A comparison of bd and tid dose regimens of quetiapine (Seroquel) in the treatment of schizophrenia.


:Quetiapine (Seroquel, ICI 204,636) is an atypical antipsychotic that is effective in the treatment of both positive and negative symptoms of schizophrenia, and has a low propensity to cause extrapyramidal symptoms. The compound has a relatively short plasma elimination half-life (approximately 7 h). However, since dopamine D2 receptor occupancies correlate poorly with plasma concentrations of antipsychotics, plasma elimination half-life may not predict either duration of clinical effect or dosing frequency. Accordingly, the efficacy and tolerability of three dosing regimens (450 mg/day given in two or three divided doses daily, and 50 mg/day given twice daily) were compared in a 6-week, double-blind, randomized, multicentre, parallel-group study. The study recruited hospitalized men and women aged 18-65 years meeting DSM-IIIR criteria for acute exacerbation of chronic or subchronic schizophrenia. Six hundred and eighteen patients were randomly assigned to treatment with quetiapine 150 mg tid (n = 209), 225 mg bd (n = 200), or a comparator dose of 25 mg bd (n = 209). At day 42, the last day of randomized treatment and the primary timepoint for efficacy, quetiapine 450 mg/day was more effective than 50 mg/day: 225 mg bd was consistently superior to 25 mg bd in all measures of efficacy (total BPRS, P = 0.006; CGI severity, CGI improvement and SANS, P < 0.03), and 150 mg tid was statistically significantly superior to 25 mg bd with respect to BPRS total score (P = 0.05). The 225 mg bd and 150 mg tid groups were not significantly different from each other with respect to any efficacy measure. Quetiapine was generally well tolerated. Extrapyramidal symptom (EPS) adverse events were generally rare, and occurred with similar frequencies in the two 450 mg/day groups. Quetiapine was not associated with sustained increases in plasma prolactin at any dose. These data support the atypical profile developed from preclinical studies and show that quetiapine is an effective, well tolerated antipsychotic that can be given twice daily.




King DJ,Link CG,Kowalcyk B




Has Abstract


1998-05-01 00:00:00












  • Mecamylamine elicits withdrawal-like signs in rats following a single dose of nicotine.

    abstract:RATIONALE:The ability of nicotine to induce dependence (result in a withdrawal syndrome) is typically thought to require long-term, daily smoking. Emerging evidence suggests that symptoms of nicotine withdrawal may occur following only a few cigarettes. Whether acute exposure to nicotine can induce dependence in animal...


    pub_type: 杂志文章


    authors: Harris AC,Manbeck KE,Schmidt CE,Shelley D

    更新日期:2013-01-01 00:00:00

  • Post-extinction fluoxetine treatment prevents stress-induced reemergence of extinguished fear.

    abstract:RATIONALE:The post-extinction exposure of rats to a sub-conditioning procedure (SCP; i.e., retraining with a shock intensity that is too weak to induce by itself significant fear conditioning) has been reported to provoke the reemergence of extinguished fear. This phenomenon can be prevented by chronic fluoxetine treat...


    pub_type: 杂志文章


    authors: Deschaux O,Zheng X,Lavigne J,Nachon O,Cleren C,Moreau JL,Garcia R

    更新日期:2013-01-01 00:00:00

  • The inhibitory effects on sexual behavior and ambulatory activity of the mixed GABAA/GABAB agonist progabide are differentially blocked by GABA receptor antagonists.

    abstract::Progabide inhibited male rat sexual behavior at a dose of 200 mg/kg. This dose had only modest effects on ambulatory activity and no effect at all on motor coordination as evaluated by a rotarod test. The GABAA antagonist bicuculline, at a dose of 1 mg/kg, blocked the effects of progabide on sex behavior. In contrast,...


    pub_type: 杂志文章


    authors: Agmo A,Paredes RG,Sierra L,Garcés I

    更新日期:1997-01-01 00:00:00

  • Phencyclidine-induced potentiation of brain stimulation reward: acute effects are not altered by repeated administration.

