Martijn Kikkert

The expert consensus guideline series

Abstract Over the past decade, many new epilepsy treatments have been approved in the United States, promising better quality of life for many with epilepsy. However, clinicians must now choose among a growing number of treatment options and possible combinations. Randomized clinical trials (RCTs) form the basis for evidence-based decision making about best treatment options, but they rarely compare active therapies, making decisions difficult. When medical literature is lacking, expert opinion is helpful, but may contain potential biases. The expert consensus method is a new approach for statistically analyzing pooled opinion to minimize biases inherent in other systems of summarizing expert opinion. We used this method to analyze expert opinion on treatment of three epilepsy syndromes (idiopathic generalized epilepsy, symptomatic localization-related epilepsy, and symptomatic generalized epilepsy) and status epilepticus. For all three syndromes, the experts recommended the same general treatment strategy. As a first step, they recommend monotherapy. If this fails, a second monotherapy should be tried. Following this, the experts are split between additional trials of monotherapy and a combination of two therapies. If this fails, most agree the next step should be additional trials of two therapies, with less agreement as to the next best step after this. One exception to these recommendations is that the experts recommend an evaluation for epilepsy surgery after the third failed step for symptomatic localization-related epilepsies. The results of the expert survey were used to develop user-friendly treatment guidelines concerning overall treatment strategies and choice of specific medications for different syndromes and for status epilepticus.

Adjuvant occupational therapy for work-related major depression works : randomized trial including economic evaluation

BACKGROUND Major depression has far-reaching consequences for work functioning and absenteeism. In most cases depression is treated by medication and clinical management. The addition of occupational therapy (OT) might improve outcome. We determined the cost-effectiveness of the addition of OT to treatment as usual (TAU). METHOD Sixty-two adults with major depression and a mean absenteeism of 242 days were randomized to TAU (out-patient psychiatric treatment) or TAU+OT [6 months, including (i) diagnostic phase with occupational history and work reintegration plan, and (ii) therapeutic phase with individual sessions and group sessions]. Main outcome domains were depression, work resumption, work stress and costs. Assessments were at baseline and at 3, 6, 12 and 42 months. RESULTS The addition of OT to TAU: (i) did not improve depression outcome, (ii) resulted in a reduction in work-loss days during the first 18 months, (iii) did not increase work stress, and (iv) had a 75.5% probability of being more cost-effective than TAU alone. CONCLUSION Addition of OT to good clinical practice does not improve depression outcome, improves productivity without increasing work stress and is superior to TAU in terms of cost-effectiveness.

Sex differences in the subjective tolerability of antipsychotic drugs.

Abstract: In recent years, research efforts have been directed to better characterize the subjective experience of taking psychotropic drugs. This study investigated the sex difference in the subjective tolerability of antipsychotic drugs. Participants were recruited from patients under the care of psychiatric services serving geographical catchment areas in Croydon (UK), Verona (Italy), Amsterdam (Netherlands), and Leipzig (Germany). Clinically unstable patients with a clinical diagnosis of schizophrenia and a research diagnosis of schizophrenia, established using the Item Group Checklist of the Schedule for Clinical Assessment in Neuropsychiatry, were enrolled. Antipsychotic subjective tolerability was rated by means of the Liverpool University Neuroleptic Side Effect Rating Scale. During the recruitment period, 245 men and 164 women with schizophrenia were recruited. In both sexes, the most frequently reported side effects were difficulty in concentrating, tiredness, and weight gain; these side effects occurred in approximately 50% of men and in up to 70% of women. Extrapyramidal and anticholinergic reactions were reported more often by women, whereas men reported sexual problems more often. After background group differences were controlled for, sex was the strongest determinant of the subjective tolerability of antipsychotic drugs. We therefore conclude that sex differences in the subjective tolerability of antipsychotic drugs should be taken into account in the pharmacological management of patients with schizophrenia. Studies should no longer consider men and women as a homogeneous group, given that the subjective tolerability of antipsychotic drugs substantially differs between sexes.

