Abstract:
BACKGROUND:Pharmacokinetic-pharmacodynamic (PK/PD) models were developed to describe the relationship between the time course of paliperidone plasma concentrations and the risk of relapse of schizophrenia symptoms following administration of paliperidone palmitate 1-month (PP1M) and 3-month (PP3M) long-acting injectables, and to identify relevant covariates for relapse and dropout events. METHODS:Patient data from two global phase 3, relapse prevention studies comparing PP3M to placebo (study A) and PP3M to PP1M (study B) were analyzed. Dropout and relapse data were assessed using survival analysis as two separate single time-to-event models. Baseline covariates included age, sex, race/country, duration of illness, previous hospitalizations, prior use of long-acting injectables and use of multiple (≥2) antipsychotics at screening. RESULTS:The PK/PD analysis data set included 305 patients who were randomized to receive PP3M or placebo in the double-blind phase of study A and 1002 patients randomized to receive PP3M or PP1M in the double-blind phase of study B. Risk of relapse decreased with increasing paliperidone concentrations for both PP1M and PP3M, while it appeared to increase in patients with higher number of previous hospitalizations and/or with higher prerandomization (trough) paliperidone concentration (study A), and in patients on concomitant benzodiazepine medication and/or at Japan centers (study B). These findings are reflective of different illness severity in the population and of differences in medical practice for Japanese patients. In model-based simulations, PP3M and PP1M displayed similar relapse rates over time. CONCLUSIONS:This PK/PD analysis confirmed that PP1M and PP3M provide comparable efficacy in terms of relapse prevention, and that PP3M is superior to placebo. The PK/PD models presented here may as well be applied to studies with similar designs as either study A or B.
journal_name
J Clin Psychopharmacoljournal_title
Journal of clinical psychopharmacologyauthors
Russu A,Savitz A,Mathews M,Gopal S,Feng Y,Samtani MNdoi
10.1097/JCP.0000000000001137subject
Has Abstractpub_date
2019-11-01 00:00:00pages
567-574issue
6eissn
0271-0749issn
1533-712Xjournal_volume
39pub_type
杂志文章,多中心研究,随机对照试验abstract::There have been an increased number of recent reports on orgasm-related sexual dysfunction coincident with selective serotonin reuptake inhibitor (SSRI) treatment. In contrast, it has also been reported that SSRIs improve sexual dysfunction. Low doses of clomipramine and paroxetine, potent 5-hydroxytryptamine reuptake...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/00004714-199610000-00006
更新日期:1996-10-01 00:00:00
abstract::Remifentanil is a short-acting, esterase-metabolized opioid analgesic. This study compared the abuse liability of remifentanil with that of fentanyl and placebo in a randomized, double-blind, crossover study. Twelve recreational users of opioids received increasing doses of remifentanil (0.6, 1.2, 1.8, 2.4, and 3.0 mi...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004714-200012000-00002
更新日期:2000-12-01 00:00:00
abstract::Central nervous system depressant drugs (CNS-Ds) are known to impair cognitive functions. Overdose of these drugs is common, and most of the hospital-treated patients are discharged within 24 to 48 hours. No previous studies have examined whether they have residual impairment at the time of discharge. Our aim was to e...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0b013e31825d6ddb
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVES:To determine if prolactin levels are associated with glucose-insulin homeostasis in antipsychotic-treated patients with schizophrenia. METHOD:Prolactin levels and glucose homeostasis (quantified using oral glucose tolerance testing, insulin measurement, and homeostasis model assessment) were measured in 15 ...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1097/01.jcp.0000239791.91330.48
更新日期:2006-12-01 00:00:00
abstract:BACKGROUND:Anxiety symptoms frequently experienced by patients with a major neurocognitive disorder (NCD) are often treated with long-term benzodiazepines despite known adverse effects. Pregabalin has shown efficacy in generalized anxiety disorders but has not been studied in patients with a major NCD. The objective of...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0000000000001029
更新日期:2019-05-01 00:00:00
abstract:PURPOSE/BACKGROUND:The aim of this study was to evaluate the effects of quetiapine XR and lithium on actigraphy-measured circadian parameters in patients with bipolar II depression. METHODS/PROCEDURES:This was an 8-week, open-label, prospective, randomized comparative study. The assessments included the 17-item Hamilt...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/JCP.0000000000000699
更新日期:2017-06-01 00:00:00
abstract:PURPOSE/BACKGROUND:For approximately one third of individuals treated for psychosis or schizophrenia, antipsychotic medications will have little or no therapeutic benefit. Clozapine remains the sole medication approved for treatment-resistant schizophrenia, and studies have demonstrated its superior efficacy in reducin...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0000000000000734
