Do antidepressants prevent transition to psychosis in individuals at clinical high-risk (CHR-P)? Systematic review and meta-analysis

Raballo, Andrea; Poletti, Michele; Preti, Antonio

doi:10.1017/s0033291722001428

Cited by 17 publications

(14 citation statements)

References 88 publications

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“…These challenges are common in psychotherapy trials . The very low adherence to fluoxetine (26.8%) led to insufficient power, though its timing (6 months postbaseline) may have been too delayed to protect against transition to psychosis . Despite the moderate fidelity to CBCM, findings indicate that the greater the change in cognitive biases or vulnerabilities, the greater the clinical improvement across both treatment groups, suggesting the psychological target of CBCM may represent more of an outcome rather than mediating variable.…”

Section: Discussionmentioning

confidence: 70%

“…The current study (Staged Treatment in Early Psychosis [STEP]) aimed to evaluate the outcomes of a sequential multiple assignment randomized clinical trial (SMART) comprising support and problem solving (SPS), cognitive-behavioral case management (CBCM), and fluoxetine for individuals at ultrahigh risk for psychosis . These treatments and their sequence were selected due to their potential benefits and safety profile . The sequential treatment strategy, which examined the efficacy of escalating the intensity and duration of treatment for individuals who did not remit on a randomized basis, was expected to produce superior outcomes over 12 months than single-phase trials.…”

Section: Introductionmentioning

confidence: 99%

“…15 These treatments and their sequence were selected due to their potential benefits and safety profile. 15,21,22 The sequential treatment strategy, which examined the efficacy of escalating the intensity and duration of treatment for individuals who did not remit on a randomized basis, 15 was expected to produce superior outcomes over 12 months than single-phase trials. Hypotheses were as follows: Hypothesis 1.…”

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confidence: 99%

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A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis

McGorry,

Mei,

Amminger

et al. 2023

JAMA Psychiatry

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ImportanceClinical trials have not established the optimal type, sequence, and duration of interventions for people at ultrahigh risk of psychosis.ObjectiveTo determine the effectiveness of a sequential and adaptive intervention strategy for individuals at ultrahigh risk of psychosis.Design, Setting, and ParticipantsThe Staged Treatment in Early Psychosis (STEP) sequential multiple assignment randomized trial took place within the clinical program at Orygen, Melbourne, Australia. Individuals aged 12 to 25 years who were seeking treatment and met criteria for ultrahigh risk of psychosis according to the Comprehensive Assessment of At-Risk Mental States were recruited between April 2016 and January 2019. Of 1343 individuals considered, 342 were recruited.InterventionsStep 1: 6 weeks of support and problem solving (SPS); step 2: 20 weeks of cognitive-behavioral case management (CBCM) vs SPS; and step 3: 26 weeks of CBCM with fluoxetine vs CBCM with placebo with an embedded fast-fail option of ω-3 fatty acids or low-dose antipsychotic medication. Individuals who did not remit progressed through these steps; those who remitted received SPS or monitoring for up to 12 months.Main Outcomes and MeasuresGlobal Functioning: Social and Role scales (primary outcome), Brief Psychiatric Rating Scale, Scale for the Assessment of Negative Symptoms, Montgomery-Åsberg Depression Rating Scale, quality of life, transition to psychosis, and remission and relapse rates.ResultsThe sample comprised 342 participants (198 female; mean [SD] age, 17.7 [3.1] years). Remission rates, reflecting sustained symptomatic and functional improvement, were 8.5%, 10.3%, and 11.4% at steps 1, 2, and 3, respectively. A total of 27.2% met remission criteria at any step. Relapse rates among those who remitted did not significantly differ between SPS and monitoring (step 1: 65.1% vs 58.3%; step 2: 37.7% vs 47.5%). There was no significant difference in functioning, symptoms, and transition rates between SPS and CBCM and between CBCM with fluoxetine and CBCM with placebo. Twelve-month transition rates to psychosis were 13.5% (entire sample), 3.3% (those who ever remitted), and 17.4% (those with no remission).Conclusions and RelevanceIn this sequential multiple assignment randomized trial, transition rates to psychosis were moderate, and remission rates were lower than expected, partly reflecting the ambitious criteria set and challenges with real-world treatment fidelity and adherence. While all groups showed mild to moderate functional and symptomatic improvement, this was typically short of remission. While further adaptive trials that address these challenges are needed, findings confirm substantial and sustained morbidity and reveal relatively poor responsiveness to existing treatments.Trial RegistrationClinicalTrials.gov Identifier: NCT02751632

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Section: Discussionmentioning

confidence: 70%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis

McGorry,

Mei,

Amminger

et al. 2023

JAMA Psychiatry

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“…In this study, APs administration was associated with an increased risk of imminent conversion to psychosis; a possible explanation is that APs prescription may be a “red flag,” an indicator of a greater baseline severity that needs to be carefully monitored ( 112 ). Moreover, recent meta-analytical evidence with CHR-P individuals ( 113 ) displayed that being already exposed to antidepressants (ADs) treatment at intake was associated with a lower conversion rate to psychosis at follow-up. In discussing this result, it is relevant to consider that conversion to psychosis is based entirely on the progression of positive symptoms.…”

