to account for poor antidepressant outcomes.

Severity
Severity of depression warrants consider­ation when formulating impressions about the nature and treatment of all presenta­tions of depression.

High-severity forms prompt decisions about treatment setting (inpatient or out­patient); suicide assessment; and thera­peutic modalities (eg, electroconvulsive therapy is more appropriate than psycho­therapy for catatonic depression).

Mild forms. A recent meta-analysis of 6 randomized trials (each of >6 weeks’ du­ration) of antidepressants for mild de­pression demonstrated that these agents exert only a modest effect compared with placebo, owing largely to higher placebo-responsivity in mild depressive episodes than in moderate and severe episodes.13 In contrast, another meta-analysis of sub­jects who had “mild” baseline depression severity scores found that antidepressant medication had greater efficacy than pla­cebo in 4 of 6 randomized trials.14 Higher depression severity levels typically dimin­ish the placebo response rate but also re­duce the magnitude of drug efficacy.

Psychosis
Before DSM-III, psychotic (as opposed to neurotic) depression was perhaps the key nosologic distinction when characteriz­ing forms of depression. The presence of psychosis and related components (eg, mood-congruence) is closely linked with the severity of depression (high) and prog­nosis and longitudinal outcome (poorer), and has implications for treatment (Table).

Bottom Line
Depressive disorders comprise a range of conditions that can be viewed along many dimensions, including polarity, chronicity, recurrence, psychosis, treatment resistance, comorbidity, and atypicality, among other classifications. Clinical characteristics vary across subtypes—and so do corresponding preferred treatments, which should be tailored to the needs of each of your patients.

Related Resources
• Goldberg JF, Thase ME. Monoamine oxidase inhibi­tors revisited: what you should know. J Clin Psychiatry. 2013;74(2):189-191.
• Goldberg JF. Antidepressants in bipolar disorder: 7 myths and realities. Current Psychiatry. 2010;9(5):41-49.
• Ketamine cousin rapidly lifts depression without side ef­fects. National Institute of Mental Health. http://www. nimh.nih.gov/news/science-news/2013/ketamine-cousin-rapidly-lifts-depression-without-side-effects.shtml. Published May 23, 2013. Accessed March 20, 2014.
• Research Domain Criteria (RDoC). National Institute of Mental Health. http://www.nimh.nih.gov/research-priorities/rdoc/index.shtml?u tm_ source = govdelivery&utm_medium=email&utm_campaign= govdelivery. Accessed March 20, 2014.

Drug Brand Names
Amisulpride • Amazeo, Lurasidone • Latuda
Amival, Amipride, Sulpitax Mirtazapine • Remeron
Aripiprazole • Abilify Moclobemide • Amira,
Armodafinil • Nuvigil Aurorix, Clobemix,
Bupropion • Wellbutrin Depnil, Manerix
Desipramine • Norpramin Modafinil • Provigil
Divalproex • Depakote, Olanzapine/fluoxetine
Depakene • Symbyax
Duloxetine • Cymbalta Paroxetine • Paxil
Escitalopram • Lexapro Phenelzine • Nardil
Fluoxetine • Prozac Pramipexole • Mirapex
Imipramine • Tofranil Quetiapine • Seroquel
Ketamine • Ketalar Riluzole • Rilutek
Lamotrigine • Lamictal Sertraline • Zoloft
Lithium • Eskalith, Lithobid Vortioxetine • Brintellix