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Trends in Pharmacological Sciences May 2016In neuropsychiatric drug development, the rate of successful translation of preclinical to clinical efficacy has been disappointingly low. Tolerance, defined as a loss... (Review)
Review
In neuropsychiatric drug development, the rate of successful translation of preclinical to clinical efficacy has been disappointingly low. Tolerance, defined as a loss of efficacy with repeated drug exposure, is rarely addressed as a potential source of clinical failures. In this review, we argue that preclinical methods of tolerance development may have predictive validity and, therefore, inclusion of studies using repeated drug exposure early during the drug discovery and development process should serve to mitigate a proportion of clinical failures. Our analysis indicates that many published preclinical efficacy studies in the neuropsychiatry arena are conducted with acute drug administration only. Furthermore, specifically in the field of schizophrenia, there are several examples where tolerance development may be suspected as a factor contributing to translational failures. These and other examples highlight the need for built-for-purpose tolerance studies to be conducted, regardless of the target interaction mode of the drugs (i.e., agonist or antagonist, allosteric or orthosteric). We suggest that, for compounds that have failed in clinical studies, preclinical efficacy data sets need to be revisited to estimate the potential impact of tolerance development, one of the most significant known unknowns in the preclinical-to-clinical translation.
Topics: Animals; Drug Discovery; Drug Evaluation, Preclinical; Drug Tolerance; Humans; Neurosciences; Psychotropic Drugs; Translational Research, Biomedical
PubMed: 26935643
DOI: 10.1016/j.tips.2016.01.008 -
JAMA Pediatrics Mar 2022This cross-sectional study examines incidence of prevalence psychotropic drug use in Manitoban children before and during the COVID-19 pandemic.
This cross-sectional study examines incidence of prevalence psychotropic drug use in Manitoban children before and during the COVID-19 pandemic.
Topics: Adolescent; COVID-19; Child; Cross-Sectional Studies; Female; Humans; Incidence; Male; Manitoba; Mental Disorders; Pandemics; Prevalence; Psychotropic Drugs; SARS-CoV-2
PubMed: 34982101
DOI: 10.1001/jamapediatrics.2021.5634 -
Naunyn-Schmiedeberg's Archives of... Aug 2020Antidepressants, antiepileptics, mood stabilizers, and antipsychotics are extremely broadly used psychoactive drugs. These drug terms are universally used in the... (Review)
Review
Antidepressants, antiepileptics, mood stabilizers, and antipsychotics are extremely broadly used psychoactive drugs. These drug terms are universally used in the literature. However, the indications of these drugs have broadened substantially and overlap. The mismatch between drug classification and clinical uses causes a lot of confusion in communication and renders literature searches increasingly difficult. Therefore, we propose to drop the above terms altogether and replace them by simple mechanistic terms. Antidepressants are re-named as norepinephrine/serotonin (NE/5-HT) enhancers, antiepileptics comprising drugs with different mechanisms become neuronal inhibitors with pleiotropic effects (NIPEs), and antipsychotics become antagonists at multiple G protein-coupled receptors (mGPCR antagonists). Alkali metal ions, comprising lithium, are integrated into NIPEs. The terms "typical/first-generation/conventional" and "atypical/second-generation/non-conventional" antipsychotics should be dropped, because the original criterion for distinction, i.e., the presence and absence of extrapyramidal motor effects, respectively, is not valid anymore. The suggested changes in drug nomenclature have already been implemented into a recent textbook (Seifert R, Basic Knowledge of Pharmacology). The revised nomenclature ensures consistency with other fields of pharmacology and assignment of drug classes to indications without causing confusion. The authors acknowledge that the change in drug nomenclature is a cultural process that will take time and openly discuss the problems associated with the proposal. Ultimately, international learned societies will have to agree on a new nomenclature.
