ecopipam (PSYRX 101) / Paragon Biosci - LARVOL DELTA

Exposure-response (ER) and Clinical Trial Simulations for Efficacy of Ecopipam in Adults and Pediatrics with Tourette's Syndrome (TS) (AAN 2026) - "PopPK, E-R, and clinical trial simulations add to the weight of evidence for the efficacy of ecopipam in pediatrics and adults with TS."

Clinical • Pediatrics • Tourette Syndrome

Receptor Selectivity Profile and Clinical Significance of Ecopipam and Relevant Metabolites: A Potential New Treatment for Tourette Syndrome (TS) (AAN 2026) - "Ecopipam demonstrated selectivity for D1Rs over ~98 off-target receptors, ion channels, enzymes, and transporters. These data are consistent with the clinical profile of the drug in the TS patient population."

Clinical • Movement Disorders • Tourette Syndrome

Efficacy and Safety of Ecopipam in Treatment of Tourette Syndrome: A Systematic Review and Meta-analysis with GRADE Assessment (AAN 2026) - "Ecopipam demonstrates potential efficacy at reducing tics in TS patients while also having a favorable safety profile. However, because of the small sample size and restricted number of included studies, additional follow-up research is required."

Retrospective data • Review • CNS Disorders • Developmental Disorders • Insomnia • Movement Disorders • Sleep Disorder • Tourette Syndrome

Efficacy and Safety of Ecopipam for Tourette Syndrome: Results from a Phase 3, Double-blind, Placebo-controlled, Randomized Withdrawal Trial (AAN 2026) - "This study demonstrated that ecopipam maintained clinically meaningful improvements in TS symptoms; was generally well-tolerated, with AEs primarily affecting the CNS; and did not cause weight gain, dyslipidemia, or drug-induced movement disorders."

Clinical • P3 data • Dyslipidemia • Insomnia • Metabolic Disorders • Mood Disorders • Movement Disorders • Sleep Disorder • Tourette Syndrome

Plain Language Summary of a Phase 2b Randomized Controlled Trial of Ecopipam and Its 12-Month Open-Label Extension in Children and Adolescents With Tourette Syndrome. (PubMed, Ther Adv Neurol Disord) - "The studies tested if ecopipam could safely improve symptoms and quality of life in children and adolescents with Tourette syndrome. Please note that ecopipam is not currently approved to treat Tourette syndrome."

Journal • P2b data • Review • Movement Disorders • Tic Disorders • Tourette Syndrome

The Effect of Uridine Diphosphate-Glucuronosyltransferase Inhibition on the Pharmacokinetics of Ecopipam and Its Metabolites. (PubMed, Clin Transl Sci) - "This open-label, fixed-sequence study evaluated the effect of mefenamic acid (UGT1A9 inhibitor) and divalproex sodium extended release (ER; general UGT inhibitor) on the pharmacokinetics (PK) of ecopipam and its metabolites. Divalproex sodium ER increased the Cmax (66%) and AUCinf (2.1×) of ecopipam, increased the Cmax (40%) and AUCinf (86%) of EBS-101-40853, and decreased the Cmax of ecopipam glucuronide and EBS-101-40853 glucuronide (23% and 32%, respectively). Inhibition of ecopipam metabolism indicated that ecopipam dose adjustments may be needed when administered with UGT inhibitors."

Journal • PK/PD data • Movement Disorders • Tourette Syndrome

Pharmacological manipulation of binge-like eating in male and female rats. (PubMed, Pharmacol Biochem Behav) - "The amphetamine prodrug lisdexamfetamine (0.1875-1.5 mg/kg IP), which is used to treat binge eating disorder in humans, suppressed intake of all foods in both sexes, with the greatest effects on chocolate. Co-administration of dopamine receptor antagonists with varying selectivity profiles (ecopipam, haloperidol, flupenthixol) reversed the suppressive effects of LDX on binge-like intake of chocolate, with haloperidol and flupenthixol producing more robust effects. The final group of studies characterized the effects of two commonly prescribed drugs for weight-loss that have been suggested as treatment options for binge eating disorder (bupropion and naltrexone). These drugs, alone and in combination, suppressed binge-like intake of chocolate. Taken together, these findings contribute to the development of animal models of BLE, which can potentially foster the development of treatments for binge eating disorder."

