Jacqueline G. Hugtenburg

Definitions, variants, and causes of nonadherence with medication: a challenge for tailored interventions

Background Nonadherence with medication is a complex and multidimensional health care problem. The causes may be related to the patient, treatment, and/or health care provider. As a consequence, substantial numbers of patients do not benefit optimally from pharmacotherapy, resulting in increased morbidity and mortality as well as increased societal costs. Several interventions may contribute to improved adherence. However, most interventions have only a modest effect. Thus, despite the many efforts made, there has been little progress made as yet in tackling the problem of nonadherence. Methods This paper summarizes the definitions and taxonomy of adherence with medication, as well as types and causes of nonadherence. In addition, interventions aimed at improvement of adherence are discussed. Conclusion There is not just one solution for the nonadherence problem that fits all patients. Most interventions to improve adherence are aimed at all patients regardless of whether they are adherent or not. Recently, a number of tailored interventions have been described in the literature. Modern techniques are useful. Electronic pill boxes combined with Short Message Service reminders are specifically designed to improve unintentional adherence and have resulted in an increase in refill adherence in diabetic patients with suboptimal adherence. Tailored Internet interventions are a possibility for influencing patient drug-taking behavior and show promising results. Tailored counseling interventions targeted at the underlying causes of nonadherence seem an attractive method for supporting patients with their use of drugs. However, despite the plausible theoretical framework, data on long-term health effects of the various interventions are not available. To improve adherence effectively, there is a need for a tailored approach based on the type and cause of nonadherence and the specific needs of the patient.

Side effects of antidepressants during long-term use in a naturalistic setting

Side effects of antidepressants are usually underreported in clinical trials and large scale naturalistic studies are restricted to six months of use. We examined the prevalence and nature of patient-perceived side effects and their determinants during long-term antidepressant use in a naturalistic setting. Subjects, aged 19 to 67 years, in the Netherlands Study of Depression and Anxiety were recruited from primary care and specialized mental health care covered 927 cases of single antidepressant use. In 64% of cases, on average, 2.9 side effects were reported. The number of side effects was higher when subjects had higher depression severity (OR=1.28; p=0.002), three or more psychiatric diagnoses (OR=1.97; p=0.02), higher dose (OR=1.44; p=0.006) and was lower when subjects were older (OR=0.83; p=0.02) and had longer duration of use (OR=0.94; p=0.04). Tricyclic antidepressants were associated with more side effects (OR=2.52; p=0.003) and, particularly, more anticholinergic effects, like dry mouth and constipation, as compared to selective serotonin reuptake inhibitors. Venlafaxine showed more profuse sweating (OR=1.79; p=0.007), whereas mirtazapine showed more weight gain and less sexual dysfunction (OR=0.36; p=0.03), as compared to selective serotonin reuptake inhibitors. Weight gain was associated with female gender (OR=1.76; p=0.004) and duration of use (OR=1.06; p=0.03). We show that antidepressant side effect, known from short-term studies, persist during long-term use and are associated with depression severity and antidepressant dose. A novel finding was that venlafaxine is associated with more profuse sweating and that weight gain appeared more specific in female users. Clinicians should be aware that, during long-term antidepressant use, side effects are common and persistent.

Potential drug interactions in cancer therapy: a prevalence study using an advanced screening method

BACKGROUND In cancer patients, drug interactions may intensify adverse events or reduce antitumour effects. We assessed the prevalence of potential drug interactions (PDIs) among ambulatory cancer patients on i.v. treatment using an advanced screening method. PATIENTS AND METHODS Data on drugs used for comorbidities, anticancer agents, over-the-counter (OTC) drugs, and comorbidities were collected by means of a structured interview among the patients and review of medical charts. PDIs were identified using electronic (Drug Interaction Facts software, version 4.0) and manual screening methods (peer-reviewed reports). RESULTS In this study, 278 patients were enrolled. We identified 348 PDIs. Of all patients, 161 (58%) had at least one PDI. Of all PDIs, 34% was classified as major and 60% as moderate. Coumarins, quinolones, antiepileptics, and hydrochlorothiazide were frequently part of a PDI. Interactions that potentially cause QT interval prolongation, gastrointestinal toxicity, and central nervous system depression were also common. In multivariate analysis, an increasing number of drugs [odds ratio (OR) = 1.4, confidence interval (CI) 1.23-1.52; P < 0.001] and the use of an OTC drug (OR = 0.56, CI 0.32-0.97; P = 0.045) were risk factors. CONCLUSIONS PDIs are common in patients treated for an (haemato-) oncological disease. Screening for potential interactions should take place routinely before administering chemotherapy.

