Psychiatric adverse effects of zonisamide in patients with epilepsy and mental disorder comorbidities

Over the last few years, zonisamide has been proposed as a potentially useful medication for patients with focal seizures, with or without secondary generalization. Since psychiatric adverse effects, including mania, psychosis, and suicidal ideation, have been associated with its use, it was suggested that the presence of antecedent psychiatric disorders is an important factor associated with the discontinuation of zonisamide therapy in patients with epilepsy. We, therefore, set out to assess the tolerability profile of zonisamide in a retrospective chart review of 23 patients with epilepsy and comorbid mental disorders, recruited from two specialist pediatric (n=11) and adult (n=12) neuropsychiatry clinics. All patients had a clinical diagnosis of treatment-refractory epilepsy after extensive neurophysiological and neuroimaging investigations. The vast majority of patients (n=22/23, 95.7%) had tried previous antiepileptic medications, and most adult patients (n=9/11, 81.8%) were on concomitant medication for epilepsy. In the majority of cases, the psychiatric adverse effects of zonisamide were not severe. Four patients (17.4%) discontinued zonisamide because of lack of efficacy, whereas only one patient (4.3%) discontinued it because of the severity of psychiatric adverse effects (major depressive disorder). The low discontinuation rate of zonisamide in a selected population of patients with epilepsy and neuropsychiatric comorbidity suggests that this medication is safe and reasonably well-tolerated for use in patients with treatment-refractory epilepsy. Given the limitations of the present study, including the relatively small sample size, further research is warranted to confirm this finding. © 2013 Elsevier Inc.

Type 2 diabetes:assessing the relative risks and benefits of glucose-lowering medications

The selection of appropriate pharmacologic therapy for any disease requires a careful assessment of benefit and risk. In the case of type 2 diabetes, this decision typically balances the benefits accrued from improved glycemic control with the risks inherent in glucose-lowering medications. This review is intended to assist therapeutic decision-making by carefully assessing the potential benefit from improved metabolic control relative to the potential risks of a wide array of currently prescribed glucose-lowering agents. Wherever possible, risks and benefits have been expressed in terms of absolute rates (events per 1000 patient-years) to facilitate cross-study comparisons. The review incorporates data from new studies (Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation, Action to Control Cardiovascular Risk in Diabetes, and the Veterans Affairs Diabetes Trial), as well as safety issues associated with newer glucose-lowering medications. © 2010 Elsevier Inc. All rights reserved.

The laboratory assessment of thyroid function with special reference to the importance of thyroid abnormality in psychiatric disease

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Do stressful times call for team-based working? A study of psychiatric nurses in UK mental healthcase

Background: Team-based working is now an inherent part of effective health care delivery. Previous research has identified that team working is associated with positive mental health and well-being outcomes for individuals operating in an effective team environment. This is a particularly important topic in the health services context, although little empirical attention has been paid to mental-health services. Psychiatric nurses work on a day-to-day basis with a particularly stressful and demanding client group in an environment which is characterised by high demands, uncertainty, and limited resources. This paper specifically focuses on psychiatric nurses working in National Health Service (NHS) and casts some light on the ways in which effective team-based working can help to alleviate a number of occupational stressors and strains. Method: A questionnaire method (2005 NHS Staff Survey) was employed to collect data from 6655 psychiatric nurses from 64 different NHS Trusts. The hypotheses were concerned with four overall measures from the survey; effective team working, occupational stress, work pressure and social support. Hypothesis 1 stated that effective team working will have a significant negative relationship with occupational stress and work pressure. Further, Hypothesis 2 stated that social support from supervisors and co-workers will moderate this relationship. Findings: Data was treated with a series of regression analyses. For Hypothesis 1, working in a real team did have main effects on work pressure and accounted for 1.6 per cent of the variance. Using the Nagelkerke R square value, working in a real team also had main effects on occupational stress an accounted for approximately 2.8 per cent of the variance. Further, the Exp (B) value of 0.662 suggests that the odds of suffering from occupational stress are cut by 33.8 per cent when a psychiatric nurse works in a real team. Results failed to provide support for Hypothesis 2. The analysis then went on to adopt a unique approach for assessing the extent of real team-based working, distinguishing between real teams, and a number of pseudo team typologies, as well as the absence of teamwork all together. As was hypothesised, results demonstrated that psychiatric nurses working in real teams (ones with clear objectives, where-by team members work closely with one another to achieve team objectives and meet regularly to discuss team effectiveness and how it can be improved) experienced the lowest levels of stress and work pressure of the sample. However, contrary to prediction, results indicated that psychiatric nurses working in any type of pseudo team actually experienced significantly higher levels of stress and work pressure than those who did not report as working in a team at all. Discussion: These findings have serious implications for NHS Mental Health Trusts, which may not be implementing, structuring and managing their nursing teams adequately. Indeed, results suggest that poorly-structured team work may actually facilitate stress and pressure in the workplace. Conversely, well-structured real teams serve to reduce stress and work pressure, which in turn not only enhances the working lives and well-being of psychiatric nurses, but also greatly improves the service that the NHS provides to its users.

