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Medicines optimisation ensures that people get the best possible outcomes from their medicines. As those with severe mental illness (SMI) are frequently prescribed psychotropic medicines with potentially significant side-effects, poor adherence to treatment and physical morbidity are common. This results in suboptimal symptom control, physical health problems and negative health outcomes. The specialist mental health pharmacist (SMHP) is best placed to provide leadership for medicines optimisation in the inpatient mental health setting. By adopting a patient-centred approach to providing information, improving adherence, screening, initiating and maintaining medicines, and supporting self-advocacy, the SMHP can ensure the patients’ experience of taking medicines is optimised. As there is currently limited understanding of what a baseline clinical pharmacy service in a mental health setting looks like, we aim to outline a framework for pharmacist-led medicines optimisation for those with SMI. This framework is suitable to be scaled and adapted to other settings.
Adverse effects are a common concern when prescribing and reviewing medication, particularly in vulnerable adults such as older people and those with intellectual disability. This paper describes the development of an app giving information on side-effects, called Medichec, and provides a description of the processes involved in its development and how drugs were rated for each side-effect. Medications with central anticholinergic action, dizziness, drowsiness, hyponatraemia, QTc prolongation, bleeding and constipation were identified using the British National Formulary (BNF) and frequency of occurrence of these effects was determined using the BNF, product information and electronic searches, including PubMed.
Results
Medications were rated using a traffic light system according to how commonly the adverse effect was known to occur or the severity of the effect.
Clinical implications
Medichec can facilitate access to side-effects information for multiple medications, aid clinical decision-making, optimise treatment and improve patient safety in vulnerable adults.
The aim of this paper is to discuss the potential consequences of modern dairy cattle breeding for the welfare of dairy cows. The paper focuses on so-called genomic selection, which deploys thousands of genetic markers to estimate breeding values. The discussion should help to structure the thoughts of breeders and other stakeholders on how to best make use of genomic breeding in the future. Intensive breeding has played a major role in securing dramatic increases in milk yield since the Second World War. Until recently, the main focus in dairy cattle breeding was on production traits, but during the past couple of decades more emphasis has been placed on a few rough, but useful, measures of traits relevant to cow welfare, including calving ease score and ‘clinical disease or not’; the aim being to counteract the unfavourable genetic association with production traits. However, unfavourable genetic trends for metabolic, reproductive, claw and leg diseases indicate that these attempts have been insufficient. Today, novel genome-wide sequencing techniques are revolutionising dairy cattle breeding; these enable genetic changes to occur at least twice as rapidly as previously. While these new genomic tools are especially useful for traits relating to animal welfare that are difficult to improve using traditional breeding tools, they may also facilitate breeding schemes with reduced generation intervals carrying a higher risk of unwanted side-effects on animal welfare. In this paper, a number of potential risks are discussed, including detrimental genetic trends for non-measured welfare traits, the increased chance of spreading unfavourable mutations, reduced sharing of information arising from concerns over patents, and an increased monopoly within dairy cattle breeding that may make it less accountable to the concern of private farmers for the welfare of their animals. It is argued that there is a need to mobilise a wide range of stakeholders to monitor developments and maintain pressure on breeding companies so that they are aware of the need to take precautionary measures to avoid negative effects on animal welfare and to invest in breeding for increased animal welfare. Researchers are encouraged to further investigate the long-term effects of various breeding schemes that rely on genomic breeding values.
Ketamine has recently received considerable attention regarding its antidepressant and anti-suicidal effects. Trials have generally focused on short-term effects of single intravenous infusions. Research on patient experiences is lacking.
Aims
To investigate the experiences over time of individuals receiving ketamine treatment in a routine clinic, including impacts on mood and suicidality.
Method
Twelve fee-paying patients with treatment-resistant depression (6 females, 6 males, age 21–70 years; 11 reporting suicidality and 6 reporting self-harm) who were assessed as eligible for ketamine treatment participated in up to three semi-structured interviews: before treatment started, a few weeks into treatment and ≥2 months later. Data were analysed thematically.
