Is clozapine—aripiprazole combination a useful regime in the                 management of treatment-resistant schizophrenia?

Karunakaran, Kanapathippillai; Tungaraza, Tongeji E.; Harborne, Giles

doi:10.1177/0269881106068289

Cited by 56 publications

(35 citation statements)

References 17 publications

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“…It is possible that some of them could have benefited by switching over to clozapine or clozapine augmentation. 22,23 However, studies on the use of clozapine augmentation remain inconclusive. Meta-analyses looking at clozapine augmentation with antipsychotics for treatment-resistant schizophrenia have arrived at differing conclusions.…”

Section: 10mentioning

confidence: 99%

Polypharmacy and high-dose antipsychotics at the time of discharge from acute psychiatric wards

2011

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Aims and methodTo determine the extent of prescribed antipsychotic polypharmacy and high-dose antipsychotics at the time of discharge from an acute psychiatric ward. Copies of discharge summaries for patients between the ages of 18 and 65 were examined; only those that had antipsychotic medications at the time of discharge were included. Names and doses of antipsychotics and all other medications concurrently prescribed were recorded.ResultsA total of 651 discharge summaries were included in the study. Nearly a quarter of individuals were discharged on one antipsychotic as the only medication to take home; only 6.8% were discharged on a high-dose antipsychotic and of those on combinations 59.6% were on depot medications. Combining antipsychotics significantly predicted the use of high dose.Clinical implicationsMost patients were discharged on doses of antipsychotics within the British National Formulary limits; however, a small proportion is still sent home on high doses of antipsychotics. Combining antipsychotics remains the strongest predictor of high-dose antipsychotic use; clinicians need to be aware of this.

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Section: 10mentioning

confidence: 99%

Polypharmacy and high-dose antipsychotics at the time of discharge from acute psychiatric wards

2011

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“…Aripiprazole is a potent (high-affinity) partial agonist at D2 27 and 5-HT1A receptors and a potent antagonist at 5-HT2A 28 receptors. In a study of 24 patients with treatment resistant schizophrenia who had aripiprazole added to decreased doses of clozapine, Karunakaren et al 29 reported an average weight loss of 5.1 kg over 34 weeks. A 6-week open-label trial to examine the effects of adjunctive aripiprazole in ten clozapine-treated subjects observed a significant decrease in weight (from 219.4 ± 40.0 lbs to 213.7 ± 38.3 lbs) and triglycerides (from 274 ± 229 to 176 ± 106 mg/dL) 30 .…”

Section: Introductionmentioning

confidence: 99%

Aripiprazole Added to Overweight and Obese Olanzapine-Treated Schizophrenia Patients

Henderson¹,

Fan²,

Copeland³

et al. 2009

Journal of Clinical Psychopharmacology

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Olanzapine treatment has been associated with clinically meaningful weight increases, hypertriglyceridemia, insulin resistance and diabetes mellitus. There are few options for olanzapine-responders who fail other antipsychotic agents. Aripiprazole is a potent (high-affinity) partial agonist at D2 and 5-HT1A receptors and a potent antagonist at 5-HT2A receptor and is associated with less weight gain than olanzapine. We report the results of a 10-week placebo controlled, double-blind crossover study that examined 15 mg/day aripiprazole's effects upon weight, lipids, glucose metabolism, and psychopathology in overweight and obese schizophrenia and schizoaffective disorder subjects treated with a stable dose of olanzapine. During the 4 weeks of aripiprazole treatment there were significant decreases in weight (p = .003) and BMI (p = .004) compared to placebo. Total serum cholesterol (p = .208), HDL-cholesterol (p = .99), HDL-2 (p=.08), HDL-3 (p=.495) and LDL- cholesterol (p=.665) did not change significantly comparing aripiprazole treatment to placebo treatment. However, total serum triglycerides (p = .001), total VLDL-cholesterol (p=.01), VLDL 1- &2-cholesterol (p=.012) decreased significantly during the aripiprazole treatment phase. VLDL-3-cholesterol tended lower during aripiprazole, but the decrease was not significant (p=.062). There was a decrease in c-reactive protein comparing aripiprazole treatment to placebo though it did not reach significance (p=.087). The addition of aripiprazole to a stable dose of olanzapine was well tolerated and resulted in significant improvements on several outcome measures that predict risk for medical morbidity.

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“…However, two cases of dyskinesia and malignant neuroleptic syndrome were reported in a sample of 26 patients [32].…”

Section: Discussionmentioning

confidence: 99%

Augmentation of Clozapine with Aripiprazole in Severe Psychotic Bipolar and Schizoaffective Disorders: A Pilot Study

Benedetti¹,

Paolo²,

Lastella³

et al. 2010

CPEMH

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Abstract:Aim: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatmentresistant schizoaffective and psychotic bipolar disorders in a retrospective manner. Pharmacodynamic and pharmacokinetic interactions between the two drugs were also investigated.Patients: Three men and 4 women (median age 36 and 40 years, respectively) who had mean scores at BPRS and CGISeverity of 59.1±12.0 and 5.4±0.5, respectively, were treated with clozapine (mean dose 292.9±220.7 mg/day). Patients received an adjunctive treatment with aripiprazole (mean dose 6.8 ± 3.7 mg/day). Clozapine, norclozapine and aripiprazole plasma levels were measured by means of a high performance liquid chromatograpy with UV detection.Results: Total scores at BPRS decreased significantly (from 59.1±12.0 to 51.1±15.6, p=0.007) after aripirazole augmentation. In particular, the factors "thought disorder" (from 10.4±4.4 to 9.0±4.5, p=.047) and "anergia" (from 10.0±2.7 to 8.0±2.4, p=.018) significantly improved. Concomitant administration of aripiprazole and clozapine did not result in an increase in side effects over the period of treatment. Dose-normalized plasma levels of both clozapine and norclozapine and the clozapine/norclozapine metabolic ratio in all patients did not vary as well.Conclusion: The augmentation of clozapine with aripirazole was safe and effective in severe psychotic schizoaffective and bipolar disorders which failed to respond to atypical antipsychotics. A possible pharmacokinetic interaction between clozapine and aripiprazole does not account for the improved clinical benefit obtained after aripiprazole augmentation.

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Is clozapine—aripiprazole combination a useful regime in the management of treatment-resistant schizophrenia?

Cited by 56 publications

References 17 publications

Polypharmacy and high-dose antipsychotics at the time of discharge from acute psychiatric wards

Polypharmacy and high-dose antipsychotics at the time of discharge from acute psychiatric wards

Aripiprazole Added to Overweight and Obese Olanzapine-Treated Schizophrenia Patients

Augmentation of Clozapine with Aripiprazole in Severe Psychotic Bipolar and Schizoaffective Disorders: A Pilot Study

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