Section: Discussionmentioning

confidence: 99%

A network analysis of anxiety, depressive, and psychotic symptoms and functioning in children and adolescents at clinical high risk for psychosis

et al. 2022

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ObjectiveYouths at clinical high risk for psychosis (CHR-P) are characterized by a high prevalence of anxiety and depressive disorders. The present study aimed at developing and analyzing a network structure of CHR-P symptom domains (i.e., positive, negative, disorganization, and general subclinical psychotic symptoms), depressive and anxiety symptoms, and general functioning.MethodsNetwork analysis was applied to data on 111 CHR-P children and adolescents (Mage = 14.1), who were assessed using the Structured Interview for Prodromal Syndromes, the Children’s Depression Inventory, the Children’s Global Assessment Scale, and the Multidimensional Anxiety Scale for Children.ResultsIn the network, negative and disorganization symptoms showed the strongest association (r = 0.71), and depressive and anxiety symptoms showed dense within-domain connections, with a main bridging role played by physical symptoms of anxiety. The positive symptom cluster was not associated with any other node. The network stability coefficient (CS) was slightly below 0.25, and observed correlations observed ranged from 0.35 to 0.71.ConclusionThe lack of association between subclinical positive symptoms and other network variables confirmed the independent nature of subclinical positive symptoms from comorbid symptoms, which were found to play a central role in the analyzed network. Complex interventions should be developed to target positive and comorbid symptoms, prioritizing those with the most significant impact on functioning and the most relevance for the young individual, through a shared decision-making process. Importantly, the results suggest that negative and disorganization symptoms, as well as depressive and anxiety symptoms, may be targeted simultaneously.

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“…Recent meta-analytical evidence on CHR-P cohorts revealed that baseline exposure to antipsychotics or antidepressants has a tangible modulating effect on the longitudinal risk of transition to a first-episode of psychosis. Indeed, baseline exposure to antipsychotics is associated with a higher risk of transition to psychosis in comparison to antipsychotic-naïve individuals (29% v. 16%, risk ratio (RR) 1.47) (Raballo, Poletti, & Preti, 2020b), whereas baseline exposure to antidepressant is associated with a lower risk of transition to psychosis in comparison to antidepressant-naïve individuals (13.5% v. 21%, RR 0.71) (Raballo, Poletti, & Preti, 2023).…”

Section: Introductionmentioning

confidence: 99%

Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis

Raballo,

Poletti,

Preti

2023

Psychol. Med.

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Background Emerging meta-analytical evidence indicates that baseline exposure to antipsychotics and to antidepressants in individuals at clinical high-risk for psychosis (CHR-P) have opposite prognostic effects as regards imminent transition to psychosis, with antipsychotics associated with higher risk and antidepressants associated with a lower risk in comparison to not-exposed individuals. Despite their common use, baseline exposure to benzodiazepines (BDZ) in CHR-P has surprisingly received poor attention as a potential risk modulator for transition to psychosis. The current systematic review and meta-analysis were performed to fix such a knowledge gap. Methods Systematic scrutiny of Medline and Cochrane library, performed up to 31 December 2022, searching for English-language studies on CHR-P reporting numeric data about the sample, the transition outcome at a predefined follow-up time and raw data on BDZ baseline exposure in relation to such outcome. Results Of 1893 identified records, five studies were included in the systematic review and meta-analysis. The proportion of participants with exposure to BDZ at baseline ranged from 5.5% (one study) to 46.2%, with an average of 16.8%. At the end of the period of observation, i.e., the follow-up as reported in the study, 28.4% [95% confidence interval (CI) 19.7–39.1%] participants developed psychosis among the BDZ-exposed against 9.3% (7.3 to 11.9%) among the controls. CHR-P participants who were already under BDZ treatment at baseline had more than double chance of transition to psychosis than CHR-P participants who were BDZ-naïve. The risk ratio (RR) was 2.42 (95% CI 1.38–4.23) in the common effects model (z = 3.09; p = 0.002), and 2.40 (1.53 to 3.77) in the random-effects model (z = 5.40; p = 0.006; tau-squared = 0.0). There was no relevant heterogeneity: Cochran's Q = 1.49; df = 4; p = 0.828; I2 = 0.0% (95% CI 0.0–79%). Quality was good in four studies. Conclusions Ongoing BDZ exposure at inception in CHR-P is associated with a higher risk of transition to psychosis at follow up. This meta-analytic association, which echoes a similar effect of baseline antipsychotic exposure, plausibly indicates that the clinicians' prescription of pharmacological intervention captures some form of prognostically-relevant information (e.g. an anxiety permeated mental state requiring BDZ prescription) that are not adequately encompassed by current CHR-P categorical criteria.

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Do antidepressants prevent transition to psychosis in individuals at clinical high-risk (CHR-P)? Systematic review and meta-analysis

Cited by 17 publications

References 88 publications

A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis

A Sequential Adaptive Intervention Strategy Targeting Remission and Functional Recovery in Young People at Ultrahigh Risk of Psychosis

A network analysis of anxiety, depressive, and psychotic symptoms and functioning in children and adolescents at clinical high risk for psychosis

Baseline benzodiazepine exposure is associated with greater risk of transition in clinical high-risk for psychosis (CHR-P): a meta-analysis

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