Assessment of medication adherence in patients with schizophrenia: the Achilles heel of adherence research

Measuring medication adherence in patients with schizophrenia is difficult and lacks a gold standard. Consequently, a great number of different methods and instruments have been proposed. Although it has been assumed that they all measure medication adherence, this study demonstrates that instruments differ significantly. Using data from an international multisite study (N = 329), we found that 3 questionnaires, designed to measure medication adherence and typical for instruments used in studies in patients with schizophrenia, do not agree in labeling patients as nonadherent. Further, they seem not to measure the same trait, are related to different established risk factors of nonadherence, and are only weakly related to these established risk factors of nonadherence. If these results are representative of the validity of other measures used in adherence research, this may have serious consequences for the interpretation of, and explanations for discrepancies found in the literature. Researchers should be aware of this problem and continue to combine objective and subjective methods in the hope of increasing the reliability and validity of measures of adherence.

Adherence to medication and quality of life in people with schizophrenia: results of a European multicenter study.

Quality of life is often severely impaired in people with schizophrenia, and adherence to antipsychotic medication has been consistently found to be low in this population. Although there is a considerable amount of evidence on these two variables in schizophrenia research, there is only limited knowledge on how they relate to one another. The aim of this study is to develop a meaningful model of the relationship between quality of life and adherence that includes mediating variables. A multicenter randomized controlled trial recruited 409 subjects in London, Verona, Amsterdam, and Leipzig. Baseline interviews obtained data on adherence, quality of life, and other variables. We used graphical modeling to investigate the relationships between the variables. No direct relation could be discerned between subjective quality of life and adherence to medication. Mediating variables, most importantly symptomatic impairment, global functioning, and medication side effects, were identified by the model. It can be concluded that, when aiming at the improvement of quality of life in people with schizophrenia, variables other than adherence, i.e., symptomatic impairment, global functioning, and medication side effects, should be targeted.

Comparison of Patient and Clinician Perspectives in the Assessment of Antipsychotic Medication Adherence

Background: Factors influencing patient and clinician perspectives in the assessment of medication adherence have never been compared. Method: This study used baseline and 12-month follow-up data from the QUATRO study, an international multicentre study. At baseline, information on patient sociodemographic characteristics, treatment factors, psychopathology, functioning and experience of antipsychotic side effects was gathered. After 12 months of follow-up, psychopathology, functioning and patient experience of antipsychotic side effects were measured once more, and a patient and clinician rating of adherence was obtained by means of the Medication Adherence Rating Scale (MARS) and the Compliance Rating Scale (CRS). Results: During the recruitment period, 409 subjects with a diagnosis of schizophrenia were recruited. Patients were more often men and single. Mean age was 41.5 years. At the time of the assessment, more than 40% were unemployed and on average had been on antipsychotic treatment for more than 10 years. Nearly 70% were receiving second-generation antipsychotics, and 50% received adherence therapy during the 12 months after enrolment. The relationship between the MARS and the CRS scores showed only a small overlap (correlation coefficient = 0.26). In the multivariate model, the only factor significantly associated with both patient and clinician ratings of adherence was psychopathology. Unemployment and poor subjective tolerability of antipsychotics were significantly associated with low levels of patient ratings of adherence. Conversely, length of treatments and use of newer antipsychotics were significantly associated with better clinician ratings of adherence. Conclusion: Patient and clinician ratings of adherence do not measure the same dimension. Factors that may positively affect adherence in terms of compliance with prescribed medication regimens may not affect patients’ views on adherence, and this should be taken into consideration when planning and negotiating treatment modalities with each individual patient suffering from schizophrenia.