Journal • Preclinical • Binge Eating Disorder • CNS Disorders

The Effect of Ecopipam on the Pharmacokinetics of Concomitant Medications. (PubMed, Clin Transl Sci) - "Cohort 3 received an oral solution containing microdoses of dabigatran (P-gp), pitavastatin (OATP1B1), rosuvastatin (BCRP, OATP, and P-gp), atorvastatin (BCRP, OATP, P-gp, and CYP3A4), and midazolam...Steady-state ecopipam administration increased dextromethorphan exposure (> 100-fold); decreased the AUCinf of midazolam, omeprazole, and dabigatran by 44.2%, 44.1%, and 37.9%, respectively; and decreased unconjugated bilirubin (UGT1A1) by 19.5%...There were no changes in caffeine, bupropion, or pitavastatin exposure. Ecopipam is a strong inhibitor of CYP2D6 and weak inducer of CYP3A4, CYP2C19, P-gp, and UGT1A1. Ecopipam did not inhibit CYP3A4, CYP2C19, CYP2B6, CYP1A2, UGT1A1, P-gp, or OATP1B1 and did not induce OATP1B1 or CYP2B6."

Journal • PK/PD data • Movement Disorders • Tourette Syndrome • CYP1A2 • CYP2C19 • CYP3A4 • UGT1A1

QUESTIONS THAT MAKE YOU TIC: A TOURETTE'S DISORDER AND RELATED DISORDERS UPDATE (AACAP 2025) - "Cathy L. Budman, MD, will provide an overview of TD pharmacology and focus on new, promising interventions, including ecopipam and gemlapodect. This Symposium highlights novel, practical, clinically relevant advances in TD and related disorders' conceptualization and treatment interventions.TICD, TRIC, NI"

ADHD (Impulsive Aggression) • Attention Deficit Hyperactivity Disorder • CNS Disorders • Inflammation • Mental Retardation • Movement Disorders • Psychiatry • Tic Disorders • Tourette Syndrome

Efficacy of Ecopipam on Motor and Phonic Tics in Tourette's Disorder: Data From a Phase 3 Randomized, Double-Blind, Placebo-Controlled Trial (AACAP 2025) - "Ecopipam significantly improved both motor and phonic tics in children, adolescents, and adults with TD and was generally well tolerated.TD"

Clinical • P3 data • CNS Disorders • Fatigue • Insomnia • Mood Disorders • Movement Disorders • Pediatrics • Psychiatry • Sleep Disorder • Tourette Syndrome

Update on Pharmacology in Tourette's Disorder (AACAP 2025) - "There are only 3 pharmacological interventions FDA-approved for TD: pimozide, haloperidol, and aripiprazole, and as such, most treatments are used off-label...She will also describe recent trials that did not meet their primary end points (eg, deutetrabenazine, nabiximols), but may still hold promise for certain individuals/subgroups with TD... There is a great need for new medications for TD that are as effective for tics as antipsychotics, but without the potential short and long-term side effects associated with typical and atypical antipsychotics. Recently, new medications currently in Phase IIb and III trials are showing great promise!.TD, TICD, PPC"

CNS Disorders • Mental Retardation • Movement Disorders • Psychiatry • Tourette Syndrome

Efficacy and Safety of Ecopipam for Tourette Syndrome (TS): Results From a Phase 3, Randomized, Double-Blind, Placebo-Controlled Withdrawal Trial (MDS Congress 2025) - "This phase 3 trial provided confirmatory evidence that clinically meaningful improvements in TS symptoms were maintained with continued ecopipam treatment, which was generally well tolerated."

