Objective: To review the literature on early intervention in psychosis and to evaluate relevant studies.

Method: Early intervention was defined as intervention in the prodromal phase (primary prevention) and intervention after the onset of psychosis, i.e. shortening of duration of untreated psychosis (DUP) (secondary prevention).

Results: We found few studies aimed at early intervention, but many papers discussing the idea at a more general level. We identified no studies that prove that intervention in the prodromal phase is possible without a high risk for treating false positives. We identified some studies aimed at reducing DUP, but the results are ambiguous and, until now, no follow-up data showing a positive effect on prognosis have been presented.

Conclusion: Early intervention in psychosis is a difficult and important challenge for the psychiatric health services. At the time being reduction of DUP seems to be the most promising strategy. Intervention in the prodromal phase is more ethically and conceptually problematic.

Early detection and intervention in first-episode schizophrenia: a critical review

OBJECTIVE: The authors examined the relationship of neurocognitive function with duration of untreated psychosis, premorbid illness factors, and clinical symptoms to determine whether long duration of untreated psychosis independently compromises cognitive function. METHOD: Patients recruited to a study of the effect of an early detection program on the duration of untreated first-episode psychosis in two catchment areas were compared to patients in a similar treatment program in two other catchment areas without an early detection program. The median duration of untreated psychosis was 10.5 weeks for all patients. A total of 301 patients entered the study, and 207 completed a comprehensive neuropsychological test battery that assessed working memory/fluency, executive function, verbal learning, impulsivity, and motor speed. The median time from start of treatment to neuropsychological testing was 108 days; all patients were tested within 9 months. RESULTS: No significant association was found between dur...

https://ajp.psychiatryonline.org/doi/pdfplus/10.1176/appi.ajp.161.3.466

Neurocognitive Dysfunction in First-Episode Psychosis: Correlates With Symptoms, Premorbid Adjustment, and Duration of Untreated Psychosis

Objective: To compare the consequences of a guided discontinuation strategy and maintenance treatment in remitted first-episode psychosis in terms of relapse rates and functional outcome. Method: The study was conducted in 7 mental health care organizations and the Department of Psychiatry of the University Medical Center Groningen in The Netherlands, covering a catchment area of 3.1 million inhabitants. A sample of 131 remitted first-episode patients, aged 18 to 45 years, with a DSM-IV diagnosis of schizophrenia or related psychotic disorder was included (i.e., all patients with a first psychotic episode from October 2001 through December 2002 who were willing to participate). After 6 months of positive symptom remission, they were randomly and openly assigned to the discontinuation strategy or maintenance treatment. Maintenance treatment was carried out according to American Psychiatric Association guidelines, preferably using low-dose atypical antipsychotics. The discontinuation strategy was carried out by gradual symptom-guided tapering of dosage and discontinuation if feasible. Follow-up was 18 months. Main outcome measures were relapse rates and social and vocational functioning. Results: Twice as many relapses occurred with the discontinuation strategy (43% vs. 21%, p = .011). Of patients who received the strategy, approximately 20% were successfully discontinued. Recurrent symptoms caused another approximately 30% to restart antipsychotic treatment, while in the remaining patients discontinuation was not feasible at all. There were no advantages of the discontinuation strategy regarding functional outcome. Conclusions: Only a limited number of patients can be successfully discontinued. High relapse rates do not allow a discontinuation strategy to be universal practice. However, if relapse risk can be carefully managed by close monitoring, in some remitted first-episode patients a guided discontinuation strategy may offer a feasible alternative to maintenance treatment. Further research is needed to find predictors of successful discontinuation.

Guided Discontinuation Versus Maintenance Treatment in Remitted First-Episode Psychosis: Relapse Rates and Functional Outcome

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.

/pdf/clinical-recovery-in-first-episode-psychosis-1hgy44x0hn.pdf

Clinical Recovery in First-Episode Psychosis

The failure by patients to take medication as prescribed is a phenomenon that is well known to clinicians in all medical specialties. Among patients with schizophrenia, adherence issues can severely limit the clinical improvement that is achievable with even the best available treatments. There is, however, no evidence that the situation has improved over the last 30 years, and, despite the introduction of new medications with improved tolerability profiles, poor adherence remains a problem. This may be because in both clinical research and day-to-day practice, adherence has often been portrayed as an all-or-nothing issue, with patients being regarded as either adherent or nonadherent. When considering interventions for adherence problems, clinicians have therefore tended to focus on those patients who openly refuse or repeatedly discontinue treatment and are regarded as difficult-to-treat cases. While this description applies to only a limited proportion of patients, in our experience, full adherence is rare. In reality, most patients are partially adherent to some extent, but the focus on treatment discontinuation may have led clinicians to discount partial adherence as an issue worthy of their attention, perhaps regarding it as inevitable and unavoidable. Unless clinicians appreciate the impact that relatively minor deviations from prescribed treatment regimens can have on treatment outcomes,1 they are unlikely to take the problem seriously or to devote sufficient time and attention to addressing suspected adherence problems among their patients.

Notably, treatment adherence is considered to have a major influence on achieving clinical remission.2 Failure to achieve remission is a predictor for poor prognosis, psychiatric complications, treatment resistance, and even death from medical comorbidities and suicide.3 Moreover, patients who fail to take their medication as prescribed are at a greatly increased risk of relapse.1,4,5 Given the devastating impact of psychotic relapse on the course of illness, relapse prevention strategies should encourage greater awareness of the impact of partial adherence and should incorporate appropriate steps to minimize or eliminate the problem, particularly during the early stages of the illness.

This article examines the issue of adherence behavior and its impact on treatment outcomes, with particular reference to early psychosis and first-episode patients, and provides observations on suggested strategies for managing these issues in patients with schizophrenia.

A search of the published literature from 1980 to 2008 was performed using the PubMed search engine. Articles written in English (original research and reviews) were identified using the following keywords: schizophrenia or psychosis combined with compliance, noncompliance, partial compliance, adherence, nonadherence, or partial adherence. Additional references were identified through citations in relevant articles.

/pdf/partial-adherence-to-antipsychotic-medication-impacts-the-2e39sift4k.pdf

Partial adherence to antipsychotic medication impacts the course of illness in patients with schizophrenia: a review.

Background The concept that early intervention with antipsychotic medications improves the long-term course of schizophrenia is discussed. Method This report reviews the literature concerning early intervention with antipsychotic medications for people with firstepisodes, and how it affects long-term morbidity. It also studies the effects of discontinuing antipsychotic medications on relapse for people with first episodes. Results Early intervention with antipsychotic medications appears to decrease the long-term morbidity of schizophrenia. Conclusions Early intervention with antipsychotic medications should be encouraged for people experiencing their first episode of schizophrenia. This report proposes that studying the various phases of subject response to treatment can be helpful in elucidating when antipsychotic medications should be tapered or withdrawn.

I D Henter

Papers

First-episode schizophrenia. Early intervention and medication discontinuation in the context of course and treatment.