Psychiatry - December 2008 - (Page 38)

receiving corticosteroids and 20 of whom were not. Although the study found that depression was more frequent in the corticosteroid group, the small sample size and use of self reports are significant limitations of the study. The second investigation by Patten et al86 (which also used self reporting as identification of depression) also found more frequent depression in the corticosteroid group. However, the results did not achieve statistical significance (p=0.07). Interestingly, the same authors presented a study one year earlier evaluating the association between corticosteroid use and the development of a depressive disorder.87 They concluded that although depressive symptoms may be a side effect of corticosteroids, their use is not associated with an elevated risk of a depressive disorder diagnosis in hospitalized patients. In contrast, in a cross-sectional analysis of 2,804 adults older than 55, Feng et al88 did find that corticosteroid use was more common among patients with depressive symptoms than among those without depressive symptoms (1.9% vs. 0.7%). Out of the total population included, 368 (13%) patients met the criteria for depressive symptoms based on the 15-item Geriatric Depression Scale (GDS). Of these 368 patients with depressive symptoms, only seven (1.9%) were receiving corticosteroids. Of the remaining 2,436 patients who did not have depressive symptoms, 16 were receiving corticosteroids (0.7%). The authors found that corticosteroid use was associated with depressive symptoms in the entire sample, although this association was of only marginal statistical significance. However, in participants aged 65 or older, systemic corticosteroid use was significantly associated with depressive symptoms (OR 4.02, 95% CI 1.12,14.42). There is certainly abundant observational evidence that depressive symptoms are present in some patients treated with corticosteroids, perhaps especially those in older age groups. However, 38 Psychiatry 2008 [ V O L U M E 5, NUMBER the evidence that corticosteroids are causally related to depression is no more than moderately strong, in our judgment. SMOKING CESSATION AGENTS (VARENICLINE) Two months after an early communication letter in November of 2007, the FDA issued an alert to the Warnings and Precautions sections for the smoking cessation agent varenicline (Chantix®), a partial agonist at the nicotinic receptor.89 Three months later, the Federal Aviation Administration banned this medication for pilots and air traffic controllers, suggesting that its neuropsychiatric effects could jeopardize public safety.90 These warnings came only two years after this agent received a “priority review” by the FDA. The FDA and the manufacturer agreed to these warnings based on post-marketing case reports received by the FDA (the actual number of reports is not provided on the FDAs webpage89). These case reports— which are subject to a variety of reporting errors—described newonset suicidal ideation and behavior in association with varenicline. Many of the symptoms developed within days to weeks after initiation. However, a recent case report describes a patient with a history of depression developing worsening symptoms six weeks after the initiation of varenicline.91 Given this report, it seems premature to assume that depressive symptoms will always occur within the first few weeks of therapy. One may argue that smoking cessation in itself may cause signs of depression; however, in the case report above, the patient was still smoking during his onset of symptoms. In addition, not all of the patients in the postmarketing data had discontinued smoking either. To our knowledge, randomized, placebo-controlled studies of varenicline have generally not assessed depression in a systematic fashion. However, one such study by Tsai et al92 found that, compared with placebo, anxiety and abnormal 12, DECEMBER] dreams were significantly more common in the varenicline group [anxiety (5.6% vs 2.4%), abnormal dreams (5.6% vs 0.8%)], based solely on self reports. Clearly, there is a pressing need, among varenicline-treated patients, for randomized, placebo-controlled studies that directly assess baseline and follow-up depression scores. In the absence of such studies or of large-scale meta-analyses implicating varenicline in DID—and without knowing the number of case reports in the FDA database—we would rate the evidence of a varenicline/DID link as only moderately strong. However, given current FDA warnings, clinicians should be cautious when prescribing this medication and seriously weigh the risks of precipitating or exacerbating depression in predisposed individuals. CONCLUSION Drug-induced depression is a significant clinical, medicolegal, and public health problem. However, our review suggests that high-quality studies of DID are generally lacking, and that causal relationships are difficult to ascertain. Moreover, ethical constraints may always impose limits on the kind of studies that can be conducted. Nonetheless, a review of the available evidence finds that some drugs or drug classes commonly used in general medicine probably do pose a relatively high risk of DID. While our findings should be considered provisional, isotretinoin, rimonabant, and alphainterferons appear to pose the highest risk of DID. Corticosteroids, varenicline, progesterone inserts, and finasteride may pose a moderately high risk of DID. Since all these agents have legitimate medical indications, the risks and benefits of each drug must be carefully weighed on a case-by-case basis. REFERENCES 1. US Food and Drug Administration. FDA Issues Public Health Advisory on Chantix. http://www.fda.gov/bbs/topics/NEW http://www.fda.gov/bbs/topics/NEWS/2008/NEW01788.html

Table of Contents Feed for the Digital Edition of Psychiatry - December 2008

Psychiatry - December 2008 Editor’s Message Contents Editorial Advisory Board Antidepressant Prescribing by Specialty and Treatment of Premenstrual Dysmorphic Disorder Pain, Pain, Go Away: Antidepressants and Pain Management Why Psychotherapy Helps the Patient in Chronic Pain General Medical Drugs Associated with Depression Katatonia: A New Conceptual Understanding of Catatonia and a New Rating Scale Thermoregulation and the Role of Calcium Signalling in Neurotransmission Cognition and Schizophrenia: Is There a Role for Cognitive Assessments in Diagnosis and Treatment? Journal Watch Information for Authors

Psychiatry - December 2008

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