Doria (risperidone extended release) / ROVI Pharmaceuticals Laboratories - LARVOL DELTA

Comparison of dopamine D2 receptor occupancy profiles between risperidone ism versus oral risperidone and monthly paliperidone palmitate based on population pharmacokinetic modelling and simulations. (PubMed, Expert Rev Clin Pharmacol) - "A much faster onset of action and better D2RO coverage during the dosing interval was predicted for Risperidone-ISM® versus PP1M. Simulations suggest that Risperidone-ISM® compares favorably with high doses of OR and PP1M, making it an effective therapeutic strategy for rapid and sustained symptom reduction."

Journal • PK/PD data • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Assessment of prolactin levels and sexual dysfunction in patients on long-acting risperidone ISM vs monthly paliperidone palmitate. (PubMed, Span J Psychiatry Ment Health) - "Risperidone ISM may be associated with a more favourable prolactin profile in women vs PP. Findings support the relevance of sex and adjunctive strategies in managing antipsychotic-induced endocrine side effects."

Journal • CNS Disorders • Endocrine Disorders • Psychiatry • Schizophrenia • Sexual Disorders

Use of risperidone "in situ microparticles" 100 mg in patients requiring higher oral doses of risperidone: a case report (ECNP 2025) - "Despite the constraints of clinical trial data, real-world experience may ultimately guide alternative dosing strategies beyond those currently approved. Further real-world studies are needed to clarify the issues raised herein and potentially support future evidence-based recommendations for currently off-label practices."

Case report • Clinical • CNS Disorders • Psychiatry • Schizophrenia

Risperidone "in situ microparticles" in the outpatient management of psychotic decompensation in an elderly patient with schizophrenia and multimorbidity (ECNP 2025) - "After discontinuing clozapine on his own initiative, he experienced clinical decompensation characterised by persecutory delusions and disorganised thought. Conflict of interest: Disclosure statement: The author declares that Laboratorios Farmacéuticos ROVI, S.A. provided financial support for congress registration. This support is unrelated to the content of the presentation."

Clinical • CNS Disorders • Psychiatry • Schizophrenia

Risperidone long-acting in-situ microimplant for acute management of manic episodes in non-adherent schizoaffective disorder: A retrospective study (ECNP 2025) - "Conclusions Single-dose R-ISM produced rapid antimanic effects and progressive improvement in psychotic thought content, with early irritability change predicting later cognitive benefit. While these findings are encouraging, their exploratory nature—retrospective design, modest sample, and concomitant therapies—warrant confirmation in prospective, randomised, placebo-controlled trials."

Retrospective data • Bipolar Disorder • CNS Disorders • Mood Disorders • Movement Disorders • Psychiatry • Schizophrenia

Risperidone ISM vs Paliperidone Palmitate on a sample of patients affected by schizophrenia: preliminary results from an observational comparative study (ECNP 2025) - "However, patient-reported results indicate some differences, which could depend on the intrinsic characteristics of the two drugs or on demographic or anamnestic differences of the patients. Further studies with larger sample, more homogeneous and comparable cohorts are needed to clarify the underlying reasons for these discrepancies in subjective outcome measures."

Clinical • CNS Disorders • Psychiatry • Schizophrenia • Substance Abuse • DRD2

Risperidone ISM injection in the acute setting for actively psychotic patients with schizophrenia: Case reports (ECNP 2025) - "His aripiprazole was changed to oral liquid risperidone 4 mg daily administered under close supervision...Moreover, as plasma levels equivalent to the oral doses of risperidone are rapidly achieved, Risperidone ISM facilitates the transition from oral to long-acting antipsychotic treatment and is therefore likely to reduce duration of hospital admissions, a hypothesis that warrants further scrutiny. Conflict of interest: Disclosure statement: The authors have participated in an international non-interventional prospective study sponsored by ROVI that evaluated Risperidone ISM"

Case report • Clinical • CNS Disorders • Cognitive Disorders • Psychiatry • Schizophrenia

Risperidone in situ microparticles, a novel drug-delivery option for schizophrenia: a comprehensive systematic review (ECNP 2025) - "Risperidone ISM emerges as a safe, well-tolerated, and effective long-term treatment for schizophrenia, providing rapid and sustained improvements in functioning regardless of baseline severity or prior treatment, indicating effectiveness in particular for severe symptoms. Differing from other LAIs, it provides rapid drug release, reaching therapeutic levels within 2 hours and maintaining them for four weeks, without the need for oral supplementation or loading doses [5]. It offers fast symptom control, excellent tolerability, and a lower risk of EPS."

