How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?
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ABSTRACT:
SUBMITTER: Carvalho Henriques B
PROVIDER: S-EPMC7753050 | biostudies-literature | 2020
REPOSITORIES: biostudies-literature
Publications
How Can Drug Metabolism and Transporter Genetics Inform Psychotropic Prescribing?
Carvalho Henriques Beatriz B Yang Esther H EH Lapetina Diego D Carr Michael S MS Yavorskyy Vasyl V Hague Joshua J Aitchison Katherine J KJ
Frontiers in genetics 20201208
Many genetic variants in drug metabolizing enzymes and transporters have been shown to be relevant for treating psychiatric disorders. Associations are strong enough to feature on drug labels and for prescribing guidelines based on such data. A range of commercial tests are available; however, there is variability in included genetic variants, methodology, and interpretation. We herein provide relevant background for understanding clinical associations with specific variants, other factors that ...[more]
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Project description:Cholesterol metabolism is vital for brain function. Previous work in cultured cells has shown that a number of psychotropic drugs inhibit the activity of 7-dehydrocholesterol reductase (DHCR7), an enzyme that catalyzes the final steps in cholesterol biosynthesis. This leads to the accumulation of 7-dehydrocholesterol (7DHC), a molecule that gives rise to oxysterols, vitamin D, and atypical neurosteroids. We examined levels of cholesterol and the cholesterol precursors desmosterol, lanosterol, 7DHC and its isomer 8-dehydrocholesterol (8DHC), in blood samples of 123 psychiatric patients on various antipsychotic and antidepressant drugs, and 85 healthy controls, to see if the observations in cell lines hold true for patients as well. Three drugs, aripiprazole, haloperidol and trazodone increased circulating 7DHC and 8DHC levels, while five other drugs, clozapine, escitalopram/citalopram, lamotrigine, olanzapine, and risperidone, did not. Studies in rat brain verified that haloperidol dose-dependently increased 7DHC and 8DHC levels, while clozapine had no effect. We conclude that further studies should investigate the role of 7DHC and 8DHC metabolites, such as oxysterols, vitamin D, and atypical neurosteroids, in the deleterious and therapeutic effects of psychotropic drugs. Finally, we recommend that drugs that increase 7DHC levels should not be prescribed during pregnancy, as children born with DHCR7 deficiency have multiple congenital malformations.
| S-EPMC5554466 | biostudies-literature
Project description:BACKGROUND:The prescribing of psychotropic drugs, i.e. antidepressants, sedatives (anxiolytics, hypnotics), and antipsychotics is considerable and a large proportion is prescribed by general practitioners (GPs). There are concerns about dependency and medicalisation, and treatment decisions in psychiatry may appear arbitrary. Increased knowledge of GPs' opinions on the prescribing of psychotropics may lead to more rational use of these drugs. We aimed to quantify GPs' attitudes, beliefs and behaviour towards various aspects of psychotropic drug prescribing. METHODS:A questionnaire was distributed to physicians in all 199 GP practices in Region Västra Götaland, Sweden. The questions concerned determinants of psychotropic drug prescribing that had been identified in a previous, qualitative study. RESULTS:Questionnaires from 516 physicians (64% of whom were specialists in family medicine, 21% interns in family medicine, 15% others) at 152 GP practices (59% of which were state owned, 72% in an urban area, with a median of 7808 registered patients) were returned (estimated response rate: 48%). A majority - 62% - of GPs found it easier to start prescribing psychotropic drugs than to stop (95% confidence interval, 57%, 66%) vs. 8% (6%, 10%). Most GPs considered psychotherapy more suitable than psychotropic drugs in cases of mild psychiatric disease: 81% (77%, 84%) vs. 4% (3%, 6%). The problems treated with psychotropic drugs were considered to be mostly socioeconomic, or mostly medical, by similar proportions of physicians: 38% (34%, 42%) vs. 40% (36%, 45%). GPs were on average satisfied with their levels of antidepressant and sedative prescribing in relation to medical needs. More GPs regarded their prescribing of antipsychotics as being too low rather than too high: 33% (28%, 39%) vs. 7% (4%, 10%). CONCLUSIONS:This study illustrates the complexities of psychiatric drug treatment in primary care and identifies potential drivers of increased prescribing of psychotropics. The manifold factors, medical and non-medical, that affect prescribing decisions may explain a sense of arbitrariness surrounding psychotropic drug treatment. This notwithstanding, GPs seem mostly content with their prescribing.
