The Italian adaptation of the Mini-SIPS, a tool for early detection of individuals at clinical high risk and first episode of psychosis: A preliminary study of implementation in an Italian FEP program.

AIMS: The study aims are to present the Italian adaptation of the Abbreviated Clinical Structured Interview for DSM-5 Attenuated Psychosis Syndrome (Mini-SIPS) and illustrate its implementation in a clinical setting. METHODS: The Mini-SIPS was developed from the original extended version as a tool designed to identify, within the clinical high risk (CHR) framework, the DSM-5 Attenuated Psychosis Syndrome (APS) and to be implemented in clinical settings. The Mini-SIPS was translated in Italian by a Yale-certified SIPS trainer, then back-translated in English by a trained psychologist, then approved by the Mini-SIPS authors. Since September 2021, the adapted Italian version of the Mini-SIPS has been implemented at the First Episode Psychosis (FEP) Program in Ferrara, Italy. RESULTS: The Italian version of Mini-SIPS was successfully administered to 15 individuals subsequently referred to the First Episode Psychosis service in Ferrara. Within this sample, the tool has proven to be both an effective and efficient tool for the identification of CHR and FEP, and a valid instrument to help with the differential diagnosis. It also performed as a valuable guide for retrieving information about psychiatric history, to date the onset of APS and/or full-blown psychosis, to track the progression from CHR to psychosis or to symptoms resolution and to describe patients' pathways to care. CONCLUSION: The Mini-SIPS is an efficient and easy-to-use interview to identify the early stages of psychosis and established psychosis in clinical contexts. The Italian adaptation of this interview could be effectively implemented in other Italian FEP Programs as a screening and monitoring tool. Formal validation of the instrument is needed to assessed validity and reliability in the diagnosis of the CHR and FEP.

Race/ethnicity and socioeconomic status as predictors of outcome following family therapy in youth at clinical high risk for psychosis.

AIM: There is limited research on the effects of sociodemographic and socioeconomic factors on treatment outcomes in youth at clinical high risk for psychosis (CHRp). This study examined sociodemographic factors that may affect functional outcomes within this population. Specifically, we investigated the influence of race/ethnicity (dichotomized as non-Hispanic whites [NHW] vs. people of colour [POC]), socioeconomic status (SES; operationalized as parental years of education), and their interaction on change in psychosocial functioning and symptoms over 6 months in a randomized trial of family-focused therapy. METHODS: CHRp youth (N = 128) participated in a randomized trial of family therapy (18 sessions of family therapy vs. 3 sessions of family psychoeducation). Sixty-four participants who self-identified as POC and 64 self-identified NHW participants completed baseline and 6-month follow-up measures of positive and negative symptoms and psychosocial (global, role, and social) functioning. Multiple regression models were conducted to test the main effect of race/ethnicity on changes in positive and negative symptoms and functioning, and whether this effect was moderated by parental education. RESULTS: There was a significant interaction between race/ethnicity and parental education, such that higher parental education was associated with greater improvement in global functioning in NHW participants, but there was no relationship between parental education and global functioning in POC. Additionally, higher parental education was associated with a decrease in negative symptoms in NHW participants but not in POC. There were no significant effects of race/ethnicity or parental education on positive symptoms, nor on social or role functioning. CONCLUSIONS: Clinicians may consider tailoring psychosocial treatments according to the needs of diverse families who vary in sociodemographic factors such as educational attainment and race/ethnicity.

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS.

AIM: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). METHODS: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. RESULTS: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and modest harmonization for CHR-P criteria. The semi-structured interview, named Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. CONCLUSIONS: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.

Development of the PSYCHS: Positive SYmptoms and Diagnostic Criteria for the CAARMS Harmonized with the SIPS.

Aim: To harmonize two ascertainment and severity rating instruments commonly used for the clinical high risk syndrome for psychosis (CHR-P): the Structured Interview for Psychosis-risk Syndromes (SIPS) and the Comprehensive Assessment of At-Risk Mental States (CAARMS). Methods: The initial workshop is described in the companion report from Addington et al. After the workshop, lead experts for each instrument continued harmonizing attenuated positive symptoms and criteria for psychosis and CHR-P through an intensive series of joint videoconferences. Results: Full harmonization was achieved for attenuated positive symptom ratings and psychosis criteria, and partial harmonization for CHR-P criteria. The semi-structured interview, named P ositive SY mptoms and Diagnostic Criteria for the C AARMS H armonized with the S IPS (PSYCHS), generates CHR-P criteria and severity scores for both CAARMS and SIPS. Conclusion: Using the PSYCHS for CHR-P ascertainment, conversion determination, and attenuated positive symptom severity rating will help in comparing findings across studies and in meta-analyses.