Stressful times call for team-based measures:psychiatric nursing in the UK National Health Service

Background: Team-based working is now an inherent part of effective health care delivery. Previous research has identified that team working is associated with positive mental health and well-being outcomes for individuals operating in an effective team environment. This is a particularly important topic in the health services context, although little empirical attention has been paid to mental-health services. Psychiatric nurses work on a day-to-day basis with a particularly stressful and demanding client group in an environment which is characterised by high demands, uncertainty, and limited resources. This paper specifically focuses on psychiatric nurses working in National Health Service (NHS) and casts some light on the ways in which effective team-based working can help to alleviate a number of occupational stressors and strains. Method: A questionnaire method (2005 NHS Staff Survey) was employed to collect data from 6655 psychiatric nurses from 64 different NHS Trusts. The hypotheses were concerned with four overall measures from the survey; effective team working, occupational stress, work pressure and social support. Hypothesis 1 stated that effective team working will have a significant negative relationship with occupational stress and work pressure. Further, Hypothesis 2 stated that social support from supervisors and co-workers will moderate this relationship. Findings: Data was treated with a series of regression analyses. For Hypothesis 1, working in a real team did have main effects on work pressure and accounted for 1.6 per cent of the variance. Using the Nagelkerke R square value, working in a real team also had main effects on occupational stress an accounted for approximately 2.8 per cent of the variance. Further, the Exp (B) value of 0.662 suggests that the odds of suffering from occupational stress are cut by 33.8 per cent when a psychiatric nurse works in a real team. Results failed to provide support for Hypothesis 2. The analysis then went on to adopt a unique approach for assessing the extent of real team-based working, distinguishing between real teams, and a number of pseudo team typologies, as well as the absence of teamwork all together. As was hypothesised, results demonstrated that psychiatric nurses working in real teams (ones with clear objectives, where-by team members work closely with one another to achieve team objectives and meet regularly to discuss team effectiveness and how it can be improved) experienced the lowest levels of stress and work pressure of the sample. However, contrary to prediction, results indicated that psychiatric nurses working in any type of pseudo team actually experienced significantly higher levels of stress and work pressure than those who did not report as working in a team at all. Discussion: These findings have serious implications for NHS Mental Health Trusts, which may not be implementing, structuring and managing their nursing teams adequately. Indeed, results suggest that poorly-structured team work may actually facilitate stress and pressure in the workplace. Conversely, well-structured real teams serve to reduce stress and work pressure, which in turn not only enhances the working lives and well-being of psychiatric nurses, but also greatly improves the service that the NHS provides to its users.

The development of Cannabidiol as a psychiatric therapeutic:a review of its antipsychotic efficacy and possible underlying pharmacodynamic mechanisms

Cannabidiol (CBD), a once-considered inert cannabis constituent, is one of two primary constituents of cannabis, alongside delta-9-tetrahydrocannabinol (?9-THC/THC). In the last 30 years, CBD has become implicated with a range of pharmaceutical mechanisms of great therapeutic interest and utility. This review details the literature speculating CBD’s attenuation of psychotic symptoms, particularly in light of a marked elevation in mean THC concentrations, and a concomitant decline in CBD concentrations in the prevalent U.K street market cannabis derivatives since c. 2000. CBD is purported to exhibit pharmacology akin to established atypical antipsychotics, whilst THC has been implicated with the precipitation of psychosis, and the induction of associated symptoms. The aim of the review was to clarify the conjecture surrounding CBD’s antipsychotic efficacy, before going on to detail prominent theories about its associated pharmacodynamics. Were CBD’s antipsychotic efficacy established, then there is potential for major latent anthropological repercussions to manifest, such as significant elevations in psychosis manifestations in the U.K. The review found a largely affirmative body of evidence asserting CBD’s antipsychotic efficacy. CBD exhibited capacity to attenuate natural and artificially induced psychoses in both animal and human cohorts, the latter of which included individuals considered resistant to conventional treatment. CBD also shows promising potential for use as an antipsychotic drug for Parkinson’s disease (PD) patients with psychosis, owing to its low rate of extra-pyramidal side-effect induction. A range of potential pharmacological mechanisms behind CBD’s neuroleptic pharmacology are outlined, with particular emphasis on its prevention of the hydrolysis and reuptake of the endogenous cannabinoid, anandamide. However, given the nebular aetiological basis for psychoses, explicit conclusions on how CBD attenuates psychotic symptoms remains to be determined.

