Five-fold increased risk of relapse following breaks in antipsychotic treatment of first episode psychosis

Winton-Brown, Toby; Elanjithara, Thomas; Power, Paddy; Coentre, Ricardo; Blanco-Polaina, Pablo; McGuire, Philip

doi:10.1016/j.schres.2016.09.029

Cited by 38 publications

(37 citation statements)

References 31 publications

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“…In a systematic review and meta‐analysis of longitudinal studies examining relapse and its risk factors in patients following stabilization after a first psychotic episode, non‐adherence was found to be the greatest predictor of relapse among twenty variables in seven long‐term studies, increasing the chance of relapse by 400%. Individuals in another study with non‐adherence for >1 month of an 18‐month follow‐up had a five‐fold greater chance of relapse than individuals with continuous treatment.…”

Section: Efficacy Effectiveness and Tolerabilitymentioning

confidence: 92%

What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?

2018

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The long-term benefit-to-risk ratio of sustained antipsychotic treatment for schizophrenia has recently been questioned. In this paper, we critically examine the literature on the long-term efficacy and effectiveness of this treatment. We also review the evidence on the undesired effects, the impact on physical morbidity and mortality, as well as the neurobiological correlates of chronic exposure to antipsychotics. Finally, we summarize factors that affect the risk-benefit ratio. There is consistent evidence supporting the efficacy of antipsychotics in the short term and mid term following stabilization of acute psychotic symptoms. There is insufficient evidence supporting the notion that this effect changes in the long term. Most, but not all, of the long-term cohort studies find a decrease in efficacy during chronic treatment with antipsychotics. However, these results are inconclusive, given the extensive risk of bias, including increasing non-adherence. On the other hand, long-term studies based on national registries, which have lower risk of bias, find an advantage in terms of effectiveness during sustained antipsychotic treatment. Sustained antipsychotic treatment has been also consistently associated with lower mortality in people with schizophrenia compared to no antipsychotic treatment. Nevertheless, chronic antipsychotic use is associated with metabolic disturbance and tardive dyskinesia. The latter is the clearest undesired clinical consequence of brain functioning as a potential result of chronic antipsychotic exposure, likely from dopaminergic hypersensitivity, without otherwise clear evidence of other irreversible neurobiological changes. Adjunctive psychosocial interventions seem critical for achieving recovery. However, overall, the current literature does not support the safe reduction of antipsychotic dosages by 50% or more in stabilized individuals receiving adjunctive psychosocial interventions. In conclusion, the critical appraisal of the literature indicates that, although chronic antipsychotic use can be associated with undesirable neurologic and metabolic side effects, the evidence supporting its long-term efficacy and effectiveness, including impact on life expectancy, outweighs the evidence against this practice, overall indicating a favorable benefit-to-risk ratio. However, the finding that a minority of individuals diagnosed initially with schizophrenia appear to be relapse free for long periods, despite absence of sustained antipsychotic treatment, calls for further research on patient-level predictors of positive outcomes in people with an initial psychotic presentation.

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Section: Efficacy Effectiveness and Tolerabilitymentioning

confidence: 92%

What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?

2018

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“…Importantly, the patients included in these trials had all experienced a clinical or functional remission that was sustained for six or 18 months (i.e., clinical stage 2). Discontinuing antipsychotic treatment before remission is achieved (e.g., for the clinical stage 3) is associated with higher time to remission and later risk of relapse.…”

Section: Early Intervention and Secondary/tertiary Preventionmentioning

confidence: 99%

Improving outcomes of first‐episode psychosis: an overview

2017

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Outcomes of psychotic disorders are associated with high personal, familiar, societal and clinical burden. There is thus an urgent clinical and societal need for improving those outcomes. Recent advances in research knowledge have opened new opportunities for ameliorating outcomes of psychosis during its early clinical stages. This paper critically reviews these opportunities, summarizing the state-of-the-art knowledge and focusing on recent discoveries and future avenues for first episode research and clinical interventions. Candidate targets for primary universal prevention of psychosis at the population level are discussed. Potentials offered by primary selective prevention in asymptomatic subgroups (stage 0) are presented. Achievements of primary selected prevention in individuals at clinical high risk for psychosis (stage 1) are summarized, along with challenges and limitations of its implementation in clinical practice. Early intervention and secondary prevention strategies at the time of a first episode of psychosis (stage 2) are critically discussed, with a particular focus on minimizing the duration of untreated psychosis, improving treatment response, increasing patients' satisfaction with treatment, reducing illicit substance abuse and preventing relapses. Early intervention and tertiary prevention strategies at the time of an incomplete recovery (stage 3) are further discussed, in particular with respect to addressing treatment resistance, improving well-being and social skills with reduction of burden on the family, treatment of comorbid substance use, and prevention of multiple relapses and disease progression. In conclusion, to improve outcomes of a complex, heterogeneous syndrome such as psychosis, it is necessary to globally adopt complex models integrating a clinical staging framework and coordinated specialty care programmes that offer pre-emptive interventions to high-risk groups identified across the early stages of the disorder. Only a systematic implementation of these models of care in the national health care systems will render these strategies accessible to the 23 million people worldwide suffering from the most severe psychiatric disorders.

