Background Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. Method From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. Results The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. Conclusions Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis. ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030

While sex differences in schizophrenia have long been reported and discussed, long-term sex differences in outcomes among first episode of psychosis (FEP) patients in terms of the efficacy of Early Intervention Services (EIS) has been an under-explored area. A total of 209 FEP patients (95 females and 114 males) were reassessed after a time window ranging from 8 to 16 years after their first contact with an EIS program (PAFIP) that we will call the 10-year PAFIP cohort. Multiple clinical, cognitive, functioning, premorbid, and sociodemographic variables were explored at 1-year, 3-year and 10-year follow-ups. At first contact, females were older at illness onset, had higher premorbid adjustment and IQ, and were more frequently employed, living independently, and accompanied by a partner and/or children. Existence of a schizophrenia diagnosis, and cannabis and alcohol consumption were more probable among men. During the first 3 years, women showed a significantly better response to minimal antipsychotic dosages and higher rates of recovery than men (50% vs. 30.8%). Ten years later, more females continued living independently and had partners, while schizophrenia diagnoses and cannabis consumption continued to be more frequent among men. Females also presented a lower severity of negative symptoms; however, functionality and recovery differences did not show significant differences (46.7% vs. 34.4%). Between the 3- and 10-year follow-up sessions, an increase in dosage of antipsychotics was observed. These results suggest that the better outcomes seen among women during the first 3 years (while they were treated in an EIS) were in the presence of more favourable premorbid and baseline characteristics. After an average period of 10 years, with the only difference being in negative symptoms course, outcomes for women approximated those of men, drawing particular attention to the increase in dosage of antipsychotic medication once FEP patients were discharged from the EIS program towards community-based services. These findings help to pose the question of whether it is advisable to target sexes and lengthen EIS interventions.

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