Once-monthly paliperidone palmitate in recently diagnosed and chronic non-acute patients with schizophrenia

OBJECTIVE: To explore the treatment response, tolerability and safety of once-monthly paliperidone palmitate (PP1M) in non-acute patients switched to oral antipsychotics stratified by time since diagnosis as recently diagnosed (3 years). RESEARCH DESIGN AND METHODS: Post-hoc analysis of a prospective, interventional, single-arm, multicentre, open-label, 6-month study performed in 233 recently diagnosed and 360 chronic patients. MAIN OUTCOME MEASURES: The proportion achieving treatment response (defined as >/=20% improvement in Positive and Negative Syndrome Scale [PANSS] total score from baseline to endpoint) and maintained efficacy (defined as non-inferiority in the change in PANSS total score at endpoint [Schuirmann's test]). RESULTS: 71.4% of recently diagnosed and 59.2% of chronic patients showed a >/=20% decrease in PANSS total score (p=0.0028 between groups). Changes in PANSS Marder factors, PANSS subscales, and the proportion of patients with a Personal and Social Performance scale (PSP) total score of 71-100 were significantly greater in recently diagnosed compared with chronic patients. PP1M was well tolerated, presenting no new safety signals. CONCLUSION: These data show that recently diagnosed patients treated with PP1M had a significantly higher treatment response and improved functioning, as assessed by the PSP total score, than chronic patients

Paliperidone palmitate in non-acute patients with schizophrenia previously unsuccessfully treated with risperidone long-acting therapy or frequently used conventional depot antipsychotics.

PALMFlexS, a prospective multicentre, open-label, 6-month, phase IIIb interventional study, explored tolerability, safety and treatment response in adults (n = 231) with non-acute but symptomatic schizophrenia switching to flexibly dosed paliperidone palmitate (PP) after unsuccessful treatment with risperidone long-acting injectable therapy (RLAT) or conventional depot antipsychotics (APs). Treatment response was measured by change in Positive and Negative Syndrome Scale (PANSS) total score from baseline (BL) to last-observation-carried-forward (LOCF) endpoint (EP). Safety and tolerability assessments included Extrapyramidal Symptom Rating Scale (ESRS) total score and treatment-emergent adverse events. Significant reductions in mean PANSS total score were observed for all groups (-7.5 to -10.6; p ⩽ 0.01 [BL to LOCF EP]). After switching to PP, more than 50% of all patients achieved ⩾20% and one-third of RLAT-treated patients even achieved ⩾50% improvement in PANSS total score. Across groups, there were significant improvements (p < 0.05) in symptom severity as measured by Clinical Global Impression-Severity (CGI-S; trend for improvement with RLAT; p = 0.0568), subjective well-being, medication satisfaction, and patient functioning with PP. PP was generally well tolerated. Clinically relevant benefits were observed in non-acute patients with schizophrenia switched from RLAT or conventional depot APs to PP

Clinical relevance of paliperidone palmitate 3-monthly in treating schizophrenia

Maju Mathews,1 Srihari Gopal,1 Isaac Nuamah,1 Ludger Hargarter,2 Adam J Savitz,1 Edward Kim,3 Wilson Tan,4 Bernardo Soares,5 Christoph U Correll6&ndash;81Department of Neuroscience, Janssen Research &amp; Development, LLC, Raritan, NJ, USA; 2Department of Neuroscience, Janssen-Cilag EMEA, Neuss, Deutschland; 3Janssen Scientific Affairs, LLC, Hopewell, NJ, USA; 4Regional Medical Affairs, Janssen Pharmaceutical Companies of Johnson and Johnson, Singapore; 5Neuroscience Medical Affairs, Janssen-Cilag, High Wycombe, Buckinghamshire, UK; 6The Zucker Hillside Hospital, Psychiatry Research, Glen Oaks, NY, USA; 7Department of Psychiatry and Molecular Medicine, Hofstra Northwell School of Medicine, East Garden City, NY, USA; 8Department of Child and Adolescent Psychiatry, Charit&eacute; Universit&auml;tsmedizin, Berlin, GermanyAbstract: Antipsychotics are the mainstay in schizophrenia management, and long-acting injectable (LAI) antipsychotics contribute to the successful maintenance of treatment by improving non-adherence and preventing relapses. Paliperidone palmitate 3-monthly (PP3M) formulation is the only available LAI antipsychotic that offers an extended 3-month window of stable plasma drug concentration, enabling only four injections per year. This paper summarizes clinically relevant endpoints from available evidence for PP3M to bridge translational research gaps and provide measurable outcomes that can be interpreted in clinical practice. Low number-needed-to-treat (NNT) for relapse prevention (NNT [95% CI] 6-month estimate: 4.8 [3.2; 10.0]; 12-month estimate: 3.4 [2.2; 7.0]), and high number-needed-to-harm (NNH [95% CI] akathisia, 27.1 [12.3; &minus;667.1]; tremor, 80.0 [22.5; 67.3]; dyskinesia, &minus;132.6 [44.5; &minus;23.2]; parkinsonism, 160.0 [28.9; &minus;49.8]) quantify the relative benefits and low propensity for adverse events with PP3M. Symptom remission and reductions in positive and negative symptoms indicate treatment stability. Additionally, meaningful functional remission, reduced dosing frequency, and freedom from daily negotiations favorably impact patient preference and attenuate burdensome aspects of caregiving, representing important healthcare determinants that enhance prospects of treatment continuity in schizophrenia. This information can potentially improve clinicians&rsquo; judgment of treatment choices, clinical response, and patient selection in routine care. Taken together, PP3M is a valuable antipsychotic treatment option, meriting consideration for a broader role in the long-term management of schizophrenia; its utility should not be limited to patients with poor adherence or when oral antipsychotics have failed.Keywords: number-needed-to-harm, number-needed-to-treat, paliperidone palmitate 3-monthly, remissio