更新日期:2017-10-01 00:00:00
abstract::Medication nonadherence in severe mental disorders is an important clinical issue, but estimates vary between studies. There is a need for valid self-reports for both research and clinical practice. This study examined the level of adherence to prescribed medication in outpatients with severe mental disorders and eval...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0b013e3181d2191e
更新日期:2010-04-01 00:00:00
abstract::The effects of daily buprenorphine treatment (4 or 8 mg/day, sublingual) on reports of subjective effects after single intravenous doses of morphine (10 mg), cocaine (30 mg), and saline placebo were studied on an inpatient clinical research ward in 26 men concurrently dependent on opioids and cocaine (DSM-III-R). Late...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1994-02-01 00:00:00
abstract:INTRODUCTION:Although medication with antipsychotic for the psychosis prodrome has often caused some ethical issues, recent studies have shown that some novel antipsychotics are safer and more tolerable for young people. This study aimed to investigate whether the administration of aripiprazole would not only relieve t...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/JCP.0b013e3181b2fe22
更新日期:2009-10-01 00:00:00
abstract:BACKGROUND:Bipolar disorder (BPD) is a chronic and recurrent mood disorder characterized by episodes of mania, hypomania, and major depression. Based on available evidence, mitochondrial dysfunction, oxidative stress, and inflammation have important roles in the pathophysiology of bipolar depression. More specifically,...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/JCP.0000000000000938
更新日期:2018-10-01 00:00:00
abstract::We compared acute effects of single intravenous administrations of metoclopramide (40 mg) and placebo in a double-blind crossover study involving 81 patients with tardive dyskinesia. Metoclopramide produced significantly greater reduction in mean total Abnormal Involuntary Movement Scale score as well as in ratings fo...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1982-12-01 00:00:00
abstract::Over the past 10 years, knowledge gained about the pharmacokinetic profiles of valproate and carbamazepine has increased the clinical effectiveness of their use. Much of the information has been gained through their use as successful antiepileptic medications. As these agents begin to play an increasing role as mood-s...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/00004714-199202001-00010
更新日期:1992-02-01 00:00:00
abstract::Recently, there has been an increased recognition of the association of clozapine with myocarditis and myocardiopathy. Commonly used diagnostic tests have very limited sensitivity in diagnosing this potentially life-threatening complication. We present 3 case reports of clozapine-induced myocarditis/cardiomyopathy tha...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/jcp.0b013e31814e5e68
更新日期:2007-10-01 00:00:00
abstract::Two experiments examined the effects of methylphenidate in male and female patients enrolled in an outpatient treatment program for primary cocaine dependence. The first study was a component of a double-blind efficacy trial wherein 57 patients were first tested in a human laboratory for their initial responsiveness t...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004714-200002000-00011
更新日期:2000-02-01 00:00:00
abstract::Disordered water balance, or polydipsia, is an underassessed and underreported phenomenon present in the severely psychiatrically disabled population. Prevalence rates for polydipsia range from 6.2 to 20%. We followed up five male patients (mean age 43) with chronic schizophrenia who met the Kane criteria for being tr...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/00004714-199608000-00010
更新日期:1996-08-01 00:00:00
abstract::The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition borderline personality disorder (BPD) seems to constitute a very heterogeneous category. Therefore, pharmacological therapy is symptom-oriented or targets comorbid conditions. A high comorbidity exists between BPD and posttraumatic stress disord...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/JCP.0b013e31819a4bae
更新日期:2009-04-01 00:00:00
abstract::Case reports of a lithium-ketorolac drug interaction have been published, but no formal investigation of this interaction has been conducted. The objective of the study presented here was to determine significant changes in lithium serum and red blood cell (RBC) concentrations after lithium and ketorolac (oral formula...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/00004714-199802000-00006
更新日期:1998-02-01 00:00:00
