Care with clozapine

Clozapine can be a lifeline for people with treatment-resistant schizophrenia. Yet the difficulty of monitoring, and serious physical health side-effects, often give pause for thought when prescribing. Authors of a recent BJPsych research paper (Casetta et al in the September Reference Casetta, Oloyede, Whiskey, Taylor, Gaughran and Shergill2020 issue)¹ suggested there might be a role for intramuscular clozapine in treatment initiation and maintenance for patients with schizophrenia who were non-adherent with the oral form. Bhattacherjee et al (pp. 357–358) respond in their Editorial this month urging caution – citing the risks that might be associated with intramuscular use, such as fatal administration errors, and the availability of other antipsychotic options with more robust safety data.

Another research paper this month may add weight to Bhattacherjee et al's argument. In their retrospective cohort study Govind et al (pp. 368–374) ask whether clozapine use increases the risk of coronavirus disease 2019 (COVID-19) infection – a pertinent question given clozapine's potential to cause suppressed immunity and an increased risk of pneumonia. They found that people with a diagnosis of schizophrenia spectrum disorder taking clozapine were significantly more likely to test positive for COVID-19 than those on other antipsychotics (with an adjusted hazard ratio of 1.76).

Hemispheres, networks and vicious circles

What of risks of developing schizophrenia in the first place? As genetic studies gather pace identifying increasing numbers of schizophrenia-related risk genes, Zhu et al (pp. 392–400) contribute the first combined genetic imaging study to investigate hemispheric asymmetry in patients with schizophrenia. They identify specific genes associated with abnormalities in white matter networks – including genes involved with signal transduction, neural development, neuron structure and calcium signalling pathways – perhaps offering future targets for intervention.

It has long been known that methamphetamine increases risk of psychosis. But is the reverse true? A prospective cohort study of 201 regular methamphetamine users by Hides et al (pp. 361–367) found a significant bidirectional relationship between psychotic symptoms and methamphetamine use – psychosis also makes methamphetamine use more likely, leading to a potential complicated vicious circle. Given that substance use is often a barrier to accessing certain interventions, such as psychotherapy, is this evidence that such policies need a rethink?

Keep thinking diabetes

It is well-known that people with schizophrenia die on average 15–20 years younger than the general population. Physical health comorbidities, such as diabetes, contribute substantially to this early mortality and morbidity. It is perhaps surprising then that, in their Hong Kong-based cohort study, Chan et al (pp. 375–382) found that patients with diabetes and schizophrenia have lower microvascular and macrovascular complication rates in the first year after diabetes diagnosis compared with patients without schizophrenia. Maybe the physical health monitoring offered to people with schizophrenia has succeeded in leading to prompt diabetes diagnoses? Unfortunately, despite this, patients with schizophrenia and diabetes still had an elevated all-cause mortality risk overall.

From risk to recovery

Recovery in schizophrenia is a complex and personal concept. Often research studies struggle to capture the many different aspects that have meaning to individuals. In a large Dutch study of survey data Castelein et al (pp. 401–408) look at three domains of recovery simultaneously – clinical, societal and personal – and identify four ‘states’ of recovery. Interestingly those in recovery with predominantly negative symptoms scored higher on the measures of happiness than those with predominantly positive symptoms, but (more predictably) the former group had worse outcomes for societal recovery.

This reflects the growing body of evidence that negative symptoms in schizophrenia are associated with worse functional outcomes. But despite these advances in knowledge, there are concerns that this often disabling aspect of schizophrenia still goes under investigated and under treated. In their Editorial van der Meer et al (pp. 359–360) suggest negative symptoms are ‘the most important unmet need in schizophrenia’. They invite authors of previous relevant studies assessing effectiveness of psychosocial treatments targeting negative symptoms to share their data with them. By re-analysing the combined data using a new model they hope to increase the likelihood of detecting clinically significant effects of interventions. This exciting and novel call to action highlights the possibilities that open data and increased transparency in research can bring.

Back to the future of services

Finally, what hope of recovery if the right services are not available? Using a neat new epidemiological model based on 2011 census data, McDonald et al (pp. 383–391) forecast the local population needs for early intervention in psychosis programmes in England up to 2025. The authors hope such modelling can provide healthcare commissioners with an accurate decision-making tool to guide allocation of resources, even down to a very local level.

And last but not least, this month's Kaleidoscope column (pp. 411–412) looks at gender differences in cognitive effort when speed dating, and finds that, for once, men appear to be exaggerating about things being shorter than they actually are.