People with a first episode of psychosis experience distressing symptoms such as unusual beliefs or abnormal behaviour (positive symptoms) and/or withdrawal or loss of interest in work or school (negative symptoms). Early intervention programs for schizophrenia and psychosis often combine many elements comprising both pharmaceutical and psychosocial therapies, and may involve enriched therapies that are tailored to an individual’s needs. The conclusions presented here are based on group data, and as such individual treatment programs need to be tailored by trained clinicians. Individual response to treatment can vary in terms of both symptoms and adverse effects.

What is the evidence on medications for first-episode psychosis?

For targeted early intervention services that include both antipsychotics and psychosocial components, moderate to high quality evidence finds small effects of greater improvements in symptoms, functioning, quality of life, and more remission and recovery than with treatment as usual.

Overall, there is a reasonable response to antipsychotics after a first-episode of psychosis; moderate quality evidence finds antipsychotics are associated with an 81% response rate when measured as a 20% reduction in symptoms, and a 52% response rate when measured as a 50% reduction in symptoms. For specific antipsychotics, high quality evidence finds greater improvement in overall symptoms with olanzapine than with haloperidol, and moderate to high quality evidence finds greater improvement in negative symptoms with olanzapine than with haloperidol, with no differences in positive symptoms. Moderate to high quality evidence finds greater improvement in overall symptoms with amisulpride or risperidone than with haloperidol. Moderate quality evidence finds greater improvement in overall symptoms with amisulpride than with quetiapine, and with ziprasidone than with haloperidol. There was greater improvement in negative symptoms with olanzapine than with risperidone, and greater improvement in positive symptoms with olanzapine than with quetiapine. There was greater improvement in both positive and negative symptoms with quetiapine than with haloperidol, and greater improvement in positive symptoms with risperidone than with quetiapine.

For relapse prevention, moderate to high quality evidence finds small effects of fewer relapses and hospitalisations with targetted early intervention services. Second-generation antipsychotics in general were found to be more effective than first-generation antipsychotics. Moderate quality evidence finds relapse and rehospitalisation rates were higher after discontinuation rather than maintenance of antipsychotics in people in remission following a first-episode of psychosis.

For treatment adherence, moderate to high quality evidence finds less all-cause discontinuation with targeted early intervention services. There was less all-cause discontinuation with risperidone than with haloperidol and less all-cause discontinuation with quetiapine than with haloperidol. Moderate to low quality evidence finds less all-cause discontinuation with aripiprazole or olanzapine than with haloperidol.

For side effects, olanzapine was associated with at least one use of drugs to treat parkinsonian symptoms. Quetiapine was associated with less akathisia than haloperidol, aripiprazole, risperidone, and olanzapine. Molindone resulted in less weight gain than risperidone, haloperidol, and olanzapine and less increase in prolactin release than risperidone.

October 2020

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After being identified as having high-risk mental states, or after an initial diagnosis of psychosis, relevant outcomes over the years following include transition to psychosis or schizophrenia, symptom severity, recovery and remission, relapse, employment, functioning, relationships, and quality of life. Investigating these outcomes and the factors influencing them provides insight into early treatment strategies.

What is the evidence for outcomes in people with first-episode psychosis or high-risk mental states?

Moderate quality evidence suggests up to 80% of people have good or intermediate outcomes following a first episode of psychosis (follow-up was for 3 years). Positive outcomes include lack of relapse or rehospitalisation, more employment, more insight and clarity, and improved relationships with family and friends. Predictors of good outcomes include being treated with a combination of pharmacotherapy and psychosocial therapy, and being from a developing rather than a developed country. Predictors of poor outcome include being treatment-naive, being medicated with first generation rather than second generation antipsychotics, and having depressive symptoms.

For people with first-episode psychosis or schizophrenia and a current substance use disorder, moderate to high quality evidence suggests worse positive and depressive symptoms, and worse global functioning compared to people with first-episode psychosis or schizophrenia and a former, or no history of a substance use disorder. Moderate quality evidence also suggests an increased risk of relapse, re-hospitalisation, and treatment non-adherence, particularly if using cocaine, opiates, or ecstasy.

Moderate quality evidence indicates the average risk of transition to full psychotic episode in people at high clinical risk of psychosis is ~24-29%. Studies assessing psychosocial treatments or antipsychotics reported lower transition rates than studies assessing standard care or no antipsychotics. People with brief, limited or intermittent psychotic symptoms have higher transition rates to full psychosis than people with attenuated or milder psychotic symptoms, who in turn have higher transition rates than people with genetic vulnerability and a marked decline in functioning. Neurocognitive deficits, negative and disorganisation subclinical symptoms, but not positive subclinical symptoms, are associated with poor functioning in people with high-risk mental states.

August 2020

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