Key factors underlying the willingness of patients with cancer to participate in medication redispensing.

BACKGROUND: Redispensing medication unused by patients to other patients could reduce the environmental burden of medication waste. Simultaneously, associated financial loss could be reduced, particularly for expensive medication such as oral anticancer drugs. An important determinant for successful medication redispensing is patient participation. OBJECTIVE(S): To identify key factors underlying the willingness of patients with cancer to participate in the redispensing of unused oral anticancer drugs. METHODS: Semi-structured interviews via telephone or video call were conducted with adult patients diagnosed with cancer from two Dutch hospitals. The interview guide was framed using the COM-B model for behavioural change, to elicit patients' capability, opportunity and motivation to participate in medication redispensing. Questions were related to patients' willingness to accept redispensed medication, reasons thereof, perceived concerns and needs. Inductive thematic analysis was applied. RESULTS: Seventeen patients (aged 38-82 years, 71% female), with nine different types of cancer participated. The majority of participants supported medication redispensing. Four categories of key factors underlying the willingness of patients with cancer to participate in medication redispensing were identified. First, the driver for participation was having positive societal impact, relating to affordability and sustainability of healthcare. Second, having trust in product quality was a requirement, influenced by preconceived beliefs, quality assurance and patients' knowledge of this process. Third, a facilitator for participating in medication redispensing was adequate provision of information. This concerned awareness of medication waste, information about medication redispensing, support from healthcare providers and other patients, and insight into medication dispensing history. Last, a convenient process for returning unused medication to pharmacies would facilitate participation in medication redispensing. CONCLUSIONS: The willingness of patients with cancer to participate in medication redispensing relates to a drive for achieving positive societal impact, provided that medication is of high quality, there is adequate information provision and a convenient process.

The effect of non-adherence to antipsychotic treatment on rehospitalization in patients with psychotic disorders.

BACKGROUND AND AIMS: Many patients with psychotic disorders are non-adherent to antipsychotic (AP) medication(s), potentially contributing to rehospitalization. It is unknown whether non-adherence in different phases of AP use is associated with rehospitalization. The aim of this study was to assess the association between non-adherence to APs and rehospitalization in patients with psychotic disorders. Non-adherence was assessed specifically for the initiation, continued drug use and early discontinuation of AP use. METHODS: A retrospective follow-up study was performed. Adult patients were included at discharge if they suffered from schizophrenia, psychotic, or bipolar I disorder; had been hospitalized in a psychiatric hospital for ⩾7 days; and were treated with oral APs. Patients discharged between January 2006 and December 2009 from Altrecht Mental Health Care were included. Non-adherence was studied in the three phases of medication use: initiation, continued drug use (implementation) and (early) discontinuation after discharge until the end of follow up or until patients were rehospitalized. Cox regression analysis was used to assess the strength of the association between non-adherence for the different phases of AP use and rehospitalization during follow up and expressed as relative risk (RR) with 95% confidence intervals (CI). RESULTS: A total of 417 patients were included. Patients who did not initiate their APs compared with those who did in the first month (RR = 1.62, 95% CI: 1.19-2.19) and between the first and third month after discharge (RR = 1.70, 95% CI: 1.04-2.79) had the highest risk for rehospitalization during follow up. Overall, patients who did not initiate their AP medication within the first year after discharge had a RR of 2.70 (95% CI: 1.97-3.68) for rehospitalization during follow up compared with those that initiated their AP. CONCLUSION: Not initiating APs right after discharge was associated with an increased risk of rehospitalization. Interventions should aim to promote the initiation of APs soon after discharge to minimize the risk of rehospitalization.

The impact of health literacy on beliefs about medication in a Dutch medication-using population.

