Psychiatry - December 2008 - (Page 31)

practice, ethical concerns virtually prohibit the use of controlled studies as a means of assessing drug side effects. Dhondt summarizes the predicament as follows: “The association of medication use with depression is not synonymous with a causal relation. Because of the multifactorial origins of depression, what is needed is a study on the etiology of depression taking into account as many possible other etiological factors. Ideally, the associations found are confirmed in prospective studies. To obtain the strongest evidence for a causal relationship between medication use and depression, randomized, controlled trials would be required. However, as ethical constraints prohibit such studies, observational epidemiological research, including health and disability factors, will probably provide the best possible evidence.15 As Dhondt describes in detail, pharmacoepidemiological research “…merges the concerns of pharmacology with those of epidemiology” by using both internal and external morbidity data. One type of internal morbidity data entails linking the use of drug A with a “rescue” drug B. For example, Thiessen et al16 demonstrated that a greater proportion of patients prescribed propranolol than prescribed other beta blockers received an antidepressant. In this model, antidepressant use is posited as a “marker” for depressive symptoms. External morbidity data entails linkage of medication records and disease records. For example, the incidence of a clinical diagnosis of depression is compared between a cohort of patients who used drug A and those who used drug B (or placebo): If the incidence of depression is higher with drug A, this is considered presumptive evidence of the drug’s depressogenic effect. In this paper, we consider randomized, controlled trials, pharmacoepidemiological studies, and large-scale meta-analyses to be at the top of the evidence hierarchy. We consider case series data (e.g., FIGURE 1. Naranjo causality scale QUESTION Are there previous conclusion reports on this reaction? Did the adverse event appear after the suspect drug was administered? Did the ADR improve when the drug was discontinued or a specific antagonist was administered? Did the ADR reappear when drug was readministered? Are there alternate causes [other than the drug] that could solely have caused the reaction? Did the reaction reappear when a placebo was given? Was the drug detected in the blood [or other fluids] in a concentration known to be toxic? Was the reaction more severe when the dose was increased, or less severe when the dose was decreased? Did the patient have a similar reaction to the same or similar drugs in any previous exposure? Was the adverse event confirmed by objective evidence? YES 1 2 1 2 -1 -1 1 1 1 1 NO 0 -1 0 -1 2 1 0 0 0 0 DON’T KNOW 0 0 0 0 0 0 0 0 0 0 Scoring: > 9 = definite ADR; 5–8 = probable ADR; 1–4 = possible ADR; 0 = doubtful ADR KEY: ADR = adverse drug reaction three or more patients in the same report) and single-case reports as lower levels of evidence. Such hierarchies, while useful for research purposes, are no substitute for clinical judgment. For example, which of the following “counts” as stronger evidence: two pharmacoepidemiologic studies finding no association between drug A and depression or 85 case reports clearly linking drug A with onset of depression? In the absence of randomized, controlled, prospective studies, the clinician is left to use his or her best judgment. Indeed, our tabular listing of drug classes and their evidentiary link with DID (Table 2) merely reflects our best clinical judgment of the data. EPIDEMIOLOGY OF DID To our knowledge, there are no large-scale, epidemiological data directly answering the question, “What is the incidence and [VOLUME 5, prevalence of DID?” in a specific population.17 To answer this question, we would need not only clear and reliable criteria for DID, but also a very large cohort of subjects and a valid method of assessing them for DID. These requirements have not yet coalesced. It is instructive, however, to note the findings of the 1988 study by Maricle et al,18 in which a community sample of 40 elderly subjects were followed up an average of two and one-half years after a diagnosis of depression. Nine subjects were identified with depressive syndromes associated with depressogenic medication— nearly a quarter of the original sample. According to Turner from the FDA’s Division of Neuropharmacologic Drug Products, there is a “lack of consensus” on the scope of DID.19 Nonetheless, a crosssectional, population-based study of 12, DECEMBER] NUMBER Psychiatry 2008 31

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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