Dataset Information

Reduced sexual dysfunction with aripiprazole once-monthly versus paliperidone palmitate: results from QUALIFY.

ABSTRACT: Sexual dysfunction, a common side effect of antipsychotic medications, may be partly caused by dopamine antagonism and elevation of prolactin. In QUALIFY, a randomized study, aripiprazole once-monthly 400?mg (AOM 400), a dopamine D2 receptor partial agonist, showed noninferiority and subsequent superiority versus paliperidone palmitate (PP), a dopamine D2 receptor antagonist, on the Heinrichs-Carpenter Quality-of-Life Scale (QLS) in patients with schizophrenia aged 18-60 years. Sexual dysfunction (Arizona Sexual Experience Scale) and serum prolactin levels were also assessed. Odds for sexual dysfunction were lower with AOM 400 versus PP [week 28 adjusted odds ratio (95% confidence interval), 0.29 (0.14-0.61); P=0.0012] in men [0.33 (0.13-0.86); P=0.023], women [0.14 (0.03-0.62); P=0.0099], and patients aged 18-35 years [0.04 (<0.01-0.34); P=0.003]. Among patients shifting from sexual dysfunction at baseline to none at week 28, there was a trend toward greater improvement in the QLS total score. The mean (SD) prolactin concentrations decreased with AOM 400 [-150.6 (274.4)?mIU/l] and increased with PP [464.7 (867.5)?mIU/l] in both men and women. Six PP-treated patients experienced prolactin-related adverse events. In addition to greater improvement on QLS, patients had a lower risk for sexual dysfunction and prolactin elevation with AOM 400 versus PP in QUALIFY.

SUBMITTER: Potkin SG

PROVIDER: S-EPMC5378005 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Reduced sexual dysfunction with aripiprazole once-monthly versus paliperidone palmitate: results from QUALIFY.

Potkin Steven G SG Loze Jean-Yves JY Forray Carlos C Baker Ross A RA Sapin Christophe C Peters-Strickland Timothy T Beillat Maud M Nylander Anna-Greta AG Hertel Peter P Steen Andersen Henrik H Eramo Anna A Hansen Karina K Naber Dieter D

International clinical psychopharmacology 20170501 3

Sexual dysfunction, a common side effect of antipsychotic medications, may be partly caused by dopamine antagonism and elevation of prolactin. In QUALIFY, a randomized study, aripiprazole once-monthly 400 mg (AOM 400), a dopamine D2 receptor partial agonist, showed noninferiority and subsequent superiority versus paliperidone palmitate (PP), a dopamine D2 receptor antagonist, on the Heinrichs-Carpenter Quality-of-Life Scale (QLS) in patients with schizophrenia aged 18-60 years. Sexual dysfunctio ...[more]

PMID: 28252452

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Project description:QUALIFY was a 28-week, randomized, open-label, head-to-head trial that assessed improvements across multiple measures in stable patients with schizophrenia with aripiprazole once-monthly 400 mg vs paliperidone palmitate.Secondary effectiveness assessments included physician-rated readiness for work using the Work Readiness Questionnaire, the Clinical Global Impression-Severity and Clinical Global Impression-Improvement scales, and quality of life with the rater-blinded Heinrichs-Carpenter Quality of Life Scale. Patients assessed their treatment satisfaction and quality of life with Subjective Well-Being under Neuroleptic Treatment-short version and Tolerability and Quality of Life questionnaires.Odds of being ready for work at week 28 were significantly higher with aripiprazole once-monthly 400 mg vs paliperidone palmitate (adjusted odds ratio, 2.67; 95% CI, 1.39-5.14; P=.003). Aripiprazole once-monthly 400 mg produced numerically or significantly greater improvements from baseline vs paliperidone palmitate in all Quality of Life Scale items. With aripiprazole once-monthly 400 mg vs paliperidone palmitate at week 28, there were significantly more Clinical Global Impression-Severity and Clinical Global Impression-Improvement responders (adjusted odds ratio, 2.26; P=.010, and 2.51; P=.0032) and significantly better Clinical Global Impression-Improvement scores (least squares mean treatment difference, -0.326; 95% CI, -0.60 to -0.05; P=.020). Numerically larger improvements with aripiprazole once-monthly 400 mg vs paliperidone palmitate were observed for patient-rated scales Subjective Well-Being under Neuroleptic Treatment-short version and Tolerability and Quality of Life. Partial correlations were strongest among clinician-rated and among patient-rated scales but poorest between clinician and patient-rated scales.Consistently greater improvements were observed with aripiprazole once-monthly 400 mg vs paliperidone palmitate across all measures. Partial correlations between scales demonstrate the multidimensionality of various measures of improvement. More patients on aripiprazole once-monthly 400 mg were deemed ready to work by the study end.National Institutes of Health registry, NCT01795547, https://clinicaltrials.gov/ct2/results?id=NCT01795547).