PURPOSE: Medication beliefs are likely contingent on aspects of health literacy: knowledge, motivation, and competences to access, understand, appraise, and apply health information. An association between medication beliefs and health literacy is expected as they both influence self-management. The aim of this study was to examine the association between health literacy and the beliefs about overuse and harmful effects of medication and to examine modifying effects of age, gender, and number of medications on this association. METHODS: The data were collected using the online "Medication panel" of the Dutch Institute for Rational Use of Medicine. A linear regression model was used to examine the association between health literacy and beliefs about medication and the modifying effects of age, gender, and number of medications on this association. RESULTS: Respondents with a lower level of health literacy had more concerns about overuse (ß adj.= -.174, p<.001) and harmful (ß adj.= -.189, p<.001) effects of medication. This study found no modifying effects. CONCLUSIONS: A lower health literacy level is associated with more concerns about the overuse and harmful effects of medication. The results of this study suggest that extra attention should be given to persons with low health literacy level by healthcare professionals, to decrease their concerns about overuse and harmful effects, and improve adherence to self-management behavior.

Predicting Unsuccessful Clozapine Treatment After First Use in Adult Patients With Psychotic Disorders.

PURPOSE/BACKGROUND: Cessation of clozapine therapy and insufficient response may result in relapse of psychotic symptoms and in clinical admissions. However, discontinuation rates are high. Identifying patients at risk for unsuccessful clozapine use might enable clinicians to direct specific attention to them. METHODS/PROCEDURES: Routinely collected data from a large insurance company were used to develop a simple prediction model for unsuccessful clozapine treatment in psychiatric patients 1 year after clozapine was first dispensed by a community pharmacy in the Netherlands. Multivariate logistic regression analyses were performed with the Nagelkerke R statistic as a measure of the predictive value of the model. FINDINGS/RESULTS: A total of 937 patients were dispensed clozapine for the first time by their community pharmacy between January 1, 2011, and December 31, 2015 (index date). Of these, 741 patients had started their clozapine treatment in hospital before the index date (inpatient starters); the remaining 196 patients started clozapine as outpatients on the index date (outpatient starters). In 191 patients (20.4%), clozapine treatment was unsuccessful 1 year after the index date. Unsuccessful treatment was more common among outpatient starters than among inpatient starters (32.1% vs 17.3%). Using backward selection of the variables, a model consisting of 61 variables had the best predictive value overall (Nagelkerke R = 0.301), whereas a model consisting of 52 variables had the best predictive value in outpatient starters (Nagelkerke R = 0.676). IMPLICATIONS/CONCLUSIONS: The likelihood of unsuccessful clozapine treatment after 1 year was higher among patients who started clozapine as outpatients. Despite the use of a diversity of variables and different statistical approaches, it was not possible to make a simple prediction model for unsuccessful clozapine treatment using relatively easily accessible data.

Evaluation of clarity of presentation and applicability of monitoring instructions for patients using lithium in clinical practice guidelines for treatment of bipolar disorder.

OBJECTIVES: Clinical practice guidelines (CPGs) for treatment of bipolar disorder (BD) aim to provide guidance to health care professionals on monitoring of patients using lithium. The aim was to assess the clarity of presentation and applicability of monitoring instructions for patients using lithium in CPGs for treatment of BD. METHODS: CPGs for treatment of BD were selected from acknowledged professional organizations from multiple continents. CPGs were rated on the clarity of presentation and applicability of lithium monitoring instructions using the Appraisal of Guidelines Research and Evaluation (AGREE) II tool. The applicability of monitoring instructions was assessed according to the Systematic Information for Monitoring (SIM) score. Monitoring instructions were considered applicable when a SIM score of ≥3 was found. RESULTS: The clarity of presentation for six out of the nine CPGs was good (>70%) using the AGREE II tool. Only one CPG scored >70% on applicability. Descriptions of the resource implications and facilitators of and barriers to monitoring were most often missing. All CPGs contained instructions for monitoring of lithium serum levels and renal and thyroid function. Information provided in monitoring instructions (n = 247) was in general applicable to clinical practice (77%) based on the SIM score. Overall, a median SIM score of 3 (interquartile range 3-4) was found. CONCLUSIONS: Improvement of the applicability of CPGs is recommended, and can be achieved by describing the resource implications and facilitators of and barriers to monitoring. In addition, information on critical values and instructions on how to respond to aberrant monitoring parameters are needed. With such improvements, CPGs may better aid health care professionals to monitor patients using lithium.

