Ursula Werneke

A systematic review and meta-analysis of Hypericum perforatum in depression: a comprehensive clinical review

The herbal remedy St Johns wort is widely used as an antidepressant but its efficacy has not been systematically investigated. Meta-analyses and systematic reviews of published trials strongly suggest St Johns wort is more effective than placebo although comparative efficacy to standard antidepressants is less clearly established. We updated and expanded previous meta-analyses of St Johns wort, scrutinised the validity of published reports and examined possible mechanisms of action. Twenty-two randomised controlled trials were identified. Meta-analysis showed St Johns wort to be significantly more effective than placebo (relative risk (RR) 1.98 (95% CI 1.49-2.62)) but not significantly different in efficacy from active antidepressants (RR 1.0 (0.90-1.11)). A sub-analysis of six placebo-controlled trials and four active comparator trials satisfying stricter methodological criteria also suggested that St Johns wort was more effective than placebo (RR 1.77 (1.16-2.70)) and of similar effectiveness to standard antidepressants (RR 1.04 (0.94-1.15)). There was no evidence of publication bias. Adverse effects occurred more frequently with standard antidepressants than with St Johns wort. The mechanism of action of St Johns wort remains unknown. Future research should include large scale, appropriately powered comparisons of St Johns wort and standard antidepressants.

Options for pharmacological management of obesity in patients treated with atypical antipsychotics

Obesity is associated with considerable morbidity and decreased life expectancy. Weight gain is a commonly encountered problem associated with antipsychotic treatment. We reviewed the literature regarding the mechanisms of weight gain in response to these agents and eight substances implicated as potential obesity prevention or treatment: orlistat, sibutramine, fluoxetine, topiramate, amantadine, nizatidine and cimetidine, and metformin. Weight gain in response to antipsychotic treatment may be mediated through serotonergic, dopaminergic, adrenergic, cholinergic, histaminergic and glutaminergic receptors. Sex hormone dysregulation and altered insulin sensitivity have also been implicated. Two compounds, orlistat and sibutramine, have been shown to help prevent weight gain following a hypocaloric diet, but orlistat requires compliance with a fat-reduced diet, and sibutramine is unsuitable for patients taking serotonergic agents. The weight reducing effect of fluoxetine, even in conjunction with a hypocaloric diet, is only transient. Topiramate, amantadine and metformin may have adverse side-effects potentially outweighing the weight reducing potential. The effectiveness of cimetidine and nizatedine remains unclear. The hazards of these agents in a psychiatric population are discussed. It is concluded that the current evidence does not support the general use of pharmacological interventions for overweight patients treated with antipsychotic medication, although individually selected patients may benefit.

Potential health risks of complementary alternative medicines in HIV patients

To determine the prevalence and purpose of complementary alternative medicines (CAMs) use in people receiving treatment for HIV infection. To identify and quantify potential health risks of CAM use in this population and to explore options for improved pharmacovigilance.

A decision analysis of long‐term lithium treatment and the risk of renal failure

Werneke U, Ott M, Salander Renberg E, Taylor D, Stegmayr B. A decision analysis of long‐term lithium treatment and the risk of renal failure.

Behavioral Interventions for Antipsychotic Induced Appetite Changes

Weight gain remains a well recognized yet difficult to treat adverse effect of many anti-psychotic drugs including agents of the first and second generation. The weight gain liabilities of antipsychotic drugs are partly associated with their ability to increase appetite. Most behavioral interventions for weight control remain of limited efficacy, possibly because they do not specifically target the neuroendocrine factors regulating appetite. Identifying new weight management interventions directly acting on the biochemical and neuroendocrine mechanisms of anti-psychotic induced weight gain may help to improve the efficacy of behavioral weight management programs. Such potentially specific strategies include (1) using diets which do not increase appetite despite calorie restriction; (2) countering thirst as an anticholinergic side-effect; (3) discouraging cannabis use and (4) adding metformin to a behavioral intervention. In view of our currently rather limited treatment repertoire it seems timely systematically to explore such novel options.

An evidence-based guideline for children presenting with acute breathing difficulty

Objective: The aim of this study was to develop an evidence-based guideline for use primarily by junior clinicians to assist with the management of children presenting to the hospital with an acute breathing difficulty. Methods: An overview of the literature provided a framework of clinical questions for the management of a child with an acute breathing difficulty on which to base a systematic literature review. Relevant articles were appraised by the research fellow and graded according to their quality. A national panel of 50 clinicians was provided, by post, with the clinical questions, research papers, appraisals and the grades of recommendations generated. They were asked to check the grades allocated to the recommendations and the accuracy of the language used. They were also provided with all the clinical questions for which there was insufficient evidence to reach a conclusion but for which a consensus recommendation was required. A Delphi method was used to formalise the consensus process. For all recommendations, panel members were asked to rate their level of agreement on a 1–9-point Likert scale. The results of the first round were fed back, and appropriate alterations to the recommendations made or additional recommendations included. The process of rating was repeated, and the final guideline was developed based on the consensus reached. Results: Following two iterative rounds, the guideline was completed as a full technical document, with a series of key recommendations and an algorithm. It was based on 10 grade A (evidence from systematic review or meta-analyses), 5 grade B, 17 grade C and 31 grade D (consensus or expert opinion) recommendations. Conclusion: We have developed an evidence-based guideline that has subsequently been successfully implemented in the paediatric emergency departments and disseminated nationally. Results showing the effect of the guideline upon practice will be published separately.

