Psychiatry - December 2008 - (Page 34)

various times during the study. One of the most rudimentary and questionable assessment methods uses the question, “Have you ever felt depressed?”26 Thus, one must carefully examine such screening methods before associating any drug with the development of DID. ANTIHYPERTENSIVES Beta blockers. One of the most touted yet controversial claims regarding DID implicates beta-1 receptor antagonists, better known as beta blockers. These agents have long been recognized for their ability to reduce morbidity and mortality in patients with hypertension27 and are also used for heart failure and arrhythmias. Unfortunately, this class of medication is often underutilized, possibly owing to concerns about side effects and tolerability.28 Thus, both medical references and patient-education information often include depression as a potential adverse reaction. Interestingly, some agents within the class (e.g., pindolol)29 have also been studied as augmenting agents in the treatment of depression, suggesting that DID may not be associated with all beta blockers. The oldest citation implicating a beta blocker and DID is from a 1967 letter to the editor of the British Medical Journal.30 It was suggested that a high incidence of depression (30%) was seen in a series of 89 patients receiving propranolol. Two of the 27 patients exhibiting depression completed suicide and two others required antidepressant therapy. These findings were immediately disputed31 and so the controversy began. Since the original 1967 report, numerous case reports16,32–35 have been published and several randomized trials36–40 have investigated depression as a side effect of many beta blockers. Although the number of studies reporting DID appears convincing, a large-scale meta-analysis conducted by Ko et al41 did not support the association. In this study, seven 34 Psychiatry 2008 [ V O L U M E 5, NUMBER trials and more than 10,500 patients were evaluated. These authors concluded that the overall incidence of depression was comparable to placebo (20.1% vs. 20.5%). In a separate multistudy analysis, Steffensmeier et al13 conducted a review of the literature on beta blockers and DID. Using the Naranjo algorithm, they found that DID was most likely to be evident soon after a dose increase; conversely, DID symptoms subsided when the dose was reduced. In addition, the highly lipophilic agent, propranolol, was the beta blocker most frequently implicated in DID, perhaps pointing to CNS penetration as an important variable.13 Large-scale, controlled, and statistically analyzed data suggest that beta blockers may not be as strongly linked to DID as previously thought. Moreover, in evaluating the literature, clinicians need to consider the generation of each beta blocker as well as its lipophilicity and receptor selectivity. Propranolol and timolol are considered first- or early- generation agents, and propranolol, carvedilol, and bucindolol are highly lipophilic. Greater lipophilicity allows greater penetration of the blood brain barrier; in theory, this might predict a greater risk of DID. Propranolol, nadolol, timolol, and pindolol are all nonselective beta blockers, demonstrating equal affinity for both beta1- and beta2-receptors; whereas, metoprolol has greater activity at beta-1 receptors. Compared to selective agents, nonselective beta blockers exert a wider variety of extracardiac manifestations; however, there are insufficient controlled data to determine whether beta selectivity, per se, is associated with greater risk of DID. It is also important to recognize that propranolol was the first marketed beta blocker. The use of propranolol as a first-line agent has significantly declined with the availability of more cardioselective agents (e.g., metoprolol for the treatment of heart failure). 12, DECEMBER] Given the conflicting data, we believe that the original concern from 1967 is not warranted for the entire beta blocker class. Physicians should not be hesitant to use these medications when appropriate. Nevertheless, individual patients may show idiosyncratic depressive reactions to a given beta blocker, and clinicians concerned about DID should exercise particular caution during initial dosing and after any dosage increase. Dosage reduction should be considered before discontinuation. If discontinuation is necessary, beta blockers should generally be tapered off gradually, to avoid “rebound” tachycardia or hypertension. Calcium channel blockers. Like beta blockers, calcium channel blockers (CCBs) are an extremely useful class of medication in certain patient populations. CCBs have approved indications for multiple cardiovascular conditions, including hypertension, angina, and arrythmias, as well as for migraine prophylaxis. And, like beta blockers, CCBs have been used in patients with various psychiatric disorders, such as bipolar disorder and panic disorder. Very few well-designed studies implicate CCBs in DID, though two separate case series (N=6) suggest nifedipine as a potential offender.42,43 Two of the depressed patients, one from each report, were resistant to treatment with nortriptyline; and, in all six patients, resolution of depression occurred when nifedipine was discontinued. Applying the Naranjo algorithm to these case reports, nifedipine would receive a score of 5, suggesting a probable association. Case reports also exist for diltiazem and verapamil.44,45 In 1996, Hallas performed an epidemiologic study examining the depression-provoking effects of various cardiovascular medications.46 The author screened more than 11,000 patients started on various cardiovascular medications and concomitant antidepressants in a predefined period. It was expected that if cardiovascular drugs did not

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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