Bridging the treatment gap: Psychedelics,prevention,pills and potions,psychotherapy and protest

There is a crisis in novel therapy development. An overview of industry-initiated trials shows a dramatic slowdown of novel therapy development over the last decade, especially the last 5 years. For this reason, there is growing interest, maybe even fervour, in repurposing drugs hitherto regarded as agents of abuse. Ketamine is now (almost) mainstream, cannabis legalised and marketed in many jurisdictions, stimulants are again in the Lazarus zone, and psychedelics are the latest carriage on this lengthening train. Meikle and colleagues (this issue) enter this spiky debate, looking at psilocybin. Unsurprisingly, given its heritage as a drug of abuse, new data suggest rapid antidepressant effects, although it is uncertain if such rapid euphorigenic or mood-elevating results equate to antidepressant effects in the traditional sense of the word. But many studies are preliminary, poorly controlled and have recruited people who are prior users. But the promising and unique effects of psilocybin on default mode networks and pathways such as neuroplasticity and neurotrophins may be informative pathophysiologically. And, a large number of studies in play suggest that answers should be forthcoming. Repurposing drugs of addiction is a high-risk undertaking, highlighted by the opiate crisis, birthed by recognition of unmet needs in pain, promising short-term data, aggressive marketing, growing public demand and bullish use patterns. We need to tread the line between embracing opportunity and not succumbing to enthusiastic solutions without sober scrutiny.

Following the theme of treatment and prevention, Newton and colleagues (this issue) used a cluster randomised trial to examine a personality-targeted alcohol prevention strategy aimed at minimising internalising and externalising symptoms in high-risk young people compared to an active control. Their results suggested the effectiveness of the personality-targeted strategy, finding it significantly reduced internalising and externalising symptoms compared to a universal alcohol prevention approach. The personality-targeted strategy significantly reduced anxiety symptoms, and there was a suggestion of decreased symptoms of depression, conduct problems and hyperactivity. The study therefore supports the potential of tailored approaches to people with specific personality profiles and simultaneously suggests utility in seemingly diverse phenotypic endpoints. These are core features of successful preventive approaches, as the cost is offset by benefits in multiple diverse disorders (O’Neil et al., 2015). The potential value of prevention is underscored by the paper by Winsper and colleagues (this issue), who used the Avon Longitudinal Study of Parents and Children to understand the relationships between adolescent borderline personality disorder symptoms and subsequent psychotic, depressive and hypomanic symptoms a decade later. They found that borderline symptoms at the ages of 11–12 years predicted greater risk for the three studied outcomes, underscoring the need for secondary prevention to ameliorate this risk.

The three papers on bipolar disorder in this issue highlight important issues for clinical decision-makers. In another randomised controlled trial (RCT), Porter and colleagues (this issue) compared 18 months of medication management and interpersonal and social rhythm therapy against non-specific supportive clinical management among young people with bipolar disorder, with cognitive function as an endpoint. While there were no between-group differences, there were significant improvements between baseline and 18 months in executive function, a global cognitive composite score and psychomotor speed domains. Their results suggest stabilisation of symptoms was associated with clinical improvement. This optimistic scenario implies that cognition may be responsive to an intensive therapeutic intervention in young people with bipolar disorder. The lack of between-group separation parallels the primary findings of the study, where mood outcomes also did not differ (Inder et al., 2015), and supports active intervention as early as feasible in the disorder. Following the bipolar disorder theme, Cheng and colleagues (this issue) examined seasonal and temperature effects on lithium levels, finding no seasonal or monthly variation in lithium levels. One less thing for clinicians to worry about. Finally, the third paper on bipolar disorder in this issue (Kang et al., this issue) reports a post hoc comparison of lithium and valproate in the maintenance phase of the disorder. Supporting the seminal finding from Bowden et al.’s (2000) study, there were no significant differences between valproate and lithium for time to any mood event or on key secondary outcomes. Geddes et al. (2010) also compared lithium and valproate, finding that lithium was superior to valproate in relapse prevention. This is an important finding, and one that can guide clinicians, as there can be few examples of an agent entering widespread use predicated on so little data as valproate for bipolar maintenance.

Nutraceuticals are an area of considerable interest, and data suggest that they are extremely widely used, despite minimal quality data supporting such use. A meta-review of meta-analyses suggested the best evidence for omega-3 fatty acids, followed by methylfolate and N-acetylcysteine, but data are generally soft (Firth et al., 2019). Recent (unpublished) Australian data suggest complementary medication use is very common with 74% of people using them either regularly or occasionally. In this context, the large (N = 171) well-controlled trial by Sarris and colleagues (this issue) of Kava in generalised anxiety disorder, which failed to demonstrate any benefit over placebo, is of considerable public health importance. Anxiety was greater in the Kava than the placebo group and some side effects such as memory complaints and tremor were more common in the Kava group, negating the public perception that these nutraceutical agents are useful and without meaningful risk. Firth’s conclusion is worth reiterating; clinicians should know not only those nutrient supplements with established efficacy for specific conditions but also those which lack evidentiary support and may even be harmful.

Times of political, social, economic and environmental turmoil have psychiatric sequelae. As devastating fires still rage across Australia, hundreds and thousands have gathered to protest the government’s climate policies. Against this backdrop, the paper by Ni (this issue) seems timely. This systematic review unsurprisingly suggests that protests can be associated with adverse mental health outcomes, but surprisingly unearths some data showing that collective actions, predicated on social cohesion and catharsis may be protective against depression and suicide. Risk factors seem to parallel those for other traumas, although novel factors such as unfriending on social media are now playing a role. Because of the increase in protest actions globally, clinicians and services will need to be aware of their mental health consequences. Continuing the theme of the psychiatrist’s role in crises, Scott (this issue) elegantly and compellingly reviews the role of the consulting psychiatrist in the Sydney Lindt café siege. He notes that notwithstanding having appropriately assessed and guided the police in the management of the event, the Coroner was unduly affected by hindsight bias and scapegoated the psychiatrist. Given the importance of psychiatric expertise in events as complex as hostage negotiations, it is very unfortunate if the Coroner’s assessment ends up inhibiting the profession from contributing for fear of adverse legal judgement. In summary, this issue of ANZJP, which focuses on treatment studies, meaningfully contributes to several clinically hot topics.