Discontinuation symptoms in users of selective serotonin reuptake inhibitors in clinical practice: tapering versus abrupt discontinuation

ObjectiveTapering of selective serotonin reuptake inhibitor (SSRI) therapy, as opposed to abrupt discontinuation, has been recommended by several guidelines and in the literature in order to diminish the occurrence of discontinuation symptoms. However, the evidence of a favourable effect of tapering is limited, and it is unclear how patients ought to discontinue SSRIs in daily life. The aim of this study was to examine the way in which patients discontinue SSRI therapy in clinical practice and to compare the effect of tapering with that of abrupt discontinuation on the occurrence of discontinuation symptoms.MethodsPatients (n=74) who recently discontinued SSRI therapy completed a questionnaire containing questions about discontinuation symptoms (DESS events), the prescribed SSRI, reasons for discontinuation, way of discontinuation, knowledge of discontinuation symptoms, impact on daily life and patient counseling and education. The number of DESS events was compared among groups (abrupt discontinuation versus tapering; age; male versus female; paroxetine versus other SSRIs; knowledge of discontinuation symptoms at start of therapy versus lack of knowledge).ResultsA total of 66 patients were eligible for analysis. Of all patients ending SSRI therapy, 21% abruptly discontinued therapy. There was a significant difference in the number of DESS events between abrupt discontinuation and tapering of SSRI therapy (12.0 versus 5.9). There was also a tendency for an adverse effect of lack of knowledge of discontinuation symptoms at the start of therapy on the number of DESS events (8.9 versus 5.5).ConclusionOne in five patients abruptly discontinued their SSRI therapy in clinical practice. Abrupt discontinuation caused a larger increase in the number of discontinuation symptoms than tapering. We therefore advise tapering SSRI therapy in clinical practice to prevent unnecessary adverse effects of discontinuation.

Identification of drug-related problems of elderly patients discharged from hospital

Background Drug-related problems (DRP) following hospital discharge are common among elderly patients using multiple drugs for the treatment of chronic diseases. The aim of this study was to investigate the occurrence of DRP in these patients using a specific tool for the identification of DRP by community pharmacists. Methods An observational study involving 340 patients aged over 60 years using at least five prescription drugs and discharged from hospital. The occurrence of DRP was assessed by means of an identification tool specifically developed for use by community pharmacists, including a semistructured patient interview and a checklist of common DRP. Results In total, 992 potential DRP were observed in the 340 patients (mean 2.9 ± 1.7). No drug prescribed but clear indication, an unnecessarily long duration of treatment, dose too low, and incorrect drug selection were the DRP most commonly observed. Ten percent of DRP occurring in 71 patients were drug–drug interactions. The number of DRP was related to the number of drugs prescribed. Frequently occurring DRP found using the patient interview were fear of side effects and no or insufficient knowledge of drug use. Medication of patients discharged from the pulmonary department and of those with type 2 diabetes was particularly associated with occurrence of DRP. Conclusion Following hospital discharge, DRP occur frequently among elderly patients using five or more drugs for the treatment of chronic disease. The number of DRP increased with the number of drugs used. An important task for community pharmacists is to identify, resolve, and prevent the occurrence of DRP among this patient group. Since DRP are associated with an increased risk of hospital readmissions, morbidity, and mortality, it is very important to develop intervention strategies to resolve and prevent DRP.

