Role of community pharmacists in the use of antipsychotics for behavioural and psychological symptoms of dementia (BPSD):a qualitative study

OBJECTIVE: This study aimed to use qualitative methodology to understand the current role of community pharmacists in limiting the use of antipsychotics prescribed inappropriately for behavioural and psychological symptoms of dementia. DESIGN: A qualitative study employing focus groups was conducted. Data were analysed using thematic analysis. SETTING: 3 different geographical locations in the England. PARTICIPANTS: Community pharmacists (n=22). RESULTS: The focus groups identified an array of factors and constraints, which affect the ability of community pharmacists to contribute to initiatives to limit the use of antipsychotics. 3 key themes were revealed: (1) politics and the medical hierarchy, which created communication barriers; (2) how resources and remit impact the effectiveness of community pharmacy; and (3) understanding the nature of the treatment of dementia. CONCLUSIONS: Our findings suggest that an improvement in communication between community pharmacists and healthcare professionals, especially general practitioners (GPs) must occur in order for community pharmacists to assist in limiting the use of antipsychotics in people with dementia. Additionally, extra training in working with people with dementia is required. Thus, an intervention which involves appropriately trained pharmacists working in collaboration with GPs and other caregivers is required. Overall, within the current environment, community pharmacists question the extent to which they can contribute in helping to reduce the prescription of antipsychotics.

Mental health pharmacists views on shared decision-making for antipsychotics in serious mental illness

Background People diagnosed with serious mental illnesses (SMIs) such as schizophrenia and bipolar affective disorder are frequently treated with antipsychotics. National guidance advises the use of shared decision-making (SDM) in antipsychotic prescribing. There is currently little data on the opinions of health professionals on the role of SDM. Objective To explore the views and experiences of UK mental health pharmacists regarding the use of SDM in antipsychotic prescribing in people diagnosed with SMI. Setting The study was conducted by interviewing secondary care mental health pharmacists in the UK to obtain qualitative data. Methods Semi-structured interviews were recorded. An inductive thematic analysis was conducted using the method of constant comparison. Main outcome measure Themes evolving from mental health pharmacists on SDM in relation to antipsychotic prescribing in people with SMI. Results Thirteen mental health pharmacists were interviewed. SDM was perceived to be linked to positive clinical outcomes including adherence, service user satisfaction and improved therapeutic relations. Despite more prescribers and service users supporting SDM, it was not seen as being practised as widely as it could be; this was attributed to a number of barriers, most predominantly issues surrounding service user’s lacking capacity to engage in SDM and time pressures on clinical staff. The need for greater effort to work around the issues, engage service users and adopt a more inter-professional approach was conveyed. Conclusion The mental health pharmacists support SDM for antipsychotic prescribing, believing that it improves outcomes. However, barriers are seen to limit implementation. More research is needed into overcoming the barriers and measuring the benefits of SDM, along with exploring a more inter-professional approach to SDM.

Quantitative assessment of the pharmacotherapy of biopolar disorder and schizophrenia