Monitoring of patients treated with lithium for bipolar disorder: an international survey.

BACKGROUND: Adequate monitoring of patients using lithium is needed for optimal dosing and for early identification of patients with (potential) ADEs. The objective was to internationally assess how health care professionals monitor patients treated with lithium for bipolar disorder. METHODS: Using networks of various professional organizations, an anonymous online survey was conducted among health care professionals prescribing lithium. Target lithium serum levels and frequency of monitoring was assessed together with monitoring of physical and laboratory parameters. Reasons to and not to monitor and use of guidelines and institutional protocols, and local monitoring systems were investigated. RESULTS: The survey was completed by 117 health care professionals incorporating responses from twenty-four countries. All prescribers reported to monitor lithium serum levels on a regular basis, with varying target ranges. Almost all (> 97%) monitored thyroid and renal function before start and during maintenance treatment. Reported monitoring of other laboratory and physical parameters was variable. The majority of respondents (74%) used guidelines or institutional protocols for monitoring. In general, the prescriber was responsible for monitoring, had to request every monitoring parameter separately and only a minority of patients was automatically invited. CONCLUSIONS: Lithium serum levels, renal and thyroid function were monitored by (almost) all physicians. However, there was considerable variation in other monitoring parameters. Our results help to understand why prescribers of lithium monitor patients and what their main reasons are not to monitor patients using lithium.

Development of a nomogram for the estimation of long-term adherence to clozapine therapy using neutrophil fluorescence.

AIMS: Previously, we have reported an association between clozapine use and elevated FL3 neutrophil fluorescence, a flow-cytometric parameter for cell viability. Here, we developed and evaluated a pharmacokinetic-pharmacodynamic model relating FL3-fluorescence to clozapine exposure and derived a nomogram for estimation of long-term adherence. METHODS: Data from 27 patients initiating clozapine were analysed using nonlinear mixed effects modelling. A previously described pharmacokinetic model for clozapine was coupled to a FL3 fluorescence model. For this, an effect compartment with clozapine concentrations as input and a first order decay rate as output was linked with an Emax model to FL3-fluorescence. FL3-fluorescence was simulated for clozapine doses of 50, 150 and 400 mg daily (n = 10 000) to establish the nomogram. Finally, true simulated adherence (% of daily doses taken over 100 days) was compared to nomogram-estimated adherence to evaluate the performance of the nomogram. RESULTS: The half-life of FL3-fluorescence was estimated at 228 h (coefficient of variation 35%). Median absolute prediction errors of the nomogram in case of fully random adherence for 50, 150 and 400 mg ranged from -0.193% to -0.525%. The nomogram performed slightly worse in case of nonrandom adherence (median prediction error up to 5.19%), but was still clinically acceptable. Compliance patterns containing longer drug holidays revealed that the nomogram adequately estimates compliance over approximately the last 3 weeks prior to FL3-measurement. CONCLUSION: Our nomogram could provide information regarding long-term adherence based on prescribed clozapine dose and FL3-fluorescence. Future studies should further explore the clinical value of this biomarker and nomogram.

Prevalence of use of erectile dysfunction medication by Dutch military personnel between 2003 and 2012.

Use of ED medication can be seen as a marker for ED. ED is associated with increasing age, exposure to traumatic events and physical injuries in military veterans. The objective of this study was to assess the prevalence of use of ED medication in Dutch military personnel in the period 2003-2012 and to assess its association with age and psychotropic medication use. Data on dispensing of ED medication, age and co-medication with psychotropic medication of all Dutch military personnel between 2003 and 2012 were collected. The prevalence of ED medication use in each year was estimated, stratified for age and use of psychotropic medication. The number of ED medication users increased a hundredfold from 0.09 to 9.29 per 1000 per year between 2003 and 2012. ED medication was more often used by men over 40 than under 40 (prevalence in 2012: 2.4% vs 0.2%, OR (2003-2012, adjusted for calendar year) 15.6, 95% CI 13.5-17.9) and by men using psychotropic medication (prevalence in 2012: 3.8% vs 0.9%, OR (2003-2012, adjusted for calendar year) 3.13, 95% CI 2.66-3.67). This study shows a strong increase between 2003 and 2012 in a number of ED medication users in male Dutch military personnel. ED medication use increases with age and with psychotropic medication use.

