Psychiatry Year in Review: 2024

This year in review highlights the top 10 psychiatry news in 2024, from groundbreaking US Food and Drug Administration (FDA) approvals and a disappointing Complete Response Letter to emerging therapies shaping the mental health field. Key updates include the approval of xanomeline and trospium chloride (Cobenfy), a first-in-class schizophrenia treatment, and over-the-counter naloxone for opioid overdose. The FDA’s rejection of MDMA-assisted therapy for PTSD sparked debate, while MM120 gained breakthrough designation for anxiety. These milestones reflect psychiatry's evolving landscape.

1. FDA Approves Xanomeline and Trospium Chloride (Cobenfy) for Schizophrenia

The FDA announced their approval of xanomeline and trospium chloride capsules (Cobenfy) for treating schizophrenia on September 26, 2024. This antipsychotic medication targets cholinergic receptors rather than dopamine receptors, offering a novel treatment option.

The approval is based on phase 3 EMERGENT trials, which showed significant improvements in schizophrenia symptoms, including positive, negative, and cognitive symptoms. Results indicated a notable reduction in the PANSS total score and long-term benefits, with 75% of participants experiencing a ≥30% symptom improvement after 52 weeks. Unlike previous treatments, xanomeline and trospium chloride capsules do not lead to adverse events such as weight gain and movement disorders.

2. FDA Issues a CRL for MDMA-Assisted Therapy for PTSD

The FDA issued a CRL letter for the treatment of MDMA-assisted therapy for PTSD, announced by Lykos Therapeutics on August 9, 2024. The decision followed negative feedback from the FDA’s Psychopharmacologic Drugs Advisory Committee who voiced concerns about the safety, cardiovascular risks, and issues related to functional unblinding in trial settings. The FDA requested that Lykos Therapeutics conduct an additional trial.

Related: Leading Experts Discuss FDA's Pending Decision on MDMA-Assisted Therapy for PTSD

The Rise, Fall (and Future?) of MDMA-Assisted Therapy

3. Psychiatry at a Crossroad Following FDA Decision on MDMA-Assisted Therapy

Following the FDA’s decision on MDMA-assisted therapy, HCPLive put together another episode of Crisis Point, a compilation of interviews with PTSD experts and a trial participant directly following the news. Everyone whom HCPLive spoke to had expressed their disappointment with this turn of events. Despite the decision, 1 of the PTSD experts, a former principal investigator for the phase 3 MAPS-sponsored MDMA-assisted therapy clinical trials from 2018 – 2023, remains optimistic that MDMA-assisted therapy will be a treatment option later down the road.

Related: MDMA-Assisted Therapy Trial Participant Reacts to FDA’s Decision on Lykos’ NDA

Reagan Udall Foundation’s PTSD Meeting Was “Reassuring,” Says Healthcare Expert

4. FDA Approves Iloperidone (Fanapt) for Acute Treatment of Bipolar I Disorder

Vanda Pharmaceuticals announced on April 2, 2024, that the FDA approved iloperidone (Fanapt) for the acute treatment of bipolar I disorder. The decision was based on the findings of a phase 3, randomized, double-blind, placebo-controlled study, which found iloperidone demonstrated significant improvement compared to placebo at week 4 for the primary and secondary endpoints, as well as had a comparable tolerability and safety profile to other clinical trials.

Despite the previous controversy of iloperidone for schizophrenia, iloperidone for bipolar disorder demonstrated significant improvements in the Young Mania Rating Scale (P = .000008). Investigators observed significant differences between iloperidone and placebo by day 28.

5. FDA Approves Over-the-Counter Naloxone Nasal Spray for Opioid Overdose

The FDA approved the over-the-counter naloxone hydrochloride (Naloxone HCI) nasal spray for emergency treatment of an opioid overdose, announced by Amneal Pharmaceuticals on April 24, 2024. The approval followed an Abbreviated New Drug Application (ANDA0 for naloxone hydrochloride (Naloxone HCI) nasal spray at 4 mg.

Naoloxone HCI is the generic, more affordable equivalent to the Narcan HCI Nasal Spray 4 mg, approved in March 2023. Both Narcan HCI Nasal and Naloxone HCI are used to treat drug overdose from opioids, such as heroin, fentanyl, and prescription opioid medications. The Narcan HCI Nasal spray was also approved for nonprescription, over-the-counter use.

6. New Psychedelic CPT Codes: Paving the Way for a New Age of Psychiatric Care

On January 1, 2024, the American Medical Association’s current procedural terminology (CPT) III codes for psychedelic-assisted therapies took effect. These temporary codes allow healthcare providers to navigate billing for emerging treatments, addressing common barriers like physician hesitation and insurance coverage challenges.

7. Daniel Karlin, MD: FDA Grants Breakthrough Designation to MM120 for Anxiety

The FDA granted MindMed breakthrough therapy designation for MM120 (lysergide d-tartrate) for generalized anxiety disorder (GAD) following phase 2B trial results showing significant efficacy and durability through 12 weeks. A single 100 µg dose of MM120, administered in a monitored clinical setting, demonstrated rapid onset by day 2, with notable improvements in anxiety severity. At week 12, 65% of participants achieved clinical response, and 48% reached remission. Chief Officer Daniel Karlin, MD, emphasized this milestone as a recognition of MM120’s potential to meet unmet needs.

Related: Evaluating MM120 for GAD with Daniel Karlin, MD, and Reid Robinson, MD, MBA

8. Phase 3 Data on Brilaroxazine for Schizophrenia with Larry Ereshefsky, PharmD

Phase 3 RECOVER trial data revealed brilaroxazine significantly reduced acute schizophrenia symptoms. At 50 mg, the drug achieved a 10.1-point reduction in PANSS scores compared to placebo (P < .001), with notable improvements in positive, negative, and social cognition symptoms, as well as overall performance and safety. Brilaroxazine targets serotonin-dopamine signaling and inflammatory cytokines, offering a novel approach beyond receptor blockade. Larry Ereshefsky, PharmD, emphasized its potential role in addressing neuroinflammation and discussed plans to explore the 30 mg dose for acute schizophrenia.

9. Jacob Ballon, MD, MPH: Discusses Takeaways from Studying Long-Term Olanzapine and Samidorphan

A phase 3, open-label extension study evaluated the long-term safety and tolerability of olanzapine and samidorphan (LYBALVI) for schizophrenia and bipolar I disorder. Conducted over 4 years, the study showed LYBALVI was well-tolerated in 523 participants, with minimal changes in metabolic parameters and rare hospitalizations. Adverse events were mostly mild to moderate, such as weight gain and headache. Jacob Ballon, MD, MPH, highlighted LYBALVI's sustained metabolic safety and clinical efficacy, noting its potential to overcome concerns about olanzapine's metabolic side effects.

Related: Olanzapine, Samidorphan Effective for Long-Term Schizophrenia, Bipolar Disorder Treatment

10. Intra-Cellular Therapies Submits sNDA to FDA for Lumateperone as an MDD Adjunctive Therapy

Intra-Cellular Therapies resubmitted a supplemental New Drug Application (sNDA) to the FDA for lumateperone (CAPLYTA) as an adjunctive therapy to antidepressants for the treatment of MDD. If approved, this will expand the on-label use of lumateperone beyond the already-approved indications of adult schizophrenia and bipolar depression. The submission included 2 phase 3 global, double-blind, placebo-controlled studies that showed participants on lumatperone had a 4.9-point and 4.5-point reduction in depression symptoms, respectively (P < .0001).