Effectiveness of the selective D4 antagonist sonepiprazole in schizophrenia: a placebo-controlled trial.


BACKGROUND:Selective localization of dopamine D(4) receptors in the prefrontal cortex and preferential affinity of clozapine for the dopamine D(4) receptor over the D(2) receptor led to the hypothesis that the superior efficacy of clozapine may be mediated via blockade of the D(4) receptor. This hypothesis was tested by evaluating sonepiprazole, a selective D(4) dopamine antagonist, in schizophrenia patients. METHODS:We treated 467 hospitalized schizophrenia patients with scores of > or = 60 on the Positive and Negative Syndrome Scale (PANSS) with sonepiprazole, olanzapine, or placebo once daily for 6 weeks. The primary efficacy end point was the mean change from baseline in the PANSS total score at 6 weeks. Secondary efficacy end points were the mean change from baseline in the PANSS factor scores, the Brief Psychiatric Rating Scale score, the Clinical Global Impressions Severity of Illness score, and the Calgary Depression Scale score. RESULTS:No statistically significant differences were observed between placebo and any sonepiprazole dose on the primary or any secondary end point after 6 weeks of treatment. Statistically significant differences, favoring olanzapine over placebo, were observed on all efficacy end points but the Calgary Depression Scale. CONCLUSIONS:Sonepiprazole was ineffective for the treatment of patients with schizophrenia.


Biol Psychiatry


Biological psychiatry


Corrigan MH,Gallen CC,Bonura ML,Merchant KM,Sonepiprazole Study Group.




Has Abstract


2004-03-01 00:00:00














  • Resting regional cerebral perfusion in recent posttraumatic stress disorder.

    abstract:BACKGROUND:Brain imaging research in posttraumatic stress disorder has been largely performed on patients with chronic disease, often heavily medicated, with current or past alcohol and substance abuse. Additionally, virtually only activation brain imaging paradigms have been done in posttraumatic stress disorder, wher...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Bonne O,Gilboa A,Louzoun Y,Brandes D,Yona I,Lester H,Barkai G,Freedman N,Chisin R,Shalev AY

    更新日期:2003-11-15 00:00:00

  • In vivo characterization and dynamic receptor occupancy imaging of TPA023B, an alpha 2/alpha 3/alpha 5 subtype selective gamma-aminobutyric acid-a partial agonist.

    abstract:BACKGROUND:A novel, high-affinity (.7-2.0 nmol) compound that selectively activates the alpha2, alpha 3, and alpha 5 (but not alpha1) gamma-aminobutyric acid-A (GABA(A)) receptor subtypes, TPA023B (2',6-difluoro-5'-[3-(1-hydroxy-1-methylethyl) imidazo[1,2-b][1,2,4]triazin-7-yl][1,1'-biphenyl]-2-carbonitrile) was pharma...

    journal_title:Biological psychiatry

    pub_type: 杂志文章,随机对照试验


    authors: Van Laere K,Bormans G,Sanabria-Bohórquez SM,de Groot T,Dupont P,De Lepeleire I,de Hoon J,Mortelmans L,Hargreaves RJ,Atack JR,Burns HD

    更新日期:2008-07-15 00:00:00

  • Relationship of dietary intake to gastrointestinal symptoms in children with autistic spectrum disorders.

    abstract:BACKGROUND:Gastrointestinal (GI) symptoms and abnormalities in stool consistency are frequently reported by parents of children with autism spectrum disorders (ASD). The purpose of this study was to 1) describe dietary intake of a cohort of children with ASD compared with normative data and 2) determine whether GI symp...

    journal_title:Biological psychiatry

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Levy SE,Souders MC,Ittenbach RF,Giarelli E,Mulberg AE,Pinto-Martin JA

    更新日期:2007-02-15 00:00:00

  • Longitudinal follow-up of reproductive and metabolic features of valproate-associated polycystic ovarian syndrome features: A preliminary report.

