G protein-coupled receptors (GPCRs) are involved in many physiological and pathophysiological processes. Conventional pharmacological models categorize the typology of pharmacologic ligands as agonists or antagonists. Biased agonism is a relatively newer pharmacodynamic characteristic that has potential to optimize therapeutic efficacy while minimizing adverse effects in psychiatric and neurological treatments. We conducted a narrative literature review of articles obtained from PubMed, Embase, and MEDLINE from inception to April 2025, focusing on pharmacologic antagonism (i.e., competitive, noncompetitive, uncompetitive) and agonism (i.e., full, partial, inverse, superagonism, biased). Primary and secondary articles defining these concepts were included, provided they addressed pharmacologic (rather than chemical) antagonism and agonism. Distinct mechanisms of antagonism and agonism were identified, each contributing nuanced receptor modulation beyond the conventional models. Notably, biased agonism facilitates targeted intracellular signaling (e.g., G protein- versus β-arrestin–mediated). Use cases demonstrate relatively greater efficacy (e.g., incretin receptor agonist, tirzepatide) and improved safety (e.g., serotonergic psychedelics, opioids). Biased agonism provides a potential avenue for future drug development, with emerging preclinical evidence suggesting potential to differentially activate intracellular pathways and thereby improve efficacy and safety profiles of psychopharmacologic agents—pending clinical validation. Future research vistas should aim to rigorously assess the long-term outcomes of biased agonism, explicitly addressing individual variability in receptor signaling and therapeutic response.

Panic disorder, characterised by sudden episodes of intense fear or anxiety, affects 1–4% of the population. Symptoms include rapid heartbeat, chest pain and fear of dying. Panic disorder often co-occurs with substance dependence and major depression. This review article examines pharmacological treatments, focusing on antidepressants and benzodiazepines, but also considering antipsychotics and anticonvulsants. It overviews the history of antidepressants and benzodiazepines in the treatment of panic disorder and their mechanisms of action. The results of a recent Cochrane Review network meta-analysis are then presented and contrasted with six current national and international treatment guidelines. Rankings of the various drugs in terms of efficacy, tolerability and safety are summarised, along with levels of evidence and lines of recommendation as a treatment option (first-, second or third-line, or reserved for treatment-resistant cases).

The term “betel” most accurately refers to the betel pepper (Piper betle). Confusingly, this term is also frequently used to refer to a street drug that often—but not always—includes the betel leaf as a constituent. This linguistic misdirection only intensifies with terms such as “betel nut,” which, in common usage, may refer to this same composite street drug or to a single isolated constituent of that street drug: the nut of the areca palm (Areca catechu), which is otherwise wholly unrelated to the betel pepper. This composite street drug, colloquially referred to as “betel” or “betel nut” or “betel quid,” is one of the most frequently used psychoactive substances in the world. It carries a cultural legacy spanning over 10,000 years and a current user base numbering in the hundreds of millions. Its primary psychoactive constituent is arecoline, a well-established parasympathomimetic agent. Early studies exploring arecoline’s ability to modulate cholinergic signaling pathways and exert therapeutic psychiatric effects on conditions such as Alzheimer’s disease were initially mired by intolerable parasympathetic side effects. Indeed, over the course of its long history, various hints regarding the therapeutic utility of arecoline have been obfuscated by a variety of challenges which have only recently been overcome. Now, developments in psychopharmacology and our growing understanding of neurochemical brain circuitry have unlocked a new mechanism of action by which arecoline-derived medications interact with dopaminergic processes to improve outcomes for schizophrenia patients. One such medication, xanomeline-trospium (Cobenfy), has emerged as the first such agent to receive U.S. Food and Drug Administration (FDA) approval for the treatment of schizophrenia and represents an entirely new class of pro-cholinergic medication within the field of psychiatry. Many in the field believe that this heralds the beginning of a new era of psychopharmacology: the era of muscarinic agonism. This article briefly described the fascinating journey from ancient betel nuts to modern muscarinic therapeutics.

