Psychopharmacotherapy Updates

Since 2024¹ and as of November 2025, the US Food and Drug Administration (FDA) has granted approvals for a number of psychotropic drugs on the market. Here is a recap to update busy prescribers.

Zepound (tirzepatide) is a twin-cretin agonist of both glucagon-like peptide-1 receptor (GLP-1R) and glucose-dependent insulinotropic polypeptide, previously approved for obesity and type 2 diabetes mellitus (branded as Mounjaro). It was recently approved for moderate-to severe obstructive sleep apnea (OSA) in adults with obesity² (December 2024) to be used in conjunction with a reduced-calorie diet and increased physical activity as a weekly subcutaneous (SQ) injection (maintenance dose of 10–15 mg). This latter approval was based on results from the SURMOUNT-OSA phase 3 clinical trials, which evaluated Zepbound (10 mg or 15 mg) for the treatment of moderate-to-severe OSA in adults with obesity, with and without positive airway pressure (PAP) therapy over the course of 52 weeks. Zepbound was about 5 times more effective than placebo in reducing apnea/hypopnea events, as measured by the Apnea-Hypopnea Index, in adults not on PAP therapy, leading to 25 fewer events per hour with Zepbound and 5 with placebo. In adults on PAP therapy, Zepbound led to 29 fewer events per hour compared to 6 with placebo. After 1 year, 42% of adults on Zepbound and 50% of adults on Zepbound with PAP therapy experienced remission or mild, nonsymptomatic OSA, compared to 16% and 14% on placebo, respectively.

In the same vein, pemvidutide, a novel peptide-based GLP-1/glucagon dual receptor agonist, is believed to potentially help moderate alcohol use disorder. GLP-1RAs reduce cravings for alcohol while glucagon reduces hepatosteatosis. It is currently being investigated in the RECLAIM trial.

Zunveyl (benzgalantamine) (July 2024) is a prodrug of galantamine (marketed as Razadyne), an acetylcholinesterase inhibitor as well as an allosteric-potentiating ligand of nicotinic acetylcholine receptors, long approved for mild-to-moderate Alzheimer disease (AD). This prodrug promises minimal gastrointestinal adverse events, insomnia, and improved bioavailability. It is dosed twice daily, 10–30 mg/d, with increments made every 4 weeks.³

Spravato (esketamine) intranasal (January 2025) is the S-enantiomer of ketamine, a broad high-trapping glutamatergic modulator, previously approved for treatment-resistant depression (TRD) or major depressive disorder (MDD) with acute suicidal ideation or behavior as adjunctive to an oral antidepressant.⁴ More recently, it was granted approval as a standalone treatment (monotherapy) for TRD (defined as failed adequate trials of 2 oral antidepressants). This approval is supported by positive results from the randomized, double-blind, multicenter, placebo-controlled study in which Spravato monotherapy showed a rapid (as early as 24 hours) and superior improvement on Montgomery-Asberg Depression Rating Scale (MADRS) total score vs. placebo. In a post hoc analysis, Spravato demonstrated numerical improvements across all 10 MADRS items at day 28.2. At week 4, 7.6% of patients taking placebo and 22.5% of patients taking Spravato achieved remission (MADRS total score ≤12). The safety profile of Spravato as monotherapy was consistent with the existing body of clinical and real-world data when used in conjunction with an oral antidepressant, and no new safety concerns were identified.

Arynta (lisdexamfetamine dimesylate) (June 2025) is an oral solution (10 mg/mL) of lisdexamfetamine (marketed as Vyvanse) approved for attention-deficit/hyperactivity disorder (ADHD) (age 6 years and above) and binge-eating disorder in adults. It is a dexamphetamine with the chemical lysine bound to it, which renders it inactive. It remains inactive until gastrointestinal enzymes cleave off lysine and convert it to active dexamphetamine. As a prodrug, it may have a lower risk of diversion or misuse. Onset of action is 60–90 minutes, and duration of action is 8–13 hours. Lisdexamfetamine 70 mg is equivalent to 30 mg of mixed amphetamine salts.⁵

Mezofy (aripiprazole) (April 2025) is an oral film formulation of the atypical antipsychotic aripiprazole (branded as Abilify), which comes in different formulations (tablets, solution, Discmelt orally disintegrating tablet, intramuscular short-acting injection, long-acting injectable antipsychotic Maintena and Asimtufii, MyCite embedded with Proteus sensor for use with sensor patch, and Opipza, which is another oral form).

Tonmya (cyclobenzaprine) (August 2025) is a sublingual form of this muscle relaxant dosed at bedtime for the treatment of fibromyalgia, providing rapid transmucosal absorption and pain relief possibly by targeting nonrestorative sleep. Cyclobenzaprine has demonstrated functional antagonism of 5-hydroxytryptamine2A (5-HT2A), α₁-adrenergic, H₁-histaminergic, and M₁-muscarinic acetylcholine receptors.⁶ Findings from the RELIEF and RESILIENT studies showed a statistically significant reduction in pain intensity scores with Tonmya compared with placebo.

