Long-Term Antipsychotic Effectiveness in First Episode of Psychosis: A 3-Year Follow-Up Randomized Clinical Trial Comparing Aripiprazole, Quetiapine, and Ziprasidone

Abstract

BackgroundDifferent effectiveness profiles among second-generation antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to affect long-term outcome. The aim of this study was to compare the clinical effectiveness of aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up.MethodFrom October 2005 to January 2011, a prospective, randomized, open-label study was undertaken. Two hundred-two first-episode, drug-naïve patients were randomly assigned to 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 the intention-to-treat principle was conducted in the analysis for clinical efficacy.ResultsThe overall dropout rate at 3 years reached 19.3%. Treatment discontinuation rates were significantly different among treatment groups (aripiprazole=73.08%, ziprasidone=79.03%, and quetiapine=95.16%) (χ2=11.680; P=.001). Statistically significant differences in terms of nonefficacy, nonadherence, and side effects were observed among treatment groups along the 3-year follow-up determining significant differences in time to all-cause discontinuation (log-rank=32.260; P=.001). Significant differences between treatments were found in the categories of sleepiness/sedation (χ2=9.617; P=.008) and increased sleep duration (χ2=6.192; P=.004). No significant differences were found in the profile of extrapyramidal symptoms. Patients on aripiprazole were more likely to be prescribed benzodiazepines.ConclusionsFirst-episode psychosis patients on quetiapine were more likely to discontinue treatment due to nonefficacy. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis.

Weight gain and metabolic screening in young people with early psychosis on long acting injectable antipsychotic medication (aripiprazole vs paliperidone)

“…Studies have mainly been conducted using oral formulations and in patients with chronic schizophrenia, and a general consensus is that it sits in the lowest rank order amongst other antipsychotics in terms of its effect on weight gain and metabolic syndrome (eg, Casey et al, 2004). Yet, emerging findings suggest the possibility of a different side-effect profile in young people (Gómez-Revuelta et al, 2018;Vázquez-Bourgon et al, 2018). For example, studies of oral aripiprazole in patients with first-episode psychosis have demonstrated weight and BMI increases, relative to baseline (Correll, Manu, Olshanskiy, et al, 2009;De Hert, Dobbelaere, et al, 2011;Robinson et al, 2015;Zhang & Dai, 2012).…”

Effect of cannabis on weight and metabolism in first-episode non-affective psychosis: Results from a three-year longitudinal study

“…Out of the 510 patients, 138 (27.1%) were initially treated with aripiprazole (a dopamine 2 [D2] and serotonin 1A [5-HT1A] receptor partial agonist, and serotonin 2A [5-HT2A] receptor antagonist), 121 (23.7%) with risperidone (a D2, 5-HT2 and norepinephrine alpha-2 receptor antagonist), 70 (13.7%) with quetiapine (a D2 and 5-HT2 receptor antagonist, and norepinephrine transporter-metabolite-reuptake inhibitor), 66 (12.9%) with ziprasidone (a D2 and 5-HT2 receptor antagonist), 58 (11.4%) with olanzapine (a D2 and 5-HT2 receptor antagonist) and 57 (11.2%) with haloperidol (a D2 receptor antagonist). All patients but 2.9% ( n =11; mean time to discontinuation: 25.2 months) remained on antipsychotic treatment at three-year follow-up; 57.4% of them were changed to a different antipsychotic from the one initially prescribed due to lack of response or tolerability (for more detailed information regarding effectiveness in our sample see Gómez-Revuelta et al, 2018, and Crespo-Facorro et al, 2012).…”

How do we select an antipsychotic for those with schizophrenia?

“…However, more than three-quarters (76.4%) of patients who discontinued treatment did so during the first year of follow-up. The median time to all-cause discontinuation for quetiapine was significantly shorter (60 days), than for ziprasidone (251 days) or aripiprazole (452 days), primarily motivated by insufficient efficacy [20].…”

“…Effectively treating the first episode of psychosis (FEP) is of particular importance because response rates fall dramatically during subsequent psychotic episodes. Medication non-adherence is associated with a 4-fold increase for relapse after a FEP, so optimizing and individualizing treatment to improve adherence should be a primary goal [20]. Pseudo-adherence, falsely believing one is taking their medication, is a common problem.…”