[Instructions for monitoring clinical parameters in the Summary of Product Characteristics (SmPC) for psychotropic drugs: overview and applicability for clinical practice]. / Instructies voor monitoren van klinische parameters in de registratieteksten van psychofarmaca: overzicht en toepasbaarheid voor de klinische praktijk1.

BACKGROUND: The Summary of Product Characteristics (Smpc) for psychotropic drugs includes instructions for clinical and biomarker monitoring intended to optimise effectiveness and minimise harm.
AIM: To evaluate which monitoring instructions are given in the Smpc and to assess the applicability in clinical practice.
METHOD: The reasons and requirements for monitoring in Smpcs for psychotropic drugs were assessed and somatic parameters were distinguished from non-somatic parameters, thereby the applicability was assessed.
RESULTS: An average of 3.3 instructions per drug label was found. Monitoring was primarily for safety reasons (78%). Requirement was predominantly mandatory (71%). Somatic parameters were most often mentioned (80%). Only 34% of the instructions were determined applicable.
CONCLUSION: Monitoring instructions for psychotropic drugs are aimed at improving safe use. However, most instructions on monitoring do not provide sufficient information to be applicable in clinical practice.

The relation between risk-taking behavior and alcohol use in young adults is different for men and women.

OBJECTIVE: The present study examined the relationship of risk-taking behavior and alcohol use and the role of sex herein, while adjusting for age, depression, anxiety, stress and lifestyle. METHODS: Participants were 6002 university students. They were classified as either abstinent, drinker but non-binge drinker, or binge drinker based on self-reported alcohol consumption. Risk-taking and risk assessment were evaluated with the RT-18 and depression, anxiety and stress with the DASS-21. RESULTS: The odds of being a binge versus non-binge drinker increased with risk-taking as well as risk assessment for both men and women. The odds being a non-binge drinker versus abstinent were increased by risk-taking for women only. For binge drinking versus abstinence, risk-taking had a significant increasing effect for both sexes, but risk assessment was only significant in women. CONCLUSION: These results may assist with alcohol use prevention techniques because risk-taking behavior exerts, even when corrected for age, lifestyle, depression, anxiety, and stress levels, a solid, sex-specific independent effect on alcohol use.

Association between concomitant psychiatric drug use, and patients' beliefs about and persistence with chronic cardiovascular medication.

OBJECTIVE: Psychiatric disorders are associated with an increased risk of cardiovascular diseases and may result in additional risk of non-adherence. No data on the influence of concomitant psychiatric drug use on patients' beliefs and persistence related to cardiovascular medication are available. The objective of this study was to assess to what extent the use of concomitant psychiatric drugs is associated with patients' beliefs about and persistence with chronic cardiovascular medication. METHODS: An observational study in patients using cardiovascular medication was conducted. A mailed questionnaire containing socio-demographical questions and a measure of beliefs about medication (Beliefs about Medicines Questionnaire - specific) was sent to patients selected from fifteen participating pharmacies. Persistence was evaluated based on pharmacy records. RESULTS: Of the 1547 included patients, 551 responded to key questions in the questionnaire and were included for beliefs about medication analysis. In concomitant users of psychiatric drugs significantly higher necessity (17.0 vs. 16.0) and higher concerns (14.3 vs. 13.3), as well as higher proportion of ambivalent (34.5% vs. 25.6%) and lower proportion of indifferent patients (24.1% vs. 33.0%) were found compared with non-users (p < 0.05). 65.2% (n = 1009) of patients were persistent on all their cardiovascular drugs. There was no significant association between concomitant use of psychiatric drugs and non-persistence (OR = 1.2; 95% CI 0.9-1.5). CONCLUSION: Concomitant use of psychiatric drugs was found to be associated with increased beliefs about the necessity of and concerns about cardiovascular medication. Clinicians caring for cardiovascular patients should give additional attention to identifying patients' beliefs about medication among those concomitantly using psychiatric drugs.