Results
Most participants hoped that ketamine would provide respite from their depression. Nearly all experienced improvement in mood following initial treatments, ranging from negligible to dramatic, and eight reported a reduction in suicidality. Improvements were transitory for most participants, although two experienced sustained consistent benefit and two had sustained but limited improvement. Some participants described hopelessness when treatment stopped working, paralleled by increased suicidal ideation for three participants. The transient nature and cost of treatment were problematic. Eleven participants experienced side-effects, which were significant for two participants. Suggestions for improving treatment included closer monitoring and adjunctive psychological therapy.
Conclusions
Ketamine treatment was generally experienced as effective in improving mood and reducing suicidal ideation in the short term, but the lack of longer-term benefit was challenging for participants, as was treatment cost. Informed consent procedures should refer to the possibilities of relapse and associated increased hopelessness and suicidality.
In forensic settings, the most common indication for clozapine is treatment-resistant schizophrenia (TRS). Clozapine has also been shown to be effective in reducing hostility, aggression and violence in patients with schizophrenia and is of benefit in comorbid substance use disorders. The decision to initiate or to discontinue recently initiated clozapine can have a profound beneficial or detrimental influence on the lives and safety of patients and the staff caring for them. We present a case in which treatment with clozapine proved effective in spite of earlier repeated discontinuation of clozapine out of fear of neuroleptic malignant syndrome (NMS). Elevation of creatine kinase was deemed to be indicative of NMS in the absence of clinical signs of NMS. In somatic medicine, it is well known that creatine kinase elevation has many causes, most of them non-harmful. Collaboration with clinical chemistry was shown to be very useful, if not essential; research in the 1980s found replicated evidence for both sex and race differences in creatine kinase levels. In addition, substantial intra-individual variation has been found over time in healthy individuals. The creatine kinase levels of this patient of African descent were within normal limits for the African population. Baseline creatine kinase assessment and repetition of this assessment after 2 weeks with careful interpretation are recommended in all clozapine-treated patients. The authors advocate the introduction of evidence-based creatine kinase cut-off points that reflect the biological differences between the sexes and among races. More intensive contact between psychiatrists and clinical chemist can facilitate faster diagnosis and better treatment.
Antipsychotic medications are used to treat a significant number of psychiatric disorders, such as schizophrenia or bipolar disorder, which have a significant impact on overall disability in Europe. Although these drugs have documented efficacy, they are also associated with side-effects such as drowsiness, weight gain, type 2 diabetes, or extrapyramidal symptoms [1]. These contribute to increasing overall morbidity and mortality [2], reduced quality of life, and can push patients to stop their medications. This often leads to relapse, and the need for a new hospital admission, which is detrimental to the patient, and create extra costs for the society. However, the monitoring of side-effects is rarely carried out in a standardized way in daily clinical practice. Smartphones are an acceptable and easy to use tool available to patients with schizophrenia [3]. The aim of the mPIVAS (mHealth psychoeducational intervention versus antipsychotic-induced side effects) project is to develop an effective and innovative smartphone application that can be used by psychiatrists and patients in order to monitor medications’ side-effects. The European Psychiatric Association (EPA) is involved in this project with the objective to develop this application in 6 languages. Part of the project includes training European early careers psychiatrists to the use Psylog and helping them to spread information about this new project in their own country, by organising local and national cascade courses. We expect an improvement in psychiatric care in all involved institutions through the education of employees, a better implication of patients in their disease, and an improved monitoring of antipsychotic side-effects.
For young people experiencing a first-episode of schizophrenia, the first and most important matter to be attended to, once the diagnosis of schizophrenia has been made and patients have entered the care system, is to establish a treatment alliance. The next step is to conceive an individually tailored treatment programme (non-pharmacological as well as pharmacological). The use of antipsychotic drugs needs to be carefully discussed with both patients and families, as medication tends to have a poor public perception. Maintaining treatment is vitally important in terms of relapse prevention, but people who suffer a first-episode tend to terminate treatment early. Patients often discontinue their medication because of side-effects, although a number of other factors can also exert a negative influence on the continuous intake of medication. Among others, these include insufficient information provided to patients and significant others as well as lack of insight and problems in the doctor-patient-relationship. The published data indicate that the outcome of treatment is better for younger patients in a first-episode of schizophrenia than it is for patients who are more chronically ill. However, young patients are much more sensitive to compliance problems than older patients. The main challenge in this phase of the illness is therefore to convince patients that maintenance treatment is necessary in order to assure the best possible outcome.