    abstract::Phencyclidine (PCP; 2.5 or 5.0 mg/kg) potentiated the effects of rewarding hypothalamic brain stimulation, causing parallel leftward shifts of the functions that relate rate of responding to stimulation frequency. Thus, like a number of other drugs of abuse, PCP lowered the "dose" of stimulation required to maintain r...


    pub_type: 杂志文章


    authors: Carlezon WA Jr,Wise RA

    更新日期:1993-01-01 00:00:00

  • On the positive and negative affective responses to cocaine and their relation to drug self-administration in rats.

    abstract:RATIONALE:Acute cocaine administration produces an initial rewarding state followed by a dysphoric/anxiogenic "crash." OBJECTIVE:The objective of this study was to determine whether individual differences in the relative value of cocaine's positive and negative effects would account for variations in subsequent drug s...


    pub_type: 杂志文章


    authors: Ettenberg A,Fomenko V,Kaganovsky K,Shelton K,Wenzel JM

    更新日期:2015-07-01 00:00:00

  • Pindolol binding to 5-HT1A receptors in the human brain confirmed with positron emission tomography.

    abstract::The augmentation effect of (-)pindolol as used in combination with SSRI to treat major depression has been ascribed to blocking of dorsal raphe nucleus cell body 5-HT autoreceptors. In this study, the radioligand [carbonyl-11C]WAY-100635 and positron emission tomography were used to establish whether pindolol at a cli...


    pub_type: 杂志文章


    authors: Andrée B,Thorberg SO,Halldin C,Farde L

    更新日期:1999-06-01 00:00:00

  • Tobacco smoke containing high or low levels of nicotine during adolescence: effects on novelty-seeking and anxiety-like behaviors in mice.

    abstract:RATIONALE:Thousands of adolescents start smoking daily but information on the effects of tobacco exposure on this age group is scarce. Moreover, the available animal models rely on the effects of nicotine, neglecting other neuroactive components of tobacco. OBJECTIVES:We investigated the effects of exposure of adolesc...


    pub_type: 杂志文章


    authors: Abreu-Villaça Y,Filgueiras CC,Correa-Santos M,Cavina CC,Naiff VF,Krahe TE,Manhães AC,Ribeiro-Carvalho A

    更新日期:2015-05-01 00:00:00

  • Delayed-non-match-to-sample performance in the radial arm maze: effects of dopaminergic and gabaergic agents.

    abstract::Central dopaminergic transmission has been implicated in memory processes. The present experiments examined the effects of several direct acting dopaminergic agents on performance of a delayed-non-match-to-sample radial arm maze task. Preadministration of apomorphine (D1-D2 agonist; 0.25, 0.5, and 1.0 mg/kg), quinpiro...


    pub_type: 杂志文章


    authors: Chrobak JJ,Napier TC

    更新日期:1992-01-01 00:00:00

  • Effects of increasing response requirement on choice between cocaine and food in rhesus monkeys.

    abstract::Rhesus monkeys were trained in a discrete-trials choice procedure and allowed to choose between intravenous injections of cocaine (0.01-1.0 mg/kg/injection) and food presentation (1 or 4 pellets; 1 g/pellet) during daily 7-h experimental sessions. When each reinforcer was available under a fixed-ratio (FR) 30 schedule...


    pub_type: 杂志文章


    authors: Nader MA,Woolverton WL

    更新日期:1992-01-01 00:00:00

  • Influence of intoxicated practice on the development of acute tolerance to the motor impairment effect of ethanol.

    abstract::The influence of practice while under intoxication was tested on the development of acute tolerance to the motor impairment effect of ethanol. In experiment 1, the motor impairment effect induced by an IP injection of 1.8 g/kg ethanol was quantified after various intervals in separate groups of animals. Lower impairme...


    pub_type: 杂志文章


    authors: Lê AD,Kalant H

    更新日期:1992-01-01 00:00:00

  • Reelin haploinsufficiency reduces the density of PV+ neurons in circumscribed regions of the striatum and selectively alters striatal-based behaviors.

