Risks,benefits and finding the best way forward

In this month’s Australian and New Zealand Journal of Psychiatry (ANZJP), the paper with immediate clinical impact addresses the tragic situation that occurs when a patient who has responded to clozapine has to stop treatment due to agranulocytosis. Often gains in functional recovery are lost, and more severe symptoms return. Myles et al. (this issue) demonstrate that by co-prescribing granulocyte-colony stimulating factor (GCSF), successful clozapine rechallenge is possible, with 76% of people treated with the combination remaining on clozapine after 12 months. Using GCSF will be a new skill for clozapine prescribers, working in collaboration with clinical haematology services. Only 30 cases have been reported, so it would make sense to set up a national database to record patient characteristics, the rechallenge protocol and outcomes. Those interested could begin by emailing the author.

Thabrew et al. (this issue) ponder the future of child psychiatry. They offer a list of recommendations to be implemented by the Royal Australian and New Zealand College of Psychiatrists (RANZCP) and strategies that individual child psychiatrists could adopt to improve their effectiveness. They observe that child mental health services often have flatter hierarchies than other areas of health and that child psychiatrists may avoid leadership positions due to time pressure, lack of confidence and lack of financial incentive. The South Australian (SA) coroner, in 2010, ¹ wrote that in his opinion ‘the Child and Adolescent Mental Health Services (CAMHS) “extremely flat structure” is fundamentally flawed’. He recommended that the number of psychiatrists employed within CAMHS be increased and that ‘all services provided by CAMHS should be provided under the same level of consultant supervision as a surgical service in a public hospital. To be absolutely clear, I refer to supervision by a consultant psychiatrist’. Thabrew et al. describe 12 clinical issues where the contribution of a child psychiatrist is essential, but there is no discussion about whether the psychiatrist should be the lead clinician in these situations. If child psychiatry is to grow up, maybe this includes advocating for system change and taking on leadership roles.

Brett et al. (this issue) report changes in psychotropic medication use by concessional beneficiaries in Australia 2007–2015. The study raises as many questions as it answers. For example, there was an increase in antipsychotic use, particularly of quetiapine, which may reflect increasing off-label use of this drug (Brett, 2015). This could parallel the reduced prescription of benzodiazepines; perhaps quetiapine is being prescribed instead of benzodiazepines. The authors are concerned that high rates of single dispensing of haloperidol and amitriptyline might also reflect off-label uses that lack a firm evidence base.

Psychological treatments tend to be considered harmless, but any potent intervention has the capacity to cure and to harm (Berk and Parker, 2009). Gordon et al. (this issue) set out to identify adverse effects associated with mindfulness, reviewing papers specifically reporting negative effects of mindfulness. There is a lack of delineation between mindfulness-based interventions, mindfulness practice in general and meditation. However, numerous studies have evaluated well-defined, manualised mindfulness interventions; a review of these studies looking for negative effects, and finding out more about those participants who did not do well, might be useful. Perhaps future studies of mindfulness and other psychological interventions should include adverse event monitoring; this is very well developed in pharmaceutical clinical trials and could readily be adapted to trials of psychological treatments.

Spencer (this issue) examines the balance between autonomy and protection, around the issue of participation of prisoners in research. The recent expansion of ethics and governance approval processes can delay and sometimes block research (Posselt et al., 2014). These requirements are more extensive with vulnerable populations, such as prisoners, children and the elderly, forming a barrier to research with these groups. Spencer asserts that measures to protect these people risk them becoming increasingly invisible, so their voices are even less likely to be heard.

Valuri et al. (this issue) use whole-population record linkage to examine criminal offending. They report that children of women with severe mental illness have almost three times the rate of offending, compared to children of mothers who do not have mental illness. Male gender, Indigenous status, social disadvantage and parental offending are associated with an increased risk of offending. Valuri et al. highlight the need to improve the social environment for these families. Understanding more about the pathway between childhood experiences and later offending would require research initiatives such as those advocated by Spencer (this issue).

This issue of ANZJP includes four papers exploring the neurobiology of schizophrenia. Kanaan et al. (this issue) investigate brain structure in schizophrenia using diffusion tensor imaging (DTI), a measure of white matter integrity. Compared with healthy controls, people with schizophrenia had abnormalities consistent with global disruption of myelination. Interestingly, there was no difference between older and younger participants with schizophrenia, while the controls had a gradual decline in myelination with age. This study was cross-sectional, and Kanaan et al. note the need for a similar study using a longitudinal design with multiple time points.

Berger et al. (this issue) report ventricular enlargement in patients with established schizophrenia, but not in ultra high-risk or first-episode psychosis (FEP) patients. However, FEP subjects who met the criteria for schizophrenia had non-significant ventricular enlargement, so it is possible the study was underpowered for this comparison.

Guo et al. focus on the specific effects of olanzapine on brain function in people with schizophrenia. This is a longitudinal study, demonstrating that olanzapine modulates the default mode network (DMN). The DMN is associated with stimulus-unrelated thoughts, mind wandering and lapses in attention. It has been described as the neurological basis for the self and for the ability to appreciate the mental states of others. This study is well designed but has a small number of participants.

Delvecchio et al. (this issue) build on the hypothesis that a failure in the development of normal cerebral asymmetry in structures involved in language is fundamental to schizophrenia. In their data, women with schizophrenia lack the normal asymmetry of the planum temporale, a region in the superior temporal gyrus associated with language. Males have a normal pattern of brain asymmetry. Delvecchio et al. (this issue) conclude that gender is an important modulator of brain morphology and lateralisation in schizophrenia.

Reviewing these studies highlights the need for researchers to work together to generate large enough numbers of participants to have adequate power. If, as proposed by Delvecchio et al. (this issue), studies in schizophrenia should undertake separate analyses for men and women, even larger numbers of participants are needed. While small studies are needed to establish hypotheses, proof-of-concept and pilot data, the next step is to establish large cohorts and use advanced analytic methods such as artificial neural networks to identify patterns in the data.

The Journal has published a series of conversations via Editorials, Debate, Commentary and Letters. This continues with Leske et al.’s (this issue) comments, responding to Brown’s (2017) critique of their systematic review of interventions for Indigenous adults (Leske et al., 2016). Brown considers that the review is premature, while Leske et al. argue that the fact that there are only a small number of relevant studies is an important finding in itself. Ongoing robust discussion about systems of care and the best ways to help individual patients, along with critique of published papers, is a strength of the ANZJP, and this month’s edition continues this tradition.