Wernicke's Encephalopathy: Increasing Clinician Awareness of This Serious, Enigmatic, Yet Treatable Disease.

OBJECTIVE: Undiagnosed and/or undertreated Wernicke's encephalopathy can result in permanent brain damage, long-term institutionalization, and death. The purpose of this article is to heighten clinical awareness of Wernicke's encephalopathy and shed light on its diagnosis and treatment, which are often inconsistent due to unclear diagnostic criteria and limited practice guidelines. An update on the management of Wernicke's encephalopathy is presented and several case reports and a quality improvement project from our hospital are described. DATA SOURCES: PubMed, the Cochrane Database of Systematic Reviews, and PsycINFO were searched for English-language articles published between January 1991 and January 2014 using combinations of the following keywords: Wernicke's encephalopathy, diagnosis, treatment/guideline(s), and thiamine. STUDY SELECTION: The automated search identified over 500 articles. A manual review of the related citations and reference lists from articles of interest was also conducted. The articles reviewed were chosen on the basis of author consensus and because they represented expert opinion or the highest quality of evidence available. RESULTS: Diagnostic criteria are reviewed in this article and should be used to diagnose Wernicke's encephalopathy with high sensitivity and specificity. The European Federation of Neurologic Societies and the Royal College of Physicians issued national guidelines for the diagnosis, prevention, and treatment of Wernicke's encephalopathy. No benchmark national guidelines for treating Wernicke's encephalopathy exist in the United States. CONCLUSIONS: Whenever Wernicke's encephalopathy is suspected, treatment should be initiated immediately with intravenous thiamine because oral thiamine is inadequate for preventing permanent brain damage. An adequate dose of intravenous thiamine administrated in a timely manner is a safe and life-saving treatment for Wernicke's encephalopathy that could preserve brain cells and function.

Effects of heart disease on depression treatment: results from the COMED study.

OBJECTIVE: To determine the impact of self-reported heart disease (HD) on major depressive disorder (MDD) treatment outcomes. METHOD: This single-blind, 7-month prospective randomized trial enrolled 665 participants, 18-75 years old, from six primary and nine psychiatric care sites across the USA. Participants had at least moderately severe (baseline 17-item Hamilton Rating Scale of Depression ≥16), nonpsychotic chronic and/or recurrent MDD. Participants with and without self-reported HD were randomized into three treatment groups (1:1:1 ratio): escitalopram plus placebo, bupropion sustained-release plus escitalopram or venlafaxine extended-release plus mirtazapine. The primary outcome (remission) was defined by the last two consecutive 16-item Quick Inventory of Depressive Symptomatology-Self-Report (QIDS-SR(16)) ratings: one had to be <8 and one <6. Secondary outcomes included response (reduction in QIDS-SR(16) >50%) side-effect burden, quality of life and functioning. A P value <.05 indicated statistical significance. RESULT: Participants with HD were less depressed at baseline and demonstrated fewer side effects at Treatment Weeks 12 and 28. The HD groups did not differ regarding remission [40.0% (16/40) vs. 38.2% (239/625), P=.5566] or response [50% (20/40) vs. 52.1% (314/625), P=.8055]. CONCLUSIONS: Despite apparent baseline and side-effect differences between participants with and without HD, the two groups did not differ regarding MDD treatment outcomes.

Antidepressant treatment and altered CYP2D6 activity: are pharmacokinetic variations clinically relevant?

BACKGROUND: Many currently used antidepressants are substrates of the cytochrome P450 (CYP) 2D6 enzyme. In patients who experience variations in the activity of this enzyme (e.g., CYP2D6 poor and ultrarapid metabolizers [PMs and UMs]), whether caused by genetic polymorphisms or concomitant administration of a CYP2D6 inhibitor (i.e., phenoconversion), the pharmacokinetics, and hence the effects, of CYP2D6 substrate antidepressants can be altered. METHODS: This literature review describes the clinical and empirical evidence indicating that alterations in CYP2D6 activity can negatively affect treatment outcomes in patients receiving antidepressant pharmacotherapies that are CYP2D6 substrates. RESULTS: Based on results from a small, prospective trial, a population analysis, and a pooled analysis, CYP2D6 PMs treated with agents dependent on CYP2D6 metabolism to form an active metabolite can experience a decline in antidepressant effect. Based on a population analysis and two case studies, CYP2D6 UMs treated with antidepressants that are CYP2D6 substrates and administered in a pharmacologically active form do not experience an antidepressant effect due to the agent being too rapidly eliminated from the body. Conversely, based on prospective trials, population analyses, and case studies, phenotypic and phenoconverted CYP2D6 PMs can experience an increase in concentration-dependent adverse events due to the agent being eliminated too slowly from the body. CONCLUSIONS: Despite these examples, few large-scale, prospective trials exploring the effect of altered CYP2D6 metabolism on antidepressant outcomes have been conducted. Future clinical trials of CYP2D6-dependent antidepressants should be designed to allow for stratification of treatment outcomes by CYP2D6 metabolizer status.

Twenty percent of a representative sample of patients taking bupropion have abnormal, asymptomatic electroencephalographic findings.

The risk of dose-dependent seizures is a safety issue with bupropion hydrochloride. To evaluate the presence of specific electroencephalographic (EEG) waveforms, 210 adult subjects taking stable doses of bupropion hydrochloride were recruited to undergo 2 EEGs in a prospective, single-center cohort study. The occurrence of spike waves, sharp waves, and focal slowing was recorded and assessed with a continuation ratio logit model for polytomous responses. This model showed that there was a relationship between sex and the incidence of these waveforms, such that the odds of female subjects having sharp waves was increased by a factor of 2.53 (P = 0.05) when compared with male subjects and controlled for both age and dose. Similarly, female subjects were 2.45 (P = 0.09) times more likely than males to have focal slowing on EEG. Overall, 19.8% (39/197) of this representative population was found to have abnormal, asymptomatic EEG findings. The presence of these waveforms in individuals taking a medication known to lower the seizure threshold may be a risk factor for developing seizures.