Review • CNS Disorders • Psychiatry • Schizophrenia

Use of risperidone ISM in real-world hospitalized patients (ECNP 2025) - "Moreover, real-world findings suggest that the 100 mg dosage is preferentially used in patients with more severe clinical presentations and longer illness duration, aligning with clinical expectations. Table 1 VariableTotal_sampleR100R75Age41,16(13,58)41,12(13,55)41,29(14,76)Duration_illness(years)17,48(11,37)18,26(10,75)14,50(14,21) DUI_no_AP(years)5,14(7,05)5,41(7,46) 4,17(5,78)BPRS_In53,44(10,74)54,06(11,28)48,50(0,71)BPRS_Out31,41(4,72)30,87(4,58)35,50(4,95)"

Clinical • Real-world • Real-world evidence • CNS Disorders • Mental Retardation • Psychiatry

QUARTZ: Pharmacokinetics, Safety and Tolerability of Different Formulations and Dose Strengths of Quarterly Risperidone (QUAR) in Patients With Schizophrenia (clinicaltrials.gov) - P1 | N=58 | Completed | Sponsor: Rovi Pharmaceuticals Laboratories | Recruiting ➔ Completed | N=100 ➔ 58 | Trial completion date: May 2026 ➔ Jul 2025 | Trial primary completion date: May 2026 ➔ Jul 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

The place of risperidone in situ microparticles (ISM®) among long-acting injectable antipsychotics in schizophrenia treatment. (PubMed, Expert Opin Pharmacother) - "The resulting plasma levels ensure consistent dopamine D2 receptor occupancy above 65% over the full 28-day dosing cycle-an established benchmark for antipsychotic efficacy. In the short-term, risperidone ISM® enables a rapid and sustained symptoms reduction among adults with acute schizophrenia exacerbations, eliminating the need for initial loading doses or concurrent oral supplementation."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Clinical Utility of Long-Acting Injectable Risperidone in Schizophrenia and Bipolar I Disorder: A Review of Clinical Studies. (PubMed, Psychol Res Behav Manag) - "To date, five different risperidone LAI formulations have been marketed - including a second biweekly microsphere injection (LY03004), a newer monthly intramuscular formulation using in situ microparticles (ISM) technology that does not require an oral risperidone run-in, and two subcutaneous formulations (RBP-7000 and TV-46000)...To facilitate this, healthcare providers should develop a comprehensive understanding of these formulations to select the most suitable option. While risperidone ISM, RBP-7000, and TV-46000 may enhance treatment feasibility and adherence, further research is needed to build an evidence base comparable to that available for BW-RLAI, particularly in the treatment of BD."

Journal • Review • Bipolar Disorder • CNS Disorders • Mood Disorders • Psychiatry • Schizophrenia

RESHAPE: Non-interventional Study of Risperidone ISM® in Schizophrenia Patients Hospitalised Due to a Relapse (clinicaltrials.gov) - P=N/A | N=275 | Completed | Sponsor: Rovi Pharmaceuticals Laboratories | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Psychiatry • Schizophrenia

Pharmacokinetic characteristics of risperidone ISM for the treatment of schizophrenia. (PubMed, Expert Opin Drug Metab Toxicol) - "Risperidone-ISM achieves therapeutic blood levels within 12-48 hours after a single injection, currently lasting for 1 month, easing the initiation of a LAI risperidone formulation in adults with schizophrenia where LAIs remain underutilized. Prescriptions of LAIs, including risperidone-ISM, are likely to increase with an improved understanding of pharmacokinetic profiles and patient acceptability and outcomes, including in real-world settings informing drug selection."

Journal • PK/PD data • Review • CNS Disorders • Psychiatry • Schizophrenia

Evaluating the Real-World Pharmacokinetics of Risperidone ISM® in Routine Clinical Practice. (PubMed, Biomedicines) - " Risperidone ISM® achieves rapid and sustained therapeutic plasma levels, offering significant benefits in schizophrenia treatment. However, the high interindividual variability observed must be thoroughly studied, and the contributing factors identified to ensure the therapy is as effective and safe as possible."

Journal • PK/PD data • Real-world evidence • CNS Disorders • Psychiatry • Schizophrenia

RESHAPE: Non-interventional Study of Risperidone ISM® in Schizophrenia Patients Hospitalised Due to a Relapse (clinicaltrials.gov) - P=N/A | N=277 | Active, not recruiting | Sponsor: Rovi Pharmaceuticals Laboratories | Recruiting ➔ Active, not recruiting | N=1200 ➔ 277 | Trial completion date: Dec 2024 ➔ Mar 2025 | Trial primary completion date: Dec 2024 ➔ Mar 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Risperidone In Situ Microparticles: A Review in Schizophrenia. (PubMed, Drugs) - "Risperidone ISM® was generally well tolerated in clinical trials, with a safety profile consistent with that of oral risperidone. Its fast onset of action, without the need for oral supplementation or loading doses, makes risperidone ISM® a promising long-acting injectable that could enhance treatment adherence."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia

Risperidone ISM®: review and update of its usefulness in all phases of schizophrenia. (PubMed, Ther Adv Psychopharmacol) - "Improvement and maintenance of personal and social functioning and health-related quality of life were observed in each setting, respectively. All these findings endorse Risperidone ISM as a useful and valuable treatment for the acute and maintenance management of patients with schizophrenia."