Clinical • P3 data • CNS Disorders • Insomnia • Mood Disorders • Movement Disorders • Psychiatry • Sleep Disorder • Tourette Syndrome

Determination of the Minimal Clinically Important Difference in the Yale Global Tic Severity Scale Total Tic Score in a Pediatric Population With Tourette Syndrome Receiving Pharmacotherapy (MDS Congress 2025) - " The study included data from 2 trials of the investigational drug ecopipam (1 randomized controlled trial and its open-label extension)... This analysis is the first to establish the MCID for YGTSS in a pediatric population with TS receiving pharmacotherapy. Whether using CGI-TS-S or CGI-TS-I as the anchor, a 25% reduction in YGTSS scores was an appropriate minimum threshold to define clinically meaningful improvement in this population. Results provide an objective threshold for classifying clinically meaningful improvement in children/adolescents receiving pharmacotherapy for TS in clinical practice."

Clinical • CNS Disorders • Movement Disorders • Tourette Syndrome

Large nesting expression in deer mice remains stable despite dopamine and adenosine modulation: insights into the psychobiology of compulsive-like rigidity (ECNP 2025) - "While selective serotonin reuptake inhibitors (SSRIs), e.g., escitalopram (ESC), are regarded as first line pharmacotherapy, treatment resistance remains a clinical dilemma. We show that NNB, as opposed to LNB, inflates over time irrespective of exposure (p = 0.0008), with LNB expression remaining stable. However, nesting inflation in NNB mice exposed to ecopipam trended towards being the least compared to all other treatment groups (0.05 > p 0.8). Collectively, our data support earlier findings that LNB is an evolutionary conserved behaviour borne from a neurobiological underpinning that drives maximal cortico-striatal activation."

Preclinical • CNS Disorders • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry

Combined inhibition of dopamine D1/D2 receptors induces cognitive and emotional dysfunction through oxidative stress and dopaminergic neuron damage. (PubMed, Front Behav Neurosci) - "In this study, we aimed to investigate the dose-dependent effects of co-DR1/2I (combined administration of dopamine receptor 1 inhibitor SCH39166 and dopamine receptor 2 inhibitor raclopride) on oxidative stress, learning, memory, emotion, and motor function in the substantia nigra, striatum, and hippocampus of mice...This is the first study to demonstrate that co-DR1/2I triggers cognitive and emotional dysfunction by exacerbating oxidative stress and dopaminergic neuronal damage, thereby advancing our understanding of the neurotoxic mechanisms of dopamine receptor antagonists. Future studies are needed to explore targeted antioxidant therapies and receptor-selective modulation strategies to reduce the side effects."

Journal • Alzheimer's Disease • CNS Disorders • Mental Retardation • Mood Disorders • Movement Disorders • Parkinson's Disease • Psychiatry

EBS-101-TD-391: A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette's Disorder (clinicaltrials.gov) - P3 | N=150 | Active, not recruiting | Sponsor: Emalex Biosciences Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Movement Disorders • Tourette Syndrome

EBS-101-TD-392: Expanded Access Program for Treatment With Ecopipam for Tourette's Disorder (clinicaltrials.gov) - P=N/A | N=0 | Temporarily Not Available | Sponsor: Emalex Biosciences Inc.

New trial • Tourette Syndrome

Tourette Syndrome and Tic Disorders. (PubMed, Continuum (Minneap Minn)) - "A first-in-class compound called ecopipam met the primary endpoint for tic reduction and was well-tolerated, and may be a promising new treatment for Tourette syndrome...Educating patients about the natural history and expected course of the disease is the most important first step in management. Choosing a treatment based on comorbidities, tic severity, and patient preference is crucial for a beneficial outcome."

