When to initiate antipsychotic treatment for psychotic symptoms: At the premorbid phase or first episode of psychosis?

Abstract

Objective: Antipsychotic drugs are widely used for treating patients with first episode of psychosis, targeting threshold psychotic symptoms. The clinical high risk of psychosis is characterized as subthreshold psychotic symptoms and it is unclear whether they can also benefit from antipsychotic drugs treatment. This study attempted to determine whether initiating antipsychotic drugs treatment in the clinical high risk of psychosis phase was superior to initiating antipsychotic drugs treatment in the first episode of psychosis phase, after the 2-year symptomatic and functional outcomes. Method: Drawing on 517 individuals with clinical high risk of psychosis from the ShangHai At Risk for Psychosis program, we identified 105 patients who converted to first episode of psychosis within the following 2 years. Patients who initiated antipsychotic drugs while at clinical high risk of psychosis (CHR_AP; n = 70) were compared with those who initiated antipsychotic drugs during a first episode of psychosis (FEP_AP; n = 35). Summary scores on positive symptoms and the global function scores at baseline and at 2 months, 1 year and 2 years of follow-up were analyzed to evaluate outcomes. Results: The CHR_AP and FEP_AP groups were not different in the severity of positive symptoms and functioning at baseline. However, the CHR_AP group exhibited significantly more serious negative symptoms and total symptoms than the FEP_AP group. Both groups exhibited a significant reduction in positive symptoms and function ( p < 0.001). Repeated-measures analysis of variance revealed group by time interaction for symptomatic ( F = 3.196, df = 3, p = 0.024) and functional scores ( F = 7.306, df = 3, p < 0.001). The FEP_AP group showed higher remission rates than the CHR_AP group (χ2 = 22.270, p < 0.001). Compared to initiating antipsychotic drug treatments in the clinical high risk of psychosis state, initiating antipsychotic drugs treatments in the first episode of psychosis state predicted remission in a regression model for FEP_AP (odds ratio = 5.567, 95% confidence interval = [1.783, 17.383], p = 0.003). Conclusion: For clinical high risk of psychosis, antipsychotic drugs might be not the first choice in terms of long-term remission, which is more reasonable to use at the first episode of psychosis phase.

Antipsychotics are related to psychometric conversion to psychosis in ultra‐high‐risk youth

“…However, we cannot exclude that for some patients, the prescription of an antipsychotic drug might prompt a sensibilization of the dopamine receptors, which may favour a further rebound of symptoms until conversion to psychosis (Chouinard et al, 2017 ). In‐depth scrutiny of the symptoms' profile is thus necessary to wisely ponder the best, individualized treatment option for UHR patients (Zhang, Xu, Tang, et al, 2020 ; Zhang, Xu, Wei, et al, 2020 ), balancing psychopharmacotherapy with psychotherapy approaches, such as cognitive‐behavioural therapy, which offers first‐line protection from conversion to psychosis (Devoe et al, 2020 ).…”

“…In analysing data from the ShangHai At Risk for Psychosis (SHARP) study, Zhang, Xu, Tang, et al ( 2020 ) found that UHR patients who did not receive antipsychotics showed a lower conversion rate than those who did (17.7% vs. 26.9%; odds ratio = 0.66; 95% confidence interval [CI] = 0.44, 0.98). Moreover, patients who initiated antipsychotic drugs whilst at clinical high risk of psychosis had lower remission rates than those who initiated antipsychotic drugs when already in the first episode of psychosis (Zhang, Xu, Wei, et al, 2020 ). In a meta‐analysis of 14 studies that reported detailed information on antipsychotics prescription in UHR patients, Raballo et al ( 2020b ) found that UHR patients who had received a prescription of antipsychotics before entering the programme of care (n = 112) had a higher relative risk (RR) of conversion to psychosis (29% vs. 16%; RR = 1.47; 95%CI: 1.18–1.83) than those who did not have received any (n = 235).…”

“…Albert et al ( 2017 ) and Raballo et al ( 2020b ) suggested that treatment with antipsychotics is a proxy for elevated levels of psychiatric symptoms, thus marking a subgroup of individuals who have per se enhanced risk of conversion to psychosis. Zhang, Xu, Tang, et al ( 2020 ); Zhang, Xu, Wei, et al ( 2020 ), instead, suggested that antipsychotics should be considered harmful in subjects at high risk of psychosis, with no preventive benefits. For these reasons, Zhang, Xu, Tang, et al ( 2020 ); Zhang, Xu, Wei, et al ( 2020 ) discourage the prescription of antipsychotics in UHR patients unless presenting with a quite specific symptoms profile: severe positive and general symptoms, but mild negative symptoms.…”

“…Zhang, Xu, Tang, et al ( 2020 ); Zhang, Xu, Wei, et al ( 2020 ), instead, suggested that antipsychotics should be considered harmful in subjects at high risk of psychosis, with no preventive benefits. For these reasons, Zhang, Xu, Tang, et al ( 2020 ); Zhang, Xu, Wei, et al ( 2020 ) discourage the prescription of antipsychotics in UHR patients unless presenting with a quite specific symptoms profile: severe positive and general symptoms, but mild negative symptoms.…”

Individualized risk components guiding antipsychotic delivery in patients with a clinical high risk of psychosis: application of a risk calculator

“…For instance, a recent study (Fusar-Poli et al, 2020a) demonstrated that CHR individuals who developed psychosis (despite antipsychotic treatment) had worse outcomes compared with patients who initially presented in first-episode groups. Our previous study (Zhang et al, 2020) provided evidence that early use of antipsychotics for the CHR population may be effective in reducing the severity of positive symptoms; however, this may not be the best approach in terms of long-term remission.…”