The first of 2 parts: A practical approach to subtyping depression among your patients
Increase treatment success by assessing for the multiple forms that depressive disorders take
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. https://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. https://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
