How effective are early interventions in psychosis services?

According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), psychosis is a common symptom in a spectrum of psychotic disorders including schizophrenia and delusional disorder (American Psychiatric Association, 2013; Arciniegas, 2015). Classified as a clinical syndrome rather than a nosological entity (or distinct disease), psychosis is characterised by clinical features such as hallucinations, disordered thinking, impaired motor functions, delusions, emotional distress, as well as negative symptoms (Gaebel & Zielasek, 2015), which include a diminished emotional range, a lack of motivation, and other deficits in social interactions (Downs et al., 2018). As reported by a recent meta-analysis based on 73 studies published over a 25-year period, its median lifetime prevalence is 7.49 per 1000 persons (Moreno-Küstner et al., 2018).

While psychotic disorders are still poorly understood, there is a growing consensus amongst researchers that they are neurodevelopmental in nature, which means that they are due to an either abnormal development or by damage of the brain at an early age (Jaaro-Peled et al., 2009; Lewis & Levitt, 2002). A neurodevelopmental model of psychotic disorders posits four main stages in the progression of psychotic disorders: the risk stage, which typically occurs before 12; the prodomal stage, between 12 and 18 years old; the psychosis stage, usually between 18 and 24 years old; and the chronic disability stage, in individuals over 24 years old (Insel, 2010). This trajectory suggests a new approach to the treatment of psychotic disorders, where the psychosis of late teenage years corresponds to the late stage of the disorder, and where intervention should begin as early as possible, if possible at the risk stage.

To that effect, early interventions in psychosis services were introduced in the UK in 1999, with the aims of preventing psychosis in high-risk individuals, reducing the duration of untreated psychosis, providing prompt treatment – both pharmacological and psychological – and involving families in care in order to improve outcomes (Neale & Kinnair, 2017).

Early interventions include family and individual psychoeducation, vocational support, help in reducing substance misuse, and in some instances prescription of clozapine in case of late or incomplete recovery (Fusar‐Poli, 2017). The variation in early intervention services provision and implementation across the world makes it complex to evaluate their effectiveness, but several studies have attempted to review the evidence.

Petersen et al. (2005) conducted the largest of such studies, comparing early interventions with standard care through a randomised controlled trial where 547 individuals with a schizophrenia spectrum diagnosis not previously treated with antipsychotic medication were separated into two groups: early intervention, which included psychological therapies and social skills training (experimental group) and treatment as usual, which consisted of regular community mental health services (control group).

The study found significantly better results with the experimental group during the two-year duration of the intervention, but no statistically significant difference between the two groups ten years later. It is worth noting that a follow-up study with a five-year treatment found no significant difference between experimental and control groups, but these contradictory results could be attributed to the fact that many early interventions attributes such as psychoeducation and family involvement have since become mandatory in community mental health services (Albert et al., 2017).

Furthermore, a Cochrane systematic review was conducted to evaluate the effectiveness of early intervention services, including early detection and phase-specific treatments in individuals with prodromal symptoms or first-episode psychosis (Marshall & Rathbone, 2011). The study demonstrated emerging evidence for early intervention services for individuals with first-episode psychosis, but questioned whether gains were maintained over the long term.

Beside the limited amount of evidence, early interventions in psychosis pose additional challenges, such as the management of comorbidities, or the inherent difficulties in correctly diagnosing a patient considering the broad spectrum of psychotic disorders (Hayes & Kyriakopoulos, 2018). In the future, true early intervention may be based on complex risk profiles including environmental and genetic factors to detect at-risk individuals in the earliest stages of psychotic disorders.

Although this is an exciting area of research, there is currently no effective method to reduce the risk of psychosis in asymptomatic individuals (Seidman & Nordentoft, 2015). At present, the evidence suggests that in order to assess the effectiveness of early interventions in psychosis services, research needs to be replicated with larger and longer trials.

References:

Albert, N., Melau, M., Jensen, H., Emborg, C., Jepsen, J. R. M., Fagerlund, B., … & Nordentoft, M. (2017). Five years of specialised early intervention versus two years of specialised early intervention followed by three years of standard treatment for patients with a first episode psychosis: randomised, superiority, parallel group trial in Denmark (OPUS II). bmj356, i6681.

American Psychiatric Association. (2013). Anxiety Disorders. Diagnostic and statistical manual of mental disorders (5th ed.).

Arciniegas, D. B. (2015). Psychosis. Continuum: Lifelong Learning in Neurology21(3 Behavioral Neurology and Neuropsychiatry), 715.

Downs, J., Dean, H., Lechler, S., Sears, N., Patel, R., Shetty, H., … & Arango, C. (2018). Negative symptoms in early-onset psychosis and their association with antipsychotic treatment failure. Schizophrenia bulletin45(1), 69-79.

Fusar‐Poli, P., McGorry, P. D., & Kane, J. M. (2017). Improving outcomes of first‐episode psychosis: an overview. World Psychiatry16(3), 251-265.

Gaebel, W., & Zielasek, J. (2015). Focus on psychosis. Dialogues in clinical neuroscience17(1), 9.

Hayes, D., & Kyriakopoulos, M. (2018). Dilemmas in the treatment of early-onset first-episode psychosis. Therapeutic advances in psychopharmacology8(8), 231-239.

Insel, T. R. (2010). Rethinking schizophrenia. Nature468(7321), 187.

Reichenberg, A., Caspi, A., Harrington, H., Houts, R., Keefe, R. S., Murray, R. M., … & Moffitt, T. E. (2009). Static and dynamic cognitive deficits in childhood preceding adult schizophrenia: a 30-year study. American Journal of Psychiatry,167(2), 160-169.

Jaaro-Peled, H., Hayashi-Takagi, A., Seshadri, S., Kamiya, A., Brandon, N. J., & Sawa, A. (2009). Neurodevelopmental mechanisms of schizophrenia: understanding disturbed postnatal brain maturation through neuregulin-1–ErbB4 and DISC1. Trends in neurosciences32(9), 485-495.

Lewis, D. A., & Levitt, P. (2002). Schizophrenia as a disorder of neurodevelopment. Annual review of neuroscience25(1), 409-432.

Marshall, M., & Rathbone, J. (2011). Early intervention for psychosis. Cochrane Database of Systematic Reviews, (6).

Moreno-Küstner, B., Martin, C., & Pastor, L. (2018). Prevalence of psychotic disorders and its association with methodological issues. A systematic review and meta-analyses. PloS one13(4), e0195687.

Neale, A., & Kinnair, D. (2017). Early intervention in psychosis services. Br J Gen Pract67(661), 370-371.

Petersen, L., Jeppesen, P., Thorup, A., Abel, M. B., Øhlenschlæger, J., Christensen, T. Ø., … & Nordentoft, M. (2005). A randomised multicentre trial of integrated versus standard treatment for patients with a first episode of psychotic illness.Bmj331(7517), 602.

Seidman, L. J., & Nordentoft, M. (2015). New targets for prevention of schizophrenia: is it time for interventions in the premorbid phase?. Schizophrenia bulletin41(4), 795-800.

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