23% of people experiencing a first episode of psychosis (FEP) develop treatment resistant schizophrenia (TRS). At present, there are no established methods to accurately identify who will develop TRS from baseline.

In this study we used patient data from three UK early intervention services (EIS) to investigate the predictive potential of routinely recorded sociodemographic, lifestyle and biological data at FEP baseline for the risk of TRS up to six years later.

We developed two risk prediction algorithms to predict the risk of TRS at 2-8 years from FEP onset using commonly recorded information at baseline. Using the forced-entry method, we created a model including age, sex, ethnicity, triglycerides, alkaline phosphatase levels and lymphocyte counts. We also produced a machine-learning-based model, including an additional four variables. The models were developed using data from two and externally validated in another UK psychosis EIS.

The development samples included 785 patients, and 1,110 were included in the validation sample. The models discriminated TRS well at internal validation (forced-entry: C 0.70, 95%CI 0.63-0.76; LASSO: C 0.69, 95%CI 0.63-0.77). At external validation, discrimination performance attenuated (forced-entry: C 0.63, 0.58-0.69; LASSO: C 0.64, 0.58-0.69) but recovered for the forced entry model after recalibration and revision of the lymphocyte predictor (C: 0.67, 0.62-0.73).

The use of commonly recorded clinical information including biomarkers taken at FEP onset could help to predict TRS. These measures should be considered in future studies modelling psychiatric outcomes.

No significant relationships.

The usage of clozapine in patients with schizophrenia and epilepsy raises many challenges due to the epileptogenic effects of the drug. There is little data about using clozapine for treatment of treatment-resistant schizophrenia (TRS) accompanied by epilepsy.

To present a case report illustrating a patient diagnosed with epilepsy and TRS, successfully treated with clozapine.

A literature review on “PubMed” database was conducted, using the keywords: clozapine, antipsychotics, epilepsy, seizures, psychoses. Information regarding the clinical case was obtained by consulting the patient’s file.

We present a woman, 33 years old with mild intellectual disability and a 10-year history of schizophrenia. At the age of 24, the patient lost consciousness and experienced tonic – clonic seizure, but epilepsy was not diagnosed. The patient was hospitalized multiple times due to positive symptoms of schizophrenia and suicidal thoughts. Various combinations of neuroleptics and electroconvulsive therapy were used for treatment without therapeutic effect. At the age of 32, a diagnosis of TRS was established, leading to treatment with a moderate clozapine dose (400mg/day). At the fifth month of treatment with clozapine un episode of generalized seizures occurred, leading to a diagnosis of idiopathic generalized epilepsy. Since then, the patient was treated with levetiracetam and the dosage of clozapine was lowered to 275mg/d. The seizures did not re-occur and clinical response to the psychiatric treatment was positive.

This case report highlights how clozapine can be used safely and effectively for patients with TRS and epilepsy and how the epileptogenic effects can be moderated by using antiepileptics in the overall treatment scheme.

No significant relationships.

To systematically review the literature on barriers to the use of clozapine and identify any interventions for optimizing clozapine use in treatment-resistant schizophrenia. Journal databases were searched from 1972 to March 2018. The following search terms were used: treatment-resistant schizophrenia, clozapine, barriers, use, prescription rates, implementation, clozaril and prescribing practices. Following a review of the literature, 15 papers were included in the review.

The major barriers that were identified included mandatory blood testing, fear of serious side-effects and lack of adherence by the patients, difficulty in identifying suitable patients, service fragmentation, and inadequate training in or exposure to using clozapine.

In view of consistent evidence across the studies on inadequate knowledge and skills as a significant barrier, we suggest that a certification requiring competence in initiating and managing side-effects of clozapine becomes a mandatory requirement in training programmes.

None.