Cognitive impairments in schizophrenics have been found to precede tardive dyskinesia and to co-exist with other motor deficits. However, little is yet known about the prevalence of cognitive disturbances in patients with neuroleptic-induced parkinsonism. From the literature on idiopathic parkinson, it was inferred that extrapyramidal symptoms (EPS) are accompanied by cognitive dysfunction. 85 schizophrenic in-patients were divided into EPS high and low scorers according to an established criterion (Simpson Angus Scale, cut-off score: 0.4). Cognitive impairments were assessed using a self-rating instrument measuring disturbances of information processing.
Patients with high EPS exhibited significantly elevated scores in six of ten cognitive and perceptual subscales (t = 2.1—3.1) as compared to low EPS patients. It is concluded that high EPS patients suffer from cognitive disturbances which are assumed to possess high relevance for both psycho-social and medical treatment. Cognitive problems may, when not considered, disturb compliance, insight of illness and transfer of learnt skills into everyday life.
The cognitive effects of bromocriptine (10 mg/day) in chronic neuroleptic-treated schizophrenic patients were studied in a 4-month trial. Ten neuropsychological variables were used for the evaluations. Nine patients and seven controls completed the study. They were tested three times: before the beginning of the study, and after 2 and 4 months of treatment. The results showed that treated patients globally performed significantly better than the controls (P < 0.05), and that the digit symbol substitution test was significantly improved (P < 0.03). The WAIS performance score was also significantly improved (P < 0.02). The picture arrangement test was improved, but did not reach significance (P < 0.07). Verbal tests were not improved. It therefore appears that addition of a D2 dopamine agonist in neuroleptic-treated patients can improve some of their cognitive functions. Two explanations can be proposed: i) bromocriptine decreases neuroleptic-induced motor side effects or ii) has an effect on a putative hypodopaminergic function in schizophrenia.
Second-generation antipsychotics (SGA) are being used more often than ever before in children and adolescents with psychotic and a wide range of non-psychotic disorders. Several SGA have received regulatory approval for some paediatric indications in various countries, but off-label use is still frequent. The aim of this paper was to perform a systematic review and critically evaluate the literature on cardiometabolic and endocrine side-effects of SGA in children and adolescents through a Medline/Pubmed/Google Scholar search of randomized, placebo controlled trials of antipsychotics in children and adolescents (<18 years old) until February 2010. In total, 31 randomized, controlled studies including 3595 paediatric patients were identified. A review of these data confirmed that SGA are associated with relevant cardiometabolic and endocrine side-effects, and that children and adolescents have a high liability to experience antipsychotic induced hyperprolactinaemia, weight gain and associated metabolic disturbances. Only weight change data were sufficiently reported to conduct a formal meta-analysis. In 24 trials of 3048 paediatric patients with varying ages and diagnoses, ziprasidone was associated with the lowest weight gain (−0.04 kg, 95% confidence interval [CI]: −0.38 to +0.30), followed by aripiprazole (0.79 kg, 95% CI: 0.54 to 1.04], quetiapine (1.43 kg, 95% CI: 1.17 to 1.69) and risperidone (1.76 kg, 95% CI: 1.27 to 2.25) were intermediate, and olanzapine was associated with weight gain the most (3.45 kg, 95% CI: 2.93 to 3.97). Significant weight gain appeared to be more prevalent in patients with autistic disorder who were also younger and likely less exposed to antipsychotics previously. These data clearly suggest that close screening and monitoring of metabolic side effects is warranted and that the least cardiometabolically problematic agents should be used first whenever possible. A good collaboration between child- and adolescent psychiatrists, general practitioners and paediatricians is essential to maximize overall outcomes and to reduce the likelihood of premature cardiovascular morbidity and mortality.
For patients with major depressive disorder (MDD) experiencing side-effects or non-response to their first antidepressant, little is known regarding the effect of switching between a tricyclic antidepressant (TCA) and a selective serotonin reuptake inhibitor (SSRI).
Aims
To compare the switch between the TCA nortriptyline and the SSRI escitalopram.
