Letters to the Editor
Ultrarapid Response to an Antidepressant: A Clue to Bipolarity?
Dear Editor:
I have noted that patients referred for treatment-resistant depression often report episodes of response to an antidepressant within a few days, with subsequent loss of efficacy.
Reflecting the literature (1,2), in recent years I have had an increasing index of suspicion for bipolarity among these patients. I observe an association between a history of ultrarapid response to antidepressant medication and the reporting of symptoms eventually recognized as compatible with bipolarity. A recent review of the spectrum of bipolar illness by Ghaemi, Ko, and Goodwin included a table (3, p 129) that did not, however, mention such a possible association. A search of the literature (specifically, Medline, using the key words antidepressant, depression and drug therapy, bipolar, and time factors; and PsycINFO, using the key words bipolar disorder, major depression, antidepressant drugs, and onset of action) failed to elicit any data related to this association.
I undertook to examine a series of cases. These included 8 patients naturalistically referred and treated in a cognitive-behavioural therapy group for patients with bipolar disorder (BD) and 6 patients consecutively referred for consultation and subsequently diagnosed with BD. I assessed these patients further, using the Mood Disorders Questionnaire (MDQ) (4). The MDQ confirmed a history of hypomania or mania, and several additional written questions were asked, including the following: “What is the least time it (the antidepressant) took to work after you started (in days)?” and “When did this most rapid response occur?” (among previous trials of antidepressant therapy). The cohort ranged in age from 24 to 48 years (average age 39.8 years). There were 8 women and 6 men. Their diagnoses according to DSM- IV-TR criteria (7) were as follows: BD I (n = 4), BD II (n = 7), and BD not otherwise specified (NOS) (n = 3).
Of the patients, 13/14 (93%) reported a therapeutic response to antidepressants at some time; 10/13 (77%) reported responding in 3 days’ time or less, at some time. The other subjects’ shortest response times were reported as 21, 10, and 7 days, respectively. The average response time was 4.4 days. Of the 11 patients reporting a response in 7 days or less, 9 (82%) had that ultrarapid response early in their course (that is, during the first or second trial). Of 14 subjects, 13 (93%) reported becoming agitated at some time in response to an antidepressant.
These findings suggest a very strong association between retrospectively reported ultrarapid response to antidepressants and bipolarity. Although retrospective data are subject to more flaws than prospective data, an examination of the longitudinal course of recurrent affective illness at the National Institutes of Mental Health showed a high correlation between retrospective “life chart” data and data gathered prospectively (5). In this series, most patients did not have a diagnosis of BD I, and the female-to-male ratio did not quite reflect the higher preponderance of female patients among individuals with BD II and BD NOS (6). Additionally, the MDQ does not include the DSM-IV-TR’s duration-of-episode criterion for hypomania (7); therefore, some subjects may have had a bipolar spectrum disorder (8).
A more rigorous test would be a prospective study in primary care, with surveillance for ultrarapid response when antidepressants are first prescribed for depression and with patients followed to identify subsequent manic or hypomanic episodes. This is important because there is evidence of a possible iatrogenic worsening of the course when BD is recognized late and antidepressant treatment has been inappropriate (3). Patients reporting agitation as an antidepressant “side effect” would be interesting to screen for hypomania.
References
1. Angst J. The emerging epidemiology of hypomania and bipolar II disorder. J Affect Disord 1998;50:143–51.
2. Akiskal HS, Pinto O. The evolving bipolar spectrum. Prototypes I, II, II and IV. Psychiatr Clin North Am 1999;22:517–34.
3. Ghaemi N, Ko JY, Goodwin FK. Cade’s disease and beyond: misdiagnosis, antidepressant use and proposed definition for bipolar spectrum disorder. Can J Psychiatry 2002;47:125–34.
4. Hirschfeld RM, Williams JB, Spitzer RL, Calabrese JR, Flynn L, Keck PE Jr, and others. Development and validation of a screening instrument for bipolar spectrum disorder: the Mood Disorder Questionnaire. Am J Psychiatry 2000;157:1873–5.
5. Roy-Byrne P, Post RM, Uhde TW, Porcu T, Davis D. The longitudinal course of recurrent affective illness: Life chart data from research patients at the NIMH. Acta Psychiatr Scand Suppl 1985;317:1–34.
6. Akiskal HS, Maser JD, Zeller PJ, Endicott J, Coryell W, Keller, M, and others. Switching from “unipolar”to bipolar II. An eleven-year prospective study of clinical and temperamental predictors in 559 patients. Arch Gen Psychiatry 1995;52:114–23.
7. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Text revision. Washington (DC): American Psychiatric Association; 2000.
8. Piver AC, Yatham LN, Lam RW. Bipolar spectrum disorders: new perspectives. Can Fam Physician 2002;48:896–904.
Andre Piver, MD
Nelson, British Columbia
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