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

Depression carries a wide differential diagnosis. Practitioners sometimes think polarity is the fundamental distinction when they conceptualize depression as a clinical entity; in fact, many nosologic frameworks have been described for defining and subtyping clinically meaningful forms of depression, and each waxed and waned in popularity.

Kraepelin, writing in the early 20th century, linked manic-depres­sive illness with “the greater part of the morbid states termed mel­ancholia,”¹ but many features other than polarity remain important components of depression, and those features often carry implications for how individual patients respond to treatment.

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 subgroups 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 nonresponse or partial response, often hinges on clinical subtyping.

The first part of this article examines major depressive disorder (MDD), minor depression, chronic depression, depression in bipolar disorder, depression that is severe or mild, and psychotic depression. Treatments for these subtypes for which there is evidence, or a clinical rationale, are given in the Table.

The subtypes of depression that I’ll discuss in the second part of the article are listed on page 47.

Major and minor depression
MDD has been the focus of most drug tri­als seeking FDA approval. As a syndrome, MDD is defined by a constellation of fea­tures that are related not only to mood but also to sleep, energy, cognition, motiva­tion, and motor behavior, persisting for ≥2 weeks.

DSM-5 has imposed few changes to the basic definition of MDD:
• bereavement (the aftermath of death of a loved one), formerly an exclusion cri­terion, no longer precludes making a diag­nosis of MDD when syndromal criteria are otherwise fulfilled
• “with anxious distress” is a new course specifier that designates promi­nent anxiety features (feeling worried, restless, tense, or keyed up; fearful of losing control or something terrible happening)
• “with mixed features” is a new course specifier pertinent when ≥3 mania or hy­pomania symptoms coexist (that is, might be a subsyndromal mania or hypomania) with a depressive syndrome; the mixed features specifier can be applied to de­pressed patients whether or not they have ever had a manic or hypomanic episode, but MDD—rather than bipolar disorder— remains the overarching diagnosis, unless criteria have ever been met for a full mania or hypomania.

More than 2 dozen medications are FDA-approved to treat MDD. Evidence-based psychotherapies (eg, cognitive-behavioral therapy [CBT] and interpersonal therapy), as adjuncts to pharmacotherapy, further improve outcomes, but with only modest additional effect.²

Minor depression. Depressive states that involve 2 to 4 associated symptoms last­ing ≥2 weeks but <2 years are sometimes described as minor depression, captured within DSM-5 as “depression not else­where defined.” The terminology of so-called “minor depression” generally is shunned, in part because it might wrongly connote low severity and therefore dis­courage treatment—even though it con­fers more than a 5-fold increase in risk of MDD.3

Chronicity
DSM-IV-TR identified long-standing de­pression by 2 constructs:
• chronic major depression (an episode of MDD lasting ≥2 years in adults, ≥1 year in children and adolescents)
• dysthymic disorder (2 to 4 depressive symptoms for ≥2 years in adults and ≥1 year in children and adolescents), affecting 3% to 6% of adults and carrying a 2-fold increased risk of MDD, eventually.⁴

Depression that begins as dysthymic disorder and blossoms into syndromal MDD is described as “double depres­sion”—although it is not recognized as a unique condition in any edition of the DSM. Subsequent incomplete recovery may revert to dysthymic disorder. DSM-5 has subsumed chronic major depression and dysthymia under the unified heading of persistent depressive disorder.

There are no FDA-approved drugs for treating dysthymia. A meta-analysis of 9 controlled trials of off-label use of antide­pressants to treat dysthymia revealed an overall response rate of 52.4%, compared with 29.9% for placebo.⁵ Notably, although the active drug response rate in these stud­ies is comparable to what seen in MDD, the placebo response rate was approxi­mately 10% lower than what was seen in major depression.

Positive therapeutic findings (typically, treatment for 6 to 12 weeks) have been reported in so-called “pure” dysthymic disorder with sertraline, fluoxetine, imip­ramine, ritanserin, moclobemide (not ap­proved for use in the United States), and phenelzine; the results of additional, posi­tive placebo-controlled studies support the utility of duloxetine⁶ and paroxetine.⁷ Randomized trials have reported negative findings for desipramine,⁸ fluoxetine,⁹ and escitalopram¹⁰ escitalopram¹⁰—although the sample size in these latter studies might have been too small to detect a drug-placebo difference.