Prevalence of medication use for somatic disease in institutionalized psychiatric patients.

INTRODUCTION: Psychiatric patients may use medications for their psychiatric condition as well as for treating concurrent somatic diseases or somatic side effects of psychiatric medicines. The objective of this study was to estimate the prevalence of use of medication for somatic disease in institutionalized psychiatric patients and changes therein during 2006-2010. METHOD: A cross-sectional study in institutionalized psychiatric patients was performed. Medication use for somatic disease on 10 time points between 2006 and 2010 was investigated and stratified by gender, age, psychiatric medication class and the number of different psychiatric medication classes used. RESULTS: The prevalence of use of medication for somatic disease increased from 67.5% in 2006 to 76.9% in 2010. The median number of medications used for somatic disease per patient was 3 between 2006 and 2010. Approximately one-third (34.1%) of the patients received ≥ 3 medications intended for treating somatic disease in 2006 which increased to 46.3% in 2010. In 2010, the prevalence of medication use for somatic disease was highest for analgesics and antirheumatics (34.0%), acid and bowel related medication (25.6%) and anticholinergic medication (24.2%). Medication use for somatic disease was highest in patients ≥ 60 years (95.3%), patients treated with more than one psychiatric medication class (87.5%) and patients treated with mood stabilizers (90.6%). DISCUSSION: Somatic medication use is high in institutionalized psychiatric patients. More attention is needed for co-use of psychiatric and somatic medications to prevent side effects, drug-disease or drug-drug interactions. More research is needed to investigate if somatic care is optimal in institutionalized psychiatric patients.

Does the use of an electronic reminder device with or without counseling improve adherence to lipid-lowering treatment? The results of a randomized controlled trial.

BACKGROUND: Lipid-lowering treatment with statins has proven to be effective in reducing cardiovascular events and mortality. In daily practice, however, adherence to medication is often low and this compromises the therapeutic effect. The aim of this study was to assess the effectiveness of an electronic reminder device (ERD) with or without counseling to improve refill adherence and persistence for statin treatment in non-adherent patients. METHODS: A multicenter, community pharmacy-based, randomized controlled trial was conducted in 24 pharmacies in the Netherlands among patients with pre-baseline refill adherence rates between 50 and 80%. Eligible patients aged 65 years or older were randomly assigned to 1 of 3 groups: (1) counseling with an ERD (n = 134), (2) ERD with a written instruction (n = 131), and a (3) control group that received the usual treatment (n = 134). MAIN OUTCOME MEASURE: refill adherence to statin treatment for a 360-day period after inclusion (PDC360). Patients with a refill rate ≥80% were considered adherent. The effect among subgroups was also assessed. RESULTS: There were no relevant differences at baseline. In the counseling with ERD group 54 of 130 eligible patients received the counseling with ERD. In the ERD group, 117 of 123 eligible patients received the ERD. The proportions of adherent patients in the counseling with ERD-group (69.2%) and in the ERD group (72.4%) were not higher than in the control group (64.8%). Among women using statins for secondary prevention, more patients were adherent in the ERD group (86.1%) than in the control group (52.6%) (p < 0.005). In men using statins for secondary prevention the ERD was found to have no effect. CONCLUSION: In this randomized controlled trial, no statistically significant improvement of refill adherence was found if an ERD was used with or without counseling. However, in a subgroup of women using statins for secondary prevention the ERD did improve adherence significantly.