Symptoms of Attenuated Psychosis Syndrome in Relatives of Clinical High-Risk Youth: Preliminary Evidence.

BACKGROUND AND HYPOTHESIS: Attenuated Psychosis Syndrome (APS) impacts functioning and predicts increased risk of psychosis. Risk for developing APS itself has received minimal attention. Knowledge of familial and environmental contributions to APS symptoms would advance understanding of APS and risk for psychosis. As an initial step, this report presents the first data on APS symptoms in family members of APS patients. STUDY DESIGN: This study utilized a discordant sibling-pair family study design. The Structured Interview for Psychosis-risk Syndromes (SIPS) was administered to 17 APS probands and 26 non-APS biological siblings. Probands and siblings were compared on positive, negative, disorganized, and general SIPS symptom scales and factors derived from those scales. STUDY RESULTS: There was significantly greater symptom severity in probands compared to siblings on nine of 19 SIPS scales. Negative/anxiety, functioning, and positive symptom factors were identified. Probands showed significantly greater severity than siblings on the negative/anxiety and positive factors. Elevated pathology on the negative/anxiety factor best differentiated between probands and siblings, over and above the contribution of the positive factor. No difference was found for the functioning factor. CONCLUSIONS: Results support the importance of non-familial effects on risk for APS and suggest differences in familial contribution to APS symptoms. Understanding the relative contribution of familial and environmental effects on APS symptoms may reveal important differences among APS patients, with implications for risk characterization, symptom course, and treatment selection.

The Mini-SIPS: development of a brief clinical structured interview guide to diagnosing DSM-5 Attenuated Psychosis Syndrome and training outcomes.

OBJECTIVE: The Mini-SIPS, a condensed version of the Structured Interview for Psychosis-Risk Syndromes (SIPS), is intended to efficiently identify for clinicians the minimum information needed to support a DSM-5 Attenuated Psychosis Syndrome (APS) diagnosis. METHODS: The instrument and the DSM-5 criteria are accessible through the online training program. RESULTS: Most individuals (67.5%) in the first 212 to complete the training program indicated an intended use of the Mini-SIPS exclusively for clinical purposes. Performance on the post-training quiz was excellent for those with and without prior training in structured diagnostic interviewing. CONCLUSION: The Mini-SIPS, and accompanying training program, are offered as public-domain clinical resources to the mental health community.

Reducing the Duration of Untreated Psychosis (DUP) in a US Community: A Quasi-Experimental Trial.

Objective: Duration of Untreated Psychosis (DUP) remains unacceptably long and limits effectiveness of care. To determine whether an early detection campaign ("Mindmap") can reduce DUP in a US community setting. Methods: In this nonrandomized controlled trial, Mindmap targeted the catchment of one specialty first-episode service or FES (STEP, Greater New Haven) from 2015 to 2019, while usual detection efforts continued at a control FES (PREP, Greater Boston). Mindmap targeted diverse sources of delay through mass & social media messaging, professional outreach & detailing, and rapid enrollment of referrals. Both FES recruited 16-35 years old with psychosis onset ≤3 years. Outcome measures included DUP-Total (onset of psychosis to FES enrollment), DUP-Demand (onset of psychosis to first antipsychotic medication), and DUP-Supply (first antipsychotic medication to FES enrollment). Results: 171 subjects were recruited at STEP and 75 at PREP. Mindmap was associated with an increase in the number of referrals and in efficiency of engagement at STEP. Pre-campaign DUP (2014-2015) was equivalent, while Mindmap was associated with DUP reductions at STEP but not PREP. DUP-Total fell significantly in both the first and the second quartile (11.5 and 58.5 days reduction per campaign year, respectively). DUP-Demand and DUP-Supply fell in the third quartiles only (46.3 and 70.3 days reduction per campaign year, respectively). No reductions were detectable across all quartiles at PREP, but between site comparisons were not significant. Conclusions: This is the first controlled demonstration of community DUP reduction in the US, and can inform future early detection efforts across diverse settings.

