Something old and something blue – Something for everyone,me and you?

Treating schizophrenia is one of psychiatry’s central tasks. The ongoing debate in the Journal about how to do this effectively is therefore welcome. In this issue, Zipursky has written a debate piece which follows on from the Royal Australian and New Zealand College of Psychiatrists (RANZCP) guidelines for the management of schizophrenia and related disorders (Galletly et al., 2016), a review by Catts and O’Toole (2016) and an editorial by Jayaram et al. (2017). At the risk of over-simplifying the argument, the major issue centres on maintenance treatment with antipsychotic medication particularly after remission of a first-episode psychosis.

The clinical practice guideline (CPG) recommendations are cautious, reflecting the inconsistencies and sometimes poor evidence around aspects of treatment. Catts and O’Toole (2016) argue for early diagnosis and assertive and long-term medication treatment which they consider may be undermined by the uncertainties and controversies in the CPGs and published literature. They propose that schizophrenia is a progressive disease with emergent treatment resistance in many cases. They further argue that relapse contributes to the treatment resistance and therefore that maintenance medication should be continued in remitted first-episode cases using the most effective method of delivery available: long-acting injectable antipsychotics (LAIs). In contrast, Jayaram et al. (2017) offer a cautionary note suggesting that treatment resistance is not inevitable and that recovery occurs in a significant number of cases. They go on to state that the case for maintenance medication does not have enough data to support it, citing a recent Cochrane review which reported that increased compliance was not associated with improved outcomes. They also note the need to balance the long-term harmful effects of antipsychotics against benefits.

In this issue, Zipursky disputes Catts and O’Toole’s first premise that schizophrenia itself leads to progressive changes in the brain, pointing out that we do not know whether the magnetic resonance imaging (MRI) changes observed over time as a result of antipsychotic medications and other factors in patients with schizophrenia are ‘neurobiologically meaningful’. The author goes on to state Catts and O’Toole’s assertions that, first, longitudinal changes observed in grey matter volumes early in the course of illness are disease related and, second, that antipsychotics protect against these volume changes has not been established and should not be part of an argument for changing clinical practice. Zipursky, however, agrees with Catts and O’Toole that there is some evidence that LAIs may be useful in the first episode of schizophrenia and that clinicians should make the diagnosis as soon as possible. In contrast, Jayaram et al., caution against both these practices.

The reason that the Journal has given so much space to this issue, and why I consider it is important, is that arguments around maintenance and prophylactic use of antipsychotics are a core issue in the practice of psychiatry. A recent analysis by Murray et al. (2016) stirred things up further by arguing for more caution in prescribing prophylactic antipsychotics and using low doses. Not surprisingly, Catts and O’Toole (2017) wrote a letter arguing that Murray et al. were proposing a therapeutic dead-end.

Where does all his leave the clinician? The arguments reflect the reality that there are insufficient data, particularly from long-term studies, to make a clear recommendation. It suggests ongoing scepticism about all strongly held positions and following the emerging data closely. Perhaps the large database studies linking antipsychotic use with recurrence and mortality may shed some light on the issue, and long-term real-world outcome studies will finally be funded.

Of course, the Journal has considered other important issues as well. Suicide has become another core issue in psychiatry. Snowdon (this issue) reports the unwelcome news that suicide rates are increasing in Australia, particularly among Indigenous children and young adults. For example, the suicide rate of Indigenous women aged 35–44 is four times higher than that of the same-aged non-indigenous women.

Sellman (this issue) points out that God has only featured in three articles in 50 years and argues for psychiatry to be more assertive as a public force for good.

Lucassen et al. (this issue) review the increasingly visible group of sexual minority youth. They report that these young people have higher rates of depressive symptoms and depressive disorders. Female sexual minority youth appear to be at particular risk.

The importance of inter-episode mood in bipolar patients has only been recognised relatively recently, so Dargel et al.’s (this issue) study is particularly welcome. In a large cross-sectional study, they report that 68% of patients had abnormal emotional reactivity between mood episodes, and this measure appeared to be a clinically relevant dimension for better characterising bipolar patients. They also reported that C-reactive protein might be an objective marker of emotional dysregulations in bipolar disorder. Such measures might help refine the bipolar disorder diagnosis and shed light on its transdiagnostic features.

Whiteford et al. (this issue) report that 1.1% of adults experience a persistent mental illness that requires ongoing services to address disability. Of these, around one-third, or 59,000, people in Australia have complex multi-agency needs. The authors suggest that service planning needs to consider this population in a more refined fashion.

Romijn et al. (this issue) present an important negative randomised controlled trial (RCT). Probiotics were not effective in treating low mood or moderating the levels of inflammatory and other biomarkers. The importance of publishing negative studies, particularly well-designed RCTs, cannot be overstated. It can save significant opportunity costs and help balance the literature. Adjunctive minocycline treatment for major depression was also ineffective although it was associated with some improvement in several secondary outcomes and minimal adverse effects. The authors conclude that it still has some potential.

Sleep problems are very common. McDonald et al. (this issue) suggest that more than one-third of us have sleep problems, and if we have mood instability, it reaches over two-thirds. In addition, sleep problems are associated with suicidal ideation and behaviour. On a more positive note, therapies that target sleep disturbance may assist those with mood instability and be particularly valuable for preventing complications such as suicidal behaviour.

Overall, a varied group of papers deal with the very old – God – the elderly – schizophrenia and suicide – and the new – inter-episode moods, probiotics and tetracycline antibiotics.