    abstract:BACKGROUND:In the Systematic Treatment Enhancement Program for Bipolar Disorder, we showed that valproate is associated with new-onset menstrual-cycle irregularities and hyperandrogenism in 10.5% of 86 women. We now determine whether polycystic ovarian syndrome (PCOS) features reverse on valproate discontinutation. ME...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Joffe H,Cohen LS,Suppes T,Hwang CH,Molay F,Adams JM,Sachs GS,Hall JE

    更新日期:2006-12-15 00:00:00

  • Identifying cognitive mechanisms targeted for treatment development in schizophrenia: an overview of the first meeting of the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia Initiative.

    abstract::This overview describes the generation and development of the ideas that led to the Cognitive Neuroscience Treatment Research to Improve Cognition in Schizophrenia (CNTRICS) initiative. It also describes the organization, process, and products of the first meeting. The CNTRICS initiative involves a series of three con...

    journal_title:Biological psychiatry

    pub_type: 共识发展会议,杂志文章


    authors: Carter CS,Barch DM,Buchanan RW,Bullmore E,Krystal JH,Cohen J,Geyer M,Green M,Nuechterlein KH,Robbins T,Silverstein S,Smith EE,Strauss M,Wykes T,Heinssen R

    更新日期:2008-07-01 00:00:00

  • Contrasting effects of pretraining, posttraining, and pretesting infusions of corticotropin-releasing factor into the lateral amygdala: attenuation of fear memory formation but facilitation of its expression.

    abstract:BACKGROUND:The lateral nucleus of the amygdala (LA) is a crucial part of the neural circuitry underlying the formation and storage of memories established through fear conditioning. To investigate corticotropin-releasing factor (CRF) contributions to fear memory in LA, the present experiments tested the effects of intr...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Isogawa K,Bush DE,LeDoux JE

    更新日期:2013-02-15 00:00:00

  • Anhedonia and reward-circuit connectivity distinguish nonresponders from responders to dorsomedial prefrontal repetitive transcranial magnetic stimulation in major depression.

    abstract:BACKGROUND:Depression is a heterogeneous mental illness. Neurostimulation treatments, by targeting specific nodes within the brain's emotion-regulation network, may be useful both as therapies and as probes for identifying clinically relevant depression subtypes. METHODS:Here, we applied 20 sessions of magnetic resona...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Downar J,Geraci J,Salomons TV,Dunlop K,Wheeler S,McAndrews MP,Bakker N,Blumberger DM,Daskalakis ZJ,Kennedy SH,Flint AJ,Giacobbe P

    更新日期:2014-08-01 00:00:00

  • Suicide and violence associated with panic attacks.

    abstract::Several studies have indicated that patients with panic attacks have a higher rate of suicide attempts as well as deaths from suicide. Additionally, several investigators have presented case reports of individuals manifesting suicidal and violent behaviors directly and temporally associated with panic attacks. We repo...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Korn ML,Kotler M,Molcho A,Botsis AJ,Grosz D,Chen C,Plutchik R,Brown SL,van Praag HM

    更新日期:1992-03-15 00:00:00

  • Prepartum and Postpartum Maternal Depressive Symptoms Are Related to Children's Brain Structure in Preschool.

    abstract:BACKGROUND:Perinatal maternal depression is a serious health concern with potential lasting negative consequences for children. Prenatal depression is associated with altered brain gray matter in children, though relations between postpartum depression and children's brains and the role of white matter are unclear. ME...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Lebel C,Walton M,Letourneau N,Giesbrecht GF,Kaplan BJ,Dewey D

    更新日期:2016-12-01 00:00:00

  • Altered neurotrophin receptor function in the developing prefrontal cortex leads to adult-onset dopaminergic hyperresponsivity and impaired prepulse inhibition of acoustic startle.