Project description:PURPOSE:Reducing the dosing frequency of antipsychotics (APs) with long-acting injectables (LAIs) such as once-monthly paliperidone palmitate (PP1M) can improve adherence and clinical outcomes for schizophrenia patients. This US study compared physical and psychiatric comorbidity-related outcomes, AP adherence, healthcare resource utilization (HRU), and costs pre- and post-transition to PP1M among schizophrenia patients treated with oral risperidone/paliperidone pre-PP1M transition. METHODS:Health insurance claims from the IQVIA™ PharMetrics Plus database (01/01/2012-07/31/2018) were used to identify adults with???2 schizophrenia diagnoses,???1 claim for PP1M, and???30 days of treatment with oral risperidone/paliperidone in the 60 days before the first PP1M claim (i.e., the index date). Comorbidity-related outcomes, adherence to APs (measured via the proportion of days covered [PDC]), all-cause per-patient-per-month (PPPM) HRU, and all-cause PPPM medical, pharmacy, and total costs (i.e., sum of medical and pharmacy costs) during the 6-month periods pre- and post-transition to PP1M were compared using generalized estimating equation models adjusted for repeated measurements. Analyses were replicated in the subset of patients with???1 all-cause inpatient stay pre-PP1M transition. FINDINGS:Among 427 schizophrenia patients transitioning from oral risperidone/paliperidone to PP1M, the mean age was 41.1 years and 37.9% were female. Following the PP1M transition, patients were less likely to have claims with a diagnosis for psychoses (odds ratio [OR] 0.41; P?<?0.001), hypertension (OR 0.80; P?=?0.011), depression (OR 0.70; P?<?0.001), drug abuse (OR 0.60; P?<?0.001), substance-related and addictive disorders (OR 0.73; P?=?0.003), bipolar and related disorders (OR 0.59; P?<?0.001), sleep-wake disorders (OR 0.68; P?=?0.017), anxiety disorders (OR 0.78; P?=?0.034), and other conditions that may require a focus of clinical attention (OR 0.58; P?<?0.001). Mean PDC by APs was higher post-PP1M (mean?=?0.81) versus pre-PP1M (mean?=?0.68) transition. Post-PP1M, patients were less likely to have an all-cause emergency room visit (OR 0.51; P?<?0.001) or inpatient stay (OR 0.39; P?<?0.001) compared to pre-PP1M. All-cause total healthcare costs remained similar post- versus pre-transition to PP1M (mean monthly cost difference [MMCD]?=?$228; P?=?0.260). Pharmacy costs increased post-PP1M (MMCD?=?$960; P?<?0.001), but were offset by decreasing medical costs (MMCD?=?- $732; P?<?0.001), largely driven by lower costs related to inpatient stays (MMCD?=?- $695; P?<?0.001) and emergency room visits (MMCD?=?- $63; P?<?0.001). For patients with???1 all-cause inpatient stay pre-PP1M transition (N?=?177), a more pronounced improvement in comorbidity-related outcomes, a more pronounced reduction in HRU, and a reduction in total healthcare costs (MMCD?=?- $1308; P?<?0.001) were observed post-transition to PP1M. IMPLICATIONS:Among schizophrenia patients in the US, transitioning to PP1M following oral risperidone/paliperidone treatment was associated with improved comorbidity-related outcomes, higher adherence, and a reduction in HRU, while remaining cost neutral. Furthermore, patients with???1 all-cause inpatient stay pre-PP1M transition had significantly lower total healthcare costs post-PP1M transition.

