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.

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.

Self-monitoring and personalized feedback based on the experiencing sampling method as a tool to boost depression treatment: a protocol of a pragmatic randomized controlled trial (ZELF-i).

BACKGROUND: Depression is a leading cause of disability worldwide. To reduce the societal burden and improve quality of life for individual patients, treatments for depression need to be optimized. There is a particular need for person-tailored interventions that reinforce self-management of patients. Systematic self-monitoring and personalized feedback through the Experience Sampling Method (ESM) could provide such a person-tailored, empowering intervention that enhances treatment outcomes. The primary aim of this study is to investigate the efficacy of self-monitoring and personalized feedback as an add-on tool in the treatment of depressive complaints in a natural setting. METHODS: The ZELF-i study is a pragmatic multi-site randomized controlled trial (RCT). We aim to recruit 150 individuals with depressive symptoms aged between 18 and 65 years, who have an intake for outpatient basic or specialized treatment at a mental health care organization in the North of the Netherlands. After the intake, participants will be randomly allocated to one of three study arms: two experimental groups engaging in 28 days of systematic self-monitoring (5 times per day) and receiving weekly personalized feedback on positive affect and activities ("Do"-module) or on negative affect and thinking patterns ("Think"-module), and a control group receiving no additional intervention. Self-report inventories of depressive symptoms, psychosocial functioning and feelings of empowerment will be administered before and after the intervention period, and at follow-up measurements at 1, 2, 3 and 6 months. The patient-experienced utility of the intervention will be investigated by a combination of quantitative and qualitative research methods. DISCUSSION: The present study is the first to examine the effects of add-on self-monitoring and personalized feedback on depressive complaints in clinical practice. It is also the first to evaluate two different ESM modules targeted at both of depression's core symptoms. Lastly, it is the first study that uses a combination of qualitative and quantitative methods to evaluate the patient-experienced utility of ESM with personalized feedback as an intervention for depression. Results of the present study may improve treatment for depression, if the intervention is found to be effective. TRIAL REGISTRATION: Dutch Trial Register, NTR5707 , registered prospectively 1 February 2016.

Identifying levels of general distress in first line mental health services: can GP- and eHealth clients' scores be meaningfully compared?

BACKGROUND: The Four-Dimensional Symptom Questionnaire (4DSQ) (Huisarts Wetenschap 39: 538-47, 1996) is a self-report questionnaire developed in the Netherlands to distinguish non-specific general distress from depression, anxiety, and somatization. This questionnaire is often used in different populations and settings and there is a paper-and-pencil and computerized version. METHODS: We used item response theory to investigate whether the 4DSQ measures the same construct (structural equivalence) in the same way (scalar equivalence) in two samples comprised of primary mental health care attendees: (i) clients who visited their General Practitioner responded to the 4DSQ paper-and-pencil version, and (ii) eHealth clients responded to the 4DSQ computerized version. Specifically, we investigated whether the distress items functioned differently in eHealth clients compared to General Practitioners' clients and whether these differences lead to substantial differences at scale level. RESULTS: Results showed that in general structural equivalence holds for the distress scale. This means that the distress scale measures the same construct in both General Practitioners' clients and eHealth clients. Furthermore, although eHealth clients have higher observed distress scores than General Practitioners' clients, application of a multiple group generalized partial credit response model suggests that scalar equivalence holds. CONCLUSIONS: The same cutoff scores can be used for classifying respondents as having low, moderate and high levels of distress in both settings.

Practical Implications of Metacognitively Oriented Psychotherapy in Psychosis: Findings From a Pilot Study.

In preparation for a multicenter randomized controlled trial, a pilot study was conducted investigating the feasibility and acceptance of a shortened version (12 vs. 40 sessions) of an individual metacognitive psychotherapy (Metacognitive Reflection and Insight Therapy [MERIT]). Twelve participants with a diagnosis of schizophrenia were offered 12 sessions of MERIT. Effect sizes were calculated for changes from baseline to treatment end for metacognitive capacity measured by the Metacognition Assessment Scale-Abbreviated. Nine of twelve patients finished treatment. However, nonsignificant moderate to large effect sizes were obtained on the primary outcome measure. This study is among the first to suggest that patients with schizophrenia will accept metacognitive therapy and evidence improvements in metacognitive capacity. Despite limitations typical to a pilot study, including a small sample size and lack of a control group, sufficient evidence of efficacy was obtained to warrant further investigation.