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“…In other words, although medication adherence is a complex phenomenon—influenced by factors related to the patient, illness characteristics, medication, and the environment —the experience of the CHR state may itself leave an imprint on subsequent adherence to antipsychotic medication in those who convert to FEP. Furthermore, symptomatology, functioning, and many other clinical outcomes—poor quality of life , psychotic relapse or hospitalization , increased risk of suicide , violence , deterioration of functioning , and possible development of resistance to treatment —have repeatedly been associated with medication non‐adherence. One example of this is that discontinuation of antipsychotic medication in a remitted first episode psychosis sample was found to confer a five‐fold increase in risk of psychotic relapse over a 5‐year period .…”

Section: Introductionmentioning

confidence: 99%

Medication adherence in first episode psychosis: the role of pre‐onset subthreshold symptoms

Daneault

Maraj

Lepage

et al. 2019

Acta Psychiatr Scand

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JL. Medication adherence in first episode psychosis: the role of pre-onset subthreshold symptomsObjective: The experience of pre-onset subthreshold psychotic symptoms (STPS, signifying a clinical high-risk state) in first episode psychosis (FEP) predicts poorer outcomes during treatment, possibly through differential adherence to medication. We explored whether adherence differs between FEP patients with and without pre-onset STPS. Methods: Antipsychotic medication adherence was compared in 263 STPS+ and 158 STPSÀ subjects in a specialized early intervention program for FEP. Data were gathered from a larger observational study conducted between 2003 and 2016. STPS status, sociodemographic, and baseline clinical variables were tested as predictors of non-adherence using univariate and multivariate logistic regressions. Time to onset of non-adherence was analyzed using Kaplan-Meier curves. The same predictors were tested as predictors of time to onset of non-adherence using Cox regression models. Results: Medication non-adherence was higher in STPS+ participants (78.9% vs. 68.9%). STPS status (OR 1.709), substance use disorder (OR 1.767), and milder positive symptoms (OR 0.972) were significant baseline predictors of non-adherence. Substance use disorder (HR 1.410), milder positive symptoms (HR 0.990), and lack of contact between the clinical team and relatives (HR 1.356) were significant baseline predictors of time to nonadherence. Conclusion: FEP patients who experience pre-onset STPS are more likely to be non-adherent to antipsychotic medication over 2 years of intervention. FEP programs should routinely evaluate pre-onset symptomatology to deliver more personalized treatments, with emphasis on engaging both patients and family members from the beginning of care. Significant outcomes• The experience of pre-onset subthreshold psychotic symptoms (STPS) was associated with higher rates of antipsychotic medication non-adherence over the first 2 years of treatment in a specialized early intervention program for first episode psychosis (FEP).• There was no difference in insight at baseline between FEP patients who had experienced pre-onset STPS and those who had not.• Substance use disorder at baseline, milder positive symptoms at baseline, and lack of contact between the clinical team and relatives at baseline were also associated with non-adherence. Limitations• Some (n = 182) patients provided consent for research but did not complete assessments required for assignment of STPS status and thus could not be included in the analyses. These may represent a subset of patients who are less engaged in services and less adherent to medication.• As with all retrospective instruments, the CORS and TOPE (used to determine STPS status) are potentially susceptible to recall bias.• The PANSS-G12, used to measure insight, may conflate several concepts in a one-dimensional measure.

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Five-fold increased risk of relapse following breaks in antipsychotic treatment of first episode psychosis

Cited by 38 publications

References 31 publications

What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?

What is the risk‐benefit ratio of long‐term antipsychotic treatment in people with schizophrenia?

Improving outcomes of first‐episode psychosis: an overview

Medication adherence in first episode psychosis: the role of pre‐onset subthreshold symptoms

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