Leqembi (lecanemab) is another amyloid β-targeted monoclonal antibody previously approved for mild cognitive impairment or the mild dementia stage of AD (the other agents being aducanumab and donanemab). It is given as intravenous (IV) infusion every 2 weeks to eligible patients with confirmed presence of Aβ pathology beforehand (using amyloid positron emission tomography scan or lumbar puncture and cerebrospinal fluid). It is recommended to remain alert for amyloid-related imaging abnormalities during the first 14 weeks of treatment.⁷ Also, the FDA has approved a subcutaneous formulation of lecanemab for maintenance dosing (August 2025). After 18 months of IV treatment, patients may either continue IV infusions at 10 mg/kg once every 4 weeks or switch to this new weekly 360-mg SQ injection using Leqembi Iqlik autoinjector. This is an important move toward making lecanemab more accessible to patients.

Lynkuet (elinzanetant) (October 2025) is a neurokinin (NK) 1 and NK-3 antagonist for moderate-to-severe vasomotor changes in menopause. It inhibits substance P and NKB through this dual NK-targeted mechanism.⁸ It comes in soft gel capsules of 60 mg strength. Dosed at 120 mg to be taken once daily every night at bedtime, elinzanetant is a cytochrome P450 3A4 substrate. Similarly, Veozah (fezolinetant), a nonhormonal, selective NK-3 antagonist, which works by blocking NKB binding on kisspeptin/NKB/dynorphin and modulating neuronal activity in the thermoregulatory center, was previously approved for moderate-to severe vasomotor symptoms (eg, hot flashes) associated with menopause. Brisdelle (paroxetine) is also FDA-approved for hot flashes. Of note, serotonin-norepinephrine reuptake inhibitors (eg, effexor/venlafaxine) and Catapres (clonidine) have been used off-label to tackle vasomotor changes in menopause.

Lumateperone (Caplyta) is a butyrophenone previously FDA-approved for adult schizophrenia and bipolar depression (I and II). It possesses a potent antagonistic activity at 5-HT2A receptors and also binds to dopamine (D1, D2) receptors with partial agonism at presynaptic D2 receptors and postsynaptic low antagonism. It uniquely acts as an indirect modulator of glutamatergic phosphoprotein with D1-dependent augmentation of both N-methyl-D-aspartic-acid and α-amino-3-hydroxy 5-methyl-4-isoxazolepropionic acid activity via the mTOR pathway and also has intrinsic selective serotonin reuptake inhibitor (SSRI) activity.⁹ It has recently been approved as augmentation in MDD at a dose of 42 mg/d, with an effect size of 0.6 and a better tolerability profile in terms of metabolic syndrome and extrapyramidal side effects, albeit sedating (November 2025). Other antipsychotics approved for MDD augmentation include aripiprazole, brexpiprazole, cariprazine, quetiapine, and olanzapine-fluoxetine combination.¹⁰

Uzedy long-acting injectable (LAI) (risperidone), similar to Perseris (discontinued), is an LAI that is given SQ every 1–2 months with an 80% decrease in relapse rates of schizophrenia. It utilizes a novel copolymer technique (SteadyTeq).¹¹ It can be initiated without oral loading or overlap. It has also been recently approved for maintenance treatment of bipolar I disorder in adults (October 2025).

Javadin (Clonidine) (October 2025) is an oral solution of the α2 agonist clonidine 0.02 mg/mL for hypertension in adults. Since clonidine has many indications in psychiatry,¹² including ADHD, opiate detox, Tourette disorder, and posttraumatic stress disorder (PTSD), we opted to include it here.

Subvenite (lamotrigine) (September 2025) is an oral suspension form of lamotrigine for epilepsy and bipolar mood disorder. The mode of action is composite and includes voltage-gated sodium and calcium channel blockade, antiglutamate and antiaspartate, antikindling, weak 5-HT3 antagonism, and neuroprotection as well. This pharmacologic portfolio clinically translates into a broad therapeutic potential, although off-label driven, for treatment-resistant schizophrenia, treatment-resistant obsessive-compulsive disorder, depersonalization disorder, and affective dysregulation and behavioral dyscontrol domains of borderline personality disorder, just to name a few.¹³

