The efficacy of antipsychotics in the treatment of physical aggressive behavior in patients with dementia in nursing homes

Patients with dementia often suffer from behavioral changes. A common behavioral change is acute physical aggressive behavior which is the most distressing change. This can lead to harm, which is especially problematic in nursing homes. Despite the serious safety concerns, antipsychotics are often prescribed to combat this problem. This article is aimed to review the evidence of the efficacy of utilizing antipsychotics in acutely treating physical aggressive behavior in patients with dementia in nursing homes. Therefore, a systematic literature search was performed. The results demonstrated that a meta-analysis confirmed statistically significant reduction in physical aggression when risperidone was compared to placebo. However, a randomized controlled trial showed no change in physical aggressive behavior between quetiapine and placebo. More research is needed to fully investigate the benefits of physical aggressive behavior and safety concerns of all the antipsychotics in patients with dementia in nursing homes

A case report: Management of carbamazepine intoxication using hemodialysis followed by continuous venovenous hemodialysis

An 18-year-old woman presented to the emergency department. She had ingested 43 extended-release tablets of carbamazepine 400 mg. Although the patient had high carbamazepine plasma levels and classified as severe intoxication, her clinical symptoms were less severe than expected. With the combination of hemodialysis and continuous venovenous hemodialysis in addition to usual care, including multiple-dose activated charcoal, a fast decrease (within 3 days) in carbamazepine plasma levels to levels in the therapeutic range was achieved. Only one session of hemodialysis was performed because the clinical status of the patient stabilized. In retrospect, the patient did not suffer severe toxicological symptoms from carbamazepine. Therefore, continuous venovenous hemodialysis could have been discontinued earlier. On the other hand, the fast decrease in carbamazepine plasma levels during extracorporeal treatment may have prevented the development of severe or rebound toxicological symptoms. This case report adds evidence to the successful management of carbamazepine intoxication using hemodialysis followed by continuous venovenous hemodialysis

A case report: Management of carbamazepine intoxication using hemodialysis followed by continuous venovenous hemodialysis

An 18-year-old woman presented to the emergency department. She had ingested 43 extended-release tablets of carbamazepine 400 mg. Although the patient had high carbamazepine plasma levels and classified as severe intoxication, her clinical symptoms were less severe than expected. With the combination of hemodialysis and continuous venovenous hemodialysis in addition to usual care, including multiple-dose activated charcoal, a fast decrease (within 3 days) in carbamazepine plasma levels to levels in the therapeutic range was achieved. Only one session of hemodialysis was performed because the clinical status of the patient stabilized. In retrospect, the patient did not suffer severe toxicological symptoms from carbamazepine. Therefore, continuous venovenous hemodialysis could have been discontinued earlier. On the other hand, the fast decrease in carbamazepine plasma levels during extracorporeal treatment may have prevented the development of severe or rebound toxicological symptoms. This case report adds evidence to the successful management of carbamazepine intoxication using hemodialysis followed by continuous venovenous hemodialysis

Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients. Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU). Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05). Discussion: This study underlines the importance to consider phenoconversion when looking at a patient’s genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy

Pharmacogenetics and phenoconversion: the influence on side effects experienced by psychiatric patients

Introduction: Preventing side effects is important to ensure optimal psychopharmacotherapy and therapeutic adherence among psychiatric patients. Obtaining the pharmacogenetic profile of CYP2C19 and CYP2D6 can play an important role in this. When the genotype-predicted phenotype shifts because of the use of co-medication, this is called phenoconversion. The aim was to study the influence of the pharmacogenetic (PGx) profile and phenoconversion on side effects experienced by psychiatric patients. Methods: A retrospective cohort study was performed using data from 117 patients from a psychiatric outpatient clinic. Patients were genotyped with a psychiatric PGx panel and side effects were evaluated using the Udvalg for Kliniske Undersølgelser side effects rating scale (UKU). Results: Of all patients, 10.3% and 9.4% underwent phenoconversion (any shift in predicted phenotype) for CYP2C19 and CYP2D6 respectively. No significant associations were found between the phenotype and UKU-score. 75% of the patients with an Intermediate metabolizer (IM) or Poor metabolizer (PM) phenoconverted phenotype of CYP2C19 experienced nausea and vomiting compared to 9.1% of the Normal metabolizer (NM) and Ultrarapid metabolizer (UM) patients (p = 0.033). 64% of the patients with an IM or PM phenoconverted phenotype of CYP2D6 experienced the side effect depression compared to 30.4% NMs and UMs (p = 0.020). CYP2D6 IM and PM patients had a higher concentration-dose ratio than NM patients (p < 0.05). Discussion: This study underlines the importance to consider phenoconversion when looking at a patient's genotype. This is important for a better prediction of the phenotype and preventing possible side effects under a specific psychopharmacotherapy