Adherence and patients experiences with the use of oral anticancer agents

Abstract A rapidly growing number of oral anticancer agents has become available in oncology and hematology. Though these introductions have several benefits, medication adherence is an issue of concern. Little is known about the factors influencing adherence to treatment with oral anticancer agents in daily practice. Material and methods. In this observational, multicenter study including 216 patients, carried out between October 2010 and March 2012, the use of oral anticancer drugs was assessed by means of a telephonic pill count, a questionnaire and a review of the patients medical file and pharmacy medication records. Parameters collected were patients’ demographics, treatment characteristics, beliefs and attitude towards disease and medicines, self-reported adherence, side effects, quality of life and satisfaction about information. Patients off treatment filled out a questionnaire about the reasons for discontinuation. Optimal adherence was defined as ≥ 95%–≤ 105%. Results. The mean adherence rate (AR) (n = 177) was 99.1% with 20.3% of patients having a sub-optimal AR (< 95%, > 105%) consisting both of under- and over-adherence. Multivariate analyses showed that being on a cyclic dosing regimen (rather than a continuous regimen), not living alone and being highly educated increased the chances of optimal adherence (ORs = 4.88, 4.59 and 2.53, respectively). In addition, optimal adherence was found to be less common in patients reporting treatment control (OR = 0.77). One third of 79 patients off treatment reported their experienced side effects as one of the reasons for discontinuation. Discussion. Although most patients are fully adherent to oral anticancer agents, there is a substantial number tending to non-adherence. Patients living alone and those on a continuous dosing regimen are most likely to adhere sub-optimally. Interventions to improve adherence should specifically address these patients and be tailored to the needs of the individual patient.

Factors related to high and low levels of drug adherence according to patients with type 2 diabetes

Objective Adherence to medication in patients with type 2 diabetes varies widely, yet the factors that influence adherence according to patients are not fully known. The aim of this study is to explore both factors related to high and lower levels of adherence that patients with type 2 diabetes experienced in their medication use. Setting Primary care in the Netherlands. Method Qualitative, semi-structured interviews were performed in 20 patients with type 2 diabetes. Interviews were audio-taped and transcribed verbatim. Transcripts were coded and analysed using content analysis and constant comparison. Main outcome measure experiences and opinions of patients concerning factors related to high and lower levels of adherence. Results Comparable aspects influenced drug adherence in more and less adherent patients. Four aspects that influenced adherence to medication emerged from the interviews: (1) information about the prescribed medication, (2) experience with medication and complications with use, (3) social support for medication behaviour and (4) routines in medication behaviour. Experience with medication and social support for medication behaviour were related to high levels of adherence in some patients, and to lower levels of adherence in others. Complicated medication regimens were mainly related to lower adherence, while social support and routines in medication behaviour were related to higher adherence. Conclusions Routines in medication behaviour were related to higher drug adherence. Patient education should not only address information about the disease and medication, but also more practical issues concerning drug intake. Hence, to improve drug adherence in patients with type 2 diabetes, pharmaceutical care might be aimed at the counselling of patients to organise drug use in their daily schedule.

Effect of medication review and cognitive behaviour treatment by community pharmacists of patients discharged from the hospital on drug related problems and compliance: design of a randomized controlled trial