Lazy sunday afternoons: the negative impact of interruptions in patients' daily routine on adherence to oral antidiabetic medication. A multilevel analysis of electronic monitoring data.

PURPOSE: Considerable variability in adherence over time exists. The aim of this study was to investigate to what extent deviations from the prescribed regimen in type 2 diabetes patients can be explained by characteristics of the individual 'medication intake moments' and the patient. METHODS: Medication intake of 104 non-adherent type 2 diabetes patients from 37 community pharmacies was electronically monitored for 6 months. The primary outcome measures were: (1) whether or not the intake occurred and (2) whether or not the intake occurred within the agreed-upon time period (correct timing). Multilevel logistic regression analyses were performed to account for the nested structure of the data. RESULTS: Medication intakes in the evening and during weekends and holidays were more likely to be incorrectly timed and also more likely to be completely missed. Irrespective of timing, most intakes occurred in the mornings of Monday through Thursday (96 %), and least intakes occurred on Saturday evening (82 %). Correctly timed intakes most often occurred on Monday and Tuesday mornings (61 %) in contrast to Sunday evenings (33 %). A patient's medication regimen was significantly associated with adherence. CONCLUSION: Based on our results, among patients who already have difficulties in taking their oral antidiabetic medication, interruptions in the daily routine negatively influence the intake of their medication. Professionals need to be aware of this variation in adherence within patients. As regular medication intake is important to maintain glycaemic control, healthcare professionals and patients should work together to find strategies that prevent deviations from the prescribed regimen at these problematic dosing times.

The association between lifting an administrative restriction on antidepressant dispensing and treatment patterns in Iceland.

PURPOSE: On March 1st 2009, restrictions on the dispensing of selective serotonin reuptake inhibitors (SSRI) in Iceland were lifted. Incident rates and changes in early discontinuation and switching before and after the change were investigated. METHODS: New users of antidepressants between March 1st 2006 and March 1st 2010 were selected from the Icelandic Prescriptions Database. The study population was split into one intervention cohort (2009) and three comparison cohorts (2006, 2007, and 2008). Incidence rate ratios (IRR) and odds ratios (OR) were used to compare incidence rates and early discontinuation. RESULTS: The overall incidence rates of antidepressant use decreased from 33.10 to 28.71 per 1000 persons per year (IRR 0.87; 95% confidence interval (CI), 0.78-0.97) from the 2006 to the 2009 cohort. The incidence rate for SSRIs did not change over the period. Early discontinuation for SSRIs increased from 30.2% in 2006 to 34.1% in 2009 (OR 1.19; 95% CI 1.06-1.33). CONCLUSIONS: The change in reimbursement does not seem to have affected incidence rates but it may be related to increased early discontinuation, which can lead to increased drug wastage. It might be more clinically rational to initiate patients on smaller supply, allowing for more frequent check-up visits.

[Risk factors for inactivity in patients in long-term care with severe mental illness]. / Risicofactoren voor inactiviteit bij patiënten met ernstige psychiatrische aandoeningen in de langdurige zorg.

BACKGROUND: Inactivity is a major problem in long-stay patients with severe mental illness. Very little research has been done into the variables that can predict and explain this inactivity. AIM: To find associations between inactivity and the variables (psychiatric, pharmacological, lifestyle and comorbidity) of patients with severe mental health illness.methods A cross-sectional study was performed at "Zon en Schild", a centre for mental health care in Amersfoort in the Netherlands. The study included 100 long-stay psychiatric patients hospitalized throughout the period February 2011 till July 2011. All of these patients were being treated with antipsychotics and were long-term inpatients at a psychiatric clinic. At the out-patient clinic of "Zon en Schild"; they were screened for inactivity via a subscale of the Nurses"; Observation Scale for Inpatient Evaluation (NOSIE-30). Data were collected and analysed by means of a validated questionnaire, physical examination and patient records. Simple and multiple regression analyses were performed in order to find associated factors associated with inactivity. RESULTS: We found that 31.3% of the variance predicted by the multiple regression analysis model for inactivity was associated with the variables parkinsonism, negative symptoms, metabolic syndrome, diabetes, body-mass index (BMI), first-generation antipsychotics and combination of first- and second-generation antipsychotics. Age (ß=0.235, p=0.04) and a combination therapy involving traditional and atypical antipsychotics (ß=0.317, p=0.04) were significantly associated with inactivity. CONCLUSION: Age and the combination of first- and second-generation antipsychotics were associated with inactivity. Cross-sectional studies do not demonstrate any causal links, but can generate a hypothesis. One possible hypothesis for the surprising link between inactivity and the combination of traditional and atypical antipsychotics is that the combination of antipsychotics promotes and fosters inactivity.key words clinical, epidemiology, inactivity, long-term care, schizophrenia.

