Hieronymus J. Derijks

The association between antidepressant use and disturbances in glucose homeostasis: evidence from spontaneous reports.

ObjectivesDepression is common in patients with diabetes, and the use of antidepressants may impair glycaemic control. We assessed the association between antidepressant use and hyper- and hypoglycaemia.MethodsBased on spontaneous reports listed in the World Health Organization (WHO) Adverse Drug Reaction Database, a case-control study was conducted. The study base consisted of all adverse drug reactions (ADRs) ascribed to antidepressants, antipsychotics and benzodiazepines between 1969 and 2005. Cases were defined as reported ADRs classified as hyper- or hypoglycaemia and separated in different study populations. All other reports were considered as controls. Exposure to antidepressants was the primary determinant investigated. Benzodiazepines and antipsychotics were chosen as reference groups. Potential confounding factors, namely, age, gender, use of antidiabetic medication, use of hyper- or hypoglycaemia-inducing comedication and reporting year, were determined on the index date. Multivariate logistic regression was used to evaluate the strength of the association, which was expressed as reporting odds ratios (RORs) with 95% confidence intervals (95% CI).ResultsOverall, the use of antidepressants was associated with hyperglycaemia [ROR 1.52 (95% CI: 1.20–1.93)] and of hypoglycaemia [ROR 1.84 (95% CI: 1.40–2.42)]. The association with hyperglycaemia was most pronounced for antidepressants with affinity for the 5-HT2c receptor, histamine-1 receptor and norepinephrinic (NE) reuptake transporter. The association with hypoglycaemia was most pronounced for antidepressants with affinity for the serotonin reuptake transporter.ConclusionThe results of this study strengthen the findings in individual case reports that the use of antidepressants is associated with disturbances in glucose homeostasis.

Comparison of a basic and an advanced pharmacotherapy-related clinical decision support system in a hospital care setting in the Netherlands

UNLABELLED OBJECTIVE To compare the clinical relevance of medication alerts in a basic and in an advanced clinical decision support system (CDSS). DESIGN A prospective observational study. MATERIALS AND METHODS We collected 4023 medication orders in a hospital for independent evaluation in two pharmacotherapy-related decision support systems. Only the more advanced system considered patient characteristics and laboratory test results in its algorithms. Two pharmacists assessed the clinical relevance of the medication alerts produced. The alert was considered relevant if the pharmacist would undertake action (eg, contact the physician or the nurse). The primary analysis concerned the positive predictive value (PPV) for clinically relevant medication alerts in both systems. RESULTS The PPV was significantly higher in the advanced system (5.8% vs 17.0%; p<0.05). Significant differences were found in the alert categories: drug-(drug) interaction (9.9% vs 14.8%; p<0.05), drug-age interaction (2.9% vs 73.3%; p<0.05), and dosing guidance (5.6% vs 16.9%; p<0.05). Including laboratory values and other patient characteristics resulted in a significantly higher PPV for the advanced CDSS compared to the basic medication alerts (12.2% vs 23.3%; p<0.05). CONCLUSION The advanced CDSS produced a higher proportion of clinically relevant medication alerts, but the number of irrelevant alerts remained high. To improve the PPV of the advanced CDSS, the algorithms should be optimized by identifying additional risk modifiers and more data should be made electronically available to improve the performance of the algorithms. Our study illustrates and corroborates the need for cyclic testing of technical improvements in information technology in circumstances representative of daily clinical practice.

The association between antidepressant use and hypoglycaemia in diabetic patients: a nested case-control study.

Hypoglycaemia is a limiting factor for glycaemic management of diabetes with intensive insulin and/or oral antidiabetic drug (OAD) regimen. Case reports suggest that antidepressants may interfere with blood glucose metabolism in patients with diabetes mellitus potentially increasing the risk of clinically relevant hypoglycaemia. Comorbid depression treated with antidepressants could therefore further complicate glycaemic control. We have carried out a nested case–control study among diabetic patients to assess the risk of hypoglycaemia requiring hospitalisation associated with the use of antidepressants.