Pharmacological treatment of attention-deficit hyperactivity disorder (ADHD) involves central stimulants and non-stimulant drugs. Because treatment preferences may vary geographically, we hypothesize that prescription data can be estimated from publicly available sources. First, we explore the relevance of internet search trends as proxies for real-life drug prescription patterns. Second, we identify geographical variations in ADHD drug trends over time. Publicly available Google Trends data for five ADHD drugs were analysed for the years 2010–2023. Temporal and spatial patterns were compared within Scandinavia, and the preference for central stimulants over non-stimulant drugs was compared across 17 countries. We find that internet search trends correlate with ADHD drug prescriptions. In the Scandinavian countries, a dominance of methylphenidate is observed, with rising internet search trends over time in Norway and Denmark. Furthermore, interest in lisdexamphetamine, relative to dextroamphetamine and atomoxetine, has increased sharply in recent years in the Scandinavian countries. The search proportion of central stimulants to non-stimulant drugs in Scandinavia ranges from 81% (Denmark) to 93% (Norway). Overall, internet search trends for ADHD drugs mirror reported prescription patterns and identify a dominance of methylphenidate, with an increasing interest in lisdexamphetamine. As such, search trends may serve as a feasible source for identifying geographical drug preferences.

Although fundamental advances in the life sciences raise the exciting possibility of novel translational therapies, optimal evidence-based usage of established treatments should be the bedrock of current clinical care. The authors argue that there are instances where well-established treatments are ‘underused’ in psychiatry; electroconvulsive therapy, clozapine and lithium are exemplars of this. This article explores possible reasons for, and strategies to address, this underuse.

Despite being the most prevalent personality disorder, borderline personality disorder remains a diagnosis with many unanswered questions, particularly concerning pharmacological management. Although many clinical practice guidelines suggest not prescribing medication unless there are significant clinical comorbidities, it is one of the psychiatric diagnoses with the highest rates of polypharmacy. This commentary on a BJPsych Advances article aims to raise clinical questions regarding the voids of knowledge and the appropriateness of medicating and, perhaps, overmedicating in this particular group.

This study explores the effectiveness of antipsychotic medications in restoring competency to stand trial in individuals with severe mental illness, particularly psychotic disorders. While antipsychotic medications are known for reducing symptoms of psychosis, this research focuses on their ability to improve functional outcomes necessary for competency to stand trial (CST). Among over 3,000 patients in California’s forensic state hospital system, 86.5% were successfully restored to competency, with 98.8% discharged on antipsychotic medications. Patients on antipsychotic monotherapy demonstrated higher restoration rates compared to those requiring additional mood stabilizers, suggesting that more complex cases demand more intensive treatment. Delusional disorder, traditionally seen as more resistant to treatment, showed a high restoration rate of 93.8% with antipsychotic use.

Our findings emphasize the pivotal role of antipsychotics in not only reducing symptoms but also in restoring critical functional abilities for participation in legal proceedings. The functional improvements they enable extend beyond the courtroom. Incorporation of antipsychotic medication as an integral evidence-based mechanism in facilitating community reintegration for individuals with severe mental illness supports the broader goal of transitioning individuals from the legal system back into society, consistent with the ultimate promise of deinstitutionalization.

Promethazine, a sedating antihistamine, is widely and increasingly prescribed for patients reporting problems sleeping. In this Against the Stream article, the case is made that promethazine is not suitable as a sleep aid for people using mental health services, because it has no good evidence base, impedes with psychological and behavioural techniques that do improve sleep in the medium-long term, has underappreciated addictive and recreational-use potential, and an unacceptable side-effect profile. Alternatives to promethazine are described, notably the NICE first-line recommendation, cognitive–behavioural therapy for insomnia.

This review examines the relationship between long-term antipsychotic use and individual functioning, emphasizing clinical implications and the need for personalized care. The initial impression that antipsychotic medications may worsen long-term outcomes is critically assessed, highlighting the confounding effects of illness trajectory and individual patient characteristics. Moving beyond a focus on methodological limitations, the discussion centers on how these findings can inform clinical practice, keeping in consideration that a subset of patients with psychotic disorders are on a trajectory of long-term remission and that for a subset of patient the adverse effects of antipsychotics outweigh potential benefits. Key studies such as the OPUS study, Chicago Follow-up study, Mesifos trial, and RADAR trial are analyzed. While antipsychotics demonstrate efficacy in short-term symptom management, their long-term effects on functioning are less obvious and require careful interpretation. Research on long-term antipsychotic use and individual functioning isn't sufficient to favor antipsychotic discontinuation or dose reduction below standard doses for most patients, but it is sufficient to highlight the necessity of personalization of clinical treatment and the appropriateness of dose reduction/discontinuation in a considerable subset of patients.

Evidence indicates that ketamine is highly effective, has a lower side effect profile and is better tolerated compared to many augmentation strategies for refractory depression. This, combined with data on psychiatric treatment outcome mediators, suggests that earlier intervention with ketamine could improve outcomes for patients suffering from refractory depression.