Drug Database
PA

paliperidone

✓ Approved

Torrent Pharmaceuticals Limited · DRD2 · Small Molecule

What is paliperidone?

paliperidone is a small molecule developed by Torrent Pharmaceuticals Limited. It is approved for therapeutic indications via oral (po).

Drug Profile

CompanyTorrent Pharmaceuticals Limited
Drug ClassSmall Molecule
Molecular TargetDRD2, HTR2A, HTR7
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Torrent Pharmaceuticals Limited

Mechanism of Action

Molecular Targets

paliperidone acts on 3 molecular targets:

DRD2dopamine receptor D2 (D2DR, D2R)
HTR2A5-hydroxytryptamine receptor 2A (5-HT2A, HTR2)
HTR75-hydroxytryptamine receptor 7 (5-HT7)
Want deeper analysis?Noah AI can explain complex mechanisms and compare to similar drugs.

Therapeutic Indications

paliperidone is developed for 1 unique indication across 1 therapeutic area.

Therapeutic AreaConditionPhase
Psychiatric disordersSchizophrenia✓ Approved

Related Research Articles

PubMedSchizophrenia bulletin open2026-10-08

Are Depot Antipsychotics Ever Self-Tapering? Exploring the Discontinuation of Long-Acting Injectable Psychosis Drugs and Those With Delayed Onset Through In Silico Modelling.

O'Neill James R JR, McLean Samantha L SL, Taylor David M DM, Horowitz Mark A MA

Reducing and stopping antipsychotic medications can have longer-term positive outcomes for some patients. Despite common wisdom, abrupt discontinuation of several long-acting injectable (LAI) antipsychotic drugs results in rapid D2 occupancy reductions. We explored if abrupt discontinuation of LAI antipsychotics with slow clearance remained within specified constraints on rate of D2 occupancy change (RODOC), which might reduce risk of emerging symptoms of psychosis related to withdrawal or relapse. Pharmacokinetic data were collated for 6 LAI antipsychotic forms (aripiprazole lauroxil, olanzapine pamoate, paliperidone palmitate 1-, 3-, and 6-monthly, and risperidone microspheres). Fifty-two studies comprising 6146 patients were included. In silico modelling was completed to predict RODOC from abrupt discontinuation. We used RODOC thresholds of 5 percentage-point (pp) difference per month as a proxy measure to theoretically estimate the likelihood of withdrawal effects emerging, with sensitivity analyses for 2.5 and 10 pp/month. Abrupt cessation of LAIs is likely to exceed 5 pp/month RODOC for all examined LAIs except paliperidone palmitate 6-monthly. Peak rates of D2 occupancy change per month for an average person ranged from 5 pp/month (paliperidone palmitate 6-monthly) to 66.1 pp/month (risperidone microspheres). Significant interpersonal variation in pharmacokinetic factors was observed. Almost all LAI antipsychotic medications could theoretically cause withdrawal effects in most patients if abruptly discontinued without oral supplementation. However, abrupt discontinuation of longer-acting paliperidone palmitate could theoretically be successful for some patients. Prescribers must collaborate with patients when devising tapering regimens to ensure schedules are personalized and responsive to individual experience.

PMID 42847024
Read full article →
PubMedThe Australian and New Zealand journal of psychiatry2026-10-08

Optimal drug, dose and duration of antipsychotic therapy following amphetamine and cannabis-induced psychosis: A systematic review.

Hall Edward E, Ratnayake Nisitha N, Waldmann Jana J, Daglish Mark M et al.

Amphetamine- and cannabis-induced psychoses are common clinical presentations that are difficult to differentiate from primary psychotic disorders. However, there are limited guidelines around the appropriate use of antipsychotic medications to treat these disorders. This review examined the literature considering the optimal drug, dose and duration of antipsychotic therapy to treat and prevent relapse of amphetamine- and cannabis-induced psychoses. A systematic review was conducted to identify original empirical studies considering antipsychotic drugs for the management of amphetamine- and cannabis-induced psychoses. Appraisal of included randomised controlled trials used the Cochrane risk-of-bias 2 and Joanna Briggs Institute critical appraisal tools, and the appropriate Joanna Briggs Institute tool for non-randomised controlled trials. Primary outcomes were measures of psychotic symptoms and rates of relapse of psychosis. Standardised mean differences were calculated where possible, and a narrative synthesis was completed. This review included 11 studies investigating amphetamine-induced psychosis, totalling 724 participants, and 4 studies investigating cannabis-induced psychosis, totalling 1872 participants. Aripiprazole, haloperidol, olanzapine, paliperidone, quetiapine and risperidone were associated with reduced psychotic symptoms in amphetamine-induced psychosis; however, no regimen was superior. Likewise, risperidone, haloperidol and olanzapine were associated with reduced psychotic symptoms in cannabis-induced psychosis. There was no data regarding relapse following antipsychotic treatment for amphetamine-induced psychosis, and limited evidence to guide practice recommendations regarding relapse prevention following antipsychotic treatment for cannabis-induced psychosis. This review found support for the effectiveness of antipsychotic drugs in reducing amphetamine- and cannabis-induced psychosis symptoms. However, a lack of studies including follow-up post-cessation of treatment meant that there is currently insufficient evidence to guide recommendations about which regimen is most effective at preventing relapse to psychosis.