Topics: Consensus; Humans; Psychotropic Drugs; Terminology as Topic
PubMed: 32535698
DOI: 10.1007/s00210-020-01918-x -
International Psychogeriatrics Mar 2018ABSTRACTBackground:We aimed to assess whether there were any changes in the use of psychotropic drugs in Norwegian nursing homes between 2004 and 2011. Also, we...
UNLABELLED
ABSTRACTBackground:We aimed to assess whether there were any changes in the use of psychotropic drugs in Norwegian nursing homes between 2004 and 2011. Also, we investigated whether the predictors of use of specific psychotropic drug groups have changed.
METHODS
We conducted a secondary analysis of two cohort studies of two Norwegian nursing home samples (2004/05 and 2010/11). Multivariate models were applied.
RESULTS
We found a significant decrease in the prescription of antipsychotic drugs between 2004 and 2011 (0.63 OR, 95%CI = 0.49-0.82, p < 0.001) even after adjusting for relevant demographic and clinical variables. There are only minor changes for the other psychotropic drugs. We found that (1) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with more affective symptoms and (2) the use of specific psychotropic drug groups as well as the number of psychotropic drugs used was associated with lower scores on the Physical Self-Maintenance scale.
CONCLUSION
This is the first study to show a robust decrease in antipsychotic drug use in nursing home patients with dementia unrelated to possible changes in case mix. The change might be explained by treatment recommendations against its use except in the most severe conditions of aggression or psychosis. Our findings indicate that it takes several years to implement scientific knowledge in clinical practice in nursing homes.
Topics: Aged; Aged, 80 and over; Antipsychotic Agents; Behavioral Symptoms; Cognition Disorders; Cohort Studies; Dementia; Drug Utilization; Female; Homes for the Aged; Humans; Length of Stay; Male; Norway; Nursing Homes; Psychotic Disorders; Psychotropic Drugs
PubMed: 28988552
DOI: 10.1017/S1041610217001788 -
Epilepsy & Behavior : E&B Jun 2018Psychiatric disorders are more common in patients with epilepsy than in the general population. The aims of the study were to assess the frequency and type of...
Psychiatric disorders are more common in patients with epilepsy than in the general population. The aims of the study were to assess the frequency and type of psychotropic drug usage in patients with epilepsy, to assess the risk factors for their use, and to assess their proconvulsive potential and the risk of interactions with antiepileptic drugs. This 20-month prospective study included patients treated at the university hospital outpatient clinic. Psychotropic drugs have been classified according to the Anatomical Therapeutic Chemical Classification System. Of the 621 patients (with a mean age of 35.4years), 60% were women, and 37.5% were in remission; 54.8% of the patients used antiepileptic drug monotherapy. The most commonly used antiepileptic drugs were valproate, levetiracetam, lamotrigine, and carbamazepine. Eighty-nine (14.3%) patients received psychiatric comedication. Sertraline, perazine, and hydroxyzine were the predominantly used psychotropic drugs. Independent variables associated with psychotropic drug usage in the logistic regression model included age, active epilepsy, combined focal and generalized epilepsy type, use of somatic comedication, and phenobarbital. Over one-third of the patients simultaneously received antiepileptic drugs and psychotropic drugs, between which clinically significant interactions may occur, 10% of patients used psychotropic drugs to lower the seizure threshold. The results of the study indicate the need for closer cooperation between doctors of various specialties when caring for patients with epilepsy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anticonvulsants; Carbamazepine; Drug Interactions; Drug Therapy, Combination; Epilepsy; Female; Humans; Male; Mental Disorders; Middle Aged; Phenobarbital; Prospective Studies; Psychotropic Drugs; Triazines; Young Adult
PubMed: 29706306
DOI: 10.1016/j.yebeh.2018.03.033 -
European Neuropsychopharmacology : the... Apr 2022Despite growing concern about reproductive safety of psychotropic drugs, there is a paucity of research assessing prenatal prescribing practices for bipolar disorder... (Review)
