Role of aripiprazole in treatment-resistant schizophrenia

Abstract

About one third of patients with schizophrenia respond unsatisfactorily to antipsychotic treatment and are termed “treatment-resistant”. Clozapine is still the gold standard in these cases. However, 40%–70% of patients do not improve sufficiently on clozapine either. In the search for more efficacious strategies for treatment-resistant schizophrenia, drugs with different pharmacological profiles seem to raise new hopes, but are they valid? The aim of this review was to evaluate the evidence for aripiprazole as a potential strategy in monotherapy or combination therapy for patients with treatment-resistant schizophrenia. The evidence for aripiprazole monotherapy and for the combination of aripiprazole with psychotropics other than clozapine is scant, and no recommendation can be made on the basis of the currently available data. More effort has been made in describing combinations of aripiprazole and clozapine. Most of the open-label and case studies as well as case reports have shown positive effects of this combination on overall psychopathology and to some extent on negative symptoms. Several reports describe the possibility of dose reduction for clozapine in combination with aripiprazole, a strategy that might help so-called “treatment-intolerant” patients. The findings of four randomized controlled trials with respect to changes in psychopathology seem less conclusive. The most commonly found beneficial effects are better metabolic outcomes and indicators of the possibility of reducing the clozapine dose. However, other side effects, such as akathisia, are repeatedly reported. Further, none of the studies report longer-term outcomes. In the absence of alternatives, polypharmacy is a common strategy in clinical practice. Combining aripiprazole with clozapine in clozapine-resistant or clozapine-intolerant patients seems to be worthy of further investigation from the pharmacological and clinical points of view.

<p>Clinical relevance of paliperidone palmitate 3-monthly in treating schizophrenia</p>

“…A limited number of antipsychotics are available for specific treatment of negative symptoms of schizophrenia and in most cases improvements are perceived as a consequence of their effects on positive symptoms 95,97. Among available evidence for antipsychotic monotherapy, clozapine and aripiprazole did not show satisfactory efficacy for improving negative symptoms, whereas olanzapine showed significant ( P ≤0.05) improvements in PANSS negative subscale vs haloperidol 98–100. In acutely ill patients with schizophrenia and predominantly negative symptoms, paliperidone ER significantly improved negative symptoms when compared with placebo 101.…”

Efficacy and safety of aripiprazole augmentation of clozapine in schizophrenia: A systematic review and meta-analysis of randomized-controlled trials

“…Although agitation, anxiety, headache, and insomnia are its common adverse effects (Marder et al, 2003;Swainston Harrison and Perry, 2004), aripiprazole is unlikely to cause weight gain or dyslipidemia (Stip and Tourjman, 2010). Little has been known about aripiprazole monotherapy and the combination of aripiprazole with psychotropic medications for clozapine-resistant schizophrenia (Mossaheb and Kaufmann, 2012). However, some open trials of aripiprazole augmentation of clozapine reported the benefits of this regimen in attenuating psychotic symptoms and/or minimizing weight gain (Henderson et al, 2006;Mitsonis et al, 2007;Ziegenbein et al, 2006).…”

Neutropenia and Thrombocytopenia Induced By Quetiapine Monotherapy: A Case Report and Review of Literature

“…Dose dependence has also been proposed in quetiapine-related neutropenia 18 . Advanced age and low body weight are factors that lead to higher plasma quetiapine concentrations.…”