PMID 42844571
Read full article →
PubMedThe lancet. Psychiatry2026-09-30

Sex differences in the efficacy, acceptability, and tolerability of antipsychotics in people with acute schizophrenia: individual participant data pairwise, dose-response, and network meta-analyses.

Furukawa Yuki Y, Siafis Spyridon S, Schneider-Thoma Johannes J, Nomura Nobuyuki N et al.

Antipsychotics are the mainstay of schizophrenia treatment, but their efficacy and tolerability might differ between females and males, and previous evidence on sex differences has been inconsistent and methodologically limited. We aimed to evaluate sex differences in the efficacy, acceptability, and tolerability of antipsychotics in adults with acute schizophrenia. We performed individual participant data pairwise, dose-response, and network meta-analyses of antipsychotics versus placebo or another antipsychotic, using data from the Vivli and YODA trial data-sharing platforms (inception to April 9, 2025); the main analyses were restricted to fixed-dose trials. The primary outcome was overall symptoms on the Positive and Negative Syndrome Scale at week 6 (or closest). Secondary outcomes included all-cause dropout and other efficacy and tolerability outcomes. We performed one-stage pairwise meta-analyses to quantitatively test sex-treatment interactions, and two-stage sex-stratified dose-response and network meta-analyses to visually examine potential sex differences. Credibility of effect modification was assessed with the Instrument to assess the Credibility of Effect Modification Analyses. People with lived experience were involved in planning and interpretation of the study. This study was registered with PROSPERO, CRD420251022957. We identified 33 eligible trials; 18 fixed-dose trials with 7062 participants (2168 females and 4894 males; of 5161 with race reported, 2954 White, 1187 Black, 752 Asian, and 268 of other or unspecified race; mean age 40·9 years; receiving haloperidol, olanzapine, paliperidone, risperidone, or placebo) were included in the main analyses. There was no evidence of sex differences in drug effects on overall symptoms (difference of standardised mean difference [DoSMD] 0·04, 95% CI -0·09 to 0·18). Dose-response curves were similar in females and males, plateauing at 3-5 mg risperidone equivalents, and the network meta-analysis showed no clear sex-specific treatment effects. Antipsychotics reduced all-cause dropout more in females than in males (ratio of odds ratios 0·74, 95% CI 0·56-0·98; moderate credibility). Prolactin increase was greater in females (DoSMD 0·83, 0·67-0·99; high credibility); other tolerability outcomes showed no clear sex difference. We found no evidence of sex differences in the efficacy or overall adverse event profiles, and no different dose-response relationships, for the drugs studied. However, we found some evidence that, among females, antipsychotics reduce all-cause dropout more, and increase antipsychotic-induced prolactin elevation versus placebo, as compared with males. Overall treatment efficacy estimates from previous meta-analyses are relevant to both sexes. To promote sex and gender equity, female participation in clinical trials and sex-stratified reporting should be encouraged. German Federal Ministry of Research, Technology and Space.

PMID 42815510
Read full article →
PubMedThe Australian and New Zealand journal of psychiatry2026-09-29

Psychosocial treatment with or without antipsychotic medication in first-episode psychosis: What have we learned from the STAGES trial about the risks and benefits?

Allott Kelly K, Chopra Sidhant S, O'Donoghue Brian B, Nelson Barnaby B et al.

STAGES trial was a triple-blind noninferiority trial that investigated intensive psychosocial treatment with or without low-dose antipsychotics in young people with first-episode psychosis with a short duration of untreated psychosis, who were low-risk and had stable family support. Participants received cognitive behavioural case management combined with either low-dose risperidone/paliperidone or placebo. Only 7% of the screened individuals were included (N = 90), with just 30% completing the protocol, reflecting trial challenges. Both groups showed significant improvements in social and occupational functioning (primary outcome) and symptoms at 6 months, with placebo demonstrating noninferior outcomes. At 24 months, the groups did not significantly differ, though noninferiority could not be confirmed. Neuroimaging findings revealed that placebo recipients showed reduced basal ganglia volume and widespread cortical thinning relative to healthy controls, while antipsychotics increased basal ganglia volume and attenuated cortical thinning. This demonstrates that antipsychotics do not cause tissue loss early in treatment, and delaying medication may hasten illness-related brain volume loss. Metabolic analyses showed that antipsychotics contributed to greater weight gain and metabolic changes, though some risk existed without medication. Cognitive analyses revealed baseline illness-associated cognitive impairment, with verbal learning/memory decline over 6 months in the medication group only, suggesting early cognitive side effects. STAGES trial findings demonstrate that carefully selected low-risk first-episode psychosis patients can achieve clinical improvement through psychosocial interventions alone while minimising potential negative metabolic and cognitive effects. However, delaying medication may result in adverse structural brain changes. The results support integrated treatment and shared decision-making approaches that balance symptom management, functional recovery and preservation of physical, cognitive and brain health.

