Longer Untreated Psychosis in Youth Associated With Worse Outcomes

So far, the clinical presentation of psychosis in childhood and adolescence has only been examined in a small number of studies which are limited by small sample sizes.
So far, the clinical presentation of psychosis in childhood and adolescence has only been examined in a small number of studies which are limited by small sample sizes.

Researchers from Denmark and New York have found that in patients who develop schizophrenia or psychoses as children or adolescents, leaving the psychosis untreated for longer periods was associated with poorer outcomes.

“The early detection and treatment of people at risk for — or in the earliest phases of — psychotic disorders is currently regarded as the most promising strategy to improve treatment outcome and long-term prognosis, and thus reduce the consequences of full-blown psychotic disorder in this population,”2,3 wrote Marie Stentebjerg-Olesen, MD, from the Child and Adolescent Mental Health Center in Copenhagen, Denmark and colleagues.

Because the information available on the clinical presentation of psychosis in childhood and adolescence is only examined in a small number of studies which are limited by small sample sizes, retrospectively defined samples, lack of standardized assessments for diagnostic evaluation, and mixing of data from first and multi-episode patients, more evidence is needed in order to work towards improving early detection in these populations and to create more effective treatment guidelines.

Dr Stentebjerg-Olesen and colleagues conducted a systematic review on studies conducted since 1990 that examined clinical characteristics and outcomes of children and adolescents with early-onset schizophrenia (EOS) spectrum psychosis. “We chose 1990 as the starting point [in order] to include only studies using either ICD-9/ICD-10 or Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV) criteria for schizophrenia (American Psychiatric Association 1994),” they wrote.

The goals of the study were to 1) describe clinical characteristics of patients with EOS; 2) examine the trajectories of illness, including diagnostic trajectories, symptomatic outcomes, and functional outcomes; 3) explore what might predict outcomes of illness and severity in the years soon after treatment began; and 4) compare data between adults and children/adolescents with schizophrenia, when the studies directly compared the two.

Dr Stentebjerg-Olesen and Pia Jeppesen, MD, PhD worked with an information specialist to choose eligible studies published since January 1, 1990 that reported non-retrospective data in children or adolescents who had been diagnosed with predominantly nonaffective psychosis.

Out of 1203 screened studies, 35 were eligible for inclusion in the review. These 35 studies represented 1506 patients at baseline and 773 at follow up (after a mean of 2.2 ± 1.7 years). Patients' mean age at baseline was 15.6 ± 1.9 years, and the mean age of psychosis onset was 14.5 ± 2.4 years. The mean duration of untreated psychosis was 17.2 ± 12.8 months. The mean percentage of males was 62.3% ± 10.8%.

At baseline, 89.0% of the patients had a diagnosis of schizophrenia spectrum psychosis, and comorbid psychiatric disorders were common. More than 90% of patients were treated with antipsychotic medications at baseline.

The researchers found that the duration of untreated psychosis was longer in early-onset psychosis compared with adult-onset psychosis, and that worse premorbid adjustment predicted more negative symptoms and higher illness severity at follow-up.

“The findings that duration of untreated psychosis was longer in early-onset psychosis than in adult-onset psychosis, and that longer duration of untreated psychosis as well as poorer premorbid adjustment predicted a less favorable outcome, emphasize the importance of early intervention strategies in order to improve long-term outcome of early-onset psychosis,” the authors wrote.

The researchers noted that the “severe delay” in recognizing psychosis in youth may be explained by several factors, including a lack of specificity in early stages of psychosis, gradual onset, presence of comorbid, nonpsychotic disorders, and a lack of clinical training in identifying psychotic disorders in youth.

Clinical Significance

The findings from this study show that psychosis in children and adolescents may be masked by negative and disorganized symptoms, and by co-occurring nonpsychotic mental disorders. This, along with the finding that longer durations of untreated psychosis leads to worse outcomes, emphases the need to detect and treat psychosis early in youth. In youth with signs of psychosis, comorbid conditions such as ADHD/disruptive behavior disorders, substance abuse, and PTSD may be helpful to target.

“More prospective studies and longer-term studies are needed in order to identify the best early identification and treatment strategies to improve outcome and functioning in youth with early-onset psychosis,” the authors concluded.

Limitations

The studies included in this review had varying designs, sampling, assessments, duration of follow-up, and reporting of specific data.

The number of studies in this analysis and the corresponding number of patients were limited, and often did not provide enough data for inferential statistics or generalizability. This also made exploratory analyses vulnerable to selection biases and unadjusted confounding.

Only studies with >50% nonaffective psychosis were included in this review to avoid including patients who may not have a predominantly psychotic disorder, which could bias results toward potentially more positive outcomes.

Outcomes were influenced by varying treatments given in each of the individually included studies.

Disclosures

Dr Fink-Jensen has received grant support from Novo Nordisk A/S. Dr Correll has been a consultant and/or advisor to or has received honoraria from: Bristol-Myers Squibb (BMS), Eli Lilly, Genentech, Gerson Lehrman Group, IntraCellular Therapies, Janssen/J&J, Lundbeck, MedAvante, Medscape, Otsuka, Pfizer, ProPhase, Roche, Sunovion, Supernus, and Takeda. He has received grant support from the American Academy of Child and Adolescent Psychiatry BMS, Janssen/J&J, National Institute of Mental Health (NIMH), Novo Nordisk A/S, Otsuka, Takeda, and the Thrasher Foundation.


References

1. Stentebjerg-Olesen Marie, Pagsberg Anne K., Fink-Jensen Anders, Correll Christoph U., and Jeppesen Pia. Clinical Characteristics and Predictors of Outcome of Schizophrenia-Spectrum Psychosis in Children and Adolescents: A Systematic Review. J Child Adol Psychop. 2016;26(5): 410-427. doi:10.1089/cap.2015.0097.

2. Marshall M, Lewis S, Lockwood A, Drake R, Jones P, Croudace T. Association between duration of untreated psychosis and outcome in cohorts of first-episode patients: A systematic review. Arch Gen Psychiatry. 2005;62:975–983.

3. Schimmelmann BG, Walger P, Schultze–Lutter F: The significance of at-risk symptoms for psychosis in children and adolescents. Can J Psychiatry. 2013;58:32–40.

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