Project description:BackgroundA post hoc analysis from a multiphase trial with open-label transition and maintenance phases, a double-blind relapse prevention phase, and an optional open-label extension examined the long-term tolerability with continuous once-monthly injectable paliperidone palmitate 39, 78, 117, or 156 mg (25, 50, 75, or 100 mg equivalents [mg eq] of paliperidone) in subjects with recently diagnosed (≤5 years; n = 216) versus chronic illness (>5 years; n = 429) schizophrenia.MethodsAdverse events reported at a ≥2% margin between subgroups were identified. Relative risks (in the recently diagnosed compared with the chronically ill) and 95% confidence intervals (CI) were determined, and CI not including 1 were considered potentially significant.ResultsIn both subgroups, the mean monthly dose was 109 mg (69.9 mg eq). Continuous mean exposures were 333.9 ± 271.9 and 308.7 ± 278.3 days in the recently diagnosed and chronic illness subgroups, respectively. Using the criteria outlined in the methods, nasopharyngitis was a potentially significant event reported in more chronically ill than recently diagnosed subjects at months 6, 9, 12, and endpoint (7.2% versus 2.8%; relative risk 0.384; 95% CI 0.163-0.907). Influenza (2.8% versus 0.7%; relative risk 3.9; 95% CI 1.003-15.730) and amenorrhea (3.2% versus 0.9%; relative risk 3.476; 95% CI 1.029-11.744) at endpoint were potentially significant events in more recently diagnosed than chronically ill subjects. Mean weight changes, sedation/somnolence, any extrapyramidal symptom-related or glucose-related events were generally similar between the groups. The mean prolactin level increased in both sexes in both subgroups (changes from baseline of +41.8 ng/mL and +26.5 ng/mL in recently diagnosed and chronic illness females and +12.3 ng/mL and +15.1 ng/mL in recently diagnosed and chronic illness males, respectively), and were higher in females with recently diagnosed illness than in females who were chronically ill (P = 0.0002 at endpoint). Prolactin-related events were reported by 7.9% of recently diagnosed subjects with schizophrenia and 3.5% of those who were chronically ill.ConclusionThe long-term tolerability of paliperidone palmitate was generally similar in recently diagnosed schizophrenia subjects and those with more chronic illness, with the exception of some prolactin-related measures.

Project description:BackgroundThe negative symptoms of schizophrenia are generally harder to recognize, more difficult to treat than positive symptoms, and have a significant impact on patient functioning and overall outcomes. Treatment with aripiprazole may be associated with benefits on negative symptoms and functioning given its partial agonism to the dopamine D2 receptor. The aim of this subanalysis was to explore the impact of flexibly dosed, long-acting paliperidone palmitate once monthly (PP1M) on negative and depressive symptoms, disorganized thoughts, anxiety, extrapyramidal symptoms, and patient functioning in nonacute adult patients with schizophrenia previously unsuccessfully treated with oral aripiprazole monotherapy.MethodsPost-hoc subanalysis of 46 nonacute but symptomatic patients enrolled in a prospective, interventional, single-arm, multicenter, open-label 6-month study.ResultsAt endpoint, improvements of ⩾ 20% and ⩾ 50% in the Positive and Negative Syndrome Scale (PANSS) total score were observed in 52.2% and 21.7% of patients, respectively. Significant and clinically relevant improvements were observed at endpoint in mean (standard deviation [SD]) PANSS negative subscale score (-3.0 (5.0); p < 0.0001) and in the PANSS Marder factor scores for negative symptoms (-2.9 (5.4); p = 0.0006), disorganized thoughts (-2.8 (4.3); p < 0.0001) and anxiety/depression (-1.8 (3.9); p = 0.0031). Patient functioning assessed by mean (SD) Personal and Social Performance scale score (3.9 (13.2); p = 0.0409), Mini International Classification of Functioning rating for Activity and Participation Disorders in Psychological Illnesses total scores (-2.9 (7.1); p = 0.0079), and Extrapyramidal Symptom Rating Scale scores (-0.6 (3.4); p = 0.0456) improved significantly at endpoint. PP1M was well tolerated with no new safety signals.ConclusionsSix-month treatment with flexibly dosed PP1M was associated with significant and clinically relevant improvements in negative and depressive symptoms, disorganized thoughts, functioning, and extrapyramidal symptoms in nonacute but symptomatic patients with schizophrenia previously unsuccessfully treated with oral aripiprazole.

