Applicability of somatic monitoring instructions in clinical practice guidelines on antipsychotic drug use

BACKGROUND: Clinical practice guidelines (CPGs) recommend the monitoring of somatic parameters in patients treated with antipsychotic drugs in order to detect adverse effects. The objective of this study was to assess, in adult and (frail) elderly populations, the consistency and applicability of the somatic monitoring instructions recommended by established CPGs prior to and during antipsychotic drug use. METHODS: A search for national and international CPGs was performed by querying the electronic database PubMed and Google. Somatic monitoring instructions were assessed for adult and (frail) elderly populations separately. The applicability of somatic monitoring instructions was assessed using the Systematic Information for Monitoring (SIM) score. Somatic monitoring instructions were considered applicable when a minimum SIM score of 3 was reached. RESULTS: In total, 16 CPGs were included, with a total of 231 somatic monitoring instructions (mean: 14; range: 0-47). Of the somatic monitoring instructions, 87% were considered applicable, although critical values and how to respond to aberrant values were only present in 28 and 52% of the available instructions respectively. Only 1 CPG presented an instruction specifically for (frail) elderly populations. CONCLUSIONS: We emphasize the need for a guideline with somatic monitoring instructions based on the SIM definition for both adult and (frail) elderly populations using antipsychotic drugs. In addition, CPGs should state that clear agreements should be made regarding who is responsible for interventions and somatic monitoring prior to and during antipsychotic drug use

Lithium surveillance by community pharmacists and physicians in ambulatory patients:a retrospective cohort study

Background Shared care agreements between clinical pharmacists and physicians can improve suboptimal lithium monitoring in in- and outpatient settings. However, it is unknown whether incorporating community pharmacists in such agreements can also improve lithium monitoring in an outpatient setting. Aim To assess the necessity for a shared care agreement for lithium monitoring in our region by investigating: intervention rates by community pharmacists and whether those are sufficient; lithium monitoring by physicians in ambulatory patients; the extent of laboratory parameter exchange to community pharmacists. Method Patient files of lithium users were surveyed in a retrospective cohort study among 21 community pharmacies in the Northern Netherlands. Outcome was the intervention rate by community pharmacists and whether those were deemed sufficient by an expert panel. Additionally, we investigated both the percentages of patients monitored according to current guidelines and of laboratory parameters exchanged to community pharmacists. Results 129 patients were included. Interventions were performed in 64.4% (n = 29), 20.8% (n = 5), and 25.0% (n = 1) of initiations, discontinuations, and dosage alterations of drugs interacting with lithium, respectively. The expert panel deemed 40.0% (n = 14) of these interventions as "insufficient". Physicians monitored 40.3% (n = 52) of the patients according to current guidelines for lithium serum levels and kidney functions combined. Approximately half of the requested laboratory parameters were available to the community pharmacist. Conclusion Intervention rates by community pharmacists and lithium monitoring by physicians can be improved. Therefore, a shared care agreement between community pharmacists, clinical pharmacists, and physicians is needed to improve lithium monitoring in ambulatory patients

The effectiveness of off-label dopamine stimulating agents in depressive disorder:A systematic review and meta-analysis

The chronicity of depressive disorders is a major problem. Dopamine stimulating agents (DSA) are suggested to hold a promising potential in depression management, particularly in older adults, in whom dopamine deficiency due to aging may be an underlying cause. More evidence is needed to support these drugs in the management of depression. Therefore, we conducted a systematic literature review and meta-analysis. Data was extracted from eighteen randomized-controlled-trials and eight open-label-studies. Additional meta-regression-analyses were performed to examine superiority of monotherapy versus augmentation, and to rule out a putative age effect. DSA were found to reduce depressive symptoms (SMD=-0.26, 95%CI[-0.43;-0.10]). Heterogeneity was high and a significant Egger's test indicated publication bias. Adjustment for missing studies, using trim-and-fill-methodology, reduced the effect size (SMD=-0.17, 95%CI[-0.39;0.05]), which lost statistical significance. Removing the outlier study from the analysis, the effect size remained marginally small, but was statistically-significant (SMD=-0.17, 95%CI[-0.31;-0.02]). Neither augmentation nor monotherapy was superior. No age effect was found. It can be concluded that off-label DSA are overall effective in reducing depressive symptoms. However, the evidence is weak, regarding the publication bias, and modest-to-weak treatment effects. Well-designed high-quality trials are highly needed, before dopamine stimulating agents can be adequately positioned in future depression treatment protocols.</p

The effectiveness of off-label dopamine stimulating agents in depressive disorder:A systematic review and meta-analysis

The chronicity of depressive disorders is a major problem. Dopamine stimulating agents (DSA) are suggested to hold a promising potential in depression management, particularly in older adults, in whom dopamine deficiency due to aging may be an underlying cause. More evidence is needed to support these drugs in the management of depression. Therefore, we conducted a systematic literature review and meta-analysis. Data was extracted from eighteen randomized-controlled-trials and eight open-label-studies. Additional meta-regression-analyses were performed to examine superiority of monotherapy versus augmentation, and to rule out a putative age effect. DSA were found to reduce depressive symptoms (SMD=-0.26, 95%CI[-0.43;-0.10]). Heterogeneity was high and a significant Egger's test indicated publication bias. Adjustment for missing studies, using trim-and-fill-methodology, reduced the effect size (SMD=-0.17, 95%CI[-0.39;0.05]), which lost statistical significance. Removing the outlier study from the analysis, the effect size remained marginally small, but was statistically-significant (SMD=-0.17, 95%CI[-0.31;-0.02]). Neither augmentation nor monotherapy was superior. No age effect was found. It can be concluded that off-label DSA are overall effective in reducing depressive symptoms. However, the evidence is weak, regarding the publication bias, and modest-to-weak treatment effects. Well-designed high-quality trials are highly needed, before dopamine stimulating agents can be adequately positioned in future depression treatment protocols.</p