Journal • Review • Infectious Disease • Movement Disorders • Novel Coronavirus Disease • Tic Disorders • Tourette Syndrome

Regulation of working memory switches from striatal dopamine D2-receptor to D1-receptor neurons under high cognitive load. (PubMed, PLoS Biol) - "Additionally, treatment with the D1R antagonist SCH39166, but not the D2R antagonist Sulpiride mitigates these impairments. Collectively, our findings propose a "relay" model wherein cognitive load-dependent WM control switches from DMS D2R- to D1R-neurons, offering nuanced, complementary, and inhibitory regulation of WM maintenance and retrieval. This study suggests potential strategies to enhance WM by promoting a suppressive state in DMS and to increase WM capacity through specific modulation of DMS D1R-neurons."

Journal • DRD2

Safety and Effect of 12-Month Ecopipam Treatment in Pediatric Patients with Tourette Syndrome. (PubMed, Mov Disord Clin Pract) - "Twelve months of ecopipam dosing was well tolerated during this study and no new adverse events were detected. Compared to baseline, significantly reduced TS symptom severity and improved QOL were observed in children and adolescents."

Journal • CNS Disorders • Depression • Developmental Disorders • Infectious Disease • Mood Disorders • Movement Disorders • Pediatrics • Psychiatry • Tic Disorders • Tourette Syndrome

Determining Clinically Meaningful Improvement in Children and Adolescents with Tourette Syndrome Receiving Pharmacotherapy. (PubMed, J Child Adolesc Psychopharmacol) - "Materials and Analyses used data from two clinical trials of ecopipam (a randomized controlled trial and its open-label extension)...Whether using CGI-TS-S or CGI-TS-I as the anchor, a 25% reduction in YGTSS scores was a generally appropriate minimum threshold to define clinically meaningful improvement in this population. Findings offer an objective threshold for classifying clinically meaningful improvement in children and adolescents receiving pharmacotherapy for TS in clinical practice."

Journal • Movement Disorders • Pediatrics • Tic Disorders • Tourette Syndrome

EBS-101-TD-391: A Study to Evaluate Long-term Safety of Ecopipam Tablets in Children, Adolescents and Adults With Tourette's Disorder (clinicaltrials.gov) - P3 | N=150 | Recruiting | Sponsor: Emalex Biosciences Inc. | Trial primary completion date: Nov 2024 ➔ Dec 2026

Trial primary completion date • Movement Disorders • Tourette Syndrome

D1AMOND: Ecopipam Tablets to Study Tourette's Disorder in Children, Adolescents and Adults (clinicaltrials.gov) - P3 | N=216 | Completed | Sponsor: Emalex Biosciences Inc. | Active, not recruiting ➔ Completed

Trial completion • Tourette Syndrome

Ecopipam Induced Hyperkalemia in an 18-Year-Old Male (NKF-SCM 2025) - "This case emphasizes the need for ongoing safety monitoring in the use of any investigational medication and identifies a potentially novel adverse effect associated with ecopipam.Conclusion This case highlights a novel adverse effect of ecopipam, an investigational Tourette Syndrome treatment, causing hyperkalemia due to renal tubular dysfunction. Monitoring renal function and serum potassium is crucial to mitigate risks, emphasizing the need for thorough safety assessments in clinical trials."

CNS Disorders • Congenital Adrenal Hyperplasia • Developmental Disorders • Endocrine Disorders • Hypotension • Movement Disorders • Nephrology • Psychiatry • Renal Disease • Tourette Syndrome

Changes in Metabolic Parameters and Determination of Minimal Clinically Important Difference in YGTSS-TTS Using Data From the Randomized Phase 2b and Open-Label Extension Studies of Ecopipam For Tourette Syndrome (AAN 2025) - "Ecopipam did not adversely affect parameters associated with an increased risk of metabolic syndrome. ROC analysis suggested that ≥25% reduction in YGTSS-TTS is an appropriate minimum threshold to define clinically meaningful improvement (MCID) in this patient population."

Clinical • P2b data • Metabolic Disorders • Movement Disorders • Tourette Syndrome