Psychiatry - December 2008 - (Page 35)

cause DID, then the number of patients starting either class of drugs first would be equal. Of all the cardiovascular medication classes examined, including beta blockers, diuretics, nitrates, and digoxin, only CCB and angiotensin-converting enzyme inhibitors (ACE inhibitors) appeared to have a depressionprovoking effect. Although somewhat suggestive, this type of analysis is questionable since it does not directly assess depressive symptoms before and during therapy. A follow-up investigation was performed two years later and examined suicide rates and the use of various cardiovascular medications including diuretics, beta blockers, ACE inhibitors, nitrates, and calcium channel blockers.47 Approximately 3,400 patients were included in the cohort, of which 18.2 percent were classified as users of CCBs. The only class not found to have a positive correlation was the ACE inhibitors. However, after statistical adjustments for the rates of use among the classes, only CCBs were found to have a statically significant positive correlation (i.e., increased risk of suicide). The authors concluded that the absolute risk of CCB use and suicide was 1.1 suicides per 1,000person years. Contrary to the above investigations, Dunn et al48 found no evidence of DID in patients treated with diltiazem and nicardipine, compared with individuals who were not receiving these drugs in general practice settings. This evaluation may be considered stronger than those reviewed above in that it screened for depression based on the general practitioners’ diagnoses over a fiveyear period. The authors do point out that depression may be underdiagnosed, but this would presumably be true in the control groups as well. In summary, given the variations in methodology and the conflicting results, the evidence for CCBs causing a DID is limited. As with beta blockers, newer agents are now available, which may be less frequently associated with a DID. ACE inhibitors. The Hallas study46 did find a significant positive correlation between ACE inhibitor use and concomitant antidepressant prescribing. However, this study did not directly assess for depression, and the method of prescription sequence symmetry may not truly assess DID. Furthermore, case reports, case series, and an openlabel trial have actually found certain ACE inhibitors effective in the treatment of major depression.49–51 Accordingly, we would conclude that, based on such limitations in study design, there is only limited evidence linking ACE inhibitors with DID. Angiotensin II blockers (ARBs). The angiotensin II blockers valsartan and losartan are generally reserved for patients who cannot tolerate or are resistant to ACE inhibitor therapy. As with the ACE inhibitors, the link between ARBs and DID is weak. A single case report of valsartan-induced depression and attempted suicide was reported in a 43-year-old female patient.52 The patient was also taking atenolol and the diuretic hydrochlorthiazide at the time of evaluation; however, the regimen of valsartan and hydrochlorothiazide was implicated in DID, since it was initiated four weeks prior to the suicide attempt. Upon discontinuation of the valsartan and hydrochlorthiazide, the symptoms resolved. Although a weak association may exist, others have found losartan to possess antidepressant-like effects in mice.53 In short, the evidence implicating ARBs in DID is based on a single case report. Future research may be geared to examining these agents as antidepressants, not depressogenics. patients treated with rimonabant were 2.5 times more likely to discontinue therapy secondary to depression. The FDA also reviewed the same studies included in this meta-analysis and concluded that 26 percent of rimonabant-treated patients were more likely to have an adverse psychiatric event. Suicidal ideation and/or attempt were almost twice as likely.55 Further strengthening the concern for these agents was the decision by Merck to halt the development of the related agent, taranabant.56 They did so based on psychiatric side effects, including depression, experienced by patients. Thus, the evidence linking cannabinoid antagonists to DID appears strong. ANTIVIRALS The clinically used interferons are classified as alpha or beta. Alpha interferons are used in the treatment of hepatitis C as well as various forms of cancer; whereas, beta interferons are used in the treatment of multiple sclerosis. Surprisingly, the literature suggests different levels of DID risk associated with the two types of interferon. Alpha interferons. The alpha interferons (2a and 2b) have been associated with depression in many uncontrolled and controlled investigations.57–61 The incidence of depression in interferon-treated hepatitis C patients ranges widely from 3 to 50 percent. Much of this discrepancy is due to the variations in screening and to the individual evaluator (i.e., psychiatrist vs. gastroenterologist). The most recent prospective, open-label investigation60 found that approximately 33 percent of interferon-treated patients developed new-onset depression after 12 weeks. Similar studies have reported essentially the same findings. It is hypothesized that interferon alpha therapy causes neurotransmission abnormalities in the basal ganglia and limbic system. Screening for depression before and during interferon alpha therapy is recommended and should be 12, DECEMBER] ANTIOBESITY AGENTS Rimonabant, a cannabinoid antagonist and antiobesity agent, is available in numerous countries, but did not receive approval from the FDA. Rimonabant’s utility as an antiobesity agent may be limited by its high incidence of psychiatric adverse events. In a meta-analysis, Christensen et al54 found that, compared to those taking placebo, [VOLUME 5, NUMBER Psychiatry 2008 35

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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