A Double-Blind Comparative Study of Clozapine  and Risperidone in the Management  of Severe Chronic Schizophrenia

Azorin, Jean‐Michel; Spiegel, René; Remington, Gary; Vanelle, Jean-Marie; Péré, Jean‐Jacques; Giguere, Monique; Bourdeix, I.

doi:10.1176/appi.ajp.158.8.1305

Cited by 151 publications

(106 citation statements)

References 24 publications

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“…Controlled trials 76,[91][92][93] have generally failed to confirm the promise of benefit in treatmentresistant schizophrenia seen in early, uncontrolled studies. For example, Wirshing and colleagues 94 compared risperidone and haloperidol in a sample of 67 subjects with treatment-resistant schizophrenia.…”

Section: Risperidonementioning

confidence: 99%

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Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

Lewis

Davies²,

Jones³

et al. 2006

Health Technol Assess

134

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Section: Risperidonementioning

confidence: 99%

“…Azorin and colleagues 91 noted the methodological problems with such comparative studies of risperidone and clozapine, such as small sample sizes and the use of suboptimal clozapine doses. They sought to remedy such deficiencies in their own prospective, double-blind study.…”

Section: Risperidonementioning

confidence: 99%

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

Lewis

Davies²,

Jones³

et al. 2006

Health Technol Assess

134

View full text Add to dashboard Cite

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“…These mice maintain large distances from wild-type littermates and actively avoid social investigation when used as the residents in a resident-intruder paradigm (Mohn et al, 1999). In both chronic PCP treated animals and the NR1 knockdown mice, the atypical antipsychotic drug, clozapine, which appears to treat negative symptoms and social deficit symptoms better than other treatments (Azorin et al, 2001;Buchanan et al, 1998), improves sociality. On the other hand, the typical antipsychotic drug, haloperidol, is inactive (Sams-Dodd, 1997;Qiao et al, 2001, Mohn et al, 1999.…”

Section: Introductionmentioning

confidence: 99%

Social Interaction Deficits Caused by Chronic Phencyclidine Administration are Reversed by Oxytocin

Lee

Brady

Shapiro

et al. 2005

Neuropsychopharmacol

184

105

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Chronic administration of phencyclidine (PCP) has been advanced as a valid animal model of the social deficit symptoms of schizophrenia. In these studies, the cumulative time that male rats treated once a day for 14 days with PCP actively engaged in social behavior was decreased approximately 75% relative to saline-treated control animals. In addition, these socially impaired rats had an increase in the relative amount of noncontact interactions compared with saline-injected peers. Social behaviors were preferentially affected by PCP treatment because in two anxiety-related behavioral assays, the open field and light/dark emergence tests, there was a failure to differentiate between the PCP-treated rats and saline-injected control rats. Considering the general importance of the neuropeptides oxytocin and vasopressin in male social behaviors, studies of molecular markers related to these neuropeptides were performed. Hypothalamic oxytocin mRNA expression was significantly decreased while oxytocin receptor binding was increased in the central nucleus of the amygdala following chronic PCP treatment. Given the significance of central nucleus of the amygdala in social behavior, oxytocin was infused into the central nucleus of experimental and control male rats, and their postinfusion social interaction and open field behaviors were analyzed. A bilateral infusion of 1 mg of oxytocin into the central amygdala selectively restored the normal quantity and quality of social behavior in chronic PCP-treated male rats without altering open field behaviors. These findings suggest that deficits in the central oxytocinergic system may underlie the social impairment exhibited in this animal model of schizophrenia.

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“…This study demonstrated that clozapine is superior to other atypical antipsychotics as well as the typical antipsychotics (McEvoy et al, 2006). Older studies showed that clozapine is one of the most effective oral atypical antipsychotics due to 1) superior improvement in positive and negative symptoms, 2) efficacy in the treatment of refractory schizophrenia, and 3) reduction in patient suicide risk (Reid et al, 1998, Volvavka et al, 2002, Azorin et al 2001, Buchanan et al, 1998. Even when observational studies are considered, as opposed to clinical trials, clozapine has been shown to have superior efficacy (Brambilla et al 2002) particularly with refractory patients.…”

Section: Introductionmentioning

confidence: 82%

An initial animal proof-of-concept study for central administration of clozapine to schizophrenia patients

Abrams¹,

Zheng²,

Choo³

et al. 2008

Schizophrenia Research

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While clozapine is the acknowledged superior pharmacotherapeutic for the treatment of schizophrenia, the side effect profile, which includes potentially fatal complications, limits its usefulness. Central administration of clozapine directly into the brain could circumvent many of the side effect issues due to the dramatic reduction in dose and the limitation of the drug primarily to the CNS. The present study demonstrates that clozapine can be formulated as a stable solution at physiological pH, which does not have in vitro neurotoxic effects at concentrations which may be effective at treating symptoms. Acute central administration improved auditory gating deficits in a mouse model of schizophrenia-like deficits. Assessment of behavioral alterations in rats receiving chronic central infusions of clozapine via osmotic minipump were performed with the open field and elevated plus mazes. Neither paradigm revealed any detrimental effects of the infusion. While these data represent only an initial investigation, they none-the-less suggest that central administration of clozapine may be a viable alternate therapeutic approach for schizophrenia patients which may be effective in symptom reduction without causing behavioral or neurotoxic effects.

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A Double-Blind Comparative Study of Clozapine and Risperidone in the Management of Severe Chronic Schizophrenia

Abstract: Clozapine showed superior efficacy over risperidone in this patient population. Both treatments were equally well tolerated as demonstrated through their adverse event profiles, although as expected clozapine was associated with a lower risk of extrapyramidal symptoms than risperidone.

Cited by 151 publications

References 24 publications

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

Randomised controlled trials of conventional antipsychotic versus new atypical drugs, and new atypical drugs versus clozapine, in people with schizophrenia responding poorly to, or intolerant of, current drug treatment

Social Interaction Deficits Caused by Chronic Phencyclidine Administration are Reversed by Oxytocin

An initial animal proof-of-concept study for central administration of clozapine to schizophrenia patients

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