OBJECTIVE: This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine-treated patients with schizophrenia.
METHOD: In an 8-week randomized, double-blind, placebo-controlled study, subjects received either aripiprazole (15 mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole-body dual-energy X-ray absorptiometry (DXA).
RESULTS: Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 vs. -0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low-density lipoprotein (LDL) levels (-15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (-376 ± 632 vs. -36 ± 301 nm, P = 0.035). Further, there was a significant reduction in the lean mass (-1125 ± 1620 vs. 607 ± 1578 g, P = 0.011) measured by whole-body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo.
CONCLUSION: Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine-treated patients with schizophrenia.
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.
Journal»The international journal of neuropsychopharmacology / official scientific journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
OBJECTIVE: 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.
METHOD: 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.
RESULTS: 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.
CONCLUSION: 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.
This study examined the effects of adjunctive aripiprazole therapy on metabolism in clozapine-treated patients with schizophrenia.
METHOD:
In an 8-week randomized, double-blind, placebo-controlled study, subjects received either aripiprazole (15 mg/day) or placebo. At baseline and week 8, metabolic parameters were assessed by the frequently sampled intravenous glucose tolerance test, nuclear magnetic resonance spectroscopy and whole-body dual-energy X-ray absorptiometry (DXA).
RESULTS:
Thirty subjects completed the study (16 in the aripiprazole group and 14 in the placebo group). Glucose effectiveness measured by the frequently sampled intravenous glucose tolerance test improved significantly in the aripiprazole group (0.003 ± 0.006 vs. -0.005 ± 0.007/min, P = 0.010). The aripiprazole group showed significant reductions in both plasma low-density lipoprotein (LDL) levels (-15.1 ± 19.8 vs. 4.4 ± 22.5 mg/dl, P = 0.019) and LDL particle numbers (-376 ± 632 vs. -36 ± 301 nm, P = 0.035). Further, there was a significant reduction in the lean mass (-1125 ± 1620 vs. 607 ± 1578 g, P = 0.011) measured by whole-body DXA scan in the aripiprazole group. All values were expressed as mean ± standard deviation, aripiprazole vs. placebo.
CONCLUSION:
Adjunctive therapy with aripiprazole may have some metabolic benefits in clozapine-treated patients with schizophrenia.
