Combined antipsychotics, psychological intervention effective for first-episode psychosis

Antipsychotic medication, psychological intervention and the two combined appeared acceptable, safe and effective among adolescents with first-episode psychosis, according to study results published in The Lancet Psychiatry.

“At present, the evidence for the effectiveness of treatments for early-onset psychosis is scarce and treatment recommendations of the U.K. National Institute for Health and Care Excellence (NICE) for psychological interventions (clinical guideline CG155) are extrapolated from the larger adult psychosis evidence base, which was considered sufficiently strong to make the current recommendations of antipsychotics, [cognitive behavioral therapy] and family intervention,” Anthony P. Morrison, ClinPsyD, of the Psychosis Research Unit at Greater Manchester Mental Health National Health Service Foundation Trust, and colleagues wrote. “The paucity of evidence specific to young people is recognized in the NICE clinical guideline CG155, on psychosis and schizophrenia management in children and young people, and led to a research recommendation for an evaluation of the clinical effectiveness and cost-effectiveness of antipsychotics vs. psychological intervention vs. a combination of both in adolescents with early-onset psychosis.”

Results of a 2015 systematic review suggested antipsychotic drugs are the mainstay of treatment for youths with psychosis, yet evidence is sparse for their effectiveness in early-onset psychosis compared with it in adult psychosis. Further, this review also showed no studies of either CBT or family intervention among individuals younger than 18 years; however, eight low-quality studies of family intervention and CBT among individuals aged younger than 25 years showed CBT and family intervention combination therapy had a small but significant effect on number of days to relapse.

Morrison and colleagues aimed to determine the feasibility of a randomized controlled trial of psychological intervention monotherapy, antipsychotic monotherapy and antipsychotics plus psychological intervention among adolescents with first-episode psychosis. Across seven U.K. National Health Service Trust sites, they recruited participants aged 14 to 18 years who were help-seeking, had presented with first-episode psychosis in the past year, were receiving care from a psychiatrist, were showing current psychotic symptoms and met criteria for schizophrenia, schizoaffective disorder or delusional disorder according to the ICD-10, or met entry criteria for early intervention for psychosis service.

The investigators assigned participants 1:1:1 among the three treatment options. The psychological intervention was comprised of CBT via up to 26 sessions over 6 months plus up to four booster sessions, as well as optional family intervention incorporating up to six sessions over 6 months. A treating consultant psychiatrist dispensed choice and dose of antipsychotic at his or her discretion. Follow-up occurred for a maximum of 12 months. Feasibility, which included data on trial referral and recruitment, session attendance or medication adherence, treatment acceptability and retention served, served as the primary outcome. Total score on the Positive and Negative Syndrome Scale (PANSS) at 6 months served as the proposed primary efficacy outcome. The investigators analyzed primary outcomes by intention to treat and reported safety outcomes according to as-treated status, for all patients who had received one or more sessions of CBT or family intervention, or one or more antipsychotic dose.

Morrison and colleagues recruited 61 patients with a mean age of 16.3 years, and the trial recruitment rate was 68% of their target sample size of 90 participants. Of these patients, they randomly assigned 18 to psychological intervention, 22 to antipsychotics and 21 to antipsychotics plus psychological intervention. They reported a low referral to recruitment ratio of around 2:1, a high rate of retention of 84% of participants at the 6-month primary endpoint, a high rate of adherence to psychological intervention of 82% and a moderate rate of adherence to antipsychotic medication of 65%. At the 6-month primary endpoint, mean total PANSS scores were 68.6 for antipsychotic monotherapy, 59.8 for psychological intervention and 62 for antipsychotics plus psychological intervention. Further, they reported achievement of a good clinical response at 6 months among 22% of patients who received antipsychotic monotherapy, 31% who received psychological intervention and 29% who received antipsychotics plus psychological intervention. Results of as-treated groups showed serious adverse events among 35% of patients in the combined group, 13% in the antipsychotics group, 24% in the psychological intervention group and among 80% who received no treatment.

Morrison and colleagues reported no serious adverse events related to trial participation.

“The main implication of this trial is that an adequately powered effectiveness trial is now required to provide evidence regarding the relative effectiveness of antipsychotic medication and psychological therapies (CBT and family intervention) in adolescents with early-onset psychosis,” they wrote. “On the basis of our trial, it seems reasonable to support young people with early-onset psychosis and their families (in the absence of immediate risk to themselves or others) to make informed treatment choices as outlined in the NICE guidelines.”

In a related editorial, Sameer Jauhar, MRCPsych, of the Institute of Psychiatry, Psychology and Neuroscience at King’s College London, outlined how a future trial for early-onset psychosis could look.

“The field urgently needs a large-scale trial in early-onset psychosis, although if such a trial is to provide clinically meaningful results, it will need to focus on clinically homogenous groups, and differentiate treatment effects,” Jauhar wrote. “This line of investigation might take time and more than one study, but the results would have wide-ranging and lasting consequences.”