Early Intervention in Psychosis: A Brief Narrative Review

Abstract

Background:

Schizophrenia and other psychotic spectrum disorders cause significant impairment, and for long, therefore, the approach of management was early recognition and intervention for first-episode psychosis (FEP). As it became apparent that nonspecific symptoms precede full blown psychosis, it led to a shift towards early identification of prodrome and intervention to improve outcomes.

Purpose:

This narrative review discusses the current interventions aimed at preventing or delaying the onset of psychosis in high-risk individuals. It explored the various evidence bases for the role of both pharmacological and psychosocial intereventions, such as low-dose antipsychotics, cognitive behavioral therapy (CBT), family interventions, as well as emerging strategies like physical exercise, virtual reality, smartphone-based apps and neuromodulation. The review also discusses clinical challenges in identifying at-risk states as well as its treatment.

Collection and Analysis (Results):

Existing treatments show varying efficacy in preventing the onset of psychosis. While low-dose antipsychotics and CBT have demonstrated some success in reducing conversion rates to psychosis, long-term outcomes remain inconsistent. Emerging interventions offer promising potential but require further research. A multimodal approach, as demonstrated by programs like NAVIGATE, has proven effective in supporting functional recovery in individuals with FEP.

Conclusion:

Early identification and intervention in individuals at risk of psychosis are vital for improving outcomes. While current treatment options show potential, there are challenges, such as the wide variation in presenting symptoms and the need for individualised care. Clinical staging and transdiagnostic models could offer promising directions for developing more targeted interventions. However, more research is required to improve treatment strategies.

Introduction

Schizophrenia and other psychotic spectrum disorders are severe mental disorders that cause significant functional impairment in the individual as well as disability. For a long time, the approach was early recognition and treatment of first-episode psychosis (FEP). During this process, it was recognized that such patients often have prolonged periods of ambiguous symptoms and impairments before the onset of psychosis. Consequently, the approach has been changed to recognition of the prodromal phase and intervention to avert or delay the onset of psychosis along with early identification and treatment of the FEP to improve the outcome. ¹

“At Risk” States for Psychosis

Early recognition of the evolving illness before the development of persistent psychotic symptoms is an important factor in improving the overall prognosis. The prodrome is the stage of nonspecific symptoms preceding psychosis. It is diagnosed retrospectively only after the full-blown syndrome has developed. So, specific sets of “at risk” criteria for psychotic disorders were defined which include basic symptom criteria and ultrahigh-risk (UHR) criteria. The basic symptom criteria comprise cognitive–perceptual disturbances that are subtle disturbances in thought, cognition, and perception experienced by the self and seldom noticeable from the outside. The UHR criteria include attenuated psychotic symptoms (APS) and brief limited intermittent symptoms (BLIPS). APS refers to the experience of subthreshold-positive psychotic symptoms during the past year. BLIPS is a period of overt psychotic symptoms that end in less than a week and resolves on its own without treatment. ² This symptomatic state of impairment in function and quality of life resembles more to other coded psychiatric disorders and FEP as compared to healthy controls. ³

Over time, a significant percentage of individuals at clinically high risk for psychosis would experience a psychotic disorder; approximately 20% have a chance of developing psychosis over the next year. ⁴ A meta-analysis reported transition risk of 18%, 22%, 29%, and 36% after six months, one year, two years, and three years, respectively. ⁵ This states that there is a high risk of converting to psychosis within three years and the risk increases over time. There is also evidence that some patients develop other psychiatric illnesses rather than proceeding to psychosis. According to a long follow-up study, 68% of UHR patients did not progress to psychosis and developed nonpsychotic disorders, primarily mood disorders (49%), anxiety disorders (35%), and substance use disorder (29%), over a follow-up period of 2–14 years. Few patients developed eating disorder (4.9%) and somatoform disorder (2.7%). ⁶ In 28%–78% of those UHR patients who have not transitioned, APS have also been observed to persist over the long term which is associated with poor functioning. ⁷