Discontinuation of anticoagulant care during admission to a psychiatric hospital.

PURPOSE: Continuation of coumarin therapy is important to prevent thromboembolic events. Continuation of medication, unrelated to the reason for hospital admission, may be at risk due to the patient's psychiatric status and the involvement of several physicians in patient care. METHODS: We performed a retrospective follow-up study of users of orally administered anticoagulants who were admitted to a psychiatric hospital. Information on patient characteristics, anticoagulant use, and International Normalized Ratio (INR) measurements was collected. Discontinuation of anticoagulant care was defined as no anticoagulant dispensing during the first 7 days of hospitalization and/or no INR measurement during hospitalization. Relative risks (RR) of discontinuation, overall and stratified by patient characteristics, was estimated using Cox regression analysis. RESULTS: Of 111 patients, 24.3 % had their anticoagulant care discontinued. For 17.1 %, no anticoagulant was dispensed during the first week, and 13.5 % had no INR measurement during hospitalization. CONCLUSIONS: Admission to a psychiatric hospital leads to discontinuation of anticoagulant care in 24.3 % of patients, with highest risk of discontinuation in patients admitted to nonpsychogeriatric wards. More research is needed to evaluate the clinical impact of this finding.

Representation of people with intellectual disabilities in randomised controlled trials on antipsychotic treatment for behavioural problems.

BACKGROUND: Behavioural problems are common in people with intellectual disability (ID) and are often treated with antipsychotics. AIM: To establish the frequency and characteristics of people with ID included in randomised controlled trials (RCTs) on antipsychotic treatment for behavioural problems, and to investigate the quality of these RCTs. METHODS: A literature search in EMBASE, PubMed and Cochrane was performed and reviewed. RESULTS: People with ID participated in 27 of the 100 included RCTs. The RCTs were of good quality but smaller compared with trials in patients with dementia or schizophrenia (average sample sizes = 55, 124 and 374). In 13/27 trials no clear definition of ID was given. Over 25 different outcome measures were used to assess behavioural problems. CONCLUSIONS: Studies in which people with ID are included are of a sufficient quality, but of a small size. The heterogeneity in the characteristics of the ID population included as well as in the applied assessment instruments makes performing meta-analyses unfeasible.

Use of serotonergic drugs and the risk of bleeding.

We assessed several classes of serotonergic drugs in order to evaluate whether they constitute a risk factor for hospitalization for bleeding (gastrointestinal, intracranial, or in the female genital tract). A case-control study was conducted using data from the PHARMO record linkage system (RLS). The study population comprised 28,289 cases and 50,786 matched controls. Current use of antidepressant drugs was associated with all three types of bleeding, whereas antipsychotic drugs were associated with an increased risk of gastrointestinal and intracranial bleeding. Current use of ergoline derivatives increased the risk of female genital tract bleeding. The risks of gastrointestinal and intracranial bleeding were higher in new users of antidepressant and antipsychotic drugs as compared with those who were already receiving these drugs. No clear association was found between the degree of affinity for the serotonin (5-HT) transporter or the 5-HT(2A) receptor and the risk of any of the three types of bleeding. The association between antipsychotic drugs and gastrointestinal bleeding may warrant further research, in view of the fact that this association was rather unexpected.