Of related interest, as of June 2025, the FDA has officially eliminated the clozapine risk evaluation and mitigation strategy (REMS) program. Accordingly, prescribers no longer need to submit patient absolute neutrophil count (ANC) results to the clozapine REMS. In the same vein, consensus guidelines from a global Delphi panel drop ANC monitoring after 2 years. Experts developed a clozapine monitoring algorithm that includes weekly ANC monitoring for the first 18 weeks after initiation, followed by monthly monitoring from week 19 through year 2 then annual complete blood counts thereafter to screen for hematologic malignancies. The algorithm includes a recommended ANC cessation threshold of 1.0 × 109 cells/L or 0.5 × 109 cells/L for individuals with benign ethnic neutropenia who are Duffy antigen receptor for chemokines null. Panel members developed a detailed checklist for regular and comprehensive adverse drug reaction monitoring including constipation and sialorrhea. Panel members also provided management guidelines for weight gain and metabolic syndrome, gastroesophageal reflux, sedation, sleep apnea, nocturnal enuresis and urinary incontinence, and tachycardia. Annual electrocardiograms did not reach consensus for routine use, so the expert panel does not recommend them.^14,15

Of note, an FDA advisory panel has resoundingly rejected the supplemental new drug application for the atypical antipsychotic brexpiprazole (Rexulti), in combination with the SSRI sertraline (Zoloft), for the treatment of adults with PTSD (October 2025). FDA reviewers flagged discordant results from the 2 phase 3 trials.¹⁶

The FDA recently cited a review of the use of leucovorin in 40 patients with a very rare genetic/metabolic disorder known as cerebral folate deficiency with autism as behavioral phenotype of this disorder. The FDA has currently initiated the approval process (September 2025). Data in favor of treatment with leucovorin remain, at best, flimsy and are derived from small-sized randomized trials, using different doses, different outcomes (verbal skills, social skills, irritability, etc), and possibly in certain biotypes.¹⁷ That said, a modicum of evidence exists to suggest that d,l leucovorin, a reduced folate that can bypass the blockage at the folate receptor α by using the reduced folate carrier, an alternate pathway, can substantially improve particular symptoms in children with ASD, especially those positive for folate receptor α autoantibodies.

Strikingly, in 2025, the FDA granted fast track designation to several psychiatric drugs, including posdinemab, a τ-directed monoclonal antibody for early-stage Alzheimer disease treatment with a potential to slow cognitive decline.¹⁸ Brilaroxazine is a third-generation antipsychotic, dopamine-serotonin–signaling modulator, promising robust broad-spectrum efficacy sustained over 1 year across all symptom domains including negative symptoms, generally well tolerated with low rates of adverse events and discontinuation and improved multiple neuroinflammatory markers.¹⁹ Intuitively, a trimodal extended-release tablet, based on tablet-in tablet technology, which provides 3 releases of dexmethylphenidate hydrochloride, is expected soon providing onset-of-action within 30 minutes and efficacy for the entire active day. These once-a-day multirelease tablets have an initial immediate-release dose providing 35% of the total daily dose beginning within 5–6 minutes after administration and designed to achieve therapeutic efficacy within 30 minutes; a second release, 3 hours after the administration, referred to as the first delayed, sustained release providing 45% of the total daily dose released over 90 minutes; and a third release, 7 hours after the administration, referred to as a second-delayed, immediate release (DR2, the built-in booster) providing 20% of the total daily dose released over approximately 30 minutes.⁵ Finally, a once-weekly, long-acting oral formulation of risperidone composed of a coated capsule developed using the LYNX drug delivery platform, combines the adherence benefits of less-frequent dosing with a patient-friendly product that could be taken orally at home. In STARLYNG-1, a multicenter, open-label, nonrandomized phase 3 trial, it achieved similar bioavailability to daily immediate-release risperidone, maintaining therapeutic concentrations over the 5 weeks of the clinical trial and preserving clinical efficacy as measured by Positive and Negative Syndrome Scale total scores, with no emerging unexpected safety signals.²⁰ With all these exciting advances in the field of psychopharmacology, the year 2026 holds promise for more agents expanding our pharmacopoeia with patients’ best interests at heart.

Article Information

Published Online: April 7, 2026.https://doi.org/10.4088/PCC.25lr04088
© 2026 Physicians Postgraduate Press, Inc.
Prim Care Companion CNS Disord 2026;28(2):25lr04088
To Cite: Naguy A, Alayadhi N, Pridmore S, et al. Psychopharmacotherapy updates. Prim Care Companion CNS Disord. 2026;28(2):25lr04088.
Author Affiliations: Al-Manara CAP Centre, Kuwait Centre for Mental Health, Shuwaikh, State of Kuwait (Naguy, Alamiri); Pharmacy Department, Kuwait Centre for Mental Health, Shuwaikh, State of Kuwait (Alayadhi); Department of Psychiatry, University of Tasmania, Hobart, Tasmania, Australia (Pridmore).
Corresponding Author: Ahmed Naguy, MBBch, MSc, MRCPsych (UK), Al-Manara CAP Centre, Kuwait Centre for Mental Health, Jamal Abdul-Nassir St, Shuwaikh, State of Kuwait ([email protected]).
Financial Disclosure: None.
Funding/Support: None.