Method
Among 811 adults with MDD treated with nortriptyline or escitalopram for up to 12 weeks, 108 individuals switched from nortriptyline to escitalopram or vice versa because of side-effects or non-response (trial registration: EudraCT No.2004-001723-38 (https://eudract.ema.europa.eu/) and ISRCTN No.03693000 (http://www.controlled-trials.com)). Patients were followed for up to 26 weeks after switching and response was measured with the Montgomery–Åsberg Depression Rating scale (MADRS). We performed adjusted mixed-effects linear regression models with full information maximum likelihood estimation reporting β-coefficients with 95% CIs.
Results
Switching antidepressants resulted in a significant decrease in MADRS scores. This was present for switchers from escitalopram to nortriptyline (n = 36, β = −0.38, 95% CI −0.51 to −0.25, P<0.001) and from nortriptyline to escitalopram (n = 72, β = −0.34, 95% CI −0.41 to −0.26, P<0.001). Both switching options resulted in significant improvement among individuals who switched because of non-response or side-effects. The results were supported by analyses on other rating scales and symptom dimensions.
Conclusions
These results suggest that switching from a TCA to an SSRI or vice versa after non-response or side-effects to the first antidepressant may be a viable approach to achieve response among patients with MDD.
Declarations of interest
K.J.A. holds an Alberta Centennial Addiction and Mental Health Research Chair, funded by the Government of Alberta. K.J.A. has been a member of various advisory boards, received consultancy fees and honoraria, and has received research grants from various companies including Johnson and Johnson Pharmaceuticals Research and Development and Bristol-Myers Squibb Pharmaceuticals Limited. D.S. has served on advisory boards for, and received unrestricted grants from, Lundbeck and AstraZeneca. A.F. and P.M. have received honoraria for participating in expert panels for Lundbeck and GlaxoSmithKline.
Few studies have looked at subjective memory impairment from electroconvulsive therapy (ECT) after treatment completion. We aimed to systematically review all available evidence for subjective post-treatment effects.
Results
We included 16 studies in this review. There was considerable between-study heterogeneity in clinical population, ECT modality and assessment scales used. The most common assessment scale (eight studies) was the Squire Subjective Memory Questionnaire. The majority of studies reported an improvement in subjective memory after ECT, which correlated with improved depression scores. Subjective complaints were fewer in studies that used ultra-brief pulse ECT. Longer pulse widths were associated with more subjective complaints, as was female gender and younger age of treatment in the largest study.
Clinical implications
There is considerable heterogeneity between studies, limiting meaningful conclusions. Ultra-brief pulse ECT appears to result in fewer subjective complaints.
This study examined factors influencing parent willingness to use D-Cycloserine (DCS) for treating child anxiety. N = 222 parents were given information about using DCS to treat anxiety. They were then asked to rate their willingness to allow their child to take DCS/antibiotics for mild anxiety, severe anxiety, or an infection. The associations between willingness to use DCS and parental trait anxiety, demographics, as well as specific concerns regarding the medication, were examined. Parents could also provide written responses regarding their attitudes to DCS, which were analysed for themes. Parents reported concerns regarding potential side-effects from DCS. More severe anxiety was associated with more willingness to consent; however, parents were more willing to use antibiotics to treat an infection than DCS to treat their child's anxiety. The degree of perceived benefit from DCS was most strongly associated with parents’ willingness to use it. Overall, parents expressed mixed views, reporting they would consider using DCS to treat their child; however, they had significant concerns about it. Results suggest providing parents with information explaining how DCS works, its risks and potential benefits may increase its acceptability.
During the 1970s there was a gross loss of public confidence in infant diphtheria-tetanus-pertussis (DTP) vaccination in the UK. As well as febrile reactions and convulsions, permanent neurological damage was ascribed to the pertussis component of the vaccine, and those concerns resonated worldwide. The subsequent recognition of human herpes virus 6 (HHV-6) and 7 (HHV-7) as common sources of fever in infancy suggests that they were the main underlying cause of what was reported as DTP constitutional side-effects. With more precise data on the incidence of HHV-6/7 and other virus infections in early life it would be possible to model the concurrence of viral illnesses with routine immunizations. Adventitious viral infections may be the cause of side-effects ascribed to the numerous childhood immunizations now being given.