The predictive validity of subjective adherence measures in patients with schizophrenia

Despite frequent use of subjective adherence measures in patients with schizophrenia as well as other chronic conditions, there are several reports that question the validity of these instruments. Three well known, representative subjective measures are the Medication Adherence Questionnaire (MAQ), the Drug Attitude Inventory (DAI), and the Compliance Rating Scale (CRS). In this study we explored the predictive validity of these instruments in a European sample of 119 stabilized outpatients with schizophrenia. Clinical outcome variables were relapse and admission to a psychiatric hospital during a follow‐up period of 12 months. Results indicate that the predictive validity of all three measures was poor. The MAQ was the least problematic predictor for relapse (Nagelkerke R2 = 0.09), and time to relapse (R2 = 0.07) and had the best sensitivity for relapse (63.6%) as well as admission (87.5%). The MAQ and CRS were both moderate predictive for admission (Nagelkerke R2 = 0.21, and R2 = 0.29). We conclude that the validity of the instruments studied here is questionable and have limited clinical relevance. Given the feasibility and ease of most subjective instruments, researchers may be tempted to use them but should be aware of the serious drawbacks of these instruments. Copyright

Psychometric Properties of the Dutch Version of the Self-Sufficiency Matrix (SSM-D)

Measuring treatment outcomes can be challenging in patients who experience multiple interlinked problems, as is the case in public mental health care (PMHC). This study describes the development and psychometric properties of a Dutch version of the self-sufficiency matrix (SSM-D), an instrument that measures outcomes and originates from the US. In two different settings, clients were rated using the SSM-D in combination with the Health of the Nation Outcome Scales (HoNOS) and the Camberwell assessment of need short appraisal schedule (CANSAS). The results provided support for adequate psychometric properties of the SSM-D. The SSM-D had a solid single factor structure and internal consistency of the scale was excellent. In addition, convergent validity of the SSM-D was indicated by strong correlations between HoNOS and CANSAS, as well as between several subdomains. Further research is needed to establish whether the results presented here can be obtained in other PMHC settings.

Effect of medication-related factors on adherence in people with schizophrenia: A European multi-centre study

AIM To investigate the relation between medication-related factors and adherence in people with schizophrenia in outpatient treatment. METHODS The sample comprised 409 outpatients (ICD-10 diagnosis of schizophrenia) with clinician-rated instability in four European cities (Amsterdam, The Netherlands; Verona, Italy; Leipzig, Germany; London, Great Britain). Adherence was assessed using the Medication Adherence Questionnaire (patient perspective), and the Clinician Rating Scale (clinician perspective). Examined medication-related factors were type (atypical vs. typical), application (oral vs. depot), daily dose frequency of antipsychotic medication (Medication History Scale), number of side effects (Liverpool University Neuroleptic Side Effect Rating Scale), and patient attitudes toward medication (Drug Attitude Inventory). Multiple regression analysis was used to identify predictors of adherence by medication-related factors. RESULTS Adherence, as rated by patient and clinician, was predicted by patient attitude towards medication, but was unrelated to type of drug, formulation or side effects of antipsychotic medication. A high daily dose frequency was associated with better adherence, but only when rated by the patient. CONCLUSIONS In order to improve adherence there is a need to seriously consider and attempt to improve patient attitude toward medication. However, type of antipsychotic and other medication-related factors may not be as closely related to adherence as it has often been suggested.

Victimisation in adults with severe mental illness: prevalence and risk factors.

BACKGROUND Patients with a severe mental illness (SMI) are more likely to experience victimisation than the general population. AIMS To examine the prevalence of victimisation in people with SMI, and the relationship between symptoms, treatment facility and indices of substance use/misuse and perpetration, in comparison with the general population. METHOD Victimisation was assessed among both randomly selected patients with SMI (n = 216) and the general population (n = 10 865). RESULTS Compared with the general population, a high prevalence of violent victimisation was found among the SMI group (22.7% v. 8.5%). Compared with out-patients and patients in a sheltered housing facility, in-patients were most often victimised (violent crimes: 35.3%; property crimes: 47.1%). Risk factors among the SMI group for violent victimisation included young age and disorganisation, and risk factors for property crimes included being an in-patient, disorganisation and cannabis use. The SMI group were most often assaulted by someone they knew. CONCLUSIONS Caregivers should be aware that patients with SMI are at risk of violent victimisation. Interventions need to be developed to reduce this vulnerability.