Changing Vistas of Psychosis and Antipsychotic Drug Dosing Toward Personalized Management of Antipsychotics in Clinical Practice

Objective: To discuss current evidence on tapering antipsychotic drugs in view of changing vistas of psychosis, suggesting a provisional framework for safely tapering antipsychotic drugs to an optimal low dose, in collaboration with patients and their relatives, to promote functional recovery while preventing relapse. Methods: Paradigm shifts during recent years regarding the nature of psychotic disorders and the role of the dopamine system are discussed, including the positive effects of dopamine blockade in acute psychosis and the limitations and drawbacks of dopamine blockade regarding negative and cognitive symptoms after remission of positive symptoms. Recent advances in tapering strategies and upcoming ways to solve the dilemma between the need to prevent relapses with antipsychotics on the one hand and the need to minimize side effects by tapering these drugs on the other are presented. Results: Modern tapering strategies appear to reduce relapse risk to acceptable levels and offer a feasible personalized option to find the least effective dose to treat and prevent positive symptoms without redundant side effects and functional incapacity. These findings need replication, and several trials that might provide more certainty are on their way. Conclusions and Implications for Practice: Preliminary evidence and clinical experience indicate that personalized dose reduction of antipsychotics is feasible and safe if carried out in close collaboration with patients and their relatives, according to a provisionally suggested framework presented here. These preliminary directions still must be confirmed, revised, and adjusted according to upcoming trial results.</p

Five-year outcome of clinical recovery and subjective well-being in older Dutch patients with schizophrenia

Outcome of schizophrenia in later life can be evaluated from different perspectives. The recovery concept has moved forward this evaluation, discerning clinical-based and patient-based definitions. Longitudinal data on measures of recovery in older individuals with schizophrenia are scant. This study evaluated the five-year outcome of clinical recovery and subjective well-being in a sample of 73 older Dutch schizophrenia patients (mean age 65.9 years; SD 5.4), employing a catchment-area based design that included both community living and institutionalized patients regardless of the age of onset of their disorder. At baseline (T1), 5.5% of participants qualified for clinical recovery, while at five-year follow-up (T2), this rate was 12.3% (p = 0.18; exact McNemar's test). Subjective well-being was reported by 20.5% of participants at T1 and by 27.4% at T2 (p = 0.27; exact McNemar's test). Concurrence of clinical recovery and subjective well-being was exceptional, being present in only one participant (1.4%) at T1 and in two participants (2.7%) at T2. Clinical recovery and subjective well-being were not correlated neither at T1 (p = 0.82; phi = 0.027) nor at T2 (p = 0.71; phi =-0.044). There was no significant correlation over time between clinical recovery at T1 and subjective well-being at T2 (p = 0.30; phi = 0.122) nor between subjective well-being at T1 and clinical recovery at T2 (p = 0.45; phi =-0.088). These results indicate that while reaching clinical recovery is relatively rare in older individuals with schizophrenia, it is not a prerequisite to experience subjective well-being

Reprint of:Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy

Background: In first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. Methods: We performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. Outcomes: BNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. Interpretation: BNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients. (C) 2019 Elsevier B.V. All rights reserved

A Web-Based Tool to Support Shared Decision Making for People With a Psychotic Disorder:Randomized Controlled Trial and Process Evaluation

Background: Mental health policy makers encourage the development of electronic decision aids to increase patient participation in medical decision making. Evidence is needed to determine whether these decision aids are helpful in clinical practice and whether they lead to increased patient involvement and better outcomes.Objective: This study reports the outcome of a randomized controlled trial and process evaluation of a Web-based intervention to facilitate shared decision making for people with psychotic disorders.Methods: The study was carried out in a Dutch mental health institution. Patients were recruited from 2 outpatient teams for patients with psychosis (N=250). Patients in the intervention condition (n=124) were provided an account to access a Web-based information and decision tool aimed to support patients in acquiring an overview of their needs and appropriate treatment options provided by their mental health care organization. Patients were given the opportunity to use the Web-based tool either on their own (at their home computer or at a computer of the service) or with the support of an assistant. Patients in the control group received care as usual (n=126). Half of the patients in the sample were patients experiencing a first episode of psychosis; the other half were patients with a chronic psychosis. Primary outcome was patient-perceived involvement in medical decision making, measured with the Combined Outcome Measure for Risk Communication and Treatment Decision-making Effectiveness (COMRADE). Process evaluation consisted of questionnaire-based surveys, open interviews, and researcher observation.Results: In all, 73 patients completed the follow-up measurement and were included in the final analysis (response rate 29.2%). More than one-third (48/124, 38.7%) of the patients who were provided access to the Web-based decision aid used it, and most used its full functionality. No differences were found between the intervention and control conditions on perceived involvement in medical decision making (COMRADE satisfaction with communication: F1,68=0.422, P=. 52; COMRADE confidence in decision: F1,67=0.086, P=. 77). In addition, results of the process evaluation suggest that the intervention did not optimally fit in with routine practice of the participating teams.Conclusions: The development of electronic decision aids to facilitate shared medical decision making is encouraged and many people with a psychotic disorder can work with them. This holds for both first-episode patients and long-term care patients, although the latter group might need more assistance. However, results of this paper could not support the assumption that the use of electronic decision aids increases patient involvement in medical decision making. This may be because of weak implementation of the study protocol and a low response rate.</p

Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy

BACKGROUND: In first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. METHODS: We performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. OUTCOMES: BNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. INTERPRETATION: BNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients

A Smart Screening Device for Patients with Mental Health Problems in Primary Health Care:Development and Pilot Study