    abstract:BACKGROUND:Survival and differentiation of neurons and the formation and maintenance of synapses in the cerebral cortex may be affected in schizophrenia. Since neurotrophins play an important role in these events, behavioral effects relevant to schizophrenia were investigated in rats that had compromised neurotrophin f...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Rajakumar N,Leung LS,Ma J,Rajakumar B,Rushlow W

    更新日期:2004-04-15 00:00:00

  • Benzodiazepines as antidepressants: does GABA play a role in depression?

    abstract::Benzodiazepines, the most widely prescribed psychotropic drugs, are often used in patients with depressive disorders, either alone or in combination with standard antidepressants. This review evaluates the efficacy of benzodiazepines (alprazolam, diazepam, chlordiazepoxide) as established in acute-phase, randomized co...

    journal_title:Biological psychiatry

    pub_type: 杂志文章,meta分析


    authors: Petty F,Trivedi MH,Fulton M,Rush AJ

    更新日期:1995-11-01 00:00:00

  • Prediction of the DST results in depressives by means of urinary-free cortisol excretion, dexamethasone levels, and age.

    abstract::This study investigates the relationships between cortisol escape from suppression by dexamethasone during a depressive episode, and the baseline activity of the hypothalamic-pituitary-adrenal (HPA) axis, circulating dexamethasone levels, and age. To this end, we measured urinary-free cortisol (UFC) excretion in 24-hr...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Maes M,Jacobs MP,Suy E,Minner B,Raus J

    更新日期:1990-08-15 00:00:00

  • Impact of Sleep and Circadian Rhythms on Addiction Vulnerability in Adolescents.

    abstract::Sleep homeostasis and circadian function are important maintaining factors for optimal health and well-being. Conversely, sleep and circadian disruptions are implicated in a variety of adverse health outcomes, including substance use disorders. These risks are particularly salient during adolescence. Adolescents requi...

    journal_title:Biological psychiatry

    pub_type: 杂志文章,评审


    authors: Logan RW,Hasler BP,Forbes EE,Franzen PL,Torregrossa MM,Huang YH,Buysse DJ,Clark DB,McClung CA

    更新日期:2018-06-15 00:00:00

  • Exposure to postnatal depression predicts elevated cortisol in adolescent offspring.

    abstract:BACKGROUND:Animal research shows that early adverse experience results in altered glucocorticoid levels in adulthood, either raised basal levels or accentuated responses to stress. If a similar phenomenon operates in humans, this suggests a biological mechanism whereby early adversity might transmit risk for major depr...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Halligan SL,Herbert J,Goodyer IM,Murray L

    更新日期:2004-02-15 00:00:00

  • Modification of ligand binding to membranes by a soluble acceptor. Alpha-1-acid glycoprotein attenuates 3H-imipramine binding to cerebral membranes.

    abstract::The effect of individual plasma proteins on the binding of 3H-imipramine (3H-IMI) was investigated, using rat cerebral membranes as the binding site source. Addition of alpha-1-acid glycoprotein (aAGLP) to an incubation medium containing 4 nm 3H-IMI resulted in a concentration-dependent inhibition of 3H-IMI binding, w...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Barkai AI,Baron M,Kowalik S,Cooper TB

    更新日期:1986-08-01 00:00:00

  • Dementia rating and nicotinic receptor expression in the prefrontal cortex in schizophrenia.

    abstract:BACKGROUND:The etiology of dementia that occurs in patients with schizophrenia is not well understood. Nicotinic acetylcholine receptors have been implicated in cognitive function, and deficits in these receptors have been reported in schizophrenia. METHODS:The present study investigates possible associations of nicot...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Martin-Ruiz CM,Haroutunian VH,Long P,Young AH,Davis KL,Perry EK,Court JA

    更新日期:2003-12-01 00:00:00

  • Guanfacine potentiates the activation of prefrontal cortex evoked by warning signals.

