New treatment paradigms for mental health conditions: A time for renewed enthusiasm?

Given the complexity of mental health conditions and apparent lack of progress in improving the prevalence of these at a population level, it is easy to become negative about progress in psychiatric treatment. Indeed, some have argued in recent years that despite increased development and provision of treatment, the prevalence of common mental disorders has increased, or at least not decreased (Mulder et al., 2017). This month in ANZJP, not only is this argument refuted, but several authors present new ideas and paradigms for improvements in the treatment of important mental health conditions, which give considerable cause for optimism.

Regarding the prevalence of mental disorders, Furukawa and Kessler (this issue) argue cogently that this situation is not as negative as it might appear. First, they argue that years lived with disability due to mental health disorders may not have increased, when figures are adjusted for age and population. Second, they argue that prevalence in psychiatric epidemiological studies may not always be an accurate reflection of the situation, being influenced significantly by participation rates and the readiness of participants to admit to symptoms of depression, which may have changed significantly over time. Third, they argue that while rates of mental disorder may not have altered, they may, however, be better controlled by current treatments, resulting in an improved quality of life for sufferers. This then sets the scene for several papers in this month’s issue that discuss exciting new paradigms for the treatment of common mental health conditions.

Anorexia nervosa is a condition which is particularly difficult to treat and Phillipou et al. (this issue) point out that compared with other mental health conditions, relatively modest advances in treatment have been made. These authors argue that although the biopsychosocial model has frequently been applied to anorexia nervosa, the biological aspects of the disorder have been relatively under researched resulting in a paucity of neurobiological therapies. They note that most of the neurobiological therapies employed are used to treat comorbidity with other conditions. They also emphasise the importance of interactions between different aspects of the biopsychosocial model. For example, they point to the interaction between the gut/brain axis and the behavioural aspects of what is ingested. In a condition in which therapeutic nihilism may easily emerge, this erudite paper that concludes with a plea to fund truly multidisciplinary initiatives to help to provide individualised treatment for anorexia nervosa signals a positive future. In their model, reference to the importance of the gut/brain axis draws the attention of readers to the relationship between the gut microbiome, the ‘leaky brain’ and mental health – an area that is of increasing interest and reviewed in detail recently in this journal (Morris et al., 2018).

This is also the subject of an excellent review by McGovern et al. (this issue), which examines the likely effects of serotonin reuptake inhibitors on gut microbiota. Based on literature regarding the pharmacokinetic and gastrointestinal transit properties of selective serotonin reuptake inhibitors (SSRIs), and their antimicrobial effects in situ, the authors conclude that for at least 4 hours per day at usual doses, SSRIs are likely to exert a significant antimicrobial effect in the gut. The review raises important questions about the possible mechanism of action of SSRIs and a possible pathway via an effect on gut microbiota. The authors suggest that not only does this have implications for the mechanism of action of SSRIs but also for understanding the effects of other treatments which may improve outcomes in depressive disorder by effects on the gut microbiome.

Another area of research in mood disorders that has attracted increasing interest in recent years is the role of cognitive dysfunction. This is often an important feature of mood disorders that can impact very significantly on functioning. Hence, the use of cognitive remediation, which has been extensively studied especially in schizophrenia, has now begun to feature in research studies of mood disorders (Porter et al., 2013). This month Douglas et al. (this issue) argue that the mood disorders field may have been hampered by the adoption, primarily from schizophrenia research, of the term ‘cognitive remediation’. Interestingly, they suggest a new term ‘cognitive enhancement therapy for mood disorders’, which recognises the more malleable nature of cognitive difficulties in a proportion of patients with mood disorders. These authors also discuss the key pillars of cognitive enhancement therapy for mood disorders, namely, psychoeducation, cognitive practice and translation of cognitive skills to everyday life. They also discuss the increasing importance of clinicians being aware of cognitive difficulties in mood disorders and having an understanding of the basic principles of how to help patients with their cognitive difficulties. This may be a new focus for some clinicians.

Further examining new paradigms or therapies, an understanding of their underlying mechanisms of action is clearly important. In this vein, Douglas et al. this issue) examine the effects of hydrocortisone on brain function in patients with post-traumatic stress disorder (PTSD) following the Canterbury earthquakes. This was prompted partly by the suggestion that cortisol administered acutely may be effective in reducing the incidence of PTSD following trauma (Sijbrandij et al., 2015). This study in real-world patients did not show a differential effect of hydrocortisone on brain activation but was probably hampered by dosing issues and other technical issues.

As we all get older, the group of mental health conditions that become increasingly personally relevant, and are unfortunately also seemingly increasing in incidence, are neurodegenerative diseases. Chief among these is Alzheimer’s disease. In a fascinating letter this month, Ong and Woodward discuss the amyloid cascade hypothesis of Alzheimer’s disease and argue that while the accumulation of Aβ into plaque is of course associated with Alzheimer’s disease, this may in fact be an adaptation to buffer the neurotoxic effects of cerebral β-amyloidosis. Without this mechanism decline in cognitive function might be even quicker, as is often the case in non-Alzheimer’s dementias. This theory, if it proves to be correct, could provide new avenues for the treatment of neurodegenerative diseases – opening the door to neuroprotection.

A treatment familiar to all readers of the journal may of course already show promise in this regard. Neuroprotective effects of lithium that have been hypothesised on the basis of varied types of evidence (e.g. Kessing et al., 2017). There is further evidence of this in this issue using a new and innovative imaging technique. Van Gestel et al. (this issue) report on structural magnetic resonance imaging scans in bipolar disorder patients with and without lithium treatment and healthy control subjects. Using a machine learning model trained to estimate brain age on a separate sample, the difference between estimated brain age from the model and actual brain age was calculated in these groups. This difference was greater in patients with bipolar disorder compared with controls but less when patients were treated with lithium. The effects appeared to be independent of response to lithium and suggest that lithium may prevent brain ageing.

Thus, although there is an abundance of reports of increasing mental distress, and the complexities and difficulties of treating this burden may leave psychiatrists and mental health professionals feeling negative and nihilistic about their efforts, this issue of the ANZJP provides positive new paradigms and data on new treatments – all of which should give cause for considerable optimism.