The work present in this thesis was aimed at assessing the efficacy of lithium in the acute treatment of mania and for the prophylaxis of bipolar disorder, and investigating the value of plasma haloperidol concentration for predicting response to treatment in schizophrenia. The pharmacogenetics of psychotropic drugs is critically appraised to provide insights into interindividual variability in response to pharmacotherapy, In clinical trials of acute mania, a number of measures have been used to assess the severity of illness and its response to treatment. Rating instruments need to be validated in order for a clinical study to provide reliable and meaningful estimates of treatment effects, Eight symptom-rating scales were identified and critically assessed, The Mania Rating Scale (MRS) was the most commonly used for assessing treatment response, The advantage of the MRS is that there is a relatively extensive database of studies based on it and this will no doubt ensure that it remains a gold standard for the foreseeable future. Other useful rating scales are available for measuring mania but further cross-validation and validation against clinically meaningful global changes are required. A total of 658 patients from 12 trials were included in an evaluation of the efficacy of lithium in the treatment of acute mania. Treatment periods ranged from 3 to 4 weeks. Efficacy was estimated using (i) the differences in the reduction in mania severity scores, and (ii) the ratio and difference in improvement response rates. The response rate ratio for lithium against placebo was 1.95 (95% CI 1.17 to 3.23). The mean number needed to treat was 5 (95% CI 3 to 20). Patients were twice as likely to obtain remission with lithium than with chlorpromazine (rate ratio = 1.96, 95% CI 1.02 to 3.77). The mean number needed to treat (NNT) was 4 (95% CI 3 to 9). Neither carbamazepine nor valproate was more effective than lithium. The response rate ratios were 1.01 (95% CI 0.54 to 1.88) for lithium compared to carbarnazepine and 1.22 (95% CI 0.91 to 1.64) for lithium against valproate. Haloperidol was no better than lithium on the basis of improvement based on assessment of global severity. The differences in effects between lithium and risperidone were -2.79 (95% CI -4.22 to -1.36) in favour of risperidone with respect to symptom severity improvement and -0.76 (95% CI -1.11 to -0,41) on the basis of reduction in global severity of disease. Symptom and global severity was at least as well controlIed with lithium as with verapamil. Lithium caused more side-effects than placebo and verapamil, but no more than carbamazepine or valproate. A total of 554 patients from 13 trials were included in the statistical analysis of lithium's efficacy in the prophylaxis of bipolar disorder. The mean follow-up period was 5-34 months. The relapse risk ratio for lithium versus placebo was 0.47 (95% CI 0.26 to 0.86) and the NNT was 3 (95% CI 2 to 7). The relapse risk ratio for lithium versus imipramine was 0.62 (95% CI 0.46 to 0.84) and the NNT was 4 (951% Cl 3 to 7), The combination of lithium and imipramine was no more effective than lithium alone. The risk of relapse was greater with lithium alone than with the lithium-divalproate combination. A risk difference of 0.60 (95% CI 0.21 to 0.99) and an NNT of 2 (95% CI 1 to 5) were obtained. Lithium was as effective as carbamazepine. Based on individual data concerning plasma haloperidol concentration and percent improvement in psychotic symptoms, our results suggest an acceptable concentration range of 11.20-30.30 ng/mL A minimum of 2 weeks should be allowed before evaluating therapeutic response. Monitoring of drug plasma levels seems not to be necessary unless behavioural toxicity or noncompliance is suspected. Pharmacokinetics and pharmacodynamics, which are mainly determined by genetic factors, contribute to interindividual and interethnic variations in clinical response to drugs. These variations are primarily due to differences in drug metabolism. Variability in pharmacokinetics of a number of drugs is associated with oxidation polymorphism. Debrisoquine/sparteine hydroxylase (CYP2D6) and the S-mephenytoin hydroxylase (CYP2C19) are polymorphic P450 enzymes with particular importance in psychopharmacotherapy. The enzymes are responsible for the metabolism of many commonly used antipsychotic and antidepressant drugs. The incidence of poor metabolisers of debrisoquine and S-mephenytoin varies widely among populations. Ethnic variations in polymorphic isoenzymes may, at least in part, explain ethnic differences in response to pharmacotherapy of antipsychotics and antidepressant drugs.

Efficacy of memantine for agitation in Alzheimer's dementia:a randomised double-blind placebo controlled trial

Background - Agitation in Alzheimer’s disease (AD) is common and associated with poor patient life-quality and carer distress. The best evidence-based pharmacological treatments are antipsychotics which have limited benefits with increased morbidity and mortality. There are no memantine trials in clinically significant agitation but post-hoc analyses in other populations found reduced agitation. We tested the primary hypothesis, memantine is superior to placebo for clinically significant agitation, in patients with moderate-to-severe AD. Methods and Findings - We recruited 153 participants with AD and clinically significant agitation from care-homes or hospitals for a double-blind randomised-controlled trial and 149 people started the trial of memantine versus placebo. The primary outcome was 6 weeks mixed model autoregressive analysis of Cohen-Mansfield Agitation Inventory (CMAI). Secondary outcomes were: 12 weeks CMAI; 6 and 12 weeks Neuropsychiatric symptoms (NPI), Clinical Global Impression Change (CGI-C), Standardised Mini Mental State Examination, Severe Impairment Battery. Using a mixed effects model we found no significant differences in the primary outcome, 6 weeks CMAI, between memantine and placebo (memantine lower -3.0; -8.3 to 2.2, p = 0.26); or 12 weeks CMAI; or CGI-C or adverse events at 6 or 12 weeks. NPI mean difference favoured memantine at weeks 6 (-6.9; -12.2 to -1.6; p = 0.012) and 12 (-9.6; -15.0 to -4.3 p = 0.0005). Memantine was significantly better than placebo for cognition. The main study limitation is that it still remains to be determined whether memantine has a role in milder agitation in AD. Conclusions - Memantine did not improve significant agitation in people with in moderate-to-severe AD. Future studies are urgently needed to test other pharmacological candidates in this group and memantine for neuropsychiatric symptoms.