Continuity of pharmaceutical care for psychiatric patients

Psychiatric diseases are common. The effective treatment of a psychiatric disease, its (somatic) side effects and any concurrent somatic diseases is important for the patient’s overall health and wellbeing. The studies conducted in psychiatric patients generally focus on the continuation of psychiatric medication, but not on the continuation of somatic medications. These studies show that psychiatric patients commonly discontinue their psychiatric medication. However, studies on the overall continuity of pharmaceutical care in patients admitted to and discharged from a psychiatric hospital are scarce and fragmented. Based on the current knowledge, the overall objective of this thesis was to assess the continuation of pharmaceutical care in psychiatric patients. The use of somatic medications is high in psychiatric patients admitted to psychiatric hospitals. We found that 67.5-76.9% of the patients admitted to a psychiatric hospital in the Netherlands were using at least one somatic medication. It is commonly acknowledged that the risk of discontinuation of medication is high when patients are admitted to or discharged from general hospitals. As indicated by the studies in this thesis, the risk of discontinuity of somatic medication is high when patients are admitted to or discharged from a psychiatric hospital. 38.9% of the patients using somatic medication discontinued the use of at least one somatic medication during the first week of psychiatric hospitalization. For instance, 34.9% of the cardiovascular and acid-and bowel-related medications were discontinued during this first week. In addition, we found that the monitoring of pharmacotherapy may fail during admission to psychiatric hospitals as in almost 25% of the hospitalized patients either anticoagulant medication and/or International Normalized Ratio (INR) monitoring was discontinued. At discharge we found that at least a single medication is discontinued in almost 70% of psychiatric patients. Of all patients using antipsychotics, 25.2% discontinued the use of their antipsychotic medications, and of all patients using cardiovascular medications, 28.4% discontinued a cardiovascular drug. Obviously, the continuity of pharmaceutical care is important for the treatment and stabilization of psychiatric diseases after discharge. Therefore, we assessed the association between adherence to antipsychotics and psychiatric rehospitalization in patients with psychotic disorders during the first year after discharge. Patients who did not initiate antipsychotic medication use during the follow up had a higher risk of rehospitalization (RR = 3.7; 95% CI: 2.4-5.5) when compared to patients who did initiate use. For patients who initiated the use of psychiatric medication during the first month after the discharge, those who discontinued use had a twofold (RR = 2.3; 95% CI: 1.2-4.5) risk for rehospitalization during 2nd to 12th month after discharge when compared to those continuing use. It is important to identify which patients are at a greater risk for rehospitalization. In a prospective study in patients with psychotic or bipolar I disorder we found that rehospitalization can be predicted by various factors. We found that rehospitalization could best be predicted when combining information on clinical and medication characteristics, patients’ beliefs about medicines (BMQ), and health care provider assessments

Pharmacogenetics Guidelines: Overview and Comparison of the DPWG, CPIC, CPNDS, and RNPGx Guidelines

Many studies have shown that the efficacy and risk of side effects of drug treatment is influenced by genetic variants. Evidence based guidelines are essential for implementing pharmacogenetic knowledge in daily clinical practice to optimize pharmacotherapy of individual patients. A literature search was performed to select committees developing guidelines with recommendations being published in English. The Dutch Pharmacogenetics Working Group (DPWG), the Clinical Pharmacogenetics Implementation Consortium (CPIC), the Canadian Pharmacogenomics Network for Drug Safety (CPNDS), and the French National Network (Réseau) of Pharmacogenetics (RNPGx) were selected. Their guidelines were compared with regard to the methodology of development, translation of genotypes to predicted phenotypes, pharmacotherapeutic recommendations and recommendations on genotyping. A detailed overview of all recommendations for gene-drug combinations is given. The committees have similar methodologies of guideline development. However, the objectives differed at the start of their projects, which have led to unique profiles and strengths of their guidelines. DPWG and CPIC have a main focus on pharmacotherapeutic recommendations for a large number of drugs in combination with a patient’s genotype or predicted phenotype. DPWG, CPNDS and RNPGx also recommend on performing genetic testing in daily clinical practice, with RNPGx even describing specific clinical settings or medical conditions for which genotyping is recommended. Discordances exist, however committees also initiated harmonizing projects. The outcome of a consensus project was to rename “extensive metabolizer (EM)” to “normal metabolizer (NM)”. It was decided to translate a CYP2D6 genotype with one nonfunctional allele (activity score 1.0) into the predicted phenotype of intermediate metabolizer (IM). Differences in recommendations are the result of the methodologies used, such as assessment of dose adjustments of tricyclic antidepressants. In some cases, indication or dose specific recommendations are given for example for clopidogrel, codeine, irinotecan. The following drugs have recommendations on genetic testing with the highest level: abacavir (HLA), clopidogrel (CYP2C19), fluoropyrimidines (DPYD), thiopurines (TPMT), irinotecan (UGT1A1), codeine (CYP2D6), and cisplatin (TPMT). The guidelines cover many drugs and genes, genotypes, or predicted phenotypes. Because of this and their unique features, considering the totality of guidelines are of added value. In conclusion, many evidence based pharmacogenetics guidelines with clear recommendations are available for clinical decision making by healthcare professionals, patients and other stakeholders