Cortical hyperostosis is a very uncommon side-effect of prolonged prostaglandin therapy with distinctive radiological signs that may be accompanied by painful swelling of the limbs and responds rapidly to withdrawal of therapy.
The belief bias effect is a phenomenon which occurs when we think that we judge an argument based on our reasoning, but are actually influenced by our beliefs and prior knowledge. Evans, Barston and Pollard carried out a psychological syllogistic reasoning task to prove this effect. Participants were asked whether they would accept or reject a given syllogism. We discuss one specific case which is commonly assumed to be believable but which is actually not logically valid. By introducing abnormalities, abduction and background knowledge, we adequately model this case under the weak completion semantics. Our formalization reveals new questions about possible extensions in abductive reasoning. For instance, observations and their explanations might include some relevant prior abductive contextual information concerning some side-effect or leading to a contestable or refutable side-effect. A weaker notion indicates the support of some relevant consequences by a prior abductive context. Yet another definition describes jointly supported relevant consequences, which captures the idea of two observations containing mutually supportive side-effects. Though motivated with and exemplified by the running psychology application, the various new general abductive context definitions are introduced here and given a declarative semantics for the first time, and have a much wider scope of application. Inspection points, a concept introduced by Pereira and Pinto, allows us to express these definitions syntactically and intertwine them into an operational semantics.
This study examined the spectrum of subjective experiences which patients attribute to the use of antipsychotic medication.
Methods:
We collected interview data and answers to structured questions based on a comprehensive checklist in 77 patients using various types of classical or atypical antipsychotic drugs.
Results:
The responses of the patients could be categorized into psychological and somatic domains. The psychological domain could be subdivided into emotional, cognitive and sociability domains. The somatic set could be subdivided into activation and physiological domains.
Conclusions:
Our data reveal that the same effects may be experienced in either a positive or a negative way by different patients. We conclude that existing scales for measuring subjective effects of antipsychotic medication are incomplete.
Objectives: To study the frequency of use, indications and reported side-effects of antidepressants in the treatment of adult inpatients at a UK secure hospital.
Methods: Cross-sectional survey of the use of antidepressants for forensic rehabilitation patients, together with structured interviews with the treating psychiatrists.
Results: A total of 94 patients (40.7%) were prescribed antidepressants. The majority (68.9%) were prescribed SSRIs. Antidepressant usage was associated with female gender, depression and emotionally unstable personality disorder. Patients with learning disabilities and pervasive developmental disorders were less likely to be prescribed antidepressants than the rest. Only 10 patients (10.6%) had a formal diagnosis of depression, anxiety or obsessive compulsive disorder. For 67.0% of patients the plan was to continue with the antidepressant long-term. Although 83.0% of psychiatrists said they had asked about side-effects, few (14.9%) had asked about sexual side-effects and only 3.2% of patients were reported as having side-effects.
Conclusions: Long-term antidepressant usage in this population was common. The reported incidence of side-effects was very low and is likely to be much higher in reality. Psychiatrists should make regular inquiry about side-effects, including sexual side-effects when appropriate, as well as regularly reviewing the need for continuing treatment.
Understanding individual differences in susceptibility to antidepressant therapy side-effects is essential to optimize the treatment of depression.
Method
We performed genome-wide association studies (GWAS) to search for genetic variation affecting the susceptibility to side-effects. The analysis sample consisted of 1439 depression patients, successfully genotyped for 421K single nucleotide polymorphisms (SNPs), from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Outcomes included four indicators of side-effects: general side-effect burden, sexual side-effects, dizziness and vision/hearing-related side-effects. Our criterion for genome-wide significance was a prespecified threshold ensuring that, on average, only 10% of the significant findings are false discoveries.
Results
Thirty-four SNPs satisfied this criterion. The top finding indicated that 10 SNPs in SACM1L mediated the effects of bupropion on sexual side-effects (p=4.98×10−7, q=0.023). Suggestive findings were also found for SNPs in MAGI2, DTWD1, WDFY4 and CHL1.
Conclusions
Although our findings require replication and functional validation, this study demonstrates the potential of GWAS to discover genes and pathways that could mediate adverse effects of antidepressant medication.