Cardiac side effects of psychiatric drugs.

This review describes the common effects of psychotropic drugs on the cardiovascular system and offers guidance for practical management. Selected reports from the literature describing common side effects associated with psychotropic drugs are reviewed, and suggestions for further reading are given throughout the text. Orthostatic hypotension is the most common adverse autonomic side effect of antipsychotic drugs. Among the atypical antipsychotics the risk of orthostatic hypotension is highest with clozapine and among the conventional drugs the risk is highest with low potency agents. Rarely, orthostatic hypotension may result in neurocardiogenic syncope. QTc prolongation can occur with all antipsychotics but an increased risk is seen with pimozide, thioridazine, sertindole and zotepine. QTc prolongation is a marker of arrhythmic risk. Torsade de pointe, a specific arrhythmia, may lead to syncope, dizziness or ventricular fibrillation and sudden death. Heart muscle disease presents most commonly in the elderly as chronic heart failure, but myocarditis and cardiomyopathy, although relatively rare, are devastating, but potentially reversible complications of psychotropic drug therapy have been particularly linked to clozapine treatment. Patients with severe mental illness (SMI) are a 'high risk' population with regard to cardiovascular morbidity and mortality. It is probable that many patients accumulate an excess of 'traditional' risk factors for the development of cardiovascular disease, but other mechanisms including psychotropic drugs may also be influential in increasing risk in this vulnerable group. These risks need to be seen in the context of the undoubted therapeutic efficacy of the psychotropic armamentarium and the relief that these drugs bring to those suffering from mental disorder.

A prospective study of monitoring practices for metabolic disease in antipsychotic-treated community psychiatric patients.

BACKGROUND: Patients with severe mental illness are at increased risk for metabolic and cardiovascular disease. A number of recent guidelines and consensus statements recommend stringent monitoring of metabolic function in individuals receiving antipsychotic drugs. METHODS: We conducted a prospective cohort study of 106 community-treated psychiatric patients from across the diagnostic spectrum from the Northeast of England to investigate changes in metabolic status and monitoring practices for metabolic and cardiovascular disease. We undertook detailed anthropometric and metabolic assessment at baseline and follow-up, and examined clinical notes and hospital laboratory records to ascertain monitoring practices. RESULTS: A high prevalence of undiagnosed and untreated metabolic disease was present at baseline assessment. Mean follow-up time was 599.3 (SD +/- 235.4) days. Body mass index (p < 0.005) and waist circumference (p < 0.05) had significantly increased at follow-up, as had the number of individuals who were either overweight or obese. Fifty-three per cent of individuals had hypertriglyceridemia, and 31% had hypercholesterolemia, but only 7% were receiving lipid-lowering therapy. Monitoring practices were poor. Recording of measures of adiposity occurred in 0% of individuals, and > 50% of subjects had neither blood glucose nor lipids monitored during the follow-up period. CONCLUSION: This cohort has a high prevalence of metabolic disease and heightened cardiovascular risk. Despite the publication of a number of recommendations regarding physical health screening in this population, monitoring rates are poor, and physical health worsened during the follow-up period.

QTc interval measurement and metabolic parameters in psychiatric patients taking typical or atypical antipsychotic drugs: a preliminary study.

BACKGROUND: Antipsychotic drugs have been associated with prolongation of the QTc interval on the electrocardiogram, and QTc prolongation is, in turn, associated with an increased risk of cardiac arrhythmias and sudden death. Antipsychotic polypharmacy has been implicated in reduced survival, possibly secondary to cardiotoxic effects of antipsychotic medication. Abnormalities of glucose homeostasis, which may be more common in individuals with major mood disorders and schizophrenia, also affect the QTc interval. METHOD: We performed detailed assessment of metabolic parameters in 103 psychiatric out-patients, from across the diagnostic spectrum, who had been taking antipsychotic medication (typical, atypical, or a combination thereof) for a minimum of 6 months. We measured the QTc interval in a subset of these patients (N = 65). RESULTS: Only 2 patients (3%) had a prolonged QTc interval. There was a statistical trend (p = .08) toward a lower QTc interval in patients receiving antipsychotic polypharmacy. QTc interval was associated with age (p = .04) but not with any metabolic parameter. CONCLUSION: QTc prolongation in this population is uncommon. There was a significant association between increasing age and QTc interval, but cardiac repolarization was not related to any metabolic parameter. Further large prospective studies of similar patients are needed to confirm these findings.

Significance of microalbuminuria in long-duration type 1 diabetes.