Lithium intoxication: Incidence, clinical course and renal function – a population-based retrospective cohort study

When prescribing lithium, the risk of toxicity remains a concern. In this study, we examined a cohort of patients exposed to lithium between 1997 and 2013. The aims of this study were to determine the frequency of lithium intoxication and to evaluate the clinical course and changes in renal function. Of 1340 patients, 96 had experienced at least one episode of lithium levels ⩾1.5 mmol/L, yielding an incidence of 0.01 per patient-year. Seventy-seven patients available for review had experienced 91 episodes, of whom 34% required intensive care and 13% were treated with haemodialysis. There were no fatalities. Acute kidney injury occurred, but renal function at baseline was not different to renal function after the episode. Renal impairment was often associated with co-morbidities and other factors. Both intermittent and continuous-venovenous haemodialysis were used, but the clearance of continuous-venovenous haemodialysis can be too low in cases where large amounts of lithium have been ingested. Saline and forced diuresis have been used and are safe. Lithium intoxication seems rare and can be safely managed in most cases. Physicians should not withhold lithium for fear of intoxication in patients who benefit from it. Yet, physicians should have a low threshold to screen for toxicity.

Conundrums in neurology: diagnosing serotonin syndrome – a meta-analysis of cases

BackgroundSerotonin syndrome is a toxic state, caused by serotonin (5HT) excess in the central nervous system. Serotonin syndrome’s main feature is neuro-muscular hyperexcitability, which in many cases is mild but in some cases can become life-threatening. The diagnosis of serotonin syndrome remains challenging since it can only be made on clinical grounds. Three diagnostic criteria systems, Sternbach, Radomski and Hunter classifications, are available. Here we test the validity of four assumptions that have become widely accepted: (1) The Hunter classification performs clinically better than the Sternbach and Radomski criteria; (2) in contrast to neuroleptic malignant syndrome, the onset of serotonin syndrome is usually rapid; (3) hyperthermia is a hallmark of severe serotonin syndrome; and (4) serotonin syndrome can readily be distinguished from neuroleptic malignant syndrome on clinical grounds and on the basis of medication history.MethodsSystematic review and meta-analysis of all cases of serotonin syndrome and toxicity published between 2004 and 2014, using PubMed and Web of Science.ResultsTwo of the four assumptions (1 and 2) are based on only one published study each and have not been independently validated. There is little agreement between current criteria systems for the diagnosis of serotonin syndrome. Although frequently thought to be the gold standard for the diagnosis of the serotonin syndrome, the Hunter criteria did not perform better than the Sternbach and Radomski criteria. Not all cases seem to be of rapid onset and only relatively few cases may present with hyperthermia. The 0 differential diagnosis between serotonin syndrome and neuroleptic malignant syndrome is not always clear-cut.ConclusionsOur findings challenge four commonly made assumptions about serotonin syndrome. We propose our meta-analysis of cases (MAC) method as a new way to systematically pool and interpret anecdotal but important clinical information concerning uncommon or emergent phenomena that cannot be captured in any other way but through case reports.

Complementary medicines in mental health

The use of complementary medicines for mental health problems generates wide public interest. Patients, particularly when suffering from chronic mental health problems such as anxiety and depression, may use complementary medicines for a variety of reasons. Some may feel that a complementary approach is more “integrative” balancing mind and body; others may wish to gain control of their mental health problems. Again others may have been disappointed by conventional treatments.1 With the ubiquitous availability of knowledge in today’s high tech world, patients are increasingly well informed about treatment options. They may even be more knowledgeable about complementary medicines than clinicians whose experience in this area of practice is usually quite limited. Indeed, current professional regulations may make it extremely difficult for doctors to practise complementary medicine. Very rarely conventional treatment options, which a clinician is professionally bound to give preference, cannot be identified. Pharmacological complementary medicines are not subject to the same strict licensing requirements as conventional medicines, and commonly complementary remedies are just registered as food supplements rather than as medicinal substances.2 The range of complementary medicines is huge. Pharmacological options include herbal medicines and food supplements. These are further reviewed in this article in regard to the most common psychiatric problems encountered. Countless non-pharmacological options also exist, including acupuncture, transcutaneous electric nerve stimulation (TENS), aromatherapy, homeopathy, yoga, biofeedback, relaxation, meditation, hypnosis, reiki/therapeutic touch and reflexology. However, a review of all treatments would be beyond the scope of this review. Evaluating the effectiveness of complementary medicines can be a daunting task. Perceived effectiveness may originate from anthropological sources describing the use of folk remedies over hundreds and sometimes even thousands of years. Many remedies have percolated this way, but systematically derived clinical evidence often remains limited (table 1). Regarding mental health problems, most of the evidence is …

Review: adding Chinese herbal medicine to antipsychotics may improve some outcomes in schizophrenia, but more high quality trials are needed.

Review : adding Chinese herbal medicine to antipsychotics may improve some outcomes in schizophrenia, but more high quality trials are needed.