BACKGROUND: Adequate recognition of mental health problems is a prerequisite for successful treatment. Although most people tend to consult their general practitioner (GP) when they first experience mental health problems, GPs are not very well equipped to screen for various forms of psychopathology to help them determine clients' need for treatment. OBJECTIVE: In this paper, the development and characteristics of CATja, a computerized adaptive test battery built to facilitate triage in primary care settings, are described, and first results of its implementation are reported. METHODS: CATja was developed in close collaboration with GPs and mental health assistants (MHAs). During implementation, MHAs were requested to appraise clients' rankings (N=91) on the domains to be tested and to indicate the treatment level they deemed most appropriate for clients before test administration. We compared the agreement between domain score appraisals and domain score computed by CATja and the agreement between initial (before test administration) treatment level advice and final treatment level advice. RESULTS: Agreements (Cohen kappas) between MHAs' appraisals of clients' scores and clients' scores computed by CATja were mostly between .40 and .50 (Cohen kappas=.10-.20), and the agreement between "initial" treatment levels and the final treatment level advised was .65 (Cohen kappa=.55). CONCLUSIONS: Using CATja, caregivers can efficiently generate summaries of their clients' mental well-being on which decisions about treatment type and care level may be based. Further validation research is needed

A manual-based individual therapy to improve metacognition in schizophrenia:protocol of a multi-center RCT

BACKGROUND: Metacognitive dysfunction has been widely recognized as a feature of schizophrenia. As it is linked with deficits in several aspects of daily life functioning, improvement of metacognition may lead to improvement in functioning. Individual psychotherapy might be a useful form of treatment to improve metacognition in patients with schizophrenia; multiple case reports and a pilot study show promising results. The present study aims to measure the effectiveness of an individual, manual-based therapy (Metacognitive Reflection and Insight Therapy, MERIT) in improving metacognition in patients with schizophrenia. We also want to examine if improvement in metacognitive abilities is correlated with improvements in aspects of daily life functioning namely social functioning, experience of symptoms, quality of life, depression, work readiness, insight and experience of stigma. METHODS/DESIGN: MERIT is currently evaluated in a multicenter randomized controlled trial. Thirteen therapists in six mental health institutions in the Netherlands participate in this study. Patients are randomly assigned to either MERIT or the control condition: treatment as usual (TAU). DISCUSSION: If proven effective, MERIT can be a useful addition to the care for schizophrenia patients. The design brings along some methodological difficulties, these issues are addressed in the discussion of this paper. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN16659871

Searching for the optimal number of response alternatives for the distress scale of the four-dimensional symptom questionnaire

BACKGROUND: The Four-Dimensional Symptom Questionnaire (4DSQ) is a self-report questionnaire designed to measure distress, depression, anxiety, and somatization. Prior to computing scale scores from the item scores, the three highest response alternatives ('Regularly', 'Often', and 'Very often or constantly present') are usually collapsed into one category to reduce the influence of extreme responding on item- and scale scores. In this study, we evaluate the usefulness of this transformation for the distress scale based on a variety of criteria. METHODS: Specifically, by using the Graded Response Model, we investigated the effect of this transformation on model fit, local measurement precision, and various indicators of the scale's validity to get an indication on whether the current practice of recoding should be advocated or not. In particular, the effect on the convergent- (operationalized by the General Health Questionnaire and the Maastricht Questionnaire), divergent- (operationalized by the Neuroticism scale of the NEO-FFI), and predictive validity (operationalized as obtrusion with daily chores and activities, the Biographical Problem list and the Utrecht Burnout Scale) of the distress scale was investigated. RESULTS: Results indicate that recoding leads to (i) better model fit as indicated by lower mean probabilities of exact test statistics assessing item fit, (ii) small (<.02) losses in the sizes of various validity coefficients, and (iii) a decrease (DIFF (SE's) = .10-.25) in measurement precision for medium and high levels of distress. CONCLUSIONS: For clinical applications and applications in longitudinal research, the current practice of recoding should be avoided because recoding decreases measurement precision for medium and high levels of distress. It would be interesting to see whether this advice also holds for the three other domains of the 4DSQ

Onset and transition of and recovery from adverse development:study methodology

AIM: Early intervention programs for first-episode psychosis have led to the awareness that the period before onset of a first episode is important in light of early intervention. This has induced a focus on the so-called 'at risk mental state' (ARMS). Individuals with ARMS are at increased risk for later psychotic disorder, but also for other psychiatric disorders as well as poor psychosocial functioning. Thus, adequate detection and treatment of ARMS is essential. METHODS: Since 2018, screening for and treatment of ARMS is recommended standard care in the Netherlands. Implementation is still ongoing. We initiated a naturalistic long-term cohort study of ARMS individuals, the onset and transition of and recovery from adverse development (OnTheROAD) study, with the aim to monitor course and outcome of symptoms and psychosocial functioning over time, as well as patterns of comorbidity and associations with factors of risk and resilience. To this end, participants complete a broad battery of instruments at baseline and yearly follow-up assessments up to 3 years. Outcome is defined in terms of symptom severity level, functioning and quality of life. In particular, we aim to investigate the impact of negative symptoms as part of the ARMS concept. Results from this study can aid in refining the existing ARMS criteria, understanding the developmental course of ARMS and investigating the hypothesized pluripotentiality in outcome of ARMS. New knowledge may inform the further development of specialized early interventions. RESULTS AND CONCLUSIONS: In this article, we describe the rationale, outline and set-up of OnTheROAD