| S-EPMC6321667 | biostudies-other
Project description:AbstractThis study examined changes in psychotropic medication use associated with the early months of the coronavirus disease 2019 (COVID-19) pandemic. Using Kaiser Permanente Northern California electronic health records, the authors identified adult patients with fills for psychotropic medications and a non-psychotropic comparator (statins) in the 13 weeks before and after the first-known COVID-19-related death in California (March 4, 2020). Generalized estimating equations were used to derive relative risk ratios (RRR) for medication fills compared with the prior year. Analyses were stratified by new and continued fills and patient characteristics. Among 2,405,824 patients, the mean (SD) age was 49.8 (17.9) years; 52.9% were female; 47.9% identified as White; 8.0% and 7.9% had anxiety and depression disorder diagnoses, respectively. Accounting for secular trends, in the 13 weeks following March 4, 2020, there were increased fills for trazodone (RRR = 1.03, 95% CI = 1.02, 1.04), decreased fills for benzodiazepines (RRR = 0.95, 95% CI = 0.94, 0.96) and hypnotics (RRR = 0.97, 95% CI = 0.96, 0.99), and stable fills for antidepressants (RRR = 1.00, 95% CI = 0.99, 1.00). Relative rates of new fills decreased across most medication classes and continued fills either remained stable or demonstrated non-clinically significant decreases. Patients aged ≥65 years demonstrated decreased fills for most medication classes. In the first 13 weeks of the COVID-19 pandemic, fills for most psychotropic medications remained constant or showed small changes relative to the previous year. Continued (compared with new) fills accounted for observed increases in some medication classes. Older adults demonstrated decreased fills of most medications.
| S-EPMC8556031 | biostudies-literature
Project description:ImportanceMedication review has been proposed to achieve improved use of psychotropic drugs, but benefits have not been confirmed.ObjectiveTo synthesize evidence for focused psychotropic medication review in medication optimization.Data sourcesMedline, PsycINFO, EMBASE, and CINAHL Plus were searched from inception to February 2018 using the index terms "drug utilization review" and "psychotropic drugs" and synonyms. Additional articles were retrieved using citation tracking and reference checking.Study selectionFull-length, peer-reviewed articles that reported focused psychotropic medication review were included. Inclusion was determined against prespecified criteria and assessed independently.Data extraction and synthesisStudy quality was assessed using National Institutes for Health appraisal tools and informed a structured synthesis of results. Meta-analysis using a random effects model was conducted.Main outcomes and measuresChange in the number or dosage of psychotropic medications, change in clinical parameters, change in patient-reported outcomes, and economic data were collected.ResultsA total of 26 studies met the inclusion criteria. Four studies were randomized clinical trials (n = 712 participants), while the remainder were before-after studies (n = 7844 participants). Most studies were conducted in elderly individuals, people with dementia, and adults with intellectual disability. Focused psychotropic medication review is a complex intervention; the professional(s) involved, target drug, degree of integration with usual care, and participant involvement varied greatly among the studies. Meta-analysis included 3 studies (n = 652 participants). Psychotropic medication review was associated with a reduction in prescribing of psychotropic drugs compared with control (pooled odds ratio, 0.24; 95% CI, 0.14-0.39) in elderly participants with cognitive impairment living in nursing homes. Before-after studies consistently reported a change in psychotropic drug prescribing after medication review, regardless of the population. Studies that reported the effects of psychotropic medication review on clinical outcomes failed to demonstrate benefit. Economic implications of focused psychotropic medication review were not adequately assessed. The quality of evidence is poor and studies are at risk of bias.Conclusions and relevanceFocused psychotropic medication review was associated with a reduction in prescribing of psychotropic drugs, but has not been shown to improve clinical outcomes or to provide economic benefit. More robust evidence is needed before programs of focused psychotropic medication review can be recommended as part of routine care for any patient group.
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Project description:ObjectivesTo describe the incidence of recorded mental illness and challenging behaviour in people with intellectual disability in UK primary care and to explore the prescription of psychotropic drugs in this group.DesignCohort study.Setting571 general practices contributing data to The Health Improvement Network clinical database.Participants33,016 adults (58% male) with intellectual disability who contributed 211,793 person years' data.Main outcome measuresExisting and new records of mental illness, challenging behaviour, and psychotropic drug prescription.Results21% (7065) of the cohort had a record of mental illness at study entry, 25% (8300) had a record of challenging behaviour, and 49% (16,242) had a record of prescription of psychotropic drugs. During follow-up, the rate of new cases of mental illness in people without a history at cohort entry was 262 (95% confidence interval 254 to 271) per 10,000 person years and the rate of challenging behaviour was 239 (231 to 247) per 10,000 person years. The rate of new psychotropic drug prescription in those without a previous history of psychotropic drug treatment was 518 (503 to 533) per 10,000 person years. Rates of new recording of severe mental illness declined by 5% (95% confidence interval 3% to 7%) per year (P<0.001), and new prescriptions of antipsychotics declined by 4% (3% to 5%) per year P<0.001) between 1999 and 2013. New prescriptions of mood stabilisers also decreased significantly. The rate of new antipsychotic prescribing was significantly higher in people with challenging behaviour (incidence rate ratio 2.08, 95% confidence interval 1.90 to 2.27; P<0.001), autism (1.79, 1.56 to 2.04; P<0.001), and dementia (1.42, 1.12 to 1.81; P<0.003) and in those of older age, after control for other sociodemographic factors and comorbidity.ConclusionsThe proportion of people with intellectual disability who have been treated with psychotropic drugs far exceeds the proportion with recorded mental illness. Antipsychotics are often prescribed to people without recorded severe mental illness but who have a record of challenging behaviour. The findings suggest that changes are needed in the prescribing of psychotropics for people with intellectual disability. More evidence is needed of the efficacy and safety of psychotropic drugs in this group, particularly when they are used for challenging behaviour.
