Clozapine is the most effective drug for schizophrenia and is the only drug indicated for use in patients with treatment resistance. The therapeutic range of clozapine is narrow with extensive interindividual differences in serum levels at similar dosing, mainly due to variability in hepatic metabolism mediated by several cytochrome P450 (CYP) enzymes. Tobacco smoking is the most important environmental factor determining clozapine metabolism, while the effect of pharmacogenetic variability is unclear.

Depressive disorders are a major global health challenge, with many individuals unresponsive to existing treatments. Novel psychedelic therapies show promise but require further research.

Results from contemporary clinical trials of serotonergic psychedelic therapies have led to an increasing focus on their potential clinical use across mental disorders. However, studies examining mechanisms of clinical response to psychedelic therapy in psychiatric populations are limited. This review aimed to synthesize evidence from studies examining biomarkers of clinical response to psychedelic therapies.

Job-related stress and its extreme form, burnout, continue to affect almost half of all frontline healthcare workers and first responders. Current treatments are inadequate.

Extrapyramidal symptoms (EPS) in association with the long-acting, injectable, atypical antipsychotic aripiprazole once monthly (AOM) have been observed in clinical trials, but information on EPS requiring treatment with anticholinergic drugs in clinical practice is limited.

Intravenous ketamine is effective in treatment-resistant bipolar depression (TRBD) with dosing typically based on actual body weight (ABW).

Valproic acid (VPA)-induced hyperammonemia is a common condition whose clinical presentations can range from asymptomatic cases to severe hyperammonemic encephalopathy. This can happen at any stage of treatment and is difficult to predict, as it often occurs without any alteration in liver function tests.

Poor adherence to antipsychotic medications is the leading cause of relapses and hospitalizations in patients with schizophrenia, resulting in worse functional outcomes and quality of life. Long-acting injectable (LAI) antipsychotics are an effective therapeutic option to improve adherence, but they are often underutilized, particularly during inpatient care.

Nonadherence jeopardizes treatment outcomes in the psychiatric care continuum. However, there was a paucity of data in the resource-limited life trajectories.

Oral contraceptives (OC) offer a range of ethinyl estradiol (EE) doses and progestin types, with evidence indicating marked differences in cognitive and emotional abilities in OC users. However, it remains unclear whether dose variations in EE (low vs high) and progestin androgenicity (androgenic vs anti-androgenic) are associated with variations in cognitive and emotional abilities.

[This corrects the article DOI: 10.1177/20451253251381074.].

Depression affects approximately 5.7% of adults worldwide, and around one-third of these individuals develop treatment-resistant depression (TRD). Intravenous (IV) ketamine and esketamine (administered IV or intranasally (IN)) are novel treatment options for TRD; however, only IN esketamine currently holds FDA approval.

Physical touch is often included as a supportive or therapeutic tool in psychedelic-assisted therapy (PAT), involving instrumental forms of physical contact, supportive touch and somatic techniques. However, participants under the influence of psychedelics have reduced capacity to provide consent, are more suggestible and may experience and interpret therapeutic touch in ways they did not expect prior to taking the drug. Yet little research has been conducted on the considerations and approaches to therapeutic touch in clinical trials of PAT.

Psychedelic-assisted therapy (PAT) has typically been evaluated using conventional randomised controlled trials (RCTs), which assess treatment efficacy under highly controlled conditions. However, PAT constitutes a complex intervention, integrating pharmacological, psychotherapeutic and contextual elements that interact dynamically with patient experiences and healthcare settings. Conventional RCTs, designed for simple interventions, may fail to capture these complexities. Pragmatic trials, by contrast, evaluate interventions under real-world conditions, assessing their effectiveness across diverse clinical environments and patient populations. This position paper advocates for the application of the UK Medical Research Council's (MRC) framework for complex interventions to the development and evaluation of PAT. This framework emphasises the necessity of articulating the underlying theory of therapeutic change, structuring intervention development into defined phases, accounting for contextual interactions and incorporating stakeholder perspectives throughout the research process. We argue that employing pragmatic trial designs, guided by the PRECIS-2 tool, will better align PAT research with the practicalities of healthcare delivery and facilitate the translation of research findings into clinical practice. Further, we address the philosophical divergence in the field between conceptualising PAT as primarily pharmacological versus psychotherapy-augmented, noting the implications of these positions for trial design and interpretation. We propose the integration of qualitative methodologies, adaptive trial designs and comparative effectiveness research to refine PAT interventions and address limitations inherent in conventional double-blind RCT approaches. Finally, we advocate for a pluralistic evidentiary model, combining academic and community-led research, to support the rigorous, equitable and sustainable development of psychedelic-assisted therapies and to avoid the historical setbacks that previously hindered progress in this field.