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.

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. (PsycInfo Database Record (c) 2024 APA, 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.

Neurocognition and recovery in first episode psychosis.

Cognitive functioning has been found to be a predictor of functional outcome of schizophrenia. It is unclear, however, whether clinical recovery can be predicted by scores on specific cognitive domains. The predictive value of specific neurocognitive domains and other clinical variables for symptomatic and functional outcome and clinical recovery after a 2-year follow-up is explored in a group of 51 patients with non-affective first-episode psychosis. A comprehensive neurocognitive battery was administered 18 and 41weeks after inclusion. Other patient characteristics, which were expected to independently predict clinical recovery, were assessed at baseline. Several neurocognitive tests, especially tests measuring speed of processing, and among others, Duration of Untreated Psychosis (DUP), were significant predictors of clinical recovery. Poor neuropsychological performance accurately predicted non-recovery, but improved neuropsychological performance did not accurately predict recovery. This study confirms previous findings of an association between neurocognition and outcome, but the results also suggest that in order to accurately predict recovery, the role of other factors needs to be investigated.

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.

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.

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.

To continue or not to continue? Antipsychotic medication maintenance versus dose-reduction/discontinuation in first episode psychosis: HAMLETT, a pragmatic multicenter single-blind randomized controlled trial.

BACKGROUND: Antipsychotic medication is effective for symptomatic treatment in schizophrenia-spectrum disorders. After symptom remission, continuation of antipsychotic treatment is associated with lower relapse rates and lower symptom severity compared to dose reduction/discontinuation. Therefore, most guidelines recommend continuation of treatment with antipsychotic medication for at least 1 year. Recently, however, these guidelines have been questioned as one study has shown that more patients achieved long-term functional remission in an early discontinuation condition-a finding that was not replicated in another recently published long-term study. METHODS/DESIGN: The HAMLETT (Handling Antipsychotic Medication Long-term Evaluation of Targeted Treatment) study is a multicenter pragmatic single-blind randomized controlled trial in two parallel conditions (1:1) investigating the effects of continuation versus dose-reduction/discontinuation of antipsychotic medication after remission of a first episode of psychosis (FEP) on personal and social functioning, psychotic symptom severity, and health-related quality of life. In total 512 participants will be included, aged between 16 and 60 years, in symptomatic remission from a FEP for 3-6 months, and for whom psychosis was not associated with severe or life-threatening self-harm or violence. Recruitment will take place at 24 Dutch sites. Patients are randomized (1:1) to: continuation of antipsychotic medication until at least 1 year after remission (original dose allowing a maximum reduction of 25%, or another antipsychotic drug in similar dose range); or gradual dose reduction till eventual discontinuation of antipsychotics according to a tapering schedule. If signs of relapse occur in this arm, medication dose can be increased again. Measurements are conducted at baseline, at 3, and 6 months post-baseline, and yearly during a follow-up period of 4 years. DISCUSSION: The HAMLETT study will offer evidence to guide patients and clinicians regarding questions concerning optimal treatment duration and when to taper off medication after remission of a FEP. Moreover, it may provide patient characteristics associated with safe dose reduction with a minimal risk of relapse. TRIAL STATUS: Protocol version 1.3, October 2018. The study is active and currently recruiting patients (since September 2017), with the first 200 participants by the end of 2019. We anticipate completing recruitment in 2022 and final assessments (including follow-up 3.5 years after phase one) in 2026. TRIAL REGISTRATION: European Clinical Trials Database, EudraCT number 2017-002406-12. Registered 7 June 2017.

Clinical recovery in first-episode psychosis.

INTRODUCTION: Generally agreed outcome criteria in psychosis are required to evaluate the effectiveness of new treatment strategies. The aim of this study is to explore clinical recovery in first-episode patients, defined by meeting criteria for both symptomatic and functional remission. METHOD: In a sample of first-episode patients (N = 125), symptomatic and functional remission during the last 9 months of a 2-year follow-up period were examined, as well as recovery and its predictors. RESULTS: Half the patients (52.0%) showed symptomatic remission and a quarter (26.4%) functional remission, while one-fifth (19.2%) met both criteria sets and were considered recovered. Recovery was significantly associated with short duration of untreated psychosis and better baseline functioning. CONCLUSION: Most functionally remitted patients were also symptomatically remitted, while a minority of symptomatically remitted patients were also functionally remitted. Treatment delay may affect chance of recovery.