    abstract:RATIONALE:Reelin, a large extracellular matrix glycoprotein, is down-regulated in the brain of schizophrenic patients and of heterozygous reeler mice (rl/+). The behavioral phenotype of rl/- mice, however, matches only partially the schizophrenia hallmarks. OBJECTIVES:We recently reported (Marrone et al., Eur J Neuros...


    pub_type: 杂志文章


    authors: Ammassari-Teule M,Sgobio C,Biamonte F,Marrone C,Mercuri NB,Keller F

    更新日期:2009-06-01 00:00:00

  • Effect of norbinaltorphimine on ∆⁹-tetrahydrocannabinol (THC)-induced taste avoidance in adolescent and adult Sprague-Dawley rats.

    abstract:RATIONALE:The aversive effects of ∆(9)-tetrahydrocannabinol (THC) are mediated by activity at the kappa opioid receptor (KOR) as assessed in adult animals; however, no studies have assessed KOR involvement in the aversive effects of THC in adolescents. Given that adolescents have been reported to be insensitive to the ...


    pub_type: 杂志文章


    authors: Flax SM,Wakeford AG,Cheng K,Rice KC,Riley AL

    更新日期:2015-09-01 00:00:00

  • Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT.

    abstract:RATIONALE:Pharmacokinetics of melatonin in children might differ from that in adults. OBJECTIVES:This study aims to establish a dose-response relationship for melatonin in advancing dim light melatonin onset (DLMO), sleep onset (SO), and reducing sleep onset latency (SOL) in children between 6 and 12 years with chroni...


    pub_type: 杂志文章,随机对照试验


    authors: van Geijlswijk IM,van der Heijden KB,Egberts AC,Korzilius HP,Smits MG

    更新日期:2010-10-01 00:00:00

  • Effect of sub-chronic hydrocortisone on responses to amphetamine in normal male volunteers.

    abstract:RATIONALE:Enhancement of dopamine (DA) release by corticosteroids may be of aetiological importance in substance misuse. OBJECTIVES:To examine the effect of sub-chronic administration of hydrocortisone on the response to amphetamine in healthy male volunteers. METHODS:Following baseline assessment, 20 volunteers were...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Hearn AJ,Gallagher P,Owen BM,Smith MS,Watson S,Young AH

    更新日期:2004-02-01 00:00:00

  • Cross-familiarisation conditioned taste aversion procedure as a method to reveal stimulus resemblance between drugs: studies on the 5-HT1A agonist 8-OHDPAT.

    abstract::In the present study a cross-familiarisation conditioned taste aversion (CTA) paradigm was utilized to reveal stimulus resemblance between the selective 5-HT1A agonist 8-OHDPAT and a variety of serotonergic and non-serotonergic drugs. In male mice, a 0.22 mg/kg dose of 8-OHDPAT was used as the reference compound induc...


    pub_type: 杂志文章


    authors: De Beun R,Rijk HW,Broekkamp CL

    更新日期:1993-01-01 00:00:00

  • Prefrontal cortical hypometabolism during low-dose interferon alpha treatment.

    abstract:OBJECTIVE:To evaluate prospectively interferon alpha (IFN-alpha) associated effects on cerebral glucose metabolism and its correlation to neuropsychiatric symptoms during low-dose IFN-alpha-treatment. METHODS:Eleven patients treated with low-dose IFN-alpha for chronic hepatitis C were prospectively evaluated by neurop...


    pub_type: 临床试验,杂志文章


    authors: Juengling FD,Ebert D,Gut O,Engelbrecht MA,Rasenack J,Nitzsche EU,Bauer J,Lieb K

    更新日期:2000-11-01 00:00:00

  • Effects of cholinergic and anticholinergic drugs on ketamine-induced linguopharyngeal motor activity.

    abstract::Benztropine mesylate (Cogentin) and physostigmine salicylate (Antilirium), were tested for changes in tongue protrusions, retrusions, and swallowing acts in rats anesthetized with a 100 mg/kg IM injection of ketamine hydrochloride. These ketamine-induced linguopharyngeal events were monitored by means of a force displ...