Challenges Encountered in Diagnosing At-risk States

Clinicians encounter several difficulties while attempting to identify at-risk states. Applying risk criteria in early adolescence or childhood is challenging as this group has a heterogeneous presentation with a peculiar clinical presentation in each individual. ⁸ The majority of those who match the criteria for a psychosis risk syndrome also have symptoms and, or formal diagnoses of psychiatric disorders, such as mood and anxiety disorders, posttraumatic stress disorder, substance abuse, autism spectrum disorder or attention-deficit/hyperactivity disorder (ADHD). ⁹ Additionally, psychotic experiences are common in the normal population, with a mean lifetime prevalence of as much as approximately 6%. ¹⁰ This raises the dilemma of whether to consider these experiences as normal or a precursor of a psychiatric illness. Moreover, psychosis associated with mood disorders or due to physical disorders like epilepsy, hormonal problems or symptoms due to neurodevelopment disorders like ADHD are possible differential diagnoses that need to be addressed.

Interventions for Prevention of Psychosis

The majority of therapies for psychosis risk syndromes have addressed the individual while some have included the family as well. The interventions include antipsychotics (in low dose), cognitive behavioral therapy (CBT), combination of risperidone and CBT, polyunsaturated fatty acids (PUFAs), psychosocial interventions, and cognitive remediation.

Antipsychotics: Low-dose antipsychotics have proved efficacious in psychosis risk groups.^11,12 High doses have no preventive benefits.^13,14 High doses may even be harmful due to developmental vulnerability to side effects which often lead to nonadherence. ¹⁵

CBT: Nonpharmacological treatment options such as CBT have been explored, and meta-analysis supports the evidence of reducing the transition rates to psychosis.^16,17 CBT aims to assist the client in understanding their experiences, and their past and current stressors, developing coping skills, and making behavioral changes. ¹⁸ It also helps to deal with comorbid anxiety and depression. ⁹

Combination of risperidone and CBT: There is also evidence for a combination of the above two approaches, in which risperidone plus CBT has delayed or prevented the onset of psychosis. ¹²

Psychosocial interventions: Other psychosocial interventions include family interventions, teaching family members to apply CBT techniques at home and the significance of a healthy home environment by improving communication and support in the family.^19,20 When disturbances in the family system occur due to psychotic symptoms, families are frequently subjected to extreme stress. The declining functioning of the individual signifies a transition in family roles and causes anxiety for the whole family structure. The acknowledgment of this stress on the whole family system is a fundamental tenet of family interventions. ²¹

Polyunsaturated fatty acids: Many studies have demonstrated a substantial decrease in PUFAs in peripheral blood (plasma and erythrocyte membranes) of patients with schizophrenia at varying phases of the illness’s development (including extremely high-risk individuals, untreated first-episode patients, and chronic patients).^22–24 Indeed, long-chain omega-3 PUFAs as an intervention technique have been an area of interest; however, data to appreciate the clinical benefits remain insufficient.^25–27

Cognitive remediation: Cognitive impairment, especially verbal memory, executive functions, and social functions, is a hallmark of at-risk states. ²⁸ Impaired social cognition results in poor social functioning, which is an acknowledged risk factor for transition to psychosis. ²⁹ Thus, cognitive remediation seems to be a viable and promising option for improvement in cognition and functional outcomes as supported by recent meta-analysis.^30,31

The current evidence of literature for the abovementioned existing psychopharmacological approaches is limited by small sample size, single-group designs, high dropout rates, failed replication studies, and inconclusive results. ³²

Regarding the efficacy of these interventions, it has been found that the treatment options have decreased 12-month conversion rates to psychosis in comparison to treatment as usual. However, the medium- to longer-term findings have been inconsistent. ³³ There is support for early interventions but whether it is maintained remains questionable. ³⁴ A recent network meta-analysis revealed a lack of evidence to favor any specific intervention in prevention. At follow-ups, the effectiveness or difference in acceptability of one intervention over others or the effective duration and order of interventions is unclear. ³⁵

