Real-world effectiveness of antipsychotic treatment in psychosis prevention in a 3-year cohort of 517 individuals at clinical high risk from the SHARP (ShangHai At Risk for Psychosis)

Abstract

Objective: Antipsychotics are widely used for treating psychosis, but it is unclear whether they can also prevent psychosis. This study attempted a longitudinal evaluation of antipsychotics under real-world conditions in China to evaluate their effect on the rate of conversion to psychosis in individuals with a clinical high risk (CHR) of psychosis. Method: A total of 517 CHR individuals were recruited between 2011 and 2016 and followed up for 3 years. Among these, 450 (87.0%) individuals completed follow-up, 108 (24.0%) showed conversion to psychosis and 309 (68.7%) received antipsychotics. The main outcome was conversion to psychosis. The sample was further stratified according to the severity of positive symptoms. Results: Patients who did not receive antipsychotics showed a lower conversion rate than those who did (17.7% vs 26.9%; odds ratio [OR] = 0.660, 95% confidence interval [CI] = [0.442, 0.985], p = 0.035). In mild CHR cases, antipsychotic treatment was more likely to be associated with conversion to psychosis, compared with the no-antipsychotics group, with no such difference observed in severe CHR cases. Among those who received antipsychotics, monotherapy or low-dose treatment was associated with lower conversion rates. Our results did not favor any specific type of antipsychotics and suggested that a very small subgroup of CHR individuals with severe positive and general symptoms but mild negative symptoms may benefit from antipsychotic treatment. Conclusions: Administration of antipsychotics to CHR patients is potentially harmful with no preventive benefits. We do not recommend antipsychotic treatment for CHR individuals, which is practiced widely in China, and strongly advise caution if these drugs are used.

Antipsychotic treatment in clinical high risk for psychosis: Protective, iatrogenic or further risk flag?

“…Zhang et al’s (2020) longitudinal data on 450 CHR individuals (out of 517 recruited at baseline) followed up for 3 years reveal that…”

“…To sum up, in the SHARP study (Zhang et al, 2020) as well as in common, real-world clinical practice, AP prescription in CHR subjects likely represents a pondered decision on a rational, need-based clinical evaluation. Such decision threshold is primarily motivated by the identification of a global mental state (not limited to positive symptoms) in urgent need of AP treatment, which is clearly a non-negligible index of clinical severity.…”

“…The intriguing report on the real-world effectiveness of antipsychotics (AP) on the rate of transition to psychosis in the SHARP (ShangHai At Risk for Psychosis) study (Zhang et al, 2020) reminds us of a basic principle of the Hippocratic oath (i.e. first do not harm aka ‘primum non nocere’) and resonates with a timely open question advanced by Carpenter and Buchanan (2020): ‘... as the clinical high-risk paradigm advances, will the field have sufficient wisdom to avoid antipsychotic medications until it is clear that the path of the individual is towards full psychosis?…”

Risks and Protective Factors of the Prodromal Stage of Psychosis: A Literature Review

“…This means that four patients would need to be treated to prevent one from progressing to psychosis over a six-month period, indicating that the intervention is relatively potent [ 20 ]. However, a most recently published article disagrees, as the administration of antipsychotics to UHR patients is potentially harmful, with no preventive benefits [ 21 ].…”

Subtypes of Clinical High Risk for Psychosis that Predict Antipsychotic Effectiveness in Long-Term Remission

“…APs, as the traditional and more accessible form of treatment for patients with psychosis, have been assumed to be effective in treating attenuated psychotic symptoms in CHR individuals in our sample. About 80 % of CHRs receive APs, with 68.7 % taking APs over the following 2 years [18]. Since no previous studies have examined whether symptom-or cognitionbased subtypes could be used to inform the decision to use AP treatment.…”