abstract::This study evaluated the impact of using long-acting injectable (LAI) antipsychotics for a longer treatment duration versus a short duration on health care resource utilization among Medicaid-insured schizophrenia patients. Schizophrenia patients 13 years or older initiating LAI antipsychotics were identified from the...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0b013e3182a6082a
更新日期:2014-02-01 00:00:00
abstract::Akathisia is a frequent and distressing side effect of neuroleptic medications. The literature regarding the pharmacologic treatment of acute neuroleptic-induced akathisia is critically reviewed, including nine reports of the use of anticholinergic agents, 15 of the use of beta-blocking agents, and six of the use of b...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,评审
doi:10.1097/00004714-199002000-00003
更新日期:1990-02-01 00:00:00
abstract::Trichotillomania (TTM) is characterized by repetitive hair pulling resulting in hair loss. Data on the pharmacological treatment of TTM are limited. This study examined the opioid antagonist, naltrexone, in adults with TTM who had urges to pull their hair. Fifty-one individuals with TTM were randomized to naltrexone o...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1097/JCP.0000000000000037
更新日期:2014-02-01 00:00:00
abstract:BACKGROUND:Dopaminergic dysfunction, namely, dopamine transporter (DAT) availability variations in patients with drug-naive schizophrenia after long-term treatment, is still not well understood. The aims of the study were to explore (i) whether the DAT availability in patients with drug-naive schizophrenia differed aft...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0000000000000632
更新日期:2017-02-01 00:00:00
abstract::Single oral doses (5 mg) of haloperidol were administered to 36 healthy men (26 black, 10 white) of whom 28 (22 black, 6 white) completed the study. Plasma samples harvested over 96 hours were analyzed for haloperidol and reduced haloperidol by means of a new high performance liquid chromatographic method. Reduced hal...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/00004714-198904000-00005
更新日期:1989-04-01 00:00:00
abstract:BACKGROUND:Second-generation antipsychotics (SGAs) are commonly used to treat children with mental health conditions (MHCs) but are associated with adverse effects including obesity, hypertension, dyslipidemia, and type 2 diabetes. The mechanisms underlying these complications are unknown, but it has been suggested tha...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0000000000000956
更新日期:2018-12-01 00:00:00
abstract::Adverse events during selective serotonin reuptake inhibitor (SSRI) treatment are frequent and may lead to premature treatment discontinuation. If attrition is associated with early worsening of adverse effects or the frequency, intensity, or burden of adverse effects, interventions to maximize retention could be focu...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/JCP.0b013e3181dbfd04
更新日期:2010-06-01 00:00:00
abstract::Therapeutic drug monitoring studies of selective serotonin reuptake inhibitor (SSRI) antidepressants thus far failed to identify a clear concentration-response relationship in major depression. Majority of the previous studies defined clinical response as 50% or greater reduction from baseline in depression rating sca...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0b013e3181730850
更新日期:2008-06-01 00:00:00
abstract::Side effect and health status changes were measured in 3 studies in which outpatients experiencing suboptimal efficacy or tolerability with their current antipsychotic were switched to 6 weeks of open-label ziprasidone. The studies differed only in the patient's prior antipsychotic; 1 study group was on olanzapine (n ...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1097/01.jcp.0000095347.32154.08
更新日期:2003-12-01 00:00:00
abstract::This article reports results for patients who completed the 16-week maintenance phase of a double-blind clinical trial comparing buprenorphine (N = 43; average dose = 9.0 mg/day sublingually) with methadone (N = 43; average dose = 54 mg/day orally) in the outpatient treatment of opioid dependence. In addition to pharm...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1097/00004714-199602000-00010
更新日期:1996-02-01 00:00:00
abstract::The incidence of treatment-emergent extrapyramidal symptoms (EPSs) and tardive dyskinesia (TD) in schizophrenic patients, and the clinical characteristics associated with an increased risk of developing EPSs and TD were examined. Patients (N = 7728) in the 3-year, prospective, observational Schizophrenia Outpatient He...
journal_title:Journal of clinical psychopharmacology
pub_type: 杂志文章
doi:10.1097/JCP.0b013e3181f14098
更新日期:2010-10-01 00:00:00
abstract::Fifty-five patients completed a 5-week double-blind study comparing alprazolam, propranolol, and placebo in the treatment of panic disorder and agoraphobia with panic attacks. There was no concomitant behavioral treatment. Patient and therapist rating scales included Sheehan's Panic and Anxiety Attack Scales, the Mark...
journal_title:Journal of clinical psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1989-02-01 00:00:00