Formal guidelines recommend that opioids should be stopped when risks outweigh benefits. These guidelines generally recommend gradual dose tapering at a rate tolerable to the patient. However, there is considerable variation regarding the pattern of dose tapering recommended, with some suggesting linear tapers (with a fixed reduction of dose at each step), while others recommend increasingly small dose reductions as the total dose gets lower. No biological rationale has been put forward for these recommendations. We examined the pharmacodynamic properties of opioids to derive pharmacologically rational principles for tapering. As dictated by the law of mass action, the relationship between dose of opioid and effect on its principal target, the mu-opioid receptor, is hyperbolic, with diminishing incremental effects for increasing doses. This suggests that in order to mitigate withdrawal symptoms, opioid doses should be tapered according to a corresponding hyperbolic pattern, with dose reductions becoming increasingly small as total dose reduces. This can be approximated by proportional decreases (e.g. 1%-10% reduction of the most recent dose every 1-2 weeks). Dose reductions should be titrated to withdrawal symptoms throughout the process, and final doses before complete cessation will need to be very small (such as 0.1 mg of buprenorphine or 1 mg of methadone, or less). The duration required for this strategy of tolerable tapering after long-term use may require many months or years for some patients. The theoretical proposals in this paper offer a pharmacologically rational strategy that should prompt review of clinical practice and guidelines. Gradual, hyperbolic tapering should be evaluated in randomised controlled trials.

Postoperative delirium (POD) is associated with higher risks of postoperative complications ‌and‌ mortality (2- to 3-fold increase). Studies investigating the effect of intraoperative ketamine on POD risk have yielded conflicting results. This study aimed to assess the effects of intraoperative ketamine and its more potent version, esketamine, on POD.

Psychotropic medications are often inappropriately prescribed for behavioural and psychological symptoms of dementia (BPSD), posing significant risks such as falls, stroke and death. Although non-pharmacological interventions (NPIs) are the first-line treatment for BPSD, their use in practice remains limited.

Suicidal ideation, attempts, and deaths present a major and tragic public health concern. Recent trials of psilocybin therapy (PT) have shown promise in treating treatment-resistant depression and have found a reduction in suicidal ideation. Given the growth of PT research, there is a need to further understand its effect on suicidal ideation, attempts, and deaths.

Patients treated in early intervention for psychosis programs have better treatment outcomes and higher rates of long-acting injection (LAI) antipsychotic medication utilization (20%-50%) versus treatment as usual. These programs usually serve patients for 2-3 years, then most patients are discharged to other mental health services and studies of patients with longer-standing schizophrenia suggest switching to oral medications may be common. However, following patients post-discharge is complicated by the challenges of migrated patient records across clinical services and providers.

Long-acting injectable (LAI) antipsychotics can improve treatment adherence in patients with schizophrenia. Despite their benefits, LAIs are underused in China compared to other countries. Little real-world evidence describes the impact of switching from oral to LAI antipsychotics on adherence and healthcare utilization in clinical practice in China, which could help address this gap.

Many antidepressant users experience the process of stopping as challenging because of withdrawal symptoms. Support factors, such as patients experiencing empathy from their healthcare providers, potentially contribute to successful discontinuation.