Clozapine Augmented With Risperidone in the Treatment of Schizophrenia: A Randomized, Double-Blind, Placebo-Controlled Trial

Department of Psychiatry, Drexel University, Filadelfia, Pennsylvania, United States
American Journal of Psychiatry (Impact Factor: 12.3). 02/2005; 162(1):130-6. DOI: 10.1176/appi.ajp.162.1.130
Source: PubMed


The authors evaluated the efficacy and safety of augmenting clozapine with risperidone in patients with treatment-resistant schizophrenia.
In a randomized, double-blind, placebo-controlled 12-week trial, 40 patients unresponsive or partially responsive to clozapine monotherapy received a steady dose of clozapine combined with either placebo (N=20) or up to 6 mg/day of risperidone (N=20). Patient psychopathology was assessed at 2-week intervals with the Brief Psychiatric Rating Scale (BPRS) and the Scale for the Assessment of Negative Symptoms (SANS), among other measures. Movement disorders were assessed with the Simpson-Angus Rating Scale.
From baseline to week 6 and week 12, mean BPRS total and positive symptom subscale scores were reduced significantly in both groups, but the reductions were significantly greater with clozapine/risperidone treatment. Reductions in SANS scores were also significantly greater with clozapine/risperidone treatment than with clozapine/placebo. The adverse event profile for clozapine/risperidone treatment was similar to that for clozapine/placebo. Simpson-Angus Rating Scale scores were lower with clozapine/risperidone treatment throughout the trial but increased to approach those of clozapine/placebo treatment at week 12. Clozapine/risperidone treatment did not induce additional weight gain, agranulocytosis, or seizures compared with clozapine/placebo treatment.
In patients with a suboptimal response to clozapine, the addition of risperidone improved overall symptoms and positive and negative symptoms of schizophrenia. The combination appears to be safe and well tolerated. Augmentation of clozapine with risperidone may provide additional clinical benefit for patients who are nonresponsive or only partially responsive to clozapine alone.

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Available from: Richard C Josiassen, Sep 30, 2015
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    • "A vizsgálatok egymásnak ellentmondó eredményekre jutottak. Egyes randomizált kontrollált vizsgálatokban (Freudenreich et al., 2007; Josiassen et al., 2005) előnyösebbnek találták a clozapinhoz adott risperidon hatását a clozapin+placebónál, más vizsgálatokban azonban (Anil Yagcioglu et al., 2005; Honer et al., 2006) nem tudtak különbséget kimutatni ugyanezen két terápia között. A vizsgálatokból készült metaanalízisben (Correll et al., 2009) a clozapint tartalmazó kombinált kezelések a hatékonyság hiányának a vizsgálatokban használt definíciói alapján szignifikánsan hatékonyabbnak mutatkoztak, mint a clozapint nem tartalmazó kombinációk. "
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    ABSTRACT: Main indication for antipsychotic medication is the treatment of schizophrenia and other psychotic disorders. Influential protocols in the treatment of schizophrenia recommend the use of antipsychotics in monotherapy. In case of therapy resistance, combination of antipsychotics is a feasible option. Applying antipsychotics in combination is common in clinical practice, although existing efficacy and safety data concerning antipsychotic combinations are scarce. Authors, after reviewing existing scientific data, make attempt to give recommendations for combined antipsychotic therapy in everyday clinical practice.
    Neuropsychopharmacologia Hungarica: a Magyar Pszichofarmakológiai Egyesület lapja = official journal of the Hungarian Association of Psychopharmacology 09/2012; 14(3):189-95. DOI:10.5706/nph201209004
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    • "A number of small, open trials published in the last century were followed by double blind RCTs, which were inconclusive. While Freudenreich et al. (2007) and Josiassen et al. (2005) found advantages when adding risperidone to clozapine over a placebo control group in double blind RCTs (n=40 and n=24, respectively), these positive results could not be confirmed by another RCT (n=30) by Anil Yagcioglu et al. (2005) and Akdede et al. (2006). In the largest sample evaluated so far, Honer et al. (2006) compared the efficacy of clozapine combined with risperidone to clozapine plus placebo in 68 patients with schizophrenia who had previously failed to respond to clozapine monotherapy in an 8 wk double blind RCT. "
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    ABSTRACT: Antipsychotic polypharmacy remains prevalent; it has probably increased for the treatment of schizophrenia in real-world clinical settings. The current evidence suggests some clinical benefits of antipsychotic polypharmacy, such as better symptom control with clozapine plus another antipsychotic, and a reversal of metabolic side-effects with a concomitant use of aripiprazole. On the other hand, the interpretation of findings in the literature should be made conservatively in light of the paucity of good studies and potentially serious side-effects. Also, although the available data are still limited, two smaller-scale clinical trials provide preliminary evidence that converting antipsychotic polypharmacy to monotherapy could be a valid and reasonable treatment option. Several studies have explored strategies to change physicians' antipsychotic polypharmacy prescribing behaviours. These have revealed that, while the impact of purely educational interventions may be limited, more aggressive procedures such as directly notifying physicians by letters or phone calls can be more effective in reducing antipsychotic polypharmacy. In conclusion, antipsychotic polypharmacy can work for some clinically difficult conditions; however, it should be the exception rather than the rule and may be avoidable in many patients. More importantly, the paucity of the data clearly emphasizes the need for further investigations on not only advantages and disadvantages of antipsychotic polypharmacy, but also regarding effective interventions in already prescribed polypharmacy regimens.
    The International Journal of Neuropsychopharmacology 05/2012; 17(07):1-11. DOI:10.1017/S1461145712000399 · 4.01 Impact Factor
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    • "Clozapine is the drug of choice in treatment-resistant schizophrenia , but 40–70% of clozapine-treated patients continue to demonstrate suboptimal clinical response [1] [2] [3] [4]. Various augmentation strategies have been tested, including the use of other atypical antipsychotics, but no clear recommendations can presently be proposed [5] [6] [7] [8] [9] [10]. "
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    ABSTRACT: There exist many case reports and studies on the antipsychotic augmentation by aripirazole in partial responders to clozapine, the most seem to be finding a slight difference in the PANSS and CGI scores after the aripirazole addition. The results of our report are compatible with those of other studies but, we have found a considerable antianxiety action in both of the cases. The 5HT1A agonism of aripirazole could be hypothesized as mechanism contributing to this effect.
    09/2011; 2011:846489. DOI:10.1155/2011/846489
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