PMID 42808577
Read full article →
PubMedGels (Basel, Switzerland)2026-09-26

Hydrogel-Based Depot Systems in Psychiatric Pharmacotherapy: A Narrative Review Rethinking Long-Acting Drug Delivery.

Predoi Emilia Denisa ED, Târtea Anca A, Taisescu Oana O, Rotaru-Zăvăleanu Alexandra Daniela AD et al.

Poor adherence to pharmacotherapy remains a major challenge in the long-term management of severe psychiatric disorders. Although long-acting injectable (LAI) antipsychotics can provide effective and sustained drug exposure while supporting treatment continuity, their pharmaceutical and clinical characteristics vary considerably according to the active pharmaceutical ingredient and formulation technology. Specific formulations may be associated with limitations such as complex release kinetics, injection-site reactions, or the need for oral supplementation during treatment initiation. Hydrogel-based delivery systems have emerged as a versatile class of biomaterials that may address these limitations through their tunable physicochemical properties, high water content, biocompatibility, and capacity for controlled, sustained drug release. Their adaptable architecture further enables diverse drug-loading strategies and multiple routes of administration, expanding the design space for next-generation long-acting formulations. In this narrative review, we provide a comprehensive overview of hydrogel-based depot systems for psychiatric pharmacotherapy, focusing on hydrogel composition (natural, synthetic, and hybrid polymers), crosslinking mechanisms, stimuli-responsive and injectable formulations, drug loading and release strategies, and their translational potential. Current research has primarily focused on antipsychotic delivery, where hydrogel formulations of risperidone, paliperidone, aripiprazole, olanzapine, quetiapine and the investigational peptide PAOPA show possible sustained drug release and prolonged therapeutic activity in preclinical models. Compared with conventional depot technologies, hydrogel systems may offer greater formulation flexibility and the potential for more controlled pharmacokinetic profiles and prolonged drug exposure. These characteristics could ultimately support reduced dosing frequency and treatment continuity. We also discuss the key challenges limiting clinical translation, including optimization of release kinetics, scalable manufacturing, sterilization, long-term stability, and regulatory considerations. Collectively, current evidence supports the technological potential of hydrogel-based systems to provide tunable drug loading, depot formation, and sustained release. However, their development as clinically meaningful next-generation LAI therapies will require long-term in vivo evaluation, robust pharmacokinetic-pharmacodynamic characterization, injection-site safety assessment, reproducible and scalable manufacturing, and well-designed clinical trials.

PMID 42794405
Read full article →
PubMedRecent advances in drug delivery and formulation2026-09-25

Formulation and Physicochemical Characterization of Paliperidone- Loaded Niosomal Vesicles for Improved Transdermal Drug Delivery.

Ayad Ayam A, Al-Kinani Khalid K

Niosomes are nonionic surfactant-based vesicular systems. Paliperidone, which is an atypical antipsychotic used in the management of schizophrenia, exhibits poor aqueous solubility and limited oral bioavailability, which could limit its therapeutic effectiveness. This study aimed to develop and optimize paliperidone (PAL)-loaded niosomal formulations for enhance transdermal delivery and improve drug release. PAL-loaded niosomes were prepared using the thin-film hydration method using different non-ionic surfactants (Span 20, Span 60, Span 65, and Span 80) at varying cholesterol/surfactant ratios. The formulations were characterized for PS, PDI, ZP, DC, and (EE%). In vitro drug release, release kinetics, and ex vivo permeation studies were performed. Structural and physicochemical characterization of the optimized formulation was conducted using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The optimized formulation (F16), composed of Span 80 and cholesterol at a ratio of (1:4), exhibited a particle size of 129.1 ± 6.6 nm, PDI of 0.26 ± 0.015, zeta potential of -15.69 ± 1.11 mV, and entrapment efficiency of 78.2 ± 1.7%. The formulation demonstrated sustained drug release, with approximately 56% released over 6 hours. Ex vivo permeation studies showed a significant enhancement in drug permeation relative to the pure drug, with higher cumulative permeation and flux. The novel niosomal formulation F16 was chosen as the optimal formula, with an optimal cholesterol-to-surfactant ratio, due to its superior physicochemical properties and delivery efficiency, including release and skin permeation, compared with other formulas and the pure drug, making it a candidate for a patented drug delivery system. The developed PAL-loaded niosomes represent a promising transdermal drug delivery system, offering improved drug release and permeation, potentially enhancing therapeutic outcomes in schizophrenia management.

PMID 42786867
Read full article →

+1820 more articles available with a free account

Sign up free to view all articles →

Ask about paliperidone