This study aimed to determine if, following two years of early intervention service for first-episode psychosis, three-year extension of that service was superior to three years of regular care. We conducted a randomized single blind clinical trial using an urn randomization balanced for gender and substance abuse. Participants were recruited from early intervention service clinics in Montreal. Patients (N5220), 18-35 years old, were randomized to an extension of early intervention service (EEIS; N5110) or to regular care (N5110). EEIS included case management, family intervention, cognitive behaviour therapy and crisis intervention, while regular care involved transfer to primary (community health and social services and family physicians) or secondary care (psychiatric outpatient clinics). Cumulative length of positive and negative symptom remission was the primary outcome measure. EEIS patients had a significantly longer mean length of remission of positive symptoms (92.5 vs. 63.6 weeks, t54.47, p<0.001), negative symptoms (73.4 vs. 59.6 weeks, t52.84, p50.005) and both positive and negative symptoms (66.5 vs. 56.7 weeks, t52.25, p50.03) compared to regular care patients. EEIS patients stayed in treatment longer than regular care patients (mean 131.7 vs. 105.3 weeks, t53.98, p<0.001 through contact with physicians; 134.8 6 37.7 vs. 89.8 6 55.2, t56.45, p<0.0001 through contact with other health care providers) and received more units of treatment (mean 74.9 vs. 39.9, t54.21, p<0.001 from physicians, and 57.3 vs. 28.2, t54.08, p<0.001 from other health care professionals). Length of treatment had an independent effect on the length of remission of positive symptoms (t52.62, p50.009), while number of units of treatment by any health care provider had an effect on length of remission of negative symptoms (t522.70, p50.008) as well as total symptoms (t522.40, p50.02). Post-hoc analysis showed that patients randomized to primary care, based on their better clinical profile at randomization, maintained their better outcome, especially as to remission of negative symptoms, at the end of the study. These data suggest that extending early intervention service for three additional years has a positive impact on length of remission of positive and negative symptoms compared to regular care. This may have policy implications for extending early intervention services beyond the current two years.

Most consenting patients with an FEP had experienced previous signs and symptoms consistent with a CHR state prior to the onset of threshold-level psychotic symptoms, although a substantial minority had not. This finding validates the viability of the CHR construct as a potential target for early case identification and preventive and therapeutic interventions.

Background With previously established efficacy of aripiprazole once-monthly injectable formulation (AOM) in pre-registration randomized controlled trials, the current study was designed to evaluate its effectiveness in patients treated for schizophrenia in regular clinical settings in Canada. Methods Following their clinicians’ decision to prescribe AOM, 193 patients with a diagnosis of schizophrenia, were recruited from 17 Canadian community or hospital-based settings. The primary outcome of global functioning was assessed with the Global Assessment of Functioning Scale (GAF) at 3-month intervals for 1 year. Secondary outcomes (social and occupational functioning and illness severity) and adverse drug reactions (ADR) were also assessed. Results A majority of the 169 evaluable patients were within the first 5 years of diagnosis (early phase). A linear mixed model analysis showed a significant main effect of time (Type III test p < 0.001) after adjusting for baseline GAF score, with a change in mean GAF scores from 49 at baseline to 61 at 12 months. No differences between early vs late phase were observed. Results on secondary outcome measures of function (Social and Occupational Functioning Scale) and illness severity (Clinical Global Impression-Severity Scale and Brief Psychiatric Rating Scale) were similar. Serious ADRs were observed in 29 (14.6%) patients and akathisia in 18 (9.1%) patients. At month-12, significant (≥7%) weight gain was observed in 25.7% ( n = 27/105) of patients. Conclusions Treatment with AOM is effective in improving symptoms and functioning in schizophrenia patients treated in regular clinical settings. Akathisia was infrequent while one quarter of patients gained clinically significant weight. Trial registration Unique identifier: NCT02131415 . First posted: 06 May 2014. Electronic supplementary material The online version of this article (10.1186/s12888-019-2103-x) contains supplementary material, which is available to authorized users.

The clinical high-risk state in psychosis is most often characterized by subthreshold psychotic symptoms (STPS) and represents a target for psychosis prevention. However, evidence suggests that between 30% and 50% of patients with a first episode of psychosis (FEP) report no prior history of STPS, indicating that not all patients with FEP experience a previous clinical high-risk phase. As with other early characteristics of illness onset, this diversity in the early course of symptoms may offer prognostic value for subsequent clinical trajectories. OBJECTIVE To determine whether a history of pre-onset STPS is associated with differential 1-year treatment outcomes in an early intervention service for FEP. DESIGN, SETTING, AND PARTICIPANTS Data on 195 patients 15 to 35 years of age who were recruited between January 17, 2003, and October 17, 2013, were collected from a catchment-based specialized early intervention service for FEP. Patients who reported experiencing at least 1 STPS prior to the onset of FEP were identified as STPS present (STPSp; n = 135); those who reported no such history were identified as STPS absent (STPSa; n = 60). Statistical analysis was conducted from December 15, 2016, to February 15, 2018. MAIN OUTCOMES AND MEASURES Summary scores on the Scale for the Assessment of Positive Symptoms and the Scale for the Assessment of Negative Symptoms, Calgary Depression Scale for Schizophrenia, Hamilton Anxiety Rating Scale, Global Assessment of Functioning scores, and Social and Occupational Functioning Assessment Scale scores at baseline and after 1 year of treatment were analyzed to evaluate 1-year outcomes. RESULTS Individuals in the STPSp group (39 female and 96 male participants; mean [SD] age, 23.4 [4.2] years) and the STPSa group (20 female and 40 male participants; mean [SD] age, 23.9 [5.1] years) did not differ in symptom severity or functioning at baseline. Although both groups improved by 1 year of treatment, mixed analyses of covariance (controlling for duration of untreated psychosis) revealed group-by-time interactions for scores on the Scale for the Assessment of Negative Symptoms (F 1,192 = 6.17; P = .01), the Global Assessment of Functioning (F 1,188 = 7.54; P = .006), and the Social and Occupational Functioning Assessment Scale (F 1,192 = 3.79; P = .05). Mixed analyses of covariance also revealed a group effect for scores on the Scale for the Assessment of Positive Symptoms (F 1,192 = 5.31; P = .02). After controlling for multiple comparisons, all significant results indicate poorer 1-year outcomes for patients with STPSp compared with patients with STPSa. CONCLUSIONS AND RELEVANCE A history of pre-onset STPS consistent with a prior clinical high-risk state is associated with poorer outcomes in psychotic symptoms and global functioning for patients after 1 year of treatment for FEP. The presence or absence of pre-onset STPS therefore has prognostic value for treatment outcomes, even during a later stage of psychotic illness.