Proplyene glycol intake from medications used on paediatric intensive care

here is an increasing number of reports of propylene glycol (PG) toxicity in the literature, regardless of its inclusion on the Generally Recognized as Safe List (GRAS).1 PG is an excipient used in many medications as a solvent for water-insoluble drugs. Polypharmacy may increase PG exposure in vulnerable PICU patients who may accumulate PG due to compromised liver and renal function. The study aim was to quantify PG intake in PICU patients and attitudes of clinicians towards PG. Method A snapshot of 50 PICU patients oral or intravenous medication intake was collected. Other data collected included age, weight, diagnosis, lactate levels and renal function. Manufacturers were contacted for PG content and then converted to mg/kg. Excipients in formulations that compete with the PG metabolism pathway were recorded. The Intensivists' opinions on PG intake was sought via e-survey. Results The 50 patients were prescribed 62 drugs and 83 formulations, 43/83 (52%) were parenteral formulations. Median weight of the patients was 5.5 kg (range 2–50 kg), ages ranged from 1 day to 13 years of age. Eleven of the patients were classed as renally impaired (defined as 1.5 times the baseline creatinine). Sixteen formulations contained PG, 2/16 were parenteral, 6/16 unlicensed preparations. Thirty-eight patients received at least one prescription containing PG and 29/38 of these patients were receiving formulations that contained excipients that may have competed with the metabolic pathways of PG. PG intake ranged from 0.002 mg/kg/day to 250 mg/kg/day. Total intake was inconclusive for 2 patients due to a of lack of availability of information from the manufacturer; these formulations were licensed but used in for off-label indications. Five commonly used formulations contributed to higher intakes of PG, namely co-trimoxazole, dexamethasone, potassium chloride, dipyridamole and phenobarbitone. Lactate levels were difficult to interpret due to the underlying conditions of the patients. One of the sixteen intensivist was aware of PG content in drugs, 16/16 would actively change therapy if intake was above European Medicines Agency recommendations. Conclusions Certain formulations used on PICU can considerably increase PG exposure to patients. Due to a lack of awareness of PG content, these should be highlighted to the clinician to assist with making informed decisions regarding risks versus benefits in continuing that drug, route of administration or formulation.

Proplyene glycol intake from medications used on paediatric intensive care

There is an increasing number of reports of propylene glycol (PG) toxicity in the literature, regardless of its inclusion on the Generally Recognized as Safe List (GRAS).1 PG is an excipient used in many medications as a solvent for water-insoluble drugs. Polypharmacy may increase PG exposure in vulnerable PICU patients who may accumulate PG due to compromised liver and renal function. The study aim was to quantify PG intake in PICU patients and attitudes of clinicians towards PG. Method A snapshot of 50 PICU patients oral or intravenous medication intake was collected. Other data collected included age, weight, diagnosis, lactate levels and renal function. Manufacturers were contacted for PG content and then converted to mg/kg. Excipients in formulations that compete with the PG metabolism pathway were recorded. The Intensivists' opinions on PG intake was sought via e-survey. Results The 50 patients were prescribed 62 drugs and 83 formulations, 43/83 (52%) were parenteral formulations. Median weight of the patients was 5.5 kg (range 2–50 kg), ages ranged from 1 day to 13 years of age. Eleven of the patients were classed as renally impaired (defined as 1.5 times the baseline creatinine). Sixteen formulations contained PG, 2/16 were parenteral, 6/16 unlicensed preparations. Thirty-eight patients received at least one prescription containing PG and 29/38 of these patients were receiving formulations that contained excipients that may have competed with the metabolic pathways of PG. PG intake ranged from 0.002 mg/kg/day to 250 mg/kg/day. Total intake was inconclusive for 2 patients due to a of lack of availability of information from the manufacturer; these formulations were licensed but used in for off-label indications. Five commonly used formulations contributed to higher intakes of PG, namely co-trimoxazole, dexamethasone, potassium chloride, dipyridamole and phenobarbitone. Lactate levels were difficult to interpret due to the underlying conditions of the patients. One of the sixteen intensivist was aware of PG content in drugs, 16/16 would actively change therapy if intake was above European Medicines Agency recommendations. Conclusions Certain formulations used on PICU can considerably increase PG exposure to patients. Due to a lack of awareness of PG content, these should be highlighted to the clinician to assist with making informed decisions regarding risks versus benefits in continuing that drug, route of administration or formulation.

