Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia

Jones, Peter B.; Barnes, Thomas R. E.; Davies, Linda; Dunn, Graham; Lloyd, Helen; Hayhurst, Karen P.; Murray, Robin M.; Markwick, Alison; Lewis, Shôn

doi:10.1001/archpsyc.63.10.1079

Cited by 1,027 publications

(631 citation statements)

References 35 publications

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“…The clinical literature has generally reported no consistent, substantial improvement in cognition (at best only a marginal improvement) with the current pharmacotherapies for schizophrenia (Harvey and McClure, 2006;Keefe et al 2007). Indeed, we have conducted our own meta-analysis of the literature and found that total PANSS score improvement was not statistically greater with second-generation antipsychotics (SGAs) when compared with the first-generation antipsychotic (FGA), haloperidol (Tomes, unpublished observations), which is in agreement with findings of the recent CUtLASS study (Jones et al 2006). Cognition was not assessed in our analysis but this provides further evidence for the urgent need for improvement in therapy.…”

Section: Introductionsupporting

confidence: 83%

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

477

322

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Cognitive deficits in schizophrenia remain an unmet clinical need. Improved understanding of the neuro-and psychopathology of these deficits depends on the availability of carefully validated animal models which will assist the development of novel therapies. There is much evidence that at least some of the pathology and symptomatology (particularly cognitive and negative symptoms) of schizophrenia results from a dysfunction of the glutamatergic system which may be modelled in animals through the use of NMDA receptor antagonists. The current review examines the validity of this model in rodents. We review the ability of acute and sub-chronic treatment with three non-competitive NMDA antagonists; phencyclidine (PCP), ketamine and MK801 (dizocilpine) to produce cognitive disturbances of relevance to schizophrenia in rodents and their subsequent reversal by first-and second-generation antipsychotic drugs. Effects of NMDA receptor antagonists on the performance of rodents in behavioural tests assessing the various domains of cognition and negative symptoms are examined: novel object recognition for visual memory, reversal learning and attentional set shifting for problem solving and reasoning, 5-choice serial reaction time for attention and speed of processing; in addition to effects on social behaviour and neuropathology. The evidence strongly supports the use of NMDA receptor antagonists to model cognitive deficit and negative symptoms of schizophrenia as well as certain pathological disturbances seen in the illness. This will facilitate the evaluation of much-needed novel therapies for improved therapy of cognitive deficits and negative symptoms in schizophrenia.

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Section: Introductionsupporting

confidence: 83%

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Neill

Barnes

Cook

et al. 2010

Pharmacology & Therapeutics

477

322

View full text Add to dashboard Cite

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“…Reductions in GABAergic interneurones in these areas have been found in post-mortem analysis from patients with schizophrenia (Benes et al, 1991;Benes and Berretta, 2001;Beasley et al, 2002;Zhang and Reynolds, 2002). We have shown that atypical but not classical antipsychotics can reverse these cognitive deficits; however, in the clinic there is differing evidence for the efficacy of atypical antipsychotics in improving cognition with the CATIE study (Lieberman, 2006;Keefe et al, 2007) and the UK Cost Utility of the Latest Antipsychotic Drugs in Schizophrenia Study (CUtLASS; Jones et al, 2006; suggesting that antipsychotics actually have a limited effect. Cognitive dysfunction is a core characteristic of schizophrenia (Sullivan et al, 1994;Elvevag and Goldberg, 2000;Kuperberg and Heckers, 2000), occurring in 75-85% of patients (Reichenberg et al, 2006), and is becoming increasingly important as impaired cognition has been implicated in poor long-term functional outcome (Marder and Fenton, 2004) which can often persist when other symptoms may be improved with treatment (Gold et al, 1991;Heinrichs, 2005).…”

Section: Introductionmentioning

confidence: 82%

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

et al. 2009

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“…In comparison to adult schizophrenia trials, these findings suggest that youth are less likely to maintain the same treatment over one year. [14][15][16][17] In addition, symptom response tended to plateau during maintenance therapy, such that most youth did not make significant improvements beyond what they had achieved at 8 weeks of acute treatment.…”

Section: Discussionmentioning

confidence: 99%

Double-Blind Maintenance Safety and Effectiveness Findings From the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

Findling

Johnson

McClellan

et al. 2010

Journal of the American Academy of Child & Adolescent Psych

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OBJECTIVE-To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders (EOSS). (age 8-19 years) who had improved during an 8-week, randomized doubleblind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed following defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. METHOD-PatientsRESULTS-Of the 116 youth randomized in the acute trial, 54 entered maintenance treatment (molindone, N=20; olanzapine, N=13; risperidone, N=21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (N=15), inadequate efficacy (N=14), or study non-adherence (N=8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom reduction or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment.CONCLUSIONS-Only 12 % of youth with EOSS continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for EOSS.

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Randomized Controlled Trial of the Effect on Quality of Life of Second- vs First-Generation Antipsychotic Drugs in Schizophrenia

Cited by 1,027 publications

References 35 publications

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Animal models of cognitive dysfunction and negative symptoms of schizophrenia: Focus on NMDA receptor antagonism

Role of 5-HT receptor mechanisms in sub-chronic PCP-induced reversal learning deficits in the rat

Double-Blind Maintenance Safety and Effectiveness Findings From the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

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