Guidelines for Clinical High-risk States for Prevention of Psychosis

Evidence-based guidelines on clinical high-risk states for psychosis have been made available by the European Psychiatric Association. ³³ The interventions should aim at preventing the persistence of functional deficits (educational, social, or vocational) and focus on early detection. It considers psychological (in particular CBT) in addition to pharmacological interventions to delay or avert an FEP in high-risk patients. A staged intervention ought to be utilized. It has recommended CBT as the first line, which should be coupled with low-dose second-generation antipsychotics if psychological treatment is found to be ineffective. The antipsychotic should be used for symptom control for a short duration only. Further, current individual needs as well as comorbidities such as depression and anxiety should be appropriately addressed and treated as per their respective treatment guidelines. Additionally, the current evidence of the predictive value of conversion and efficacy of interventions in children and young adolescents is insufficient to rationalize primarily preventive interventions. The emphasis is laid upon the need for assessment of high-risk individuals for extended periods (up to three years) and modification of intervention as per need.

Interventions for Psychosis

Individuals with FEP have been treated mainly with antipsychotics and with psychosocial interventions that are mostly based on evidence-based strategies for treating schizophrenia. CBT works well for positive symptoms, social skills training for negative symptoms, and cognitive remediation for all symptoms along with psychoeducation about the illness and treatment adherence.^36,37

Challenges in Treatment

Even though constant efforts are made to prevent and delay progression, there are many factors that impede the treatment process. There is a wide range of presenting symptoms of varying severity which demand continuous need to modify the treatment. As the response to treatment depends on the presenting symptoms, the “one-size-fits-all” approach proves futile. Comorbid substance use, presence of stressors, history of traumatic past experiences as well stressors beyond coping such as homelessness are barriers to effective treatment.^38,39 Negative symptoms, cognitive deficits and decline in social and occupational functioning often exist in these individuals due to which engagement and response to therapy are hampered. ²¹ Cultural and ethnic factors also influence experiences of psychosis risk syndrome, the willingness to engage in psychiatric treatment and seeking alternative options such as religious practices. ⁴⁰ Though preliminary evidence indicated that early intervention works in adolescents, and despite early detection attempts, the duration of untreated psychosis in adolescents was distinctly longer than in adults; multiple reasons for which were speculated.^41,42

Keeping these challenges in mind, a comprehensive multimodal program has been developed by the US healthcare system to address a variety of issues in FEP. NAVIGATE program was developed as part of the Recovery After an Initial Schizophrenia Episode Early Treatment therapy. ⁴³ The program’s name, NAVIGATE, reflects its mission to support and guide people experiencing their FEP toward psychological and functional recovery by either offering these services directly to them or assisting them in obtaining them from the mental health system. A large-scale randomized controlled trial with 34 locations spread across 21 states in the United States was created to evaluate the NAVIGATE program to standard community services. The subjects underwent at least two years of follow-up. The program primarily targets those between the ages of 15 and 40 years, as this is the window of time when schizophrenia spectrum disorders are most likely to manifest. It is meant for both, those whose acute psychosis has subsided or stabilized and those who are still symptomatic from their initial episode. It provides four core treatment services, namely, individualized medication treatment, family psychoeducation, individual resilience training, supported employment, and education. A comparison of NAVIGATE with clinician-choice treatment revealed a reduction in PANSS scores, better adherence, improved quality of life, psychosis and depressive symptom outcomes, and more participation in work/school than usual care. ⁴⁴

Newer Options for Intervention

Numerous initiatives are underway to investigate potential intervention avenues along the development trajectory. Some of the notable ones include physical exercise, smartphone-based apps, virtual reality (VR), neuromodulation, and other psychotropics.

