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Existing pharmacotherapies and psychotherapies are often inadequate, and discovery for new pharmacological treatments in psychiatry is slow. Existing pharmacotherapies are, however, often inadequate. Few truly novel pharmacotherapies have emerged in the past four decades, largely due to the absence of a known pathophysiology for each disorder. In this Personal View, we describe the platform we have

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ImportanceSleep disorders have different etiologies yet share some nocturnal and daytime symptoms, suggesting common neurobiological substrates; healthy individuals undergoing experimental sleep deprivation also report analogous daytime symptoms. However, brain similarities and differences between long-term sleep disorders and short-term sleep deprivation are unclear.ObjectiveTo investigate the shared

OBJECTIVE The authors sought to determine whether an inflammatory challenge with lipopolysaccharide (LPS) differentially impacts symptoms of anhedonia in participants with major depressive disorder with high (≥3 mg/L) and low (≤1.5 mg/L) serum C-reactive protein (CRP) concentrations. METHODS Sixty-eight participants with major depressive disorder were randomly assigned, in a 1:1 ratio, to receive LPS

People who are incarcerated in Africa are not a focus of global mental health research, and incarceration is absent from many international mental health guidelines. Given the dearth of knowledge and services, priorities for research and practice should be established. The Delphi method was used to identify priority challenges related to mental health and substance use disorders among people who are

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The Lancet Psychiatry. Thanks to our peer reviewers for 2024. The Lancet Psychiatry 2025; 12: e3–6—In this Comment, Ángel Aguilera Martín should have been included in the list of peer reviewers for 2024. This correction has been made to the online version as of April 15, 2025.

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BackgroundFewer than 25% of patients with borderline personality disorder (BPD) receive guideline-adherent psychotherapy. Digital therapeutics can help reduce this gap. Therefore, we tested the effectiveness and safety of priovi, a digital therapeutic for BPD. MethodsWe conducted a pragmatic, assessor-blind, parallel-group, randomised controlled trial, recruiting patients with BPD, according to DSM-5

ImportanceCognitive behavior therapy (CBT) is a first-line treatment for most mental disorders. However, no meta-analytic study has yet integrated the results of randomized clinical trials on CBT across different disorders, using uniform methodologies and providing a complete overview of the field.ObjectiveTo examine the effect sizes of CBT for 4 anxiety disorders, 2 eating disorders, major depression

This Viewpoint explores potential justifications underlying the US Food and Drug Administration (FDA)’s rejection of methylenedioxymethamphetamine (MDMA) as a treatment for posttraumatic stress disorder, including lack of blinding and issues around the integrity of relevant clinical trials.

ImportanceAnalyzing effects within placebo groups allows for transdiagnostic comparisons, as placebo is the only substance systematically studied across all major psychiatric diagnoses. Recently, the study team meta-analytically showed that improvement under placebo varies across major psychiatric diagnoses. However, comprehensive transdiagnostic comparisons of negative effects under placebo (nocebo

Although information from real-world data can be used to identify factors that aid treatment choice, there are no guidelines for the use of such data. The aim of this Review is to summarise and evaluate definitions of treatment outcomes for antidepressants, antipsychotics, and mood stabilisers when using real-world data, and to suggest standards for the field. Given that no standards for the use of

ImportanceIndividuals whose chronic pain is managed with opioids are at high risk of developing an opioid use disorder. Electronic health records (EHR) allow large-scale studies to identify a continuum of problematic opioid use, including opioid use disorder. Traditionally, this is done through diagnostic codes, which are often unreliable and underused.ObjectiveTo determine whether regular expressions

ImportanceDespite evidence that individuals with a cannabis use disorder (CUD) are at elevated risk of psychosis and that the neurotransmitter dopamine has a role in psychosis, the mechanism linking cannabis use and psychosis remains unclear.ObjectiveTo use neuromelanin-sensitive magnetic resonance imaging (MRI), referred to as the neuromelanin-MRI signal, a practical, proxy measure of dopamine function

ImportanceClinical practice guidelines recommend suicide risk screening and assessment across behavioral health settings. The predictive accuracy of real-world clinician assessments for stratifying patients by risk of future suicidal behavior, however, remains understudied.ObjectiveTo evaluate routine clinical suicide risk assessment for prospectively predicting suicide attempt.Design, Setting, and

INTRODUCTION Emotion dysregulation is prevalent in autistic adults without intellectual disability whereby it has been associated with heightened non-suicidal self-injury and suicidal behaviours. Dialectical behaviour therapy (DBT) has shown to be feasible and preliminary findings suggest that it might reduce emotion dysregulation in this population. Yet studies evaluating the efficacy of DBT in this