Journal • Review • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Exposure-Efficacy Analysis and Dopamine D2 Receptor Occupancy in Adults with Schizophrenia after Treatment with the Monthly Intramuscular Injectable Risperidone ISM. (PubMed, J Clin Pharmacol) - "Pharmacokinetic/pharmacodynamic modeling quantified a PANSS improvement over time after Risperidone ISM administration. The response was not significantly different in either dose group, likely because D2RO was already above the proposed efficacy threshold (65%) within 1 h after the first Risperidone ISM injection and remained above this level following repeated administrations."

Journal • CNS Disorders • Psychiatry • Schizophrenia • DRD2

Preliminary experience in a "real world" setting with risperidone ISM for the treatment of acute patients affected by schizophrenia (ECNP 2024) - "Our preliminary data showed that Risperidone ISM is effective and well tolerated for the treatment of acute psychotic relapse also in a "real world" setting, confirming the Results of RCT and OLE studies and placing it among the AP LAI first-options in schizophrenia."

Clinical • Real-world • Real-world evidence • CNS Disorders • Mental Retardation • Mood Disorders • Psychiatry • Schizophrenia • Schizophreniform Disorder

RESHAPE: Non-interventional Study of Risperidone ISM® in Schizophrenia Patients Hospitalised Due to a Relapse (clinicaltrials.gov) - P=N/A | N=1200 | Recruiting | Sponsor: Rovi Pharmaceuticals Laboratories | Trial completion date: Jun 2024 ➔ Dec 2024 | Trial primary completion date: Jun 2024 ➔ Dec 2024

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

Development of a population pharmacokinetic model for the novel long-acting injectable antipsychotic risperidone ISM®. (PubMed, Br J Clin Pharmacol) - "The population PK model adequately described active moiety concentrations from five clinical studies after risperidone ISM® administration. Relationships between active moiety exposure and covariates were defined in order to facilitate simulations for future studies. The model showed that risperidone ISM® rapidly achieves therapeutic plasma levels within the first hours after the first injection that are maintained sustainedly throughout the whole dosing interval following once-monthly gluteal injections of 100 mg and 75 mg."

Journal • PK/PD data • CNS Disorders • Psychiatry • Schizophrenia

Clinical experience with once-monthly risperidone ISM in a mental health center. A retrospective study. (EPA 2024) - "Among the switches made to monthly risperidone, 69,2% (n=9) were previously treated with oral risperidone, 15,4% (n=2) were treated with once-biweekly risperidone long-acting injectable, 7,9% (n=1) with oral paliperidone and 7,9% with aripiprazole monthly injectable. In the sample analyzed, once-monthly Risperidone ISM had reasonable tolerance levels. Also, it´s shown to be effective in preventing psychotic decompensations and hospital admissions. Therefore, this new injectable of monthly risperidone represents a therapeutic alternative to consider in order to guarantee therapeutic adherence and improve the quality of life of patients with psychotic symptoms."

Retrospective data • CNS Disorders • Dystonia • Mood Disorders • Obsessive-Compulsive Disorder • Psychiatry • Schizophrenia

QUARTZ: Pharmacokinetics, Safety and Tolerability of Different Formulations and Dose Strengths of Quarterly Risperidone (QUAR) in Patients With Schizophrenia (clinicaltrials.gov) - P1 | N=100 | Recruiting | Sponsor: Rovi Pharmaceuticals Laboratories

New P1 trial • CNS Disorders • Psychiatry • Schizophrenia

Pharmacokinetic/pharmacodynamic modeling and simulation of dopamine D2-receptor occupancy-time profiles comparing Risperidone ISM versus daily oral risperidone (ECNP 2023) - "Simulated D2RO profiles revealed that Risperidone ISM (100 mg) provides a similar likelihood of clinical response (D2RO above 65%) than the equivalent 4mg oral risperidone, and even when comparing with higher doses of 6 or 8 mg QD, assuming a perfect adherence. Moreover, Risperidone ISM shows superiority for the real clinical practice of medium or bad oral treatment compliance. Thus, Risperidone ISM 100 mg is adequate to achieve a similar or improved D2RO occupancy level than higher doses of oral risperidone and thus could be satisfactorily switched for maintenance treatment of adult patients treated with 4 mg or higher oral risperidone doses."

PK/PD data • CNS Disorders • Psychiatry • Schizophrenia • DRD2