OBJECTIVE: The value of microalbuminuria (MA) in predicting renal disease and premature mortality in longer duration type 1 diabetes is unclear. RESEARCH DESIGN AND METHODS: We followed 135 patients with long-standing type 1 diabetes (>30 years' duration) over a 7-year period, recording albuminuria and other clinical variables. Vital status was ascertained and cause of death was recorded. RESULTS: A total of 27 of 135 patients (20%) died during the follow-up period. Patients with MA (10 of 30, 33.3%) or proteinuria (5 of 6, 83.3%) at initial examination were more likely to die during follow-up than patients who had normal albumin excretion at baseline (12 of 99, 12%; chi(2) for trend 21.9, P < 0.0001). The presence of abnormal albumin excretion and low BMI were independent risk factors of premature death. The causes of death were similar in patients with normal and abnormal urine albumin excretion. A total of 24.4% of initially normoalbuminuric survivors developed MA, and persistent proteinuria developed in 3.5%. Progressors had significantly higher albumin excretion rate at baseline compared with those who remained normoalbuminuric: 9.0 microg/min (3.8-18) vs. 4.0 microg/min (0.4-17.5); P < 0.001. A total of 21% of patients with MA at baseline reverted to normoalbuminuria, and persistent proteinuria developed in 32%. The likelihood of progression to persistent proteinuria was significantly greater in those with baseline MA compared with those with normal albumin excretion (P < 0.001). CONCLUSIONS: Even in long-standing type 1 diabetes of >30 years' duration, MA and proteinuria predict all-cause mortality. MA is a good predictor of persistent proteinuria.

Prolactin and smoking status in antipsychotic-treated patients.

Studies investigating the relationship between cigarette smoking and prolactin secretion in the general population have yielded inconsistent results. Many antipsychotic drugs increase prolactin secretion, but there are no published studies that have investigated the relationship between smoking and prolactinaemia in antipsychotic-treated patients. We obtained prolactin levels from 228 antipsychotic-treated patients in secondary care mental health services and investigated the relationship between prolactinaemia and cigarette smoking. Twenty-three percent (n = 52) of patients had hyperprolactinaemia. Patients prescribed typical or a combination of typical and atypical antipsychotics had a significantly higher prevalence of hyperprolactinaemia and higher mean prolactin concentration. Both current and ex-cigarette smokers had significantly lower mean prolactin levels and a lower prevalence of hyperprolactinaemia, but after controlling for potentially confounding variables, only current smoking status was a significant predictor of lower prolactin levels (OR 2.3, 95% CI 1.2 to 4.7, p = 0.002). In this preliminary, cross-sectional study, there was a robust statistical relationship between cigarette smoking and prolactinaemia. The mechanism(s) underpinning this association needs further investigation.

Wake-up call for British psychiatry.

The recent drive within the UK National Health Service to improve psychosocial care for people with mental illness is both understandable and welcome: evidence-based psychological and social interventions are extremely important in managing psychiatric illness. Nevertheless, the accompanying downgrading of medical aspects of care has resulted in services that often are better suited to offering non-specific psychosocial support, rather than thorough, broad-based diagnostic assessment leading to specific treatments to optimise well-being and functioning. In part, these changes have been politically driven, but they could not have occurred without the collusion, or at least the acquiescence, of psychiatrists. This creeping devaluation of medicine disadvantages patients and is very damaging to both the standing and the understanding of psychiatry in the minds of the public, fellow professionals and the medical students who will be responsible for the specialty's future. On the 200th birthday of psychiatry, it is fitting to reconsider the specialty's core values and renew efforts to use psychiatric skills for the maximum benefit of patients.

Metabolic disease and cardiovascular risk in people treated with antipsychotics in the community.

BACKGROUND: Prevalence of physical comorbidity in severe mental illness is a significant public health concern, but comparative data in people with diagnoses other than schizophrenia are sparse. AIMS: To investigate the prevalence of metabolic disease and cardiovascular risk in people with severe mental illness treated with antipsychotics in the community. METHODS: Case-control study of 90 people treated with antipsychotics in the community and 92 age- and gender-matched controls. The prevalence of metabolic syndrome and 10-year cardiovascular risk were calculated. RESULTS: People on antipsychotics had a significantly worse metabolic profile than controls (F=6.583, d.f.=15,161, P<0.0001). Moreover, metabolic syndrome was more prevalent (OR=3.68, 95% CI 1.71-7.93, P=0.001), as was cardiovascular risk across a number of outcomes. These results are consistent across diagnostic groups. CONCLUSIONS: People with severe mental illness treated with antipsychotics have excess metabolic dysfunction and heightened risk for cardiovascular disease.

Changes in brain-derived neurotrophic factor following treatment with mifepristone in bipolar disorder and schizophrenia.