    pub_type: 杂志文章


    authors: Marco LA,Joshi RS,Brown C,Aldes LD,Chronister RB

    更新日期:1988-01-01 00:00:00

  • Environmental enrichment decreases chronic psychosocial stress-impaired extinction and reinstatement of ethanol conditioned place preference in C57BL/6 male mice.

    abstract:RATIONALE:During the last few decades, alcohol use disorders (AUD) have reached an epidemic prevalence, yet social influences on alcoholism have not been fully addressed. Several factors can modulate alcohol intake. On one hand, stress can reinforce ethanol-induced behaviors and be an important component in AUD and alc...


    pub_type: 杂志文章


    authors: Bahi A,Dreyer JL

    更新日期:2020-03-01 00:00:00

  • 2,4-Dithiobiuret in rats: cognitive facilitation after acute injection precedes motor impairment after repeated daily injections.

    abstract::2,4-Dithiobiuret (DTB) is a sulfonated derivative of urea that is used as a reducing agent in chemical manufacture. Its low acute toxicity to rodents belies a peripherally mediated, delayed-onset muscle weakness which develops during repeated daily exposure. In experiment 1, a standard dose regimen of DTB (0.5 mg/kg p...


    pub_type: 杂志文章


    authors: Bushnell PJ,Oshiro WM

    更新日期:1996-02-01 00:00:00

  • Pre-encoding administration of amphetamine or THC preferentially modulates emotional memory in humans.

    abstract:RATIONALE:Many addictive drugs are known to have effects on learning and memory, and these effects could motivate future drug use. Specifically, addictive drugs may affect memory of emotional events and experiences in ways that are attractive to some users. However, few studies have investigated the effects of addictiv...


    pub_type: 杂志文章,随机对照试验


    authors: Ballard ME,Gallo DA,de Wit H

    更新日期:2013-04-01 00:00:00

  • Kappa opioid mediation of cannabinoid effects of the potent hallucinogen, salvinorin A, in rodents.

    abstract:RATIONALE:Salvinorin A, the primary psychoactive derivative of the hallucinogenic herb Salvia divinorum, is a potent and highly selective kappa-opioid receptor (KOR) agonist. Several recent studies, however, have suggested endocannabinoid system mediation of some of its effects. OBJECTIVES:This study represents a syst...


    pub_type: 杂志文章


    authors: Walentiny DM,Vann RE,Warner JA,King LS,Seltzman HH,Navarro HA,Twine CE Jr,Thomas BF,Gilliam AF,Gilmour BP,Carroll FI,Wiley JL

    更新日期:2010-06-01 00:00:00

  • Behavioural analysis of the anorectic effects of fluoxetine and fenfluramine.

    abstract::Two sets of experiments were carried out to compare the effects of fenfluramine and fluoxetine on consummatory and operant behaviour. In food-deprived rats allowed access to a 35% sucrose solution, an initial period of sucrose consumption was followed by a short period of grooming and exploratory behaviour, later supe...


    pub_type: 杂志文章


    authors: Willner P,McGuirk J,Phillips G,Muscat R

    更新日期:1990-01-01 00:00:00

  • Restoration of brain myo-inositol levels in rats increases latency to lithium-pilocarpine seizures.

    abstract::Lithium pretreatment in rats potentiates the epileptogenic effects of pilocarpine and other cholinergic agonists. In order to determine if this effect of lithium could be reversed by myo-inositol, rats were pretreated with intracerebroventricular (ICV) injections of myoinositol, artificial CSF or L-chiro-inositol. Lit...


    pub_type: 杂志文章


    authors: Kofman O,Sherman WR,Katz V,Belmaker RH

    更新日期:1993-01-01 00:00:00

  • Effect of subcutaneous nicotine injections of EEG alpha frequency in non-smokers: a placebo-controlled pilot study.