Influence of antidepressants on glycaemic control in patients with diabetes mellitus.

Anecdotal evidence suggests that antidepressants (ADs) may complicate glycaemic control. The objective of this longitudinal study was to investigate the influence of ADs on glycaemic control within diabetes patients.

Visualizing Pharmacological Activities of Antidepressants: A Novel Approach

Antidepressants have different receptor binding profiles, which are related to therapeutic action and adverse drug reactions. We constructed a model to classify antidepressants on the basis of their binding properties of most common transporter- and receptor sites. Receptor binding was quantified by calculating receptor occupancy for the 5-HT (serotonin) reuptake transporter, norepinephrinic reuptake transporter, 5-HT2C-receptor, M3-receptor, H1-receptor and 1- receptor. To identify groups of antidepressants that show similar patterns of receptor occupancy for different receptors, hierarchical cluster analysis (HCA) and principle component analysis (PCA) were used. In addition, to visualize (a)symmetry between binding profiles of antidepressants, radar plots were constructed. On the basis of both analyses, four clusters of antidepressants which exert similar pharmacological properties were identified. Potentially, this model could be a helpful tool in medical practice and may be used as a prediction model for adverse effects of drugs entering the market.

Individualizing Pharmacotherapy in Patients with Renal Impairment: The Validity of the Modification of Diet in Renal Disease Formula in Specific Patient Populations with a Glomerular Filtration Rate below 60 Ml/Min. A Systematic Review

Background The Modification of Diet in Renal Disease (MDRD) formula is widely used in clinical practice to assess the correct drug dose. This formula is based on serum creatinine levels which might be influenced by chronic diseases itself or the effects of the chronic diseases. We conducted a systematic review to determine the validity of the MDRD formula in specific patient populations with renal impairment: elderly, hospitalized and obese patients, patients with cardiovascular disease, cancer, chronic respiratory diseases, diabetes mellitus, liver cirrhosis and human immunodeficiency virus. Methods and Findings We searched for articles in Pubmed published from January 1999 through January 2014. Selection criteria were (1) patients with a glomerular filtration rate (GFR) < 60 ml/min (/1.73m2), (2) MDRD formula compared with a gold standard and (3) statistical analysis focused on bias, precision and/or accuracy. Data extraction was done by the first author and checked by a second author. A bias of 20% or less, a precision of 30% or less and an accuracy expressed as P30% of 80% or higher were indicators of the validity of the MDRD formula. In total we included 27 studies. The number of patients included ranged from 8 to 1831. The gold standard and measurement method used varied across the studies. For none of the specific patient populations the studies provided sufficient evidence of validity of the MDRD formula regarding the three parameters. For patients with diabetes mellitus and liver cirrhosis, hospitalized patients and elderly with moderate to severe renal impairment we concluded that the MDRD formula is not valid. Limitations of the review are the lack of considering the method of measuring serum creatinine levels and the type of gold standard used. Conclusion In several specific patient populations with renal impairment the use of the MDRD formula is not valid or has uncertain validity.

Drug therapy management in patients with renal impairment: how to use creatinine-based formulas in clinical practice

PurposeThe use of estimated glomerular filtration rate (eGFR) in daily clinical practice.MethodseGFR is a key component in drug therapy management (DTM) in patients with renal impairment. eGFR is routinely reported by laboratories whenever a serum creatinine testing is ordered. In this paper, we will discuss how to use eGFR knowing the limitations of serum creatinine-based formulas.ResultsBefore starting a renally excreted drug, an equally effective drug which can be used more safely in patients with renal impairment should be considered. If a renally excreted drug is needed, the reliability of the eGFR should be assessed and when needed, a 24-h urine creatinine clearance collection should be performed. After achieving the best approximation of the true GFR, we suggest a gradual drug dose adaptation according to the renal function. A different approach for drugs with a narrow therapeutic window (NTW) is recommended compared to drugs with a broad therapeutic window. For practical purposes, a therapeutic window of 5 or less was defined as a NTW and a list of NTW drugs is presented. Considerations about the drug dose may be different at the start of the therapy or during the therapy and depending on the indication. Monitoring effectiveness and adverse drug reactions are important, especially for NTW drugs. Dose adjustment should be based on an ongoing assessment of clinical status and risk versus the benefit of the used regimen.ConclusionWhen determining the most appropriate dosing regimen serum creatinine-based formulas should never be used naively but always in combination with clinical and pharmacological assessment of the individual patient.