Brain structural changes associated with chronicity and antipsychotic treatment in schizophrenia

Accumulating evidence suggest a life-long impact of disease related mechanisms on brain structure in schizophrenia which may be modified by antipsychotic treatment. The aim of the present study was to investigate in a large sample of patients with schizophrenia the effect of illness duration and antipsychotic treatment on brain structure. Seventy-one schizophrenic patients and 79 age and gender matched healthy participants underwent brain magnetic resonance imaging (MRI). All images were processed with voxel based morphometry, using SPM5. Compared to healthy participants, patients showed decrements in gray matter volume in the left medial and left inferior frontal gyrus. In addition, duration of illness was negatively associated with gray matter volume in prefrontal regions bilaterally, in the temporal pole on the left and the caudal superior temporal gyrus on the right. Cumulative exposure to antipsychotics correlated positively with gray matter volumes in the cingulate gyrus for typical agents and in the thalamus for atypical drugs. These findings (a) indicate that structural abnormalities in prefrontal and temporal cortices in schizophrenia are progressive and, (b) suggest that antipsychotic medication has a significant impact on brain morphology. © 2009 Elsevier B.V. and ECNP.

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.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

Pathway to clozapine use:a comparison between a patient cohort from New Zealand and a cohort from the United Kingdom

Background and Objective: Clozapine has been available since the early 1990s. Studies continue to demonstrate its superior efficacy in treatment-resistant schizophrenia. Despite this, numerous studies show under-utilisation, delayed access and reluctance by psychiatrists to prescribe clozapine. This retrospective cross-sectional study compared the prescribing of clozapine in two adult cohorts under the care of large public mental health services in Auckland (New Zealand) and Birmingham (United Kingdom) on 31 March 2007. Method: Time from first presentation to clozapine initiation, prior antipsychotics trialled and antipsychotic co-prescribing were compared. Data included demographics, psychiatric diagnosis, co-morbid conditions, year of first presentation, admissions and pharmacological treatment (clozapine dose, start date, prior antipsychotics, co-prescribed antipsychotic). Results: Overall, 664 people were prescribed clozapine (402 Auckland; 262 Birmingham); mean daily dose of 384 mg (Auckland) and 429 mg (Birmingham). 53 % presented after 1990 and the average duration of time before starting clozapine was significantly longer in the Birmingham cohort (6.5 vs. 5.3 years) but this reduced in both cohorts to a 1-year mean in those presenting within the last 3 years. The average number of antipsychotics trialled pre-clozapine for those presenting since 1990 was significantly higher in the Birmingham cohort (4.3 vs. 3.1) but in both cohorts this similarly reduced in those presenting within the last 3 years. Antipsychotic co-prescribing was significantly higher in the Birmingham cohort (22.9 vs. 10.7 %). Conclusions: There is evidence that access to clozapine has improved over time in both cohorts, with a reduction in the duration between presentation and initiation of clozapine and number of different antipsychotics trialled pre-clozapine. These are very positive findings in terms of optimising outcomes with clozapine and are possibly due to the impact of guideline recommendations, increasing clinician, consumer and carer knowledge, and experience with clozapine and funding changes. © 2014 Springer International Publishing.

Improving the management of behaviour that challenges associated with dementia in care homes:protocol for pharmacy-health psychology intervention feasibility study

INTRODUCTION: The inappropriate use of antipsychotics in people with dementia for behaviour that challenges is associated with an estimated 1800 deaths annually. However, solely focusing on antipsychotics may transfer prescribing to other equally dangerous psychotropics. Little is known about the role of pharmacists in the management of psychotropics used to treat behaviours that challenge. This research aims to determine whether it is feasible to implement and measure the effectiveness of a combined pharmacy-health psychology intervention incorporating a medication review and staff training package to limit the prescription of psychotropics to manage behaviour that challenges in care home residents with dementia. METHODS/ANALYSIS: 6 care homes within the West Midlands will be recruited. People with dementia receiving medication for behaviour that challenges, or their personal consultee, will be approached regarding participation. Medication used to treat behaviour that challenges will be reviewed by the pharmacist, in collaboration with the general practitioner (GP), person with dementia and carer. The behavioural intervention consists of a training package for care home staff and GPs promoting person-centred care and treating behaviours that challenge as an expression of unmet need. The primary outcome measure is the Neuropsychiatric Inventory-Nursing Home version (NPI-NH). Other outcomes include quality of life (EQ-5D and DEMQoL), cognition (sMMSE), health economic (CSRI) and prescribed medication including whether recommendations were implemented. Outcome data will be collected at 6 weeks, and 3 and 6 months. Pretraining and post-training interviews will explore stakeholders' expectations and experiences of the intervention. Data will be used to estimate the sample size for a definitive study. ETHICS/DISSEMINATION: The project has received a favourable opinion from the East Midlands REC (15/EM/3014). If potential participants lack capacity, a personal consultee will be consulted regarding participation in line with the Mental Capacity Act. Results will be published in peer-reviewed journals and presented at conferences.