Association Between the 1291-C/G Polymorphism in the Adrenergic alpha-2a Receptor and the Metabolic Syndrome

The prevalence of the metabolic syndrome is increased in patients with schizophrenia compared with the general population. The strong interindividual differences in susceptibility to developing the metabolic syndrome suggests that the genetic makeup is a modulating factor. Part of the genetic puzzle can possibly be explained by variations in the gene coding for the adrenergic alpha-2a receptor (ADRA2A) because this receptor plays an important role in lipolysis. Three studies have found an association between the alpha-2a 1291-C/G polymorphism and antipsychotic induced weight gain, with conflicting results between whites and Asians. No studies have been published investigating the association between the 1291-C/G polymorphism and the metabolic syndrome. The primary objective of this cross-sectional study was to investigate the association between the ADRA2A 1291-C/G polymorphism and the metabolic syndrome in 470 patients using antipsychotic drugs. There was no significant association between carriership of the variant 1291-G allele and prevalence of the metabolic syndrome (odds ratio, 0.73; 95% confidence interval, 0.49Y1.15). Exploratory analysis showed an association between carriership of the variant 1291-G allele and a reduced prevalence of the metabolic syndrome in patients not currently using antipsychotics (odds ratio, 0.05; 95% confidence interval, 0.003Y0.97; P = 0.048). In conclusion, this study shows that the ADRA2A 1291-C/G polymorphism does not seem to be a strong predictor for long-term occurrence of the metabolic syndrome in antipsychotic using patients. Studies investigating this association using a prospective, or retrospective, design, as well as studies investigating this association in a nonpsychiatric population, are warranted

Association between HTR2C polymorphisms and weight loss in obese patients

OBJECTIVE To investigate whether the HTR2C rsUU334 and 759 C/T polymorphisms are associated with weight loss in an anti- obesity programme. DESIGN AND METHODS A longitudinal observational follow-up study was used to assess the association between HTR2C genotypes and weight loss during a nine month programme in an obesity clinic. Caucasian patients aged 18 years or older were included. Data were extracted from the patients' medical records. In total, 128 patients were included 129 males). RESULTS There was a significant association between the HTR2C 759 T allele and resistance to weight loss in the first month of the programme. For each T allele present, there was 0.78% (95% confidence interval [95%-CI] 0.19-1.38; P = 0.011 less weight loss (as a percentage of the body weight at start). Patients carrying the variant HTR2C 759 T allele were also less likely to reach > 7% weight loss (odds ratio [OR] 0.23; 95%-CI 0.06- 0,85; P = 0.028), and dropped out of the programme sooner [-0.78 months; 95%-CI -1.51- -0.06; P = 0.035; corrected for gender). No associations with the HTR2C rsUU334- genotype and any of the primary endpoints for weight loss or secondary endpoints were found. CONCLUSION Patients carrying the HTR2C 759 T allele were more resistant to weight loss and dropped out of the programme sooner. However, these effects were small and only explained a small part of a very complex puzzle. Genotyping HTR2C to predict a patient's chance of success in an obesity clinic is therefore not warranted

Effects of Pharmacogenetic Screening for CYP2D6 Among Elderly Starting Therapy With Nortriptyline or Venlafaxine:A Pragmatic Randomized Controlled Trial (CYSCE Trial)

PURPOSE/BACKGROUND: The duration of untreated depression is a predictor for poor future prognosis, making rapid dose finding essential. Genetic variation of the CYP2D6 isoenzyme can influence the optimal dosage needed for individual patients. The aim of this study was to determine the effectiveness of CYP2D6 pharmacogenetic screening to accelerate drug dosing in older patients with depression initiating nortriptyline or venlafaxine. METHODS/PROCEDURES: In this randomized controlled trial, patients were randomly allocated to one of the study arms. In the intervention arm (DG-I), the specific genotype accompanied by a standardized dosing recommendation based on the patients' genotype and the prescribed drug was directly communicated to the physician of the participant. In both the deviating genotype control arm (DG-C) and the nonrandomized control arm, the physician of the participants was not informed about the genotype and the associated dosing advise. The primary outcome was the time needed to reach adequate drug levels: (1) blood levels within the therapeutic range and (2) no dose adjustments within the previous 3 weeks. FINDINGS/RESULTS: No significant difference was observed in mean time to reach adequate dose or time to adequate dose between DG-I and DG-C. Compared with the nonrandomized control arm group, adequate drug levels were reached significantly faster in the DG-I group (log-rank test; P = 0.004), and there was a similar nonsignificant trend for the DG-C group (log-rank test; P = 0.087). IMPLICATIONS/CONCLUSIONS: The results of this study do not support pharmacogenetic CYP2D6 screening to accelerate dose adjustment for nortriptyline and venlafaxine in older patients with depression