Aripiprazole In Patients Research Articles

Efficacité de l’aripiprazole dans le traitement de la schizophrénie : quelle dose pour quel effet ?

Problem of the choice of antipsychotic dose is a key issue in clinical practice. It determines the efficacy and safety of treatment. Aripiprazole is recommended at a dose of between 10 and 15 mg/day in the treatment of schizophrenia, with a dose range considered to be effective, between 10 and 30 mg/day. This wide therapeutic range prompted us to investigate the existence of a possible dose-effect relationship for aripiprazole in the treatment of schizophrenia. We conducted a literature review from PubMed and EMBASE database, with the keywords: aripiprazole, schizophrenia. We limited it to studies published in English and French, with the main objective to assess the efficacy of aripiprazole in patients with schizophrenia. We selected only randomized clinical trials, double-blind, controlled against placebo or against an active comparator. Studies in which aripiprazole was studied added to another antipsychotic were not retained. Twenty-two randomized, double-blind, controlled studies were selected. Three studies assessed the efficacy of aripiprazole on agitation symptoms in patients with schizophrenia and for which a dose of aripiprazole between 1 and 15mg showed significant efficacy compared to placebo. Seven clinical trials focused on the effect of aripiprazole short term (less than 12weeks). For the primary endpoint (PANSS scores), aripiprazole was superior to placebo or equivalent to active comparators (risperidone, olanzapine or haloperidol). These short-term studies revealed a range of effective doses from 10 mg/day to 20 mg/day. Five studies, lasting between 16 and 52 weeks, with a primary endpoint being the time to discontinuation for any cause for two studies, the time before relapse in one study, and the improvement in PANSS scores for the two other studies. On these different endpoints, aripiprazole was effective at average doses between 15 and 28.1 mg/day. The safety of aripiprazole was particularly favourable in these trials. Finally, we listed seven post-hoc analyses. In support of these long-term analyses on different endpoints, aripiprazole showed significant efficacy at higher doses (20 and 30 mg/day) than those used in the agitation treatment. No study was designed to compare aripiprazole doses in schizophrenia. Nevertheless, efficacy on agitation and hostility components had been observed for doses of 10mg/day, or lower; whereas the antipsychotic effect in acute or maintenance phase appeared optimal for doses ranging from 10 to 25 mg/day. Only one study retained a minimum effective dose of 10mg/day on the PANSS scores. This literature review reveals an effective dose range between 10 and 25 mg/day for aripiprazole in schizophrenia. Less than 10 mg/day did not show significant efficacy on symptoms of schizophrenia, apart from a specific short-term effect on agitation, at very low doses (starting at 1