Counterpoint. Early intervention for psychosis risk syndromes: Minimizing risk and maximizing benefit.

BACKGROUND: Malhi et al. in this issue critique the clinical high risk (CHR) syndrome for psychosis. METHOD: Response to points of critique. RESULTS: We agree that inconsistency in CHR nomenclature should be minimized. We respectfully disagree on other points. In our view: a) individuals with CHR and their families need help, using existing interventions, even though we do not yet fully understand disease mechanisms; b) substantial progress has been made in identification of biomarkers; c) symptoms used to identify CHR are specific to psychotic illnesses; d) CHR diagnosis is not "extremely difficult"; e) the pattern of progression, although heterogenous, is discernible; f) "psychosis-like symptoms" are common but are not used to identify CHR; and g) on the point described as 'the real risk,' CHR diagnosis does not frequently cause harmful stigma. DISCUSSION: Malhi et al.'s arguments do not fairly characterize progress in the CHR field nor efforts to minimize stigma. That said, much work remains in areas of consistent nomenclature, mechanisms of disease, dissecting heterogeneity, and biomarkers. With regard to what the authors term the "real risk" of stigma associated with a CHR "label," however, our view is that avoiding words like "risk" and "psychosis" reinforces the stigma that both they and we mean to oppose. Moreover, patients and their families benefit from being given a term that describes what is happening to them.

Evidence for Differential Predictive Performance of the Prime Screen Between Black and White Help-Seeking Youths.

OBJECTIVE: Self-report screening instruments for emerging psychosis have the potential to improve early detection efforts by increasing the number of true positives among persons deemed to be at "clinical high risk" of the disorder, but their practical utility depends on their validity across race. This study sought to examine whether a commonly used self-report screening tool for psychosis risk performed equally among black and white youths in its ability to predict clinical high-risk status. METHODS: Black (N=58) and white (N=50) help-seeking individuals ages 12-25 (61% female) were assessed with the Prime Screen and the Structured Interview for Psychosis-Risk Syndromes (SIPS). A logistic regression model estimated race differences in the strength of the relation between Prime Screen scores and SIPS-defined risk status. RESULTS: Higher Prime Screen scores significantly predicted clinical high-risk status among white (p<.01) but not black participants. Among black youths without clinical high risk, self-reported Prime Screen scores more closely resembled scores for youths (black or white) with clinical high risk than scores of white peers who were also without clinical high risk. CONCLUSIONS: Results suggest that consideration of race or ethnicity and associated cultural factors is important when screening for clinical high-risk status. Findings support the need to develop culturally valid early psychosis screening tools to promote appropriately tailored early intervention efforts.

First-Episode Services for Psychotic Disorders in the U.S. Public Sector: A Pragmatic Randomized Controlled Trial.

OBJECTIVE: This study sought to determine the effectiveness of a comprehensive first-episode service, the clinic for Specialized Treatment Early in Psychosis (STEP), in an urban U.S. community mental health center by comparing it with usual treatment. METHODS: This pragmatic randomized controlled trial enrolled 120 patients with first-episode psychosis within five years of illness onset and 12 weeks of antipsychotic exposure. Referrals were mostly from inpatient psychiatric units, and enrollees were randomly allocated to STEP or usual treatment. Main outcomes included hospital utilization (primary); the ability to work or attend age-appropriate schooling-or to actively seek these opportunities (vocational engagement); and general functioning. Analysis was by modified intent to treat (excluding only three who withdrew consent) for hospitalization; for other outcomes, only data for completers were analyzed. RESULTS: After one year, STEP participants had less inpatient utilization compared with those in usual treatment: no psychiatric hospitalizations, 77% versus 56% (risk ratio [RR]=1.38, 95% confidence interval [CI]=1.08-1.58); mean hospitalizations, .33±.70 versus .68±.92 (p=.02); and mean bed-days, 5.34±13.53 versus 11.51±15.04 (p=.05). For every five patients allocated to STEP versus usual treatment, one additional patient avoided hospitalization over the first year (number needed to treat=5; CI=2.7-26.5). STEP participants also demonstrated better vocational engagement (91.7% versus 66.7%; RR=1.40, CI=1.18-1.48) and showed salutary trends in global functioning measures. CONCLUSIONS: This trial demonstrated the feasibility and effectiveness of a U.S. public-sector model of early intervention for psychotic illnesses. Such services can also support translational research and are a relevant model for other serious mental illnesses.