BackgroundDrug related problems (DRPs) are common among elderly patients who are discharged from the hospital and are using several drugs for their chronic diseases. Examples of drug related problems are contra-indications, interactions, adverse drug reactions and inefficacy of treatment. Causes of these problems include prescription errors and non-compliance with treatment. The aim of this study is to examine the effect of medication review and cognitive behaviour therapy of discharged patients by community pharmacists to minimize the occurrence of drug related problems.Methods/DesignA randomized controlled trial will be performed. Community pharmacists will be randomized into a control group and an intervention group. 342 Patients, aged over 60 years, discharged from general and academic hospitals, using five or more prescription drugs for their chronic disease will be asked by their pharmacy to participate in the study.Patients randomized to the control group will receive usual care according to the Dutch Pharmacy Standard. The medication of patients randomised to the intervention group will be reviewed by the community pharmacist with use of the national guidelines for the treatment of diseases, when patients are discharged from the hospital. The Pharmaceutical Care network Europe Registration form will be used to record drug related problems. Trained pharmacy technicians will counsel patients at home at baseline and at 1,3,6,9 and 12 months, using Cognitive Behaviour Treatment according to the Theory of Planned Behaviour. The patients attitude towards medication and patients adherence will be subject of the cognitive behaviour treatment. The counselling methods that will be used are motivational interviewing and problem solving treatment. Patients adherence towards drug use will be determined with use of the Medication Adherence Report Scale Questionnaire. There will be a follow-up of 12 months.The two primary outcome measures are the difference in occurrence of DRPs between intervention and control group and adherence with drug use. Secondary endpoints are attitude towards drug use, incidence of Re-hospitalisations related to medicines, functional status of the patient, quality of life and the cost-effectiveness of this intervention.DiscussionCombining both medication review and Cognitive Behaviour Treatment may decrease DRPs and may result in more compliance with drug use among patients discharged from the hospital and using 5 or more chronic drugs.Trial registrationDutch Trial Register NTR1194

Potential drug interactions and duplicate prescriptions among ambulatory cancer patients: a prevalence study using an advanced screening method.

BackgroundThe pharmacotherapeutic treatment of patients with cancer is generally associated with multiple side-effects. Drug interactions and duplicate prescriptions between anti-cancer drugs or interactions with medication to treat comorbidity can reinforce or intensify side-effects.The aim of the present study is to gain more insight into the prevalence of drug interactions and duplicate prescriptions among patients being treated in the outpatient day care departments for oncology and hematological illnesses. For the first time the prevalence of drug interactions with OTC-drugs in cancer patients will be studied. Possible risk factors for the occurrence of these drug-related problems will also be studied.Methods/DesignA multicenter cross-sectional observational study of the epidemiology of drug interactions and duplicate prescriptions is performed among all oncology and hemato-oncology patients treated with systemic anti-cancer drugs at the oncology and hematology outpatient day care department of the VU University medical center and the Zaans Medical Center.DiscussionIn this article the prevalence of potential drug interactions in outpatient day-care patients treated with anti-cancer agents is studied using a novel more extensive screening method. If this study shows a high prevalence of drug interactions clinical pharmacists and oncologists must collaborate to develop a pharmaceutical screening programme, including an automated electronic warning system, to support drug prescribing for ambulatory cancer patient. This programme could minimize the occurrence of drug related problems such as drug interactions and duplicate prescriptions, thereby increasing quality of life.Trial registrationThis study is registered, number NTR2238.

Communicating with patients the second time they present their prescription at the pharmacy. Discovering patients' drug-related problems.

Objective: To assess the effect of a short inquiry the second time that the prescription was presented at the pharmacy (SP) counter on the detection of drug related-problems as perceived by patients in a community pharmacy. The implementation of the SP procedure is also described.Method: At SP patients were asked to give a short description of their experience with their newly prescribed drug. Patients’ drug-related problems were recorded on a SP form and were categorised into three groups: side effects, inefficacy, and problems with use or instruction. Data were also matched with drug categories. The ATC classification was used. A comparison with a control pharmacy was made.Main outcome measures: Drug experience, patients’ drug-related problems, side effects, inefficacy, problems with the use or instruction.Results: Data from 700 SP forms showed that in 78% of cases patients did not have problems with the use of their new drugs. In the remainder of cases (22%), drug- related problems mainly concerned side effects (49%; 76 out of 156) and complaints about the drugs not being as effective as expected (inefficacy: 49%; 77 out of 156). In the control pharmacy no drug-related problems were detected in 30 SP contacts. Patients using gastrointestinal drugs reported fewer side effects than patients using cardiovascular drugs. Patients using respiratory drugs reported more often that the drug was not effective than patients using cardiovascular drugs.Conclusion: It was concluded that the SP procedure encourages patients to report their drug problems at the counter in the pharmacy.