Therapeutic drug monitoring (TDM) is the quantification and interpretation of drug concentrations in blood to optimize pharmacotherapy. It considers the interindividual variability of pharmacokinetics and thus enables personalized pharmacotherapy. In psychiatry and neurology, patient populations that may particularly benefit from TDM are children and adolescents, pregnant women, elderly patients, individuals with intellectual disabilities, patients with substance abuse disorders, forensic psychiatric patients or patients with known or suspected pharmacokinetic abnormalities. Non-response at therapeutic doses, uncertain drug adherence, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM. However, the potential benefits of TDM to optimize pharmacotherapy can only be obtained if the method is adequately integrated in the clinical treatment process. To supply treating physicians and laboratories with valid information on TDM, the TDM task force of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued their first guidelines for TDM in psychiatry in 2004. After an update in 2011, it was time for the next update. Following the new guidelines holds the potential to improve neuropsychopharmacotherapy, accelerate the recovery of many patients, and reduce health care costs.

/pdf/consensus-guidelines-for-therapeutic-drug-monitoring-in-18b8y5mu39.pdf

Consensus Guidelines for Therapeutic Drug Monitoring in Neuropsychopharmacology: Update 2017.

Practice guideline for the treatment of patients with obsessive-compulsive disorder.

The aims of severe perioperative bleeding management are three-fold. First, preoperative identification by anamesis and laboratory testing of those patients for whom the perioperative bleeding risk may be increased. Second, implementation of strategies for correcting preoperative anaemia and stabilisation of the macro- and microcirculations in order to optimise the patient’s tolerance to bleeding. Third, targeted procoagulant interventions to reduce the amount of bleeding, morbidity, mortality and costs. The purpose of these guidelines is to provide an overview of current knowledge on the subject with an assessment of the quality of the evidence in order to allow anaesthetists throughout Europe to integrate this knowledge into daily patient care wherever possible. The Guidelines Committee of the European Society of Anaesthesiology (ESA) formed a task force with members of scientific subcommittees and individual expert members of the ESA. Electronic databases were searched without language restrictions from the year 2000 until 2012. These searches produced 20 664 abstracts. Relevant systematic reviews with meta-analyses, randomised controlled trials, cohort studies, case-control studies and cross-sectional surveys were selected. At the suggestion of the ESA Guideline Committee, the Scottish Intercollegiate Guidelines Network (SIGN) grading system was initially used to assess the level of evidence and to grade recommendations. During the process of guideline development, the official position of the ESA changed to favour the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. This report includes general recommendations as well as specific recommendations in various fields of surgical interventions. The final draft guideline was posted on the ESA website for four weeks and the link was sent to all ESA members. Comments were collated and the guidelines amended as appropriate. When the final draft was complete, the Guidelines Committee and ESA Board ratified the guidelines.

https://epub.ub.uni-muenchen.de/24023/1/oa_24023.pdf

Management of severe perioperative bleeding Guidelines from the European Society of Anaesthesiology

Social anxiety disorder.

Therapeutic drug monitoring (TDM), i. e., the quantification of serum or plasma concentrations of medications for dose optimization, has proven a valuable tool for the patient-matched psychopharmacotherapy. Uncertain drug adherence, suboptimal tolerability, non-response at therapeutic doses, or pharmacokinetic drug-drug interactions are typical situations when measurement of medication concentrations is helpful. Patient populations that may predominantly benefit from TDM in psychiatry are children, pregnant women, elderly patients, individuals with intelligence disabilities, forensic patients, patients with known or suspected genetically determined pharmacokinetic abnormalities or individuals with pharmacokinetically relevant comorbidities. However, the potential benefits of TDM for optimization of pharmacotherapy can only be obtained if the method is adequately integrated into the clinical treatment process. To promote an appropriate use of TDM, the TDM expert group of the Arbeitsgemeinschaft fur Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP) issued guidelines for TDM in psychiatry in 2004. Since then, knowledge has advanced significantly, and new psychopharmacologic agents have been introduced that are also candidates for TDM. Therefore the TDM consensus guidelines were updated and extended to 128 neuropsychiatric drugs. 4 levels of recommendation for using TDM were defined ranging from “strongly recommended” to “potentially useful”. Evidence-based “therapeutic reference ranges” and “dose related reference ranges” were elaborated after an extensive literature search and a structured internal review process. A “laboratory alert level” was introduced, i. e., a plasma level at or above which the laboratory should immediately inform the treating physician. Supportive information such as cytochrome P450 substrate- and inhibitor properties of medications, normal ranges of ratios of concentrations of drug metabolite to parent drug and recommendations for the interpretative services are given. Recommendations when to combine TDM with pharmacogenetic tests are also provided. Following the guidelines will help to improve the outcomes of psychopharmacotherapy of many patients especially in case of pharmacokinetic problems. Thereby, one should never forget that TDM is an interdisciplinary task that sometimes requires the respectful discussion of apparently discrepant data so that, ultimately, the patient can profit from such a joint effort.