Review
Despite growing concern about reproductive safety of psychotropic drugs, there is a paucity of research assessing prenatal prescribing practices for bipolar disorder (BD). This population-based cohort study identified women aged 15-50 years with BD diagnosis, who delivered their first and singleton child between 2003 and 2018 in Hong Kong, with an aim to examine temporal trends and predictors of prenatal psychotropic drug use as well as drug utilization patterns before and during pregnancy were evaluated. Data were retrieved from territory-wide medical-record database of public healthcare services. Of 302 identified women, 202 (66.9%) and 180 (59.6%) redeemed at least 1 prescription for psychotropic drugs in 12 months pre-pregnancy and during pregnancy, respectively. Psychotropic drug treatment (OR = 16.14 [95% CI: 8.79-29.65]) and psychiatric admission (OR = 4.12 [95% CI: 1.66-10.24]) within 12 months pre-pregnancy were associated with prenatal drug use. Second-generation antipsychotic use during pregnancy increased over time, while prenatal use of lithium, anti-epileptics and first-generation-antipsychotics showed declining trend. Use of psychotropic drugs progressively decreased across pre-pregnancy and trimesters of pregnancy. Forty-two (23.3%) women received polypharmacy during pregnancy. Antidepressant use accounted for 17% of all monotherapy episodes. A significant proportion of women exposed to valproate in 12 months pre-pregnancy (27.2%) and first-trimester (16%). In conclusion, our results generally indicate trajectories of reduced psychotropic drug use across pregnancy. Deviations between real-world prescribing patterns and treatment guidelines underscore the need for comprehensive review of current clinical practices. Further research clarifying relationships of prenatal psychotropic drug exposure with maternal and fetal outcomes is warranted.
Topics: Antipsychotic Agents; Bipolar Disorder; Child; Cohort Studies; Drug Utilization; Female; Humans; Pregnancy; Pregnant Women; Psychotropic Drugs
PubMed: 35151952
DOI: 10.1016/j.euroneuro.2022.01.115 -
Current Medicinal Chemistry 2022Oxytocin is a nonapeptide synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Historically, this molecule has been involved as a key factor in... (Review)
Review
BACKGROUND
Oxytocin is a nonapeptide synthesized in the paraventricular and supraoptic nuclei of the hypothalamus. Historically, this molecule has been involved as a key factor in the formation of infant attachment, maternal behavior and pair bonding and, more generally, in linking social signals with cognition, behaviors and reward. In the last decades, the whole oxytocin system has gained a growing interest as it was proposed to be implicated in etiopathogenesis of several neurodevelopmental and neuropsychiatric disorders.
METHODS
With the main goal of an in-depth understanding of the oxytocin role in the regulation of different functions and complex behaviors as well as its intriguing implications in different neuropsychiatric disorders, we performed a critical review of the current state of the art. We carried out this work through the PubMed database up to June 2021 with the search terms: 1) "oxytocin and neuropsychiatric disorders"; 2) "oxytocin and neurodevelopmental disorders"; 3) "oxytocin and anorexia"; 4) "oxytocin and eating disorders"; 5) "oxytocin and obsessive- compulsive disorder"; 6) "oxytocin and schizophrenia"; 7) "oxytocin and depression"; 8) "oxytocin and bipolar disorder"; 9) "oxytocin and psychosis"; 10) "oxytocin and anxiety"; 11) "oxytocin and personality disorder"; 12) "oxytocin and PTSD".
RESULTS
Biological, genetic, and epigenetic studies highlighted quality and quantity modifications in the expression of oxytocin peptide or in oxytocin receptor isoforms. These alterations would seem to be correlated with a higher risk of presenting several neuropsychiatric disorders belonging to different psychopathological spectra. Collaterally, the exogenous oxytocin administration has shown to ameliorate many neuropsychiatric clinical conditions.
CONCLUSION
Finally, we briefly analyzed the potential pharmacological use of oxytocin in a patient with severe symptomatic SARS-CoV-2 infection due to its anti-inflammatory, antioxidative and immunoregulatory properties.
Topics: Anti-Obesity Agents; COVID-19; DNA-Binding Proteins; Female; Humans; Infant; Mental Disorders; Oxytocin; Psychotropic Drugs; Receptors, Oxytocin; SARS-CoV-2
PubMed: 35894453
DOI: 10.2174/0929867329666220727120646 -
BMC Family Practice Jan 2019The prescribing of psychotropic drugs, i.e. antidepressants, sedatives (anxiolytics, hypnotics), and antipsychotics is considerable and a large proportion is prescribed...
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.
Topics: Anti-Anxiety Agents; Antidepressive Agents; Antipsychotic Agents; Attitude of Health Personnel; Female; General Practitioners; Humans; Hypnotics and Sedatives; Male; Practice Patterns, Physicians'; Primary Health Care; Psychotropic Drugs; Surveys and Questionnaires; Sweden
PubMed: 30611211
DOI: 10.1186/s12875-018-0885-4 -
European Journal of Hospital Pharmacy :... Mar 2021The aims of the present study were: (1) to describe psychotropic drug consumption patterns in an outpatient population aged 65 years and older; (2) to determine the... (Review)
Review
OBJECTIVES
The aims of the present study were: (1) to describe psychotropic drug consumption patterns in an outpatient population aged 65 years and older; (2) to determine the impact of a number of demographic and clinical factors on psychotropic consumption; and (3) to determine the ratio of potentially inappropriate psychotropic agents prescribed to the above population.
METHODS
Cross-sectional, observational study of outpatients aged 65 years and older. Data on sociodemographic and clinical variables were collected. Psychotropic drugs were classified into three categories: anxiolytics-hypnotics, antidepressants, and antipsychotics. To determine the risk factors for psychotropic drug use among these patients, a multivariate logistic regression model was developed and subsequently validated using bootstrap resampling techniques. To identify the psychotropic drugs to be avoided, a review of treatments received by the patients was performed based on the 2015 version of the Beers criteria.
RESULTS
The study included 225 outpatients of whom 30.7% were on psychotropic drugs for chronic treatment. The highest likelihood of psychotropic utilisation corresponded to the following profile: female, living in a nursing home, having two or more prescribing physicians, and having received six or more different diagnoses. According to Beers criteria, 51 patients (22.7% of the sample and 73.9% of patients on psychotropic drugs) had been prescribed at least one potentially inappropriate psychotropic drug.
CONCLUSION
Elderly patients commonly use psychotropic medications and are the most vulnerable to the adverse effects of these drugs. It is necessary to re-evaluate the pertinence and accuracy of these medical prescriptions.
Topics: Aged; Cross-Sectional Studies; Female; Humans; Observational Studies as Topic; Psychotropic Drugs; Risk Factors
PubMed: 33608436
DOI: 10.1136/ejhpharm-2019-001927 -
Journal of Psychosocial Nursing and... Feb 2020Many clients do not take their medications as prescribed. One of the reasons may be the common adverse drug effects and drug-drug interactions of certain medications....
Many clients do not take their medications as prescribed. One of the reasons may be the common adverse drug effects and drug-drug interactions of certain medications. This article reviews adverse drug effects (including less serious side effects), the pharmacokinetics and pharmacodynamics involved in adverse effects, and the pharmacokinetics of drug interactions. For medications to be effective in treating mental disorders, nurses need to carefully assess clients and their motivations for taking medications, routinely inquire about when and how they are taking their prescriptions, any adverse effects they are experiencing, and how they are managing common, less severe adverse effects. [Journal of Psychosocial Nursing and Mental Health Services, 58(2), 9-13.].
Topics: Drug Interactions; Drug-Related Side Effects and Adverse Reactions; Humans; Mental Disorders; Psychiatric Nursing; Psychotropic Drugs; Treatment Adherence and Compliance
PubMed: 32003860
DOI: 10.3928/02793695-20200117-02