    abstract:BACKGROUND:Warning signals evoke an alert state of readiness that prepares for a rapid response by priming a thalamo-frontal-striatal network that includes the dorsolateral prefrontal cortex (DLPFC). Animal models indicate that noradrenergic input is essential for this stimulus-driven activation of DLPFC, but the preci...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Clerkin SM,Schulz KP,Halperin JM,Newcorn JH,Ivanov I,Tang CY,Fan J

    更新日期:2009-08-15 00:00:00

  • Cortisol circadian rhythms during the menstrual cycle and with sleep deprivation in premenstrual dysphoric disorder and normal control subjects.

    abstract:BACKGROUND:In this study we extended previous work by examining whether disturbances in the circadian rhythms of cortisol during the menstrual cycle distinguish patients with premenstrual dysphoric disorder (PMDD) from normal control (NC) subjects. In addition, we tested the differential response to the effects of earl...

    journal_title:Biological psychiatry

    pub_type: 临床试验,杂志文章,随机对照试验


    authors: Parry BL,Javeed S,Laughlin GA,Hauger R,Clopton P

    更新日期:2000-11-01 00:00:00

  • Single trial analysis of event related potentials: a comparison between schizophrenics and depressives.

    abstract::The aim of the present paper was to perform a single trial analysis of event-related potentials in order to elucidate the mechanisms behind a reduced P300 amplitude occurring in unmedicated depressives (n = 11) and schizophrenics (n = 18). For this purpose, tools from linear system theory were applied to single trials...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Röschke J,Wagner P,Mann K,Fell J,Grözinger M,Frank C

    更新日期:1996-11-01 00:00:00

  • Impaired motor skill learning in schizophrenia: implications for corticostriatal dysfunction.

    abstract::We assessed skill learning in young and older schizophrenic patients using the rotary pursuit task. Schizophrenic patients displayed impaired learning on this task compared with normal control subjects, but older patients were not more impaired than young ones. The patients' rotary pursuit learning was not correlated ...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Schwartz BL,Rosse RB,Veazey C,Deutsch SI

    更新日期:1996-02-15 00:00:00

  • Platelet [3H]imipramine binding in patients with panic disorder.

    abstract::[3H]imipramine binding to platelets was measured in 17 drug-free panic disorder patients and 14 healthy controls. No difference in Bmax or Kd values was found between the two groups. Patients with a past history of major melancholic depression or severe agoraphobia had similar binding parameters as panic disorder pati...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Uhde TW,Berrettini WH,Roy-Byrne PP,Boulenger JP,Post RM

    更新日期:1987-01-01 00:00:00

  • Can a subtype of conduct disorder linked to bipolar disorder be identified? Integration of findings from the Massachusetts General Hospital Pediatric Psychopharmacology Research Program.

    abstract::Our intent was to investigate systematically the overlap between conduct disorder (CD) and bipolar disorder (BPD). We hypothesized that neither CD nor manic symptoms were secondary to the other disorder and that children with the two disorders would have correlates of both. Results from a series of programmatic studie...

    journal_title:Biological psychiatry

    pub_type: 杂志文章,评审


    authors: Biederman J,Mick E,Wozniak J,Monuteaux MC,Galdo M,Faraone SV

    更新日期:2003-06-01 00:00:00

  • Familial and sporadic subtypes of early-onset Obsessive-Compulsive disorder.

    abstract:BACKGROUND:Family studies of Obsessive-Compulsive (OCD) indicate there is substantial heterogeneity in the familiality of the disorder. This study was done to determine whether there are differences between familial and sporadic probands with early-onset OCD in obsessive-compulsive (OC) symptom categories and comorbid ...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Hanna GL,Fischer DJ,Chadha KR,Himle JA,Van Etten M

    更新日期:2005-04-15 00:00:00

  • Microarray analysis of hippocampal CA1 neurons implicates early endosomal dysfunction during Alzheimer's disease progression.