/pdf/agnp-consensus-guidelines-for-therapeutic-drug-monitoring-in-18q2ciintb.pdf

AGNP Consensus Guidelines for Therapeutic Drug Monitoring in Psychiatry: Update 2011

The use of antidepressants has increased over the years, which may be due to more new antidepressant users, but also may be due to a longer duration of use. We aimed to assess the prevalence, incidence and average duration of selective serotonin reuptake inhibitor (SSRI) and tricyclic antidepressant (TCA) use in the Netherlands during 1992–2001. In addition, we assessed the incidence of long-term use of SSRIs and identified possible determinants of long-term use. We assessed prevalence (number of current users of an antidepressant per 1000 persons assessed on a single day) and incidence (number of new users per 1000 persons per year) of antidepressant use for each year in the PHARMO record linkage system. Long-term use was defined as the consecutive use of any antidepressant for at least 12 months. Relative risks and hazard ratios were calculated and adjusted for possible determinants using Poisson and Cox regression analyses. Both prevalent and incident use of SSRIs increased during 1992–2001, while TCA use remained stable. A total of 9857 patients using SSRIs were included in a follow-up study. During the follow-up period, more patients became long-term users, either directly after the start of the initial SSRI or anytime during follow-up (29.5%). The average number of days before start of long-term use decreased from 595 days in 1991 to 19 days in 1997. Female patients, older age, previous use of benzodiazepines and being treated by a psychiatrist increased the probability of becoming a long-term user. Both prevalent and incident use of SSRIs increased during the 1990s, implicating an increased number of patients starting SSRIs, but also a longer duration of use of antidepressant therapy. Over the entire follow-up period, almost 30% of the patients became long-term users at anytime during the follow-up period.

/pdf/incidence-and-determinants-of-long-term-use-of-4eg9y2q39d.pdf

Incidence and determinants of long-term use of antidepressants

Background: Previous research that atypical antipsychotics were switched less often compared to typical antipsychotics, suggesting overall better treatment satisfaction. The objective of this study was to investigate the reasons for switching antipsychotics after initiating oral treatment with either typical or atypical antipsychotics in a clinical setting. Patients and Methods: A total of 123 patients that switched antipsychotic therapy were recruited from 17 psychiatric hospitals, of which 46 % switched because of lack of effect and 45 % because of adverse effects. Results: No significant differences were found between users of atypical versus typical antipsychotics in reasons for switching, both for overall adverse events, and lack of effect. In users of atypical antipsychotics extrapyramidal effects were reported less often as reason for switching (adjusted OR = 0.18 (95 % Cl = (0.07-0.51)). Patients on atypical antipsychotics switched more often because of weight gain (adjusted OR = 12.8 (95 % Cl = (1.50-109)). Conclusion: in conclusion, when switching occurred, no difference was found in the frequency of general tolerability or reported lack of effectiveness. However, the type of adverse event as a reason for switching differed between atypical and typical antipsychotics.

/pdf/reasons-for-switching-between-antipsychotics-in-daily-3w0d8yvr72.pdf

Reasons for switching between antipsychotics in daily clinical practice.

SUMMARY Purpose To evaluate the safety profile of sertraline versus other Selective Serotonin Reuptake Inhibitors (SSRIs) directly following the introduction of sertraline to the Dutch market. Methods In a prospective follow-up study, 109 psychiatrists included patients with a new episode of treatment with sertraline and an equal number of patients starting treatment with other SSRIs. All Adverse Events (AEs) during follow-up were recorded by the psychiatrists for the duration of SSRI treatment until discontinuation or until at least 12 months. Results A total of 1251 patients were included in the study of which 659 used sertraline and 592 used other SSRIs (paroxetine, fluoxetine or fluvoxamine). The most frequently reported events in sertraline users and users of other SSRIs were nausea (160 (24.3%) sertraline patients versus 160 (27.0%) patients using other SSRIs), headache (127 (19.3%) sertraline patients versus 101 (17.1%) patients using other SSRIs), diarrhoea (94 (14.0%) sertraline patients versus 40 patients using other SSRIs (6.8%, p < 0.05)), sweating (88 (13.4%) sertraline patients versus 69 (11.7%) patients using other SSRIs) and dizziness (75 (11.4%) sertraline patients versus 70 (11.8%) patients using other SSRIs). A total of 121 patients reported 134 different unlabelled AEs of which 10 were reported by more than 1% of the population. Conclusions In this study we found that almost three out of four patients reported an adverse event. When comparing with other SSRIs and the literature, we found a similar distribution of the most frequently reported adverse events in patients using sertraline. However, in this observational study we found over 100 different unlabelled adverse events. Copyright # 2002 John Wiley & Sons, Ltd.

/pdf/adverse-events-in-users-of-sertraline-results-from-an-2i1pahyest.pdf

Adverse events in users of sertraline: results from an observational study in psychiatric practice in The Netherlands

Background In previous research, lapses in dosing of paroxetine or sertraline were associated with significantly more discontinuation symptoms and deterioration of depressive symptomatology compared with fluoxetine. Aims To evaluate dosing lapses in patients chronically treated with selective serotonin reuptake inhibitors (SSRIs) in uncontrolled circumstances. Method In a prospective observational study we evaluated compliance data in chronic users of SSRIs using electronic drug exposure monitors. Results During a 3-month follow-up we found that 50/69 (72.5%) patients missed at least one dosing day and 20/69 (29.0%) missed two or more consecutive days. Conclusions About 30% of patients treated with short-acting SSRIs had dosing lapses of 2 or more days, which, as described in prior studies, is long enough to result in clinically relevant deterioration of mental status.

/pdf/spontaneous-lapses-in-dosing-during-chronic-treatment-with-qn9hr75jiw.pdf

Spontaneous lapses in dosing during chronic treatment with selective serotonin reuptake inhibitors

As pointed out in the debate between Parker and Anderson & Haddad ([2003][1]), a gap exists between the results of randomised controlled trials (RCTs) and what is seen in daily psychiatric practice. While both parties in the debate come to more or less opposing conclusions, they agree upon the fact

/pdf/need-for-medicine-based-evidence-in-pharmacotherapy-2ikzm377mb.pdf

Need for medicine-based evidence in pharmacotherapy

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