Effect of medications with anti-cholinergic properties on cognitive function, delirium, physical function and mortality:a systematic review

Objectives: to determine the effect of drugs with anti-cholinergic properties on relevant health outcomes.Design: electronic published and unpublished literature/trial registries were systematically reviewed. Studies evaluating medications with anti-cholinergic activity on cognitive function, delirium, physical function or mortality were eligible.Results: forty-six studies including 60,944 participants were included. Seventy-seven percent of included studies evaluating cognitive function (n = 33) reported a significant decline in cognitive ability with increasing anti-cholinergic load (P < 0.05). Four of five included studies reported no association with delirium and increasing anti-cholinergic drug load (P > 0.05). Five of the eight included studies reported a decline in physical function in users of anti-cholinergics (P < 0.05). Three of nine studies evaluating mortality reported that the use of drugs with anti-cholinergic properties was associated with a trend towards increased mortality, but this was not statistically significant. The methodological quality of the evidence-base ranged from poor to very good.Conclusion: medicines with anti-cholinergic properties have a significant adverse effect on cognitive and physical function, but limited evidence exists for delirium or mortality outcomes. © The Author 2014. Published by Oxford University Press on behalf of the British Geriatrics Society. All rights reserved.

What factors influence concordance with medications? Findings from the UK Asian Diabetes study

Aims: To investigate concordance with medication, as assessed at baseline and at 1- and 2-year follow-up, and to examine factors associated with non-concordance in a UK-resident South-Asian population. Methods: Data from the UK Asian Diabetes Study were analysed. Concordance with medications was assessed and recorded at three time points during the study. Multiple logistic regression was used to investigate the factors associated with non-concordance; the associations of baseline factors with year 1 concordance and baseline plus year 1 factors with year 2 concordance. Results: Data for 403 patients from seven practices participating in the UK Asian Diabetes Study were analysed. The numbers of patients who were non-concordant were: 63 (16%) at baseline 101 (25%) at year 1; and 122 (30%) at year 2. The baseline-measured variables that were significantly associated with year 1 non-concordance included diabetes duration, history of cardiovascular disease, components of the EuroQol quality of life questionnaire, the EQ-5D score, and number of medications prescribed. In multivariable analyses, the most important determinant of year 1 non-concordance was baseline non-concordance: odds ratio 13.6 (95% confidence limits 4.7, 39.9). Number of medications prescribed for blood pressure control was also significant: odds ratio 1.8 (95% confidence limits 1.4, 2.4). Similar results were observed for year 2 non-concordance. Conclusions: Non-concordance with medications was common and more likely in people prescribed more medications. The current target-driven management of risk factor levels may lead to increasing numbers and doses of medications. Considering the high cost of medications and the implications of poor health behaviours on morbidity and mortality, further investigation of prescribing behaviours and the factors affecting patient concordance are required.

Use of medications with anticholinergic activity and self-reported injurious falls in older community-dwelling adults

Objectives: To assess the association between the use of medications with anticholinergic activity and the subsequent risk of injurious falls in older adults. Design: Prospective, population-based study using data from The Irish Longitudinal Study on Ageing. Setting: Irish population. Participants: Community-dwelling men and women without dementia aged 65 and older (N = 2,696). Measurements: Self-reported injurious falls reported once approximately 2 years after baseline interview. Self-reported regular medication use at baseline interview. Pharmacy dispensing records from the Irish Health Service Executive Primary Care Reimbursement Service in a subset (n = 1,553). Results: Nine percent of men and 17% of women reported injurious falls. In men, the use of medications with definite anticholinergic activity was associated with greater risk of subsequent injurious falls (adjusted relative risk (aRR) = 2.55, 95% confidence interval (CI) = 1.33-4.88), but the risk of having any fall and the number of falls reported were not significantly greater. Greater anticholinergic burden was associated with greater injurious falls risk. No associations were observed for women. Findings were similar using pharmacy dispensing records. The aRR for medications with definite anticholinergic activity dispensed in the month before baseline and subsequent injurious falls in men was 2.53 (95% CI = 1.15-5.54). Conclusion: The regular use of medications with anticholinergic activity is associated with subsequent injurious falls in older men, although falls were self-reported after a 2-year recall and so may have been underreported. Further research is required to validate this finding in men and to consider the effect of duration and dose of anticholinergic medications.