    abstract:BACKGROUND:Endocytic dysfunction and neurotrophin signaling deficits may underlie the selective vulnerability of hippocampal neurons during the progression of Alzheimer's disease (AD), although there is little direct in vivo and biochemical evidence to support this hypothesis. METHODS:Microarray analysis of hippocampa...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Ginsberg SD,Alldred MJ,Counts SE,Cataldo AM,Neve RL,Jiang Y,Wuu J,Chao MV,Mufson EJ,Nixon RA,Che S

    更新日期:2010-11-15 00:00:00

  • Increased glucocorticoid production and altered cortisol metabolism in women with mild to moderate Alzheimer's disease.

    abstract:BACKGROUND:Abnormalities at several levels of the hypothalamic-pituitary-adrenal axis, which may promote glucocorticoid dependent neurodegeneration, have been reported in patients with Alzheimer's disease. In this study we have explored the possibility that peripheral cortisol metabolism is enhanced and glucocorticoid ...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Rasmuson S,Andrew R,Näsman B,Seckl JR,Walker BR,Olsson T

    更新日期:2001-03-15 00:00:00

  • Familial transmission of risk factors in the first-degree relatives of schizophrenic people.

    abstract::Schizophrenia is a complex illness with multiple pathophysiologic factors that contribute to its psychopathology. One strategy to identify these factors is to observe them in isolation from each other, by characterizing their expression in the relatives of schizophrenic probands. By Mendel's second law, each genetic f...

    journal_title:Biological psychiatry

    pub_type: 杂志文章,评审


    authors: Waldo MC,Adler LE,Leonard S,Olincy A,Ross RG,Harris JG,Freedman R

    更新日期:2000-02-01 00:00:00

  • Remote and recent memory in long-hospitalized chronic schizophrenics.

    abstract::This study shows that chronic, long-hospitalized schizophrenics perform (tested by the Famous Events Questionnaire) at a higher level on remote memory than they do on word list recall. A post hoc, matched-tasks check suggested that this finding was not due to differences in the discriminating power of the tasks. Relat...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Calev A,Berlin H,Lerer B

    更新日期:1987-01-01 00:00:00

  • Microanatomy of dendritic spines: emerging principles of synaptic pathology in psychiatric and neurological disease.

    abstract::Psychiatric and neurologic disorders ranging from mental retardation to addiction are accompanied by structural and functional alterations of synaptic connections in the brain. Such alterations include abnormal density and morphology of dendritic spines, synapse loss, and aberrant synaptic signaling and plasticity. Re...

    journal_title:Biological psychiatry

    pub_type: 杂志文章,评审


    authors: Blanpied TA,Ehlers MD

    更新日期:2004-06-15 00:00:00

  • Differential Valuation and Learning From Social and Nonsocial Cues in Borderline Personality Disorder.

    abstract:BACKGROUND:Volatile interpersonal relationships are a core feature of borderline personality disorder (BPD) and lead to devastating disruption of patients' personal and professional lives. Quantitative models of social decision making and learning hold promise for defining the underlying mechanisms of this problem. In ...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Fineberg SK,Leavitt J,Stahl DS,Kronemer S,Landry CD,Alexander-Bloch A,Hunt LT,Corlett PR

    更新日期:2018-12-01 00:00:00

  • Plasma dexamethasone concentrations and the dexamethasone suppression test.

    abstract::Altered bioavailability or altered pharmacokinetics of dexamethasone (dex) may contribute to a positive Dexamethasone Suppression Test (DST) in psychiatric patients. We measured plasma dex and plasma cortisol concentrations in 32 patients with primary major depressive disorder (MDD), 14 patients with other psychiatric...

    journal_title:Biological psychiatry

    pub_type: 杂志文章


    authors: Ritchie JC,Belkin BM,Krishnan KR,Nemeroff CB,Carroll BJ

    更新日期:1990-01-15 00:00:00