OBJECTIVE: Brain-derived neurotrophic factor (BDNF) is stress-responsive and has been implicated in a number of disparate neuropsychiatric disorders. Glucocorticoid antagonists have been shown to have beneficial effects on mood and cognitive function in bipolar disorder but not in schizophrenia. The aim of the present study was to investigate BDNF levels in patients with bipolar disorder and schizophrenia before and after treatment with the glucocorticoid receptor antagonist mifepristone. METHODS: Peripheral BDNF levels were measured in patients with bipolar disorder (n=20), schizophrenia (n=20) and 14 matched healthy controls following 7 days of adjunctive mifepristone (600 mg day(-1)) treatment in a double-blind, placebo-controlled crossover design study. RESULTS: Baseline BDNF values were similar in both patient groups and in healthy controls. Following treatment with mifepristone, cortisol levels were significantly increased and BDNF levels decreased in both schizophrenia and bipolar disorder. A significant correlation existed between change in cortisol level and change in BDNF levels following mifepristone treatment in schizophrenia, but not in bipolar disorder. CONCLUSION: Differing BDNF responses to increasing cortisol levels between patients with schizophrenia and with bipolar disorder may reflect underlying pathophysiological mechanisms.

Sleep disordered breathing in community psychiatric patients

Background and Objectives: Sleep disturbance is prominent in many neuropsychiatric disorders and may precipitate or exacerbate a range of psychiatric conditions. Few studies have investigated sleep disordered breathing and in particular obstructive sleep apnoea in community psychiatric patients and the commonly used screening instruments have not been evaluated in patients with psychiatric disorders. The objective is to evaluate the prevalence of sleep disordered breathing in a community cohort with chronic mental illness on long term psychotropic medication, and to assess the effectiveness of commonly used screening instruments to detect abnormal sleep. Methods: 52 patients completed sleep questionnaires and 50 undertook overnight oximetry. Results: 52% (n = 26) had sleep-disordered breathing; 20% (n = 10) had moderate/severe sleep apnoea. The Epworth Sleepiness Score and the Pittsburgh Sleep Quality Inventory did not predict sleep disordered breathing. Conclusions: Patients with psychiatric disorders in the community have a high rate of undiagnosed sleep disordered breathing, which is not reliably detected by established sleep disorder screening questionnaires (AU)

Culture and assessment of manic symptoms.

Cultural background may influence the perception of psychiatric symptoms. We examined the effects of cultural biases on the identification of manic symptoms using the Young Mania Rating Scale. Two video interviews, each with an American person with mania, were shown to psychiatrists from three countries (US, UK and India). Total scores on the scale differed significantly between the US and UK (P<0.001) and between India and UK (P<0.001) rater groups. Overall, differences between India and US rater groups were less marked (P=0.28). These differences suggest that cultural biases influence the interpretation of manic symptoms.

Executive and visuospatial sketchpad resources in euthymic bipolar disorder: Implications for visuospatial working memory architecture.

Visuospatial working memory theory is used to interpret the cognitive impairment in euthymic bipolar disorder. Such patients show deficits in the Corsi Blocks Test (CBT) and executive control. To understand these deficits, 20 euthymic bipolar patients and controls were administered the CBT, Visual Patterns Test (VPT), and a new visual memory task designed to make minimal demands on executive resources. Initial analyses validated the visual memory task and implicated executive involvement in the CBT and VPT. Subsequent analyses on a number of tests confirmed CBT and executive deficits while performance was normal on the VPT and visual memory test. ANCOVA indicated that impaired executive function underpinned patients' CBT performance. Implications for the interface between executive and slave systems of working memory are discussed.

Frontotemporal dementia: remembering images from the past.

Frontotemporal dementia (FTD) is the most common form of primary degenerative dementia after Alzheimer's disease that affects people in middle age. The average delay in reaching an accurate diagnosis has been reported to be around 3 years. We report a case of FTD in a 35-year-old female who presented with complex symptoms and no clear physical signs. This case draws attention to the problems inherent in the traditional functional-organic divide that continues to characterize investigation and diagnosis in modern psychiatric practice, and highlights the importance of reevaluating the results of previous "normal" investigations in the light of the developing clinical picture.

Rapid cycling bipolar disorder: historical overview and focus on emerging treatments.

OBJECTIVE: Rapid cycling bipolar disorder presents a significant challenge with respect to treatment. The cyclical nature of bipolar disorder has been well recognised for over a century, and following Dunner and Fieve's landmark paper in 1974, investigators have increasingly turned their attention to issues such as the definition of rapid cycling, demographic characterisation, treatment response and pharmacologic intervention. METHODS: A literature search using Medline was performed, and selected articles which consider important developments in the definition, demographics and course of rapid cycling are reviewed. In addition, a systematic review of the literature published during the past 5 years (1999-2004) relating to treatment was conducted. RESULTS: Relevant articles are reviewed. CONCLUSIONS: This review highlights the important developments in our understanding of rapid cycling bipolar disorder, and focuses particularly on the recent literature regarding treatment.