Project description:Background and objectivesIdentifying key factors for a successful transition from once-monthly paliperidone palmitate (PP1M) to three-monthly paliperidone palmitate (PP3M) is crucial for improving treatment outcomes, enhancing patient adherence, and reducing relapse risk in patients with schizophrenia. Providing region-specific insights for evidence-based clinical decisions can aid clinicians in optimizing transition strategies for Chinese patients with schizophrenia. Therefore, the objective of this post hoc analysis of a double-blind parallel-group multicenter phase 3 study (NCT01515423) was to identify factors related to the disease stabilization that may allow for a successful transition from PP1M to PP3M in the treatment of Chinese patients with schizophrenia.MethodsAdults (18-70 years) diagnosed with schizophrenia using the Diagnostic and Statistical Manual of Mental Disorders, fourth edition text revision, for over 1 year and with a baseline Positive and Negative Syndrome Scale (PANSS) total score between 70 and 120 were entered into an open-label (OL) phase receiving PP1M for 17 weeks. After the 17-week OL phase, patients who met the criteria necessary for stabilization were randomized (1:1) to PP1M (fixed-dose, 50, 75, 100, or 150 mg eq.) or PP3M (fixed-dose, 175, 263, 350, or 525 mg eq.) in a 48-week double-blind phase. Stabilization was defined as a PANSS total score < 70, PANSS item (P1, P2, P3, P6, P7, G8, G14) scores ≤ 4, and a reduction in Clinical Global Impression Severity (CGI-S) score of ≥ 1 from OL baseline. This post hoc analysis evaluated changes and trends in symptom severity using PANSS, changes in mental states using CGI-S, and changes in personal and social functioning using Personal and Social Performance (PSP) scores from baseline to the endpoint of the OL phase in patients who either met or did not meet the stabilization criteria (stabilized versus non-stabilized group). Comparison of changes and trends in the clinical scores between the stabilized group and non-stabilized group were conducted using linear mixed model and Mann-Kendall trend analysis, respectively. Univariate and multivariate logistic regression analyses were conducted to explore factors associated with stabilization status for transition.ResultsOf 296 patients enrolled, 210 achieved disease stabilization (106 patients and 104 patients were randomized to PP1M and PP3M, respectively). Significant downward trends in the PANSS and CGI-S scores were detected in the stabilized patients (n = 210, ZPANSS = -2.21, p = 0.028; ZCGI-S = -2.21, p = 0.028) but not in the non-stabilized patients (n = 86). No significant trends in the PSP scores were observed in either group. The factors significantly associated with disease stabilization were the CGI-S score at baseline [odds ratio (OR) = 0.22, 95% confidence interval (CI): 0.09, 0.5), reduction of the PANSS score at week 13 (OR = 1.11, 95% CI: 1.06, 1.17), and reduction of CGI-S score at week 13 (OR = 2.27, 95% CI: 1.03, 5.02).ConclusionA lower CGI-S total score at baseline and greater reductions in PANSS and CGI-S scores at week 13 were associated with patients achieving disease stabilization, that may allow for a successful transition. Evidence from this study indicates that better disease condition at baseline, early functional improvement and symptomatic relief were the key factors associated with disease stabilization. The findings may guide clinicians to identify suitable patients for transition from PP1M to PP3M and further optimize the use of PP3M in China.Clinical trials registrationEudraCT number: 2011-004889-15 and ClinicalTrials.gov (identifier: NCT01515423) for the original double-blind randomized study.

Dataset Information

Reduced sexual dysfunction with aripiprazole once-monthly versus paliperidone palmitate: results from QUALIFY.

Publications

Reduced sexual dysfunction with aripiprazole once-monthly versus paliperidone palmitate: results from QUALIFY.

Similar Datasets

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