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Aims: Aripiprazole is an atypical antipsychotic indicated for the treatment of adult patients with schizophrenia. It is effective and well tolerated in patients with schizophrenia or schizoaffective disorder. The aim of the present study was to investigate therapeutic efficacy and tolerability of aripiprazole in patients with first-episode schizophrenia.
Methods: Twenty-one patients meeting the DSM-IV criteria for schizophrenia were recruited. The Positive and Negative Symptom Scale (PANSS) and the Clinical Global Impressions Scale (CGI) were completed at the beginning of the study and again after 1, 2, 4, and 8 weeks of aripiprazole treatment. Side-effects were analyzed using the Udvalg for Kliniske Undersøgelser Side-Effect Rating Scale. Weight was checked at each testing session, and prolactin levels were measured at baseline and after 8 weeks of aripiprazole treatment.
Results: Significant benefits were observed after the first week of treatment. After 1 week of aripiprazole treatment, subscale and total scores on the PANSS had decreased significantly. This significant decrease was maintained throughout the study period. The mean score of CGI severity was also significantly different after 2 weeks of aripiprazole administration when compared to baseline score, and the significance was maintained thereafter. Weight did not significantly change after aripiprazole administration. Although mean prolactin level was decreased at 8 weeks, the difference was not significant.
Conclusions: Aripiprazole is an effective and well-tolerated antipsychotic agent in patients with first-episode schizophrenia. Further investigations with larger samples are needed.
THE FIRST EPISODE of schizophrenia typically occurs during adolescence or early adulthood. For the majority of patients, schizophrenia is a recurrent or chronic disorder accompanied by significant impairment in psychosocial functioning. A growing body of evidence indicates that early intervention with appropriate pharmacological treatment can contribute to improving the course of the illness.1–3 A delay in initial treatment is associated with slower and less complete symptom response and overall poorer outcome.1
Patients experiencing their first episode of schizophrenia should be treated early and optimally with antipsychotic agents to lessen the morbidity of the first episode and possibly improve the course of the illness. At an early stage of the illness, patients are more responsive to pharmacological treatment but are also more susceptible to side-effects.4
Low doses of antipsychotic agents have been reported as effective and well tolerated in first-episode psychosis.5 Moreover, a common perception has been that first-episode patients should be treated with lower doses of some atypical antipsychotics than patients in the chronic stages of this disorder.6
First-episode patients are highly responsive to pharmacologic treatment, and the first treatment intervention in drug-naive patients represents a critical therapeutic opportunity with the potential to influence the course and outcome of what could be a lifelong illness.7 This is particularly significant because longer first episodes of psychosis have been associated with poorer treatment responses and outcomes.8
Aripiprazole is a new atypical antipsychotic with a unique receptor binding profile that combines partial agonist activity at dopamine 2 receptor (D2) and serotonin 1A receptor (5HT1A) with potent antagonism at serotonin 2A receptor (5HT2A).9 Aripiprazole appears to be well tolerated, with most studies suggesting a frequency of adverse effects similar to placebo;9 it also has a low propensity for causing clinically significant weight gain, hyperprolactinemia, and extrapyramidal symptoms in patients with schizophrenia or schizoaffective disorder.10 Few studies, however, have been specifically designed to test the safety and efficacy of aripiprazole for the treatment of first-episode schizophrenia. The aim of the present study was therefore to investigate the therapeutic efficacy and tolerability of aripiprazole for treating first-episode schizophrenia following 8 weeks of treatment in routine clinical conditions.
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We investigated the therapeutic efficacy and tolerability of aripiprazole among patients experiencing first-episode schizophrenia. We found that aripiprazole had good efficacy and acceptable levels of safety and tolerability during the 8-week treatment of patients with first-episode schizophrenia. The results also showed that the subscale and total PANSS scores significantly decreased from those at baseline after 1 week of aripiprazole administration, and this significance was maintained at each evaluation. A significant difference from CGI baseline scores appeared at 2 weeks and was maintained for the remainder of the study. Thus, a significant therapeutic effect occurred during the initial period of aripiprazole treatment among patients with first-episode schizophrenia. Consistent with these results, many prior studies have demonstrated that first-episode patients have good therapeutic responses to antipsychotic medications.14,15 Results of a naturalistic study showed that aripiprazole was effective for both long- and short-term treatment among both inpatients and outpatients.16 In an open multicenter naturalistic study, aripiprazole decreased the severity of psychotic symptoms and improved the global level of functioning.17 Compared with placebo, aripiprazole had superior efficacy in the short-term treatment of acute schizophrenia.18,19 Compared with such active comparators as typical antipsychotic agents,18,20 risperidone,19,21 and ziprasidone,22 aripiprazole has shown comparable efficacy in the short-term treatment of acute schizophrenia. Many findings have emerged from similar studies regarding the effectiveness of aripiprazole in patients with schizophrenia. Moreover, similar evidence has been found for risperidone, olanzapine, and quetiapine.23 Few studies, however, have been specifically designed to test the efficacy of aripiprazole in the treatment of patients with first-episode schizophrenia. The present study indicates that aripiprazole might represent one of the antipsychotic agents appropriate for treating first-episode schizophrenia.
We demonstrated the tolerability of aripiprazole in first-episode schizophrenia. Prolactin levels were not significantly increased after aripiprazole treatment in the present study. Hyperprolactinemia, a common side-effect of many atypical antipsychotics, is associated with a number of distressing clinical manifestations including sexual dysfunction, gynecomastia, galactorrhea, infertility, bone mineral loss, and possibly breast cancer.24–27 Consistent with the present study, review articles have shown that aripiprazole offers significant advantages over typical and atypical antipsychotics insofar as aripiprazole has been associated with lower rates of hyperprolactinemia.28 In the present study, weight and fasting blood glucose levels were not significantly changed after aripiprazole treatment. Weight gain is a common side-effect of antipsychotic drugs, particularly atypical agents.29 The American Psychiatric Association's Practice Guideline for the Treatment of Schizophrenia endorses second-generation antipsychotics (other than clozapine) as the preferred initial antipsychotics.30 The data on efficacy and tolerability indicate that aripiprazole could be a candidate antipsychotic for first-episode schizophrenia. These results suggest that aripiprazole is an effective and tolerable antipsychotic agent among patients with first-episode schizophrenia.
The present study has some limitations. First, it is premature to draw conclusions on the basis of so few subjects and an open-label design. Second, comparative efficacy of aripiprazole can never be known due to lack of active comparator (vs other atypicals). Third, long-term effect of aripiprazole could not be determined because of a relatively short-term follow-up period. Notwithstanding the aforementioned limitations, this is the first study to examine the therapeutic efficacy and tolerability of aripiprazole in a Korean population with first-episode schizophrenia.