    abstract::The effect of two subcutaneous injections of 0.6 mg nicotine, administered 40 min apart, was compared with placebo in four non-smoking subjects in a counter-balanced double-blind crossover design. The nicotine injections produced mean peak plasma nicotine concentrations of 5.3 ng/ml 10 min after the first injection an...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Foulds J,McSorley K,Sneddon J,Feyerabend C,Jarvis MJ,Russell MA

    更新日期:1994-06-01 00:00:00

  • Anti-inflammatory and antinociceptive activities of glucagon-like peptides: evaluation of their actions on serotonergic, nitrergic, and opioidergic systems.

    abstract:RATIONALE:Glucagon-like peptide-1 (GLP-1) and glucagon-like peptide-2 (GLP-2) are gut derived hormones. GLP-1 and GLP-2 were shown to have pleiotropic effects in intestinal and pancreatic diseases. OBJECTIVE:We aimed to investigate the activities of GLP-1 and GLP-2 on nociception and inflammation in mice, involving th...


    pub_type: 杂志文章


    authors: Aykan DA,Kesim M,Ayan B,Kurt A

    更新日期:2019-06-01 00:00:00

  • Central serotonin transporter levels are associated with stress hormone response and anxiety.

    abstract:RATIONALE:Negative mood states are characterized by both stress hormone dysregulation and serotonergic dysfunction, reflected by altered thalamic serotonin transporter (5-HTT) levels. However, so far, no study examined the individual association between cortisol response and cerebral in vivo 5-HTT levels in patients su...


    pub_type: 杂志文章


    authors: Reimold M,Knobel A,Rapp MA,Batra A,Wiedemann K,Ströhle A,Zimmer A,Schönknecht P,Smolka MN,Weinberger DR,Goldman D,Machulla HJ,Bares R,Heinz A

    更新日期:2011-02-01 00:00:00

  • MDPV self-administration in female rats: influence of reinforcement history.

    abstract:RATIONALE:A subset of male rats that self-administer 3,4-methylenedioxypyrovalerone (MDPV) have unusually high levels of drug intake; however, factor(s) that influence this behavior (e.g., reinforcement history and sex) are unknown. OBJECTIVES:Characterize the reinforcing potency and effectiveness of MDPV in female ra...


    pub_type: 杂志文章


    authors: Doyle MR,Sulima A,Rice KC,Collins GT

    更新日期:2020-11-24 00:00:00

  • Global impairment of prospective memory following acute alcohol.

    abstract:RATIONALE:Whilst the deleterious effects of alcohol on retrospective remembering have been widely documented, no study has yet objectively determined alcohol's effects on prospective memory (PM)--remembering to do something in the future. OBJECTIVES:With this aim, the present study determined the acute effects of alco...


    pub_type: 杂志文章,随机对照试验


    authors: Leitz JR,Morgan CJ,Bisby JA,Rendell PG,Curran HV

    更新日期:2009-08-01 00:00:00

  • Double dissociation of serotonergic and dopaminergic mechanisms on attentional performance using a rodent five-choice reaction time task.

    abstract:RATIONALE:Converging evidence suggests that dopaminergic and serotonergic mechanisms affect distinct aspects of cognitive performance. Experiments using the rodent five-choice reaction time task have established a critical role for dopaminergic mechanisms in the rat medial prefrontal cortex (mPFC), but have yielded onl...


    pub_type: 杂志文章


    authors: Passetti F,Dalley JW,Robbins TW

    更新日期:2003-01-01 00:00:00

  • Naltrexone decreases craving and alcohol self-administration in alcohol-dependent subjects and activates the hypothalamo-pituitary-adrenocortical axis.

    abstract:BACKGROUND:This laboratory study investigated the mechanisms by which the opioid antagonist, naltrexone, reduces the risk of relapse to heavy drinking in individuals with alcohol dependence. METHODS:Eighteen alcohol-dependent, non-treatment-seeking volunteers were randomized to 50 mg naltrexone or placebo for 6 days a...


    pub_type: 临床试验,杂志文章,随机对照试验


    authors: O'Malley SS,Krishnan-Sarin S,Farren C,Sinha R,Kreek MJ

    更新日期:2002-02-01 00:00:00