INTRODUCTION Repetitive transcranial magnetic stimulation (rTMS) of the left dorsolateral prefrontal cortex (DLPFC) is an established treatment for refractory major depressive disorder (MDD), but treatment outcomes vary substantially from person to person. Recent evidence suggests that incorporating neuroimaging-based targeting may help improve clinical outcomes. Here, we report the initial clinical

Depression among young people (aged 18–29 years) transitioning to adulthood is becoming more widespread. Knowing which factors in which systems co-enable resilience to depression is crucial, but there is no comprehensive synthesis of the physiological, psychological, social, economic, institutional, cultural, and environmental system factors associated with no or minimal emerging adult depression,

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New treatment options are needed for adolescent schizophrenia, partly due to an unfavourable risk–benefit profile of current options. This trial aimed to evaluate the short-term efficacy and safety of brexpiprazole in adolescents with schizophrenia.

Concerns about the cardiovascular safety of medications used for the treatment of attention-deficit hyperactivity disorder (ADHD) remain. We aimed to compare the effects of pharmacological treatments for ADHD on haemodynamic values and electrocardiogram (ECG) parameters in children, adolescents, and adults.

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ImportanceMajor depressive disorder (MDD) is a severe mental illness characterized more by functional rather than structural brain abnormalities. The pattern of regional homogeneity (ReHo) deficits in MDD may relate to underlying regional hypoperfusion. Capturing this functional deficit pattern provides a brain pattern–based biomarker for MDD that is linked to the underlying pathophysiology.ObjectiveTo

ImportanceTreatment-resistant depression (TRD) remains a critical challenge in psychiatry, with limited effective options. Esketamine, a rapid-acting antidepressant, is usually combined with a selective serotonin reuptake inhibitor (SSRI) or a serotonin-norepinephrine reuptake inhibitor (SNRI), but comparative evidence of these combinations’ effectiveness in real-world settings is sparse.ObjectiveTo

This Viewpoint discusses the opportunity to include inflammatory biomarkers as specifiers for major depression in the upcoming Sixth Edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-6).

ImportanceTraumatic brain injury is common and occurs across all ages. Observational studies have shown that traumatic brain injury is associated with a wide range of mental disorders and suicide. Whether these associations represent a causal effect is, however, difficult to establish, and confounding by genetic liability for mental disorder may play a substantial role.ObjectiveTo investigate whether

OBJECTIVE Schizophrenia is a neurodevelopmental disorder characterized by an excessive loss of synapses. Kynurenic acid (KYNA), a neuroactive metabolite of tryptophan along the kynurenine pathway, can induce schizophrenia-related phenotypes in rodents, and clinical studies have revealed elevated KYNA levels in the CNS of individuals with schizophrenia. However, the factors that cause elevated KYNA

OBJECTIVE Estimating the current association between childhood adversity and the risk of psychosis is crucial for prevention and intervention. We provided an updated synthesis of evidence from the past four decades, expanded the available data by investigating a broad array of adversity subtypes, and explored sex differences and the age of psychosis onset as relevant factors. METHODS We searched PubMed

The field of neuromodulation has evolved tremendously and now includes a vast array of interventions utilizing different technologies that span electrical, magnetic, and ultrasound forms of stimulation. The evolution of interventions holds the promise of fewer adverse effects and a noninvasive approach, increasing the scale at which these interventions may be offered in hospital and community settings

Schizophrenia is a mental illness involving multiple symptom domains and is often associated with substantial physical health comorbidities. Guidelines exist, but these tend to be country-specific and are often missing a concise yet comprehensive algorithmic approach. From May 1, 2023, to Jan 1, 2025, International Guidelines for Algorithmic Treatment (INTEGRATE) authors from all UN regions collaborated

BACKGROUND Brief concentrated exposure and response prevention (cERP) has shown promise as an efficacious treatment for obsessive-compulsive disorder (OCD). with higher response and remission rates compared to the first-line treatment. However, the mechanisms driving this success remain unclear. METHODS This longitudinal study included 56 patients with OCD who underwent cERP (Bergen four-day treatment;

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The brain disease model of addiction has dominated public and scientific discourse on addiction (termed substance use disorder [SUD] in the DSM-5) over the past 3 decades. The model framed addiction as a chronic and relapsing brain disease caused by structural and functional brain alterations. The purpose of this model was purportedly dual, as both an aetiological theory and a tool to reduce stigma