FDA approves novel antipsychotic lumateperone as a new adjunctive treatment for depression
The Food and Drug Administration (FDA) has approved lumateperone, a drug originally developed to treat psychosis, as an adjunctive treatment for major depressive disorder.
Lumateperone is an atypical antipsychotic with a distinctive mechanism of action. It is a serotonin 5-HT2A receptor antagonist and a partial agonist at central dopamine D2 receptors. Already approved for schizophrenia and depressive episodes associated with bipolar disorder, lumateperone gained approval in November 2025 as an adjunctive therapy to antidepressants for major depressive disorder in adults who experience only partial response to standard antidepressants.
The decision was underpinned by two positive phase 3 randomized controlled trials, demonstrating that lumateperone, when added to an oral antidepressant, significantly reduced depressive symptoms compared with placebo. Participants tolerated the treatment well over six weeks, with somnolence, dry mouth, diarrhea, and dizziness the most frequently reported adverse effects. Importantly, rates of metabolic disturbance, extrapyramidal symptoms, and prolactin elevation, often problematic with other antipsychotic augmentation strategies, remained low.[381][382] An accompanying open-label extension study suggests this favorable tolerability profile may persist over 6 months.[383]
Lumateperone’s unique mechanism of action and safety profile may make it a valuable option in the future for select patients with depression, particularly those with a partial response to antidepressants, or for whom there are concerns about tolerability with other augmentation treatments. However, longer-term and real-world data are lacking, and head-to-head trials with established augmentation drugs are still needed. Additionally, availability in the US is limited by cost. Lumateperone is not currently approved in Europe.
Summary
Definition
ანამნეზი და გასინჯვა
ძირითადი დიაგნოსტიკური ფაქტორები
- depressed mood
- anhedonia
- functional impairment
სხვა დიაგნოსტიკური ფაქტორები
- weight change
- libido changes
- sleep disturbance
- changes in movement
- low energy
- excessive guilt
- poor concentration
- suicidal ideation
- somatic symptoms
- bipolar disorder excluded
- substance abuse/medication side effects excluded
- medical illness excluded
- schizophrenia excluded
რისკფაქტორები
- postpartum status
- personal or family history of depressive disorder or suicide
- history of an anxiety disorder, or anxiety symptoms
- adverse childhood experiences
- dementia
- corticosteroid use
- interferon use
- oral contraceptive use
- coexisting medical conditions
- female sex
- comorbid substance use
- personality disorders
- history of violent victimization
- obesity
- older age (≥65 years)
- separated/divorced marital status
დიაგნოსტიკური კვლევები
1-ად შესაკვეთი გამოკვლევები
- clinical diagnosis
- metabolic panel
- CBC
- thyroid function tests
- Patient Health Questionnaire-2 (PHQ-2)
- Patient Health Questionnaire-9 (PHQ-9)
- Edinburgh Postnatal Depression Scale
- Geriatric Depression Scale
- Cornell Scale for Depression in Dementia
გასათვალისწინებელი კვლევები
- 24-hour free cortisol
- vitamin B12
- folic acid
მკურნალობის ალგორითმი
at risk of harm to self or others (psychotic, suicidal, severe psychomotor retardation impeding activities of daily living, catatonia, or severe agitation): nonpregnant
at risk of harm to self or others (psychotic, suicidal, severe psychomotor retardation impeding activities of daily living, catatonia, or severe agitation): pregnant
more severe depression (PHQ score ≥16): nonpregnant
less severe depression (PHQ <16): nonpregnant
treatment-resistant/refractory depression
pregnant
treatment responsive
recurrent episode
კონტრიბუტორები
ავტორები
Dean F. MacKinnon, MD
Associate Professor
Psychiatry and Behavioral Sciences
The Johns Hopkins Hospital
Baltimore
MD
გაფრთხილება:
DFM declares that he has no competing interests.
მადლიერება
Dr Dean F. MacKinnon would like to gratefully acknowledge Dr Roger S. McIntyre, Dr Tonya Fancher, and Dr Richard Kravitz, the previous contributors to this topic.
გაფრთხილება:
RSM has received research funds from Stanley Medical Research Institute and National Alliance for Research on Schizophrenia and Depression (NARSAD). RSM is on the advisory board for AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen-Ortho, Solvay/Wyeth, Eli Lilly, Organon, Lundbeck, Biovail, Pfizer, Shire, and Schering-Plough. RSM is on the Speakers Bureau for Janssen-Ortho, AstraZeneca, Eli Lilly, Lundbeck, Biovail, and Wyeth. RSM has received research grants from Eli Lilly, Janssen-Ortho, Shire, and AstraZeneca. RSM has received travel funds from Bristol-Myers Squibb. TF declares that she has no competing interests. RK has received research grants from Pfizer on non-depression-related topics.
რეცენზენტები
Christopher Dowrick, BA MBChB MSc MD
Emeritus Professor
University of Liverpool
UK
გაფრთხილება:
CD has been reimbursed by Novartis for participating in an educational event.
Erin K. Ferenchick, MD
Center for Family and Community Medicine
Columbia University Medical Center
Upper Manhattan
NY
გაფრთხილება:
EKF declares that she has no competing interests.
რეცენზენტების განცხადებები
BMJ Best Practice-ის თემების განახლება სხვადასხვა პერიოდულობით ხდება მტკიცებულებებისა და რეკომენდაციების განვითარების შესაბამისად. ქვემოთ ჩამოთვლილმა რეცენზენტებმა თემის არსებობის მანძილზე კონტენტს ერთხელ მაინც გადახედეს.
გაფრთხილება
რეცენზენტების აფილიაციები და გაფრთხილებები მოცემულია გადახედვის მომენტისთვის.
წყაროები
ძირითადი სტატიები
American Psychiatric Association. Diagnostic and statistical manual of mental disorders, 5th ed., text revision (DSM-5-TR). Washington, DC: American Psychiatric Publishing; 2022.
National Institute for Health and Care Excellence. Depression in adults: treatment and management. Jun 2022 [internet publication].სრული ტექსტი
American College of Physicians. Nonpharmacologic and pharmacologic treatments of adults in the acute phase of major depressive disorder: a living clinical guideline from the American College of Physicians. Feb 2023 [internet publication].სრული ტექსტი
გამოყენებული სტატიები
ამ თემაში მოხსენიებული წყაროების სრული სია ხელმისაწვდომია მომხმარებლებისთვის, რომლებსაც აქვთ წვდომა BMJ Best Practice-ის ყველა ნაწილზე.
დიფერენციული დიაგნოზები
- Adjustment disorder with depressed mood
- Substance-/medication- or medical illness-associated and other depressive disorders
- Bipolar disorder
მეტი დიფერენციული დიაგნოზებიგაიდლაინები
- Mental Health Gap Action Programme (mhGAP) guideline for mental, neurological and substance use disorders
- WHO Clinical descriptions and diagnostic requirements for ICD-11 mental, behavioral and neurodevelopmental disorders (CDDR)
მეტი გაიდლაინებიპაციენტის ბროშურები
Depression in adults: what is it?
Depression in adults: what are the treatment options?
მეტი პაციენტის ბროშურებიCalculators
Geriatric Depression Scale
Depression (any) Screening by a Two Item PHQ-2
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