Physical exercise: Considering that high-risk groups participate less in indoor and outdoor activities, strength training, and activities that require social interaction, it is a rational choice to include physical exercise as an intervention. A pilot study where 12 weeks of aerobic exercise (two to three times a week) for 30 min per session was administered to psychosis-risk individuals revealed a reduction in symptoms, improved social and neurocognitive functions, and increased functional connectivity between the occipital cortex and left hippocampus after exercise. ⁴⁵ Physical activity has a potential correlation to a lesser risk of incident psychosis, according to crude analysis; however, the evidence is limited by a small number of studies. ⁴⁶

Phone applications: The popularity of smartphone apps is being utilized for their ease of accessibility and availability to monitor mood changes, triggering factors or sleep disturbances ensuring greater adherence.^47,48 A recent systematic review highlighted user engagement and interest among patients, the correlation between app assessments and clinical outcomes, and the potential of these apps to advance care in prodromal and early course schizophrenia. ⁴⁹

Virtual reality: Virtual reality has been used in psychiatric disorders using audio-visual, somatosensory, olfactory, and haptic stimuli to enhance learning and general wellness, target deviant behaviors, or cognitive patterns as well as add recreation and entertainment.^50,51 VR can treat and diagnose psychosis and is a beneficial supplement to evidence-based treatments. ⁵² VR may enhance role and social functioning and its capacity to simulate interactive situations can facilitate evaluation of real-life responses to environmental stress. ³² In individuals with psychosis, VR has been used to test persecutory delusions in randomized controlled trials. ⁵³

Noninvasive brain stimulation: NIBS techniques such as tDCS have shown improvement in positive, negative, and cognitive symptoms of schizophrenia with a higher number of sessions producing a better response. ⁵⁴ Significant improvements in the severity of negative and cognitive symptoms have been observed with excitatory NIBS protocols over the left dorsolateral prefrontal cortex as evidenced in recent meta-analysis and systematic reviews.^55,56 Neuromodulation provides a plethora of techniques to target specific symptoms.

Other psychotropics: Other psychotropics such as antidepressants have been explored for targeting affective symptoms, but it is crucial to consider the risk of precipitating a manic episode and the presence of comorbid bipolar disorder with psychosis. ³² Evidence suggests that early antidepressant exposure in CHR leads to reduced conversion rates to psychosis later on. ⁵⁷

Transdiagnostic Approach and Clinical Staging

As stated earlier, subthreshold psychotic symptoms always do not precede an episode of frank psychosis.^58,59 Depression, anxiety, and poor functioning are common symptoms. ⁵⁹ The nature of mental illness is heterotypic, that is, the same disorder can have different clinical presentations and pluripotent, that is, similar symptoms may give rise to different psychiatric disorders. The diverse and unpredictable symptom patterns in early stages and their pluripotent nature have already been discussed in this article with respect to convertors and nonconvertors of at-risk states. This paved the way for a transdiagnostic approach which includes various input and output syndromes. ⁶⁰ It transcends or even abandons conventional diagnostic boundaries to offer fresh perspectives on how we could comprehend mental health problems. ⁶¹ The clinical identification approach for transdiagnostic preventive intervention trials comprises biopsychosocial interventions in combinations and/or sequences and targets the spectrum of presenting symptoms instead of focusing on a specific set of symptoms. Interventions have to be tailored according to the symptoms, response, and patient preference.

Clinical staging approaches emphasize where an individual may fall on a developmental trajectory (through stages) rather than the confines of diagnostic criteria and permit differentiation into broad psychopathology. The original clinical staging model of psychotic disorders consists of stages 0–4. Stage 0 is an at-risk but asymptomatic state, stage 1 is increasing severity to nonspecific symptoms, stage 2 is an attenuated syndrome full-threshold disorder, stage 3 is recurrence and persistence of illness, and stage 4 is a severe, unremitting illness. ⁶² The precise demarcation for stages to guide treatment modifications may hinge on the interconnection of psychopathological, psychological, and neurobiological factors. ⁶³

Conclusion

The purpose of intervention and prevention research is to alleviate the symptomology and delay and reduce the onset of psychosis. Numerous challenges exist in the early diagnosis and treatment of high-risk states. While both conventional and recent therapy modalities show promise in the prevention of psychosis, more research is still needed, and clinical staging models can help provide the path forward.