Rating scales to measure side effects of antipsychotic medication: A systematic review

Introduction: Many patients experience side effects during treatment with antipsychotics. This article reviews the clinical use and psychometric characteristics of rating scales used to assess side effects in patients treated with antipsychotics. Methods: A systematic literature search was performed using the electronic databases PubMed and Embase, with predefined search terms. Results: In total, 52 different scales were used in the 440 articles retrieved. For multiple side effects measured with one scale, the Udvalg for Kliniske Undersøgelser Side Effects Rating Scale for Clinicians was used the most, whereas the Liverpool University Neuroleptic Side Effect Rating Scale had the best psychometric characteristics (Cronbach’s α 0.81 and test–retest reliability 0.89). The Simpson Angus Scale was used the most to rate extrapyramidal side effects, although the Maryland Psychiatric Research Center scale had the best characteristics (Cronbach’s α 0.80, test–retest reliability 0.92 and inter-rater reliability 0.81–0.90). The Arizona Sexual Experience Scale was used the most to assess sexual dysfunction, but the Antipsychotics and Sexual Functioning Questionnaire and the Nagoya Sexual Functioning Questionnaire had the best characteristics. Conclusion: This review will help researchers and clinicians make a purpose-oriented choice of which scale to use. Systematic review registration number: CRD42014013010.

Antipsychotic drug use associated with urinary tract infections in older women

OBJECTIVES Antipsychotic drugs are frequently prescribed to elderly patients, but they are associated with serious adverse effects. The objective of the current study was to investigate the association between use of antipsychotics by elderly women and the risk of urinary tract infections (UTIs). COHORT STUDY SETTING Dispensing data were obtained from the PHARMO Database Network for the period 1998-2008. PARTICIPANTS Ambulatory Dutch women (≥65 years) with current and past use of antipsychotics. MEASUREMENTS Incidence rates of UTIs, as defined by use of nitrofurantoin, was calculated within and outside the period of exposure to antipsychotic drugs. Cox proportional hazard regression analysis with Andersen-Gill extension for recurrent events was used to calculate crude and adjusted hazard ratios (HRs). RESULTS During the study period, 18,541 women with a first prescription of an antipsychotic were identified. Current use of antipsychotics was associated with an increased risk of UTI compared to past use: HR, adjusted for age and history of UTIs, 1.33, 95% CI 1.27-1.39. A strong temporal relationship was found: the risk of being treated for a UTI was higher in the first week after the start of the treatment (adjusted HR 3.03, 95% CI 2.63-3.50) and decreased after 3 months (adjusted HR 1.22, 95% CI 1.17-1.28). Cumulative exposure was not associated with an increased risk of UTIs. There was no difference in effect between conventional and atypical antipsychotics. CONCLUSION Our results show an increased risk of uncomplicated UTIs during antipsychotic use in older female patients, especially in the first week of treatment.

Muscle spasms: an unexpected adverse drug reaction of pemetrexed?:

In this report we describe a 53-year-old woman with advanced non-small cell lung cancer, treated with pemetrexed and cisplatin combination therapy, followed by pemetrexed monotherapy. The patient developed severe muscle spasms at least twice, shortly after administration of pemetrexed monotherapy. A possible explanation for this observation is that in combination with cisplatin therapy, the patient was hyperhydrated before administration to promote renal excretion and reduce toxicity. Pemetrexed is also renally excreted, which supports the finding that toxicity did not occur when the patient was hyperhydrated. After discontinuation of pemetrexed the symptoms did not reoccur. All aspects of this case point to a possible relationship between pemetrexed and an adverse drug reaction (ADR). We conclude that muscle spasms are a rare, but possibly dose-related ADR of pemetrexed-based therapy.