Anticholinergic burden in older adults with intellectual disability; relationships with multimorbidity and adverse effects

Background: Anticholinergic medications may be associated with adverse clinical outcomes, including acute impairments in cognition and anticholinergic side effects, the risk of adverse outcomes increasing with increasing anticholinergic exposure. Older people with intellectual disability may be at increased risk of exposure to anticholinergic medicines due to their higher prevalence of comorbidities. We sought to determine anticholinergic burden in ageing people with intellectual disability. Methods: Medication data (self-report/proxy-report) was drawn from Wave 1 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing (IDS-TILDA), a study on the ageing of 753nationally representative people with an IDC40 years randomly selected from the National Intellectual Disability Database. Each individual’s cumulative exposure to anticholinergic medications was calculated using the Anticholinergic Cognitive Burden Scale (ACB) amended by a multi-disciplinary group with independent advice to account for the range of medicines in use in this population. Results: Overall, 70.1 % (527) reported taking medications with possible or definite anticholinergic properties (ACBC1), with a mean (±SD) ACB score of 4.5 (±3.0) (maximum 16). Of those reporting anticholinergic exposure (n=527), 41.3 % (217) reported an ACB score o fC5. Antipsychotics accounted for 36.4 % of the total cumulative ACB score followed by anticholinergics (16 %) and antidepressants (10.8 %). The most frequently reported medicine with anticholinergic activity was carbamazepine 16.8 % (127). The most frequently reported medicine with high anticholinergic activity (ACB 3) was olanzapine13.4 % (101). There was a significant association between higher anti-cholinergic exposure and multimorbidity, particularly mental health morbidity, and some anticholinergic adverse effects such as constipation and day-time drowsiness but not self-rated health. Conclusion: Using simple cumulative measures proved an effective means to capture total burden and helped establish that anticholinergic exposure in the study population was high. The finding highlights the need for comprehensive reviews of medications.

Factors associated with high anticholinergic burden in aging adults with intellectual disabilities:a cross-sectional study

Background: Anticholinergic (AC) medications are associated with cognitive and functional decline in older people, with risk of adverse outcomes increasing with increasing AC exposure. Older people with intellectual disabilities are at increased risk of high AC exposure owing to higher prevalence of multimorbidity, particularly psychiatric morbidities. Objectives: The aims of this study were to determine individual’s AC exposure using the AC cognitive burden (ACB) scale, identify therapeutic classes contributing to burden and determine clinical and demographic factors associated with two levels of AC exposure (ACB score 1–4, ACB 5+). Methods: Cross-sectional (self-report/proxy report)medication data were drawn from Wave 1 of the Intellectual Disability Supplement to the Irish Longitudinal Study on Ageing, a study on ageing of 753nationally representative people with ID aged over40 randomly selected from the National Intellectual Disability Database. Medication data were available for 736 (98%). Each individual’s cumulative AC exposure was calculated using the ACB. Multinomiallogistic regression was performed identifying clinical and demographic factors associated with ACB score1–4, and ACB 5+. Results: In the eligible population of 736 participants(mean (±SD) age 54.1 (±8.8) years,55% female), 522(70.9%) were exposed to an ACB medicine (ACB 1+); 214 (29%) had an ACB score of 5+; mean total ACB score= 4.5 (±3.0). Antipsychotics accounted for35.6% of the cumulative ACB score. Age over 65yearswas associated with increased likelihood of both levels of AC exposure (ACB 1–4—adjusted OR 3.28; 95%CI 1.49–7.25, ACB 5+—adjusted OR 3.08; 95%CI1.21–7.63) and having a mental health condition(ACB 1–4—adjusted OR 9.79; 95%CI 5.63–17.02, ACB 5+—adjusted OR 23.74; 95%CI 12.29–45.83). Conclusions: Using a simple cumulative measure proved an effective means to capture total burden and established that AC exposure was high and associated with older age and mental health morbidity. This highlights need for comprehensive medication reviews for older people with intellectual disabilities.