Mood

Atypical Depression

This form of depression is actually very common.

Don't be fooled. Atypical depression is actually the most common subtype of depression in outpatients, according to Andrew Nierenberg MD, Associate Director of the Depression and Clinical Research Program at Massachusetts General Hospital, affecting anywhere from 25 to 42 percent of the depressed population.

Atypical Depression Symptoms

According to the DSM-IV, as opposed to major depression, the patient with atypical features experiences mood reactivity, with improved mood when something good happens. In addition, the DSM-IV mandates at least two of the following: increase in appetite or weight gain (as opposed to the reduced appetite or weight loss of "typical" depression); excessive sleeping (as opposed to insomnia); leaden paralysis; and sensitivity to rejection.

A study by Agosti and Stewart published in the Journal of Affective Disorders in 2001 found that patients with atypical depression experienced greater functional impairment than their non-atypical counterparts, as well as exhibiting more interpersonal sensitivity, more chronic dysphoria, and more bipolar II disorder. Women comprised 70 percent of the study population of those with atypical depression.

A study by Posternak and Zimmerman published in Psychiatry Research in 2001 cast doubt on the only feature of atypical depression that is mandatory under the DSM - that of mood reactivity. In their study, the authors evaluated the five symptoms of atypical depression across five different groups of patients (including women, different age groups, and according to severity and length of time of symptoms), and discovered mood reactivity only featured among the women patients, suggesting this particular criteria should be dropped.

The same study also found at best a limited association between the five atypical features among the five clinical profiles. Women, for instance, consistently displayed four of the five symptoms for atypical depression while patients under age 30 exhibited only one. Two patients, then, may have two different sets of symptoms, which suggests there is nothing typical about atypical depression.

A multi-center study identified a group with atypical depression, representing 36.4 percent of the depressed sample in the US National Comorbidity Survey. The study found that those with atypical depression were mostly women, had higher rates of depressive symptoms, more co-occurring psychiatric illnesses, more suicidal thoughts and attempts, greater disability and restricted activity days, more use of some healthcare services, greater paternal depression, and more childhood neglect and sexual abuse.

Atypical Depression Treatment

A study by McGrath et al published in the American Journal of Psychiatry in 2000 found that Prozac was no better than the tricyclic antidepressant imipramine for the treatment of atypical depression, though the side effects were less. A study by Quitkin et al published in 1993 in the British Journal of Psychiatry found a response rate of 72 percent for patients with atypical depression on the MAOI Nardil compared to 44 percent on imipramine. The American Psychiatric Association's 2000 Practice Guidelines for the Treatment of Patients with Major Depression states: "MAOIs may be particularly effective in treating subgroups of patients ... with atypical features."

The MAOIs we are familiar with, however, have a notorious side effects profile, including possible tyramine reaction that necessitates severe restrictions in diet, tending to make these drugs a treatment of last resort. A kinder and gentler MAOI, selegiline, used in the treatment of Parkinson's, belongs to a different class of MAOIs (an MAO-B inhibitor as opposed to MAO-A inhibitors such as Nardil). Studies using oral doses of selegiline on patients have found a 50 percent response rate among both atypical and typical depressed patients. The drug is now in development as a transdermal patch. A study of two trials presented at the 2001 American Psychiatric Association's annual meeting revealed completion rates of 86 and 72 percent over six and eight weeks, respectively, for patients on the patch. A meta-analysis of four clinical trials by Somerset Pharmaceuticals, which is developing the patch, shows close to a 40 percent reduction in depression symptoms over six to eight weeks, though a 2003 study showed only "a modest, but statistically significant, antidepressant benefit compared with placebo."

A different class of MAOIs called RIMAs (reversible monoamine inhibitors) - without the tyramine reaction risk and other bad side effects - are available outside the US. These include moclobemide, brofaromine, and befloxatone. A quick search of online Canadian pharmacies found that moclobemide was being sold by least two of them. There has been talk of the authorities cracking down on from-across-the border meds, but your prescribing physician can arrange for an above-board FDA IND exemption for compassionate or emergency use.

A drug that may be effective for the oversleeping that is part and parcel of atypical depression is the novel stimulant, Provigil, which has few side effects and does not disrupt normal sleep. The drug is FDA-approved for narcolepsy, and is in trials for other uses. Three studies presented at the APA annual meeting in 2001 and 2002 have found the drug to be a useful adjunct in the treatment of major depression. The drug is metabolized through the same pathway as many of the tricyclic antidepressants, which may necessitate dose adjustments for some patients.

Only one study has been done on talking therapy for atypical depression. In that study, by Jarrett et al published in the Archives of General Psychiatry in 1999, cognitive therapy was found to work as well as Nardil after 10 weeks, with a nearly 60 percent response. Talking therapy is particularly well-equipped to handle the eating, sleeping, and rejection issues that arise from atypical depression.

Conclusion

The same treatments that work for "typical" depression also work for atypical depression, but the difference between mere response and remission may depend on your ability to communicate to your psychiatrist and therapist. Matters that don't seem important to you at the time, such as how you sleep, may make all the difference in devising medications and talking therapy strategies that really work..

Updated Oct 14, 2003, reviewed Feb 10, 2008

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