Reducing the duration of untreated psychosis and its impact in the U.S.: the STEP-ED study.

BACKGROUND: Early intervention services for psychotic disorders optimally interlock strategies to deliver: (i) Early Detection (ED) to shorten the time between onset of psychotic symptoms and effective treatment (i.e. Duration of Untreated Psychosis, DUP); and (ii) comprehensive intervention during the subsequent 2 to 5 years. In the latter category, are teams ('First-episode Services' or FES) that integrate several empirically supported treatments and adapt their delivery to younger patients and caregivers. There is an urgent need to hasten access to established FES in the U.S. Despite improved outcomes for those in treatment, these FES routinely engage patients a year or more after psychosis onset. The Scandinavian TIPS study was able to effectively reduce DUP in a defined geographic catchment. The guiding questions for this study are: can a U.S. adaptation of the TIPS approach to ED substantially reduce DUP and improve outcomes beyond existing FES? METHODS/DESIGN: The primary aim is to determine whether ED can reduce DUP in the US, as compared to usual detection. ED will be implemented by one FES (STEP) based in southern Connecticut, and usual detection efforts will continue at a comparable FES (PREP(R)) serving the greater Boston metropolitan area. The secondary aim is to determine whether DUP reduction can improve presentation, engagement and early outcomes in FES care. A quasi-experimental design will compare the impact of ED on DUP at STEP compared to PREP(R) over 3 successive campaign years. The campaign will deploy 3 components that seek to transform pathways to care in 8 towns surrounding STEP. Social marketing approaches will inform a public education campaign to enable rapid and effective help-seeking behavior. Professional outreach and detailing to a wide variety of care providers, including those in the healthcare, educational and judicial sectors, will facilitate rapid redirection of appropriate patients to STEP. Finally, performance improvement measures within STEP will hasten engagement upon referral. DISCUSSION: STEP-ED will test an ED campaign adapted to heterogeneous U.S. pathways to care while also improving our understanding of these pathways and their impact on early outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02069925 . Registered 20 February 2014.

Family-focused treatment for adolescents and young adults at high risk for psychosis: results of a randomized trial.

OBJECTIVE: Longitudinal studies have begun to clarify the phenotypic characteristics of adolescents and young adults at clinical high risk for psychosis. This 8-site randomized trial examined whether a 6-month program of family psychoeducation was effective in reducing the severity of attenuated positive and negative psychotic symptoms and enhancing functioning among individuals at high risk. METHOD: Adolescents and young adults (mean age 17.4 ± 4.1 years) with attenuated positive psychotic symptoms, brief and intermittent psychosis, or genetic risk with functional deterioration were randomly assigned to 18 sessions of family-focused therapy for individuals at clinical high risk (FFT-CHR) in 6 months or 3 sessions of family psychoeducation (enhanced care [EC]). FFT-CHR included psychoeducation about early signs of psychosis, stress management, communication training, and problem-solving skills training, whereas EC focused on symptom prevention. Independent evaluators assessed participants at baseline and 6 months on positive and negative symptoms and social-role functioning. RESULTS: Of 129 participants, 102 (79.1%) were followed up at 6 months. Participants in FFT-CHR showed greater improvements in attenuated positive symptoms over 6 months than participants in EC (F1,97 = 5.49, p = .02). Negative symptoms improved independently of psychosocial treatments. Changes in psychosocial functioning depended on age: participants more than 19 years of age showed more role improvement in FFT-CHR, whereas participants between 16 and 19 years of age showed more role improvement in EC. The results were independent of concurrent pharmacotherapy. CONCLUSION: Interventions that focus on improving family relationships may have prophylactic efficacy in individuals at high risk for psychosis. Future studies should examine the specificity of effects of family intervention compared to individual therapy of the same duration and frequency. Clinical trial registration information-Prevention Trial of Family Focused Treatment in Youth at Risk for Psychosis; http://clinicaltrials.gov/; NCT01907282.