Personalizing antipsychotic treatment: evidence and thoughts on individualized tailoring of antipsychotic dosage in the treatment of psychotic disorders.

Effectiveness of relapse prevention with antipsychotic drugs has been robustly demonstrated. However, the drawbacks of antipsychotic maintenance treatment have prompted alternative strategies to reduce antipsychotic load. A prominent drawback of antipsychotics is their negative impact on subjective well-being, initiative, and drive related to dopamine D2 blockade. This might compromise functional capacity. First-episode studies from 1980 to 2018, including relevant reviews and meta-analyses, are evaluated, showing a lack of functional outcome data. In addition to relapse rates, which is the primary outcome in the great majority of studies, long-term functional outcome is pivotal, because these two outcome domains may point in opposite directions. The trade-off between relapse rates and functional outcome is discussed by our 2013 dose-reduction study. We conclude that divergent outcomes and various individual risk-profiles preclude the construction of a generic outcome measure. The relationship of relapse and functional outcome is considered, as well as the conceivable role of negative symptoms and some related issues. Future profiling of individual risk/benefit characteristics combined with personal preferences may offer better guidance in antipsychotic pharmacotherapy. More studies are needed to elucidate individual risk profiles, predictive of functional capacity and relapse rates, to draw differential conclusions on long-term risks and benefits of antipsychotics across the spectrum of psychosis.

Course and predictors of symptomatic remission in late-life schizophrenia: A 5-year follow-up study in a Dutch psychiatric catchment area.

BACKGROUND: The number of older schizophrenia patients is growing, the majority being treated in outpatient settings. Reported symptomatic remission rates in younger cohorts vary largely. Further insight into course trajectories and putative predictors of remission in older persons with schizophrenia is needed. METHODS: 5-year follow-up course trajectories of symptomatic remission were examined in a catchment area-based group of 77 older Dutch patients (mean age 66.0 years) with schizophrenia or schizoaffective disorder. A modified version of the 'Remission in Schizophrenia Working Group' criteria was used to determine remission status. In individuals who did not fulfil remission criteria at baseline (n = 56), predictors of conversion to remission status at 5-year follow-up were analysed using multivariable regression analyses. RESULTS: A substantial increase in remission rate at 5-year follow-up (27.3% at baseline (T1), 49.4% at follow-up (T2)) was found. Of all participants, 23.4% was in remission at both assessments and 46.8% was in non-remission at both assessments. 26.0% of the participants converted from non-remission at T1 to remission at T2, while 3.9% fell back from remission at T1 to non-remission at T2. Two significant baseline predictors of conversion to remission at follow-up were found: lower score on the PANSS positive symptom subscale, and having a partner. CONCLUSION: Symptomatic remission was as an attainable goal for almost half of all older patients with schizophrenia or schizoaffective disorder at 5-year follow-up. With a lower PANSS positive symptom subscale score, and having a partner emerging as the only predictors of conversion to remission, there remains a need to search for modifiable predictors.

Can antipsychotic dose reduction lead to better functional recovery in first-episode psychosis? A randomized controlled-trial of antipsychotic dose reduction. The reduce trial: Study protocol.

Antipsychotic medication has been the mainstay of treatment for psychotic illnesses for over 60 years. This has been associated with improvements in positive psychotic symptoms and a reduction in relapse rates. However, there has been little improvement in functional outcomes for people with psychosis. At the same time there is increasing evidence that medications contribute to life shortening metabolic and cardiovascular illnesses. There is also uncertainty as to the role played by antipsychotic medication in brain volume changes. AIM: The primary aim of the study is, in a population of young people with first-episode psychosis, to compare functional outcomes between an antipsychotic dose reduction strategy with evidence-based intensive recovery treatment (EBIRT) group (DRS+) and an antipsychotic maintenance treatment with EBIRT group (AMTx+) at 24-months follow-up. METHODS: Our single-blind randomized controlled trial, within a specialist early psychosis treatment setting, will test the whether the DRS+ group leads to better vocational and social recovery than, the AMTx+ group over a 2-year period in 180 remitted first-episode psychosis patients. Additionally, we will examine the effect of DRS+ vs AMTx+ on physical health, brain volume and cognitive functioning. This study will also determine whether the group receiving DRS+ will be no worse off in terms of psychotic relapses over 2 years follow-up. RESULTS: This paper presents the protocol, rationale and hypotheses for this study which commenced recruitment in July 2017. CONCLUSION: This study will provide evidence as to whether an antipsychotic dose-reduction recovery treatment leads to improved functioning and safer outcomes in first-episode psychosis patients. In addition, it will be the first-controlled experiment of the effect of exposure to antipsychotic maintenance treatment on brain volume changes in this population.

