Aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia: An 8-week, randomized, double-blind, placebo-controlled trial

Department of Psychiatry, Seoul Municipal Eunpyeong Hospital, Seoul, Republic of Korea.
The Journal of Clinical Psychiatry (Impact Factor: 5.14). 04/2008; 69(5):720-31.
Source: PubMed

ABSTRACT Inadequate response to clozapine poses a substantial problem in the pharmaco-therapy of refractory schizophrenia. This randomized, double-blind, placebo-controlled study evaluated the efficacy and safety of aripiprazole augmentation in clozapine-treated patients with refractory schizophrenia.
Patients with DSM-IV schizophrenia who had a history of treatment failure or partial response to long-term clozapine treatment were recruited. A total of 62 patients with either a baseline Brief Psychiatric Rating Scale (BPRS) score of at least 35 or more than 2 Schedule for Assessment of Negative Symptoms (SANS) global rating item scores of at least 3 were randomly assigned to double-blind augmentation treatment with either aripiprazole (5-30 mg/day) or placebo over 8 weeks. The primary outcome measure was change in BPRS total score from baseline. The study was conducted between December 1, 2005, and December 10, 2006.
There was no significant difference in the primary outcome measure between the 2 groups. In secondary analyses, improvement was significantly greater with aripiprazole treatment than with placebo for negative symptoms assessed by both the BPRS negative symptom sub-scale and the SANS total score but not for positive symptoms. Prolactin and triglyceride levels were significantly lower in the aripiprazole group than in the placebo group. No significant differences between the 2 groups were observed in adverse effects, including extrapyramidal symptoms and serum glucose levels.
Although aripiprazole augmentation of clozapine did not lead to a significant improvement of total symptom severity in schizophrenia, a favorable change in the negative symptom domain was observed.

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    • "In the case of resistance to clozapine, augmentation with second AP or lamotrigine is recommended in some guidelines [25]. This strategy is based on the results of randomized studies demonstrating, among other things, that clozapine augmentation with aripiprazole, had a favorable impact on both the negative [47] and positive symptoms [47] [48] and appeared to be safe. Consequently, one may hypothesize that adding aripiprazole to olanzapine or quetiapine might have a similar impact on the earliest stages of treatment. "
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    ABSTRACT: Background The term antipsychotic polypharmacy (APP) refers to the concurrent use of two or more antipsychotic drugs in schizophrenia. The aim of this study was to investigate the range of APP in schizophrenic patients discharged from psychiatric units in Poland, and to determine its demographical and clinical correlates. Methods Data on the pharmacological treatment of 207 patients with a diagnosis of schizophrenia, discharged from six psychiatric hospitals from September–December 2011 were recorded by experienced psychiatrists. Clinical and demographical information was obtained on each patient. The severity of symptoms at admission, and their improvement during hospitalization were assessed using the Clinical Global Impression Scale. Results At discharge, 52.7% of the patients were prescribed one, 42.5% two and 4.8% three antipsychotic drugs (AP). When two AP were applied, it was usually a combination of two second generation antipsychotics (SGA) (46%), or of both first generation antipsychotics (FGA) and SGA (48%). The SGA's olanzapine and risperidone were those most commonly prescribed. Patients treated with two or more AP had a higher number of previous hospitalizations than patients receiving antipsychotic monotherapy. Mood stabilizers were prescribed for nearly one third of the patients, while antidepressants and benzodiazepines were prescribed for fewer than 10%. Conclusions The prevalence of polypharmacy in Poland is similar to that reported in other countries. This may suggest that, in a substantial proportion of schizophrenic patients clinical response to the antipsychotic monotherapy is unsatisfactory. Further studies focusing on the efficacy and safety of strategies in the treatment of patients with schizophrenia not responding to antipsychotic monotherapy are necessary.
    Pharmacological reports: PR 01/2014; 66(4):613–617. · 2.17 Impact Factor
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    • "Augmentation with aripiprazole has been documented in case reports [11], in open trials [5] [12], and in a randomized controlled study [13]. "
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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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    • "Conversely, our results confirm the effect on positive symptoms and overall clinical state, whereas the reduction of negative symptoms is lower than expected. It should be recognized, however, that in our study population negative symptoms were almost mild, as documented by mean baseline SANS total score; this may explain the lack of effect on negative symptoms compared to the previous double-blind study (Chang et al., 2008). Among negative symptoms, whereas Avolition/apathy and Anhedonia/Asociality may occur in association and/or partially overlap with depressive symptoms (Kitamura and Suga, 2001), alogia is thought to reflect some aspects of cognitive dysfunctioning in schizophrenia (Buchanan, 2007; Chemerinski et al., 2006). "
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    ABSTRACT: The simultaneous prescription of two or more antipsychotic drugs in combination is a common treatment strategy for those patients who have demonstrated a suboptimal response to clozapine; nevertheless, evidence suggesting potential advantages of combination treatment with clozapine plus one antipsychotic in terms of efficacy and tolerability are still sparse. The present 24-week double-blind, randomized, placebo-controlled trial of adjunctive aripiprazole to clozapine therapy in schizophrenia was aimed to explore the efficacy of aripiprazole add-on pharmacotherapy on clinical symptomatology and cognitive functioning in a sample of patients with treatment-resistant schizophrenia receiving clozapine. After clinical and neurocognitive assessments patients were randomly allocated to receive, in a double-blind design, either up to 15 mg/day of aripiprazole or a placebo. A final sample of thirty-one patients completed the study. The results obtained indicate that aripiprazole added to stable clozapine treatment showed a beneficial effect on the positive and general psychopathological symptomatology in a sample of treatment-resistant schizophrenia patients. Regarding executive cognitive functions, aripiprazole augmentation of clozapine had no significant effects. The findings provide evidence that aripiprazole augmentation of clozapine treatment is well-tolerated and may be of benefit for patients who are partially responsive to clozapine monotherapy; further double-blind, placebo-controlled trials in a larger number of patients are required to evaluate the therapeutic potential of aripiprazole augmentation of clozapine.
    Schizophrenia Research 04/2011; 127(1-3):93-9. DOI:10.1016/j.schres.2010.12.011 · 4.43 Impact Factor
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