Current status specifiers for patients at clinical high risk for psychosis.

BACKGROUND: Longitudinal studies of the clinical high risk (CHR) syndrome for psychosis have emphasized the conversion vs non-conversion distinction and thus far have not focused intensively on classification among non-converters. The present study proposes a system for classifying CHR outcomes over time when using the Structured Interview for Psychosis-risk Syndromes and evaluates its validity. METHOD: The system for classifying CHR outcomes is referred to as "current status specifiers," with "current" meaning over the month prior to the present evaluation and "specifiers" indicating a set of labels and descriptions of the statuses. Specifiers for four current statuses are described: progression, persistence, partial remission, and full remission. Data from the North American Prodromal Longitudinal Study were employed to test convergent, discriminant, and predictive validity of the current status distinctions. RESULTS: Validity analyses partly supported current status distinctions. Social and role functioning were more impaired in progressive and persistent than in remitted patients, suggesting a degree of convergent validity. Agreement between CHR current statuses and current statuses for a different diagnostic construct (DSM-IV Major Depression) was poor, suggesting discriminant validity. The proportion converting to psychosis within a year was significantly higher in cases meeting progression criteria than in those meeting persistence criteria and tended to be higher than in those meeting full remission criteria, consistent with a degree of predictive validity. DISCUSSION: CHR syndrome current status specifiers could offer a potentially valid and useful description of current clinical status among non-converters. Study in additional samples is needed.

A randomized trial of family focused therapy with populations at clinical high risk for psychosis: effects on interactional behavior.

OBJECTIVE: This study investigated whether family focused therapy (FFT-CHR), an 18-session intervention that consisted of psychoeducation and training in communication and problem solving, brought about greater improvements in family communication than enhanced care (EC), a 3-session psychoeducational intervention, among individuals at clinical high risk for developing psychosis. METHOD: This study was conducted within a randomized controlled trial across 8 sites. We examined 10-min problem-solving discussions at baseline and 6-month reassessment among 66 adolescents and young adults and their parents. Trained coders who were blind to treatment and time of assessment achieved high levels of interrater reliability when evaluating family discussions on categories of calm-constructive and critical-conflictual behavior. RESULTS: Individuals at high risk and their family members who participated in FFT-CHR demonstrated greater improvement from baseline to 6-month reassessment in constructive communication and decreases in conflictual behaviors during family interactions than those in EC. Participants in FFT-CHR showed greater increases from baseline to 6 months in active listening and calm communication and greater decreases in irritability and anger, complaints and criticism, and off-task comments compared to participants in EC. These changes occurred equally in high-risk participants and their family members. CONCLUSIONS: A 6-month family skills training treatment can bring about significant improvement in family communication among individuals at high risk for psychosis and their parents. Future studies should examine the association between enhancements in family communication and reduced risk for the onset of psychosis among individuals at high risk.

Glycine treatment of the risk syndrome for psychosis: report of two pilot studies.

Patients meeting criteria for the risk syndrome for psychosis have treatment needs including positive and negative symptoms and cognitive impairment. These features could potentially respond to NMDA glycine-site agonists. The present objective was to determine which symptoms or domains of cognition promise to show the greatest response to glycine in risk syndrome patients. We conducted two short-term pilot studies of glycine used without adjunctive antipsychotic medication. In the first trial, 10 risk syndrome subjects received open-label glycine at doses titrated to 0.8 g/kg/d for 8 weeks, followed by discontinuation and 16 weeks of evaluation for durability of effects. In the second, 8 subjects were randomized to double-blind glycine vs. placebo for 12 weeks, followed by open-label glycine for another 12 weeks. Patients were evaluated every 1-2 weeks with the Scale Of Psychosis-risk Symptoms (SOPS) and before and after treatment with a neurocognitive battery. Within-group and between-group effect sizes were calculated. Effect sizes were large for positive (open-label within-group -1.10, double-blind between-group -1.11) and total (-1.39 and -1.15) symptoms and medium-to-large (-0.74 and -0.79) for negative symptoms. Medium or large effect sizes were also observed for several neurocognitive measures in the open-label study, although data were sparse. No safety concerns were identified. We conclude that glycine was associated with reduced symptoms with promising effect sizes in two pilot studies and a possibility of improvement in cognitive function. Further studies of agents that facilitate NMDA receptor function in risk syndrome patients are supported by these preliminary findings.