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Project description:BackgroundAgitation is a common challenging behaviour in dementia with a negative influence on patient's quality of life and a high caregiver burden. Treatment is often difficult. Current guidelines recommend restrictive use of psychotropic drug treatment, but guideline recommendations do not always suffice.ObjectiveTo explore how physicians decide on psychotropic drug treatment for agitated behaviour in dementia when the guideline prescribing recommendations are not sufficient.MethodsWe conducted five online focus groups with a total of 22 elderly care physicians, five geriatricians and four old-age psychiatrists, in The Netherlands. The focus groups were thematically analysed.ResultsWe identified five main themes. Transcending these themes, in each of the focus groups physicians stated that there is 'not one size that fits all'. The five themes reflect physicians' considerations when deciding on psychotropic drug treatment outside the guideline prescribing recommendations for agitated behaviour in dementia: (1) 'reanalysis of problem and cause', (2) 'hypothesis of underlying cause and treatment goal', (3) 'considerations regarding drug choice', (4) 'trial and error' and (5) 'last resort: sedation'.ConclusionWhen guideline prescribing recommendations do not suffice, physicians start with reanalysing potential underlying causes. They try to substantiate and justify medication choices as best as they can with a hypothesis of underlying causes or treatment goal, using other guidelines, and applying personalised psychotropic drug treatment.
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Project description:OBJECTIVES:To survey current prescribing practices of psychotropic drugs by child and adolescent eating disorder (CAED) psychiatrists in the treatment of anorexia nervosa (AN). DESIGN:Cross-sectional self-administered survey. SETTING:All children and young people eating disorder services (CYP EDS) in England during a national training programme. PARTICIPANTS:44 CAED psychiatrists practising in CYP EDS in England. PRIMARY AND SECONDARY OUTCOME MEASURES:CAED psychiatrists completed a questionnaire regarding the pattern of psychopharmacological care in AN that they provide and the medication treatment pattern at their CYP EDS. Secondary outcome measures included the process of continuing pharmacotherapy from secondary care to primary care. RESULTS:Of the 77 CYP EDS representing every team in England, 44 teams represented by a CAED psychiatrist responded, despite 13 having no psychiatrists in post at the time of the study (response rate 69%). Most (40%) respondents estimated that <10% of patients with AN were prescribed psychotropic medications. Olanzapine was reported as the most commonly prescribed medication for AN by 38% of the respondents, followed by fluoxetine (29%) and sertraline (10%). The most common minimum olanzapine initiation dose in this study was at 2.5?mg/day for a duration of 2-4 weeks, reaching a maximum dose of 5?mg/day. Most (68%) reviewed medications every week (30%) or every 2?weeks (38%). Over 50% of the respondents reported continuation of olanzapine prescribing within the CYP EDS teams. CONCLUSIONS:This nationally representative survey showed that despite a lack of evidence, psychotropic medications are commonly prescribed to a minority of patients, most frequently, olanzapine. Further evidence is needed on which patients may potentially benefit from pharmacotherapy as an adjunct to psychological interventions.
| S-EPMC6756572 | biostudies-literature
Project description:Treatment with psychotropic medication may sometimes be jeopardised because of the COVID-19 pandemic. One underlying reason is the lack of COVID-19-specific psychopharmacology guidelines. Here, we discuss five considerations arising from our clinical experience and pharmacological background knowledge to enable safe and well-informed psychopharmacotherapy during the COVID-19 pandemic.
| S-EPMC7248582 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2013-07-18 | GSE48955 | GEO
Project description:PURPOSEPeople with Intellectual disability (ID) are likely to be prescribed psychotropic medication particularly antipsychotics without a clear clinical indication. This has given rise to a national initiative in the UK to stop overprescribing medication in this vulnerable population. While the goals are simple it is unclear if specialist ID services or primary care services in the UK should look to lead. Further, it is uncertain if primary care practitioners (GPs) can be systematically educated of the latest good practice developments and concerns in this specialised area. This study surveyed the knowledge level of a sample of GPs in Cornwall UK (county of 538,000) post a structured tutorial on psychotropic medication and people with ID.METHODSA 21 item questionnaire was delivered in meetings organised for all the county GPs a year after a talk given to the same demographic. The questionnaire conducted an assessment of the knowledge of national guidance on use of psychotropic medication in ID based on the subjects covered in the tutorial.RESULTSOf the 60 expected GP participants the tutorial was attended by 44 GPs (73%) and the follow up meeting by 42 (70%). Ninety percent GPs in the follow up meeting filled the questionnaire. For 16 questions, more than 80% GPs gave correct responses whereas five questions attracted a correct answer from less than 80%. Majority of the GPs felt psychotropic medication management in people with ID should be specialist led.CONCLUSIONSGPs' knowledge of issues relevant to prescribing in people with ID benefitted from the tutorial. However a clear need for the psychotropic medication management to be delivered via specialist care emerged. This raises issues of resource allocation and debate on whether people with ID require specialist provision due to lack of ability in main stream primary care to manage their needs.
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