Individualized Prediction of Transition to Psychosis in 1,676 Individuals at Clinical High Risk: Development and Validation of a Multivariable Prediction Model Based on Individual Patient Data Meta-Analysis.

Background: The Clinical High Risk state for Psychosis (CHR-P) has become the cornerstone of modern preventive psychiatry. The next stage of clinical advancements rests on the ability to formulate a more accurate prognostic estimate at the individual subject level. Individual Participant Data Meta-Analyses (IPD-MA) are robust evidence synthesis methods that can also offer powerful approaches to the development and validation of personalized prognostic models. The aim of the study was to develop and validate an individualized, clinically based prognostic model for forecasting transition to psychosis from a CHR-P stage. Methods: A literature search was performed between January 30, 2016, and February 6, 2016, consulting PubMed, Psychinfo, Picarta, Embase, and ISI Web of Science, using search terms ("ultra high risk" OR "clinical high risk" OR "at risk mental state") AND [(conver* OR transition* OR onset OR emerg* OR develop*) AND psychosis] for both longitudinal and intervention CHR-P studies. Clinical knowledge was used to a priori select predictors: age, gender, CHR-P subgroup, the severity of attenuated positive psychotic symptoms, the severity of attenuated negative psychotic symptoms, and level of functioning at baseline. The model, thus, developed was validated with an extended form of internal validation. Results: Fifteen of the 43 studies identified agreed to share IPD, for a total sample size of 1,676. There was a high level of heterogeneity between the CHR-P studies with regard to inclusion criteria, type of assessment instruments, transition criteria, preventive treatment offered. The internally validated prognostic performance of the model was higher than chance but only moderate [Harrell's C-statistic 0.655, 95% confidence interval (CIs), 0.627-0.682]. Conclusion: This is the first IPD-MA conducted in the largest samples of CHR-P ever collected to date. An individualized prognostic model based on clinical predictors available in clinical routine was developed and internally validated, reaching only moderate prognostic performance. Although personalized risk prediction is of great value in the clinical practice, future developments are essential, including the refinement of the prognostic model and its external validation. However, because of the current high diagnostic, prognostic, and therapeutic heterogeneity of CHR-P studies, IPD-MAs in this population may have an limited intrinsic power to deliver robust prognostic models.

Detection of psychosis by mental health care services; a naturalistic cohort study.

BACKGROUND: Detection of psychotic disorders is an important issue, since early treatment might improve prognosis. Timely diagnosis of psychotic disorders depends on recognition of psychotic symptoms and their interpretation. The aim of this study is to examine to what extent reported psychotic symptoms are accounted for in clinical diagnosis. METHODS: The medical files of all patients who had a first contact with one of two mental health care services (N = 6477) were screened for reported psychotic symptoms and subsequent clinical diagnosis. Patients who reported psychotic symptoms and who were diagnosed with a psychotic disorder were followed-up for two years to register prescription of antipsychotic treatment and continuity of care. RESULTS: In the files of 242 (3.7%) patients specific psychotic symptoms were recorded. 37% of these patients were diagnosed with a non-affective psychotic disorder, 7% with other psychotic disorders and 56% with non-psychotic disorders or no diagnosis at all. About 90% of the patients diagnosed with a psychotic disorder did receive any prescription of antipsychotics, and about 50% were in continuous care during the first 2 years. CONCLUSION: Relatively large proportions of patients presenting with psychotic symptoms were diagnosed with a non-psychotic diagnosis or not diagnosed at all. This applies also to patients reporting at least two or more psychotic symptoms. Although we did not verify the appropriateness of clinical diagnosis, these findings are an indication that psychotic disorders may be underdetected. Improving the diagnostic process in mental health care services may be the most obvious way to promote early intervention in psychosis.