The case for including Attenuated Psychotic Symptoms Syndrome in DSM-5 as a psychosis risk syndrome.

The American Psychiatric Association Task Force on DSM-5 has recently proposed consideration of Attenuated Psychotic Symptoms Syndrome as a new diagnosis, based on nearly 15 years of prospective research in centers across the globe. The condition is also known as "psychosis risk syndrome," "at-risk mental state," "ultra-high risk," and "putative prodrome." We review evidence favoring its inclusion as a new diagnosis in DSM-5 and report new preliminary findings on DSM-IV diagnoses in current clinical use for these patients and on results of diagnostic interviews in unselected volunteers. The main evidence supporting inclusion is: (1) the patients are currently ill, (2) the patients are at high risk for getting worse, (3) no DSM-IV diagnosis accurately captures their current illness or future risk, (4) the diagnosis has been made with reliability and validity in the research setting, and (5) placement in DSM-5 would help promote the needed treatment and prevention research to enable articulation of a standard of care to benefit these patients and their families. Potential harms can be minimized by patient, family, and provider education. It will be important to demonstrate through well-designed field trials whether the diagnostic criteria can be used with reliability in everyday clinical practice.

Incidence of tardive dyskinesia with atypical versus conventional antipsychotic medications: a prospective cohort study.

OBJECTIVE: Most previous studies of the incidence of tardive dyskinesia with atypical antipsychotics compared with conventional antipsychotics have not had tardive dyskinesia as their primary focus. The current study aimed to compare the incidence of tardive dyskinesia with atypical vs conventional antipsychotics using methods similar to those from a previous prospective cohort study at our site in the 1980s. METHOD: Three hundred fifty-two initially tardive dyskinesia-free psychiatric outpatients (diagnosed at baseline using the Structured Clinical Interview for DSM-IV) were examined for a new diagnosis of tardive dyskinesia (using the Abnormal Involuntary Movement Scale and Glazer-Morgenstern criteria) every 6 months for up to 4 years at a community mental health center. At baseline, subjects were receiving conventional antipsychotics only (23%), atypicals only (64%), or both (14%). Only 26 subjects had never received conventional antipsychotics. Baseline evaluations were conducted from November 2000 through May 2003. Follow-ups were conducted through February 2005. RESULTS: Compared with subjects treated with conventional antipsychotics alone since the previous visit, the adjusted tardive dyskinesia incidence rate-ratio for subjects treated with atypical antipsychotics alone was 0.68 (95% CI, 0.29-1.64). The incidence and prevalence of tardive dyskinesia was similar to previous findings at this site in the 1980s. CONCLUSIONS: The incidence of tardive dyskinesia with recent exposure to atypical antipsychotics alone was more similar to that for conventional antipsychotics than in most previous studies. Despite high penetration of atypical antipsychotics into clinical practice, the incidence and prevalence of tardive dyskinesia appeared relatively unchanged since the 1980s. Clinicians should continue to monitor for tardive dyskinesia, and researchers should continue to pursue efforts to treat or prevent it.

Aripiprazole in the treatment of the psychosis prodrome: an open-label pilot study.

BACKGROUND: Research studies for the treatment of the putative prodromal phase of psychotic disorders have begun to appear. AIMS: To obtain preliminary evidence of the short-term efficacy and safety of aripiprazole treatment in people with the psychosis prodrome. METHOD: Fifteen participants meeting prodrome criteria (mean age 17.1 years, s.d.=5.5) enrolled in an open-label, single-site trial with fixed-flexible dosing of aripiprazole (5-30 mg/day) for 8 weeks. RESULTS: In the mixed-effects repeated-measures analysis, improvement from baseline on the Scale of Prodromal Symptoms total score was statistically significant by the first week. No participant converted to psychosis and 13 completed treatment. Neuropsychological measures showed no consistent improvement; mean weight gain was 1.2 kg. Akathisia emerged in 8 participants, but the mean Barnes Akathisia Scale score fell to baseline levels by the final visit. Adverse events were otherwise minimal. CONCLUSIONS: Aripiprazole shows a promising efficacy and safety profile for the psychosis prodrome. Placebo-controlled studies are indicated.