Antipsychotic treatment in clinical high risk for psychosis: Iatrogenesis related to dopamine supersensitivity psychosis?

Abstract Background Antipsychotics are widely used for treating patients with psychosis, and target threshold psychotic symptoms. Individuals at clinical high risk (CHR) for psychosis are characterized by subthreshold psychotic symptoms. It is currently unclear who might benefit from antipsychotic treatment. Our objective was to apply a risk calculator (RC) to identify people that would benefit from antipsychotics. Methods Drawing on 400 CHR individuals recruited between 2011 and 2016, 208 individuals who received antipsychotic treatment were included. Clinical and cognitive variables were entered into an individualized RC for psychosis; personal risk was estimated and 4 risk components (negative symptoms-RC-NS, general function-RC-GF, cognitive performance-RC-CP, and positive symptoms-RC-PS) were constructed. The sample was further stratified according to the risk level. Higher risk was defined based on the estimated risk score (20% or higher). Results In total, 208 CHR individuals received daily antipsychotic treatment of an olanzapine-equivalent dose of 8.7 mg with a mean administration duration of 58.4 weeks. Of these, 39 (18.8%) developed psychosis within 2 years. A new index of factors ratio (FR), which was derived from the ratio of RC-PS plus RC-GF to RC-NS plus RC-CP, was generated. In the higher-risk group, as FR increased, the conversion rate decreased. A small group (15%) of CHR individuals at higher-risk and an FR >1 benefitted from the antipsychotic treatment. Conclusions Through applying a personal risk assessment, the administration of antipsychotics should be limited to CHR individuals with predominantly positive symptoms and related function decline. A strict antipsychotic prescription strategy should be introduced to reduce inappropriate use.

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

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867420969810 ◽

2020 ◽

pp. 000486742096981 ◽

Cited By ~ 1

Author(s):

TianHong Zhang ◽

LiHua Xu ◽

YanYan Wei ◽

XiaoChen Tang ◽

YeGang Hu ◽

...

Keyword(s):

High Risk ◽

Repeated Measures ◽

Antipsychotic Drugs ◽

Psychotic Symptoms ◽

First Episode ◽

Antipsychotic Treatment ◽

Positive Symptoms ◽

Clinical High Risk ◽

First Choice ◽

Functional Scores

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.

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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)

Australian & New Zealand Journal of Psychiatry ◽

10.1177/0004867420917449 ◽

2020 ◽

Vol 54 (7) ◽

pp. 696-706 ◽

Cited By ~ 4

Author(s):

TianHong Zhang ◽

LiHua Xu ◽

XiaoChen Tang ◽

YanYan Wei ◽

Qiang Hu ◽

...

Keyword(s):

High Risk ◽

Real World ◽

Negative Symptoms ◽

Low Dose ◽

Antipsychotic Treatment ◽

Positive Symptoms ◽

Clinical High Risk ◽

Small Subgroup ◽

Conversion Rates

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.

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