Psychiatric medication use before and after the onset of type 1 diabetes in children and adolescents : A population-based cohort study

BACKGROUND: Several studies showed a bidirectional association between type 2 diabetes and psychiatric disorders in adults. Because there is limited information on the association between type 1 diabetes (T1D) and psychiatric disorders (including psychiatric medication use) in children and adolescents, we assessed frequency of use of these medications before and after the onset of T1D. METHODS: A population-based cohort study was conducted in the Dutch PHARMO Record Linkage System (1999-2009). Children and adolescents (<19 years) with at least 2 insulin dispensings from community pharmacies (T1D cohort, N = 925) were matched by age and sex (reference cohort without insulin use, N = 3591). The 5-year prevalence of psychiatric medication use (psycholeptics [ATC N05] and psychoanaleptics [ATC N06]) before and after onset of T1D were estimated, compared, and stratified by age, sex, and medication subgroup. RESULTS: The mean age of study participants was 10.1 years and 51% were boys. The 5-year prevalence of psychiatric medication use before the index date was significantly higher in the T1D cohort than in the reference cohort (7.2% vs 4.7%, respectively; P = .002) with the same pattern after developing T1D (10.4% vs 7.9%, respectively; P = .015). In both cohorts, adolescents (15-19 years) and boys had higher prevalences of use. This increased prevalence of psychiatric medication use both before and after the index date in T1D cohort was mainly driven by an increased use of psycholeptics (predominantly anxiolytics). CONCLUSIONS: Children with T1D were more likely to use psychiatric medication in the years before and after the onset of T1D which was mainly driven by psycholeptic use

Psychiatric medication use before and after the onset of type 1 diabetes in children and adolescents: A population-based cohort study

Background: Several studies showed a bidirectional association between type 2 diabetes and psychiatric disorders in adults. There is limited information available about the association of type 1 diabetes (T1D) and psychiatric disorders in children and adolescents. Objectives: To assess the extent of psychiatric medication use before and after the onset of T1D in children and adolescents compared with a reference cohort without T1D. Methods: A population-based cohort study was conducted in the Dutch PHARMO Record Linkage System. All children and adolescents <19 years) with at least two insulin dispensings between 1999 and 2009 were identified as a T1D cohort (N=925) and matched with an up to four times larger diabetes-free reference cohort (N=3591) by age and sex. The period prevalences of psychiatric medication use (psycholeptics (ATC N05) and psychoanaleptics (ATC N06)) were calculated by dividing the number of patients with at least one dispensing by the number of patients available in the cohort during that time. Prevalences were calculated from 5 years before until 5 years after the onset of T1D (the index date in both cohorts) and stratified by age, sex, medication subgroup, and before/after the onset of T1D. Results: The mean age of the study participants was 10.1 years and 51% were boys. The 5-year prevalence of psychiatric medication use before the index date was significantly higher in the T1D cohort than in the reference cohort (7.2 vs. 4.7%, respectively, p=0.002). The same pattern was observed for the period after developing T1D (10.4 vs. 7.9% in the T1D and reference cohort respectively, p=0.015). In both cohorts adolescents (15-19 years) and boys had higher prevalences of psychiatric medication use. This increased prevalence of psychiatric medication use both before and after the index date in T1D cohort was mainly driven by an increased use of psycholeptics (mainly anxiolytics). Conclusions: Children with T1D were more likely to use psychiatric medication in the years before and after the onset of type 1 diabetes. This increased use was mainly driven by psycholeptics both before and after onset of T1D

Psychiatric medication use before and after the onset of type 1 diabetes in children and adolescents : A population-based cohort study

BACKGROUND: Several studies showed a bidirectional association between type 2 diabetes and psychiatric disorders in adults. Because there is limited information on the association between type 1 diabetes (T1D) and psychiatric disorders (including psychiatric medication use) in children and adolescents, we assessed frequency of use of these medications before and after the onset of T1D. METHODS: A population-based cohort study was conducted in the Dutch PHARMO Record Linkage System (1999-2009). Children and adolescents (<19 years) with at least 2 insulin dispensings from community pharmacies (T1D cohort, N = 925) were matched by age and sex (reference cohort without insulin use, N = 3591). The 5-year prevalence of psychiatric medication use (psycholeptics [ATC N05] and psychoanaleptics [ATC N06]) before and after onset of T1D were estimated, compared, and stratified by age, sex, and medication subgroup. RESULTS: The mean age of study participants was 10.1 years and 51% were boys. The 5-year prevalence of psychiatric medication use before the index date was significantly higher in the T1D cohort than in the reference cohort (7.2% vs 4.7%, respectively; P = .002) with the same pattern after developing T1D (10.4% vs 7.9%, respectively; P = .015). In both cohorts, adolescents (15-19 years) and boys had higher prevalences of use. This increased prevalence of psychiatric medication use both before and after the index date in T1D cohort was mainly driven by an increased use of psycholeptics (predominantly anxiolytics). CONCLUSIONS: Children with T1D were more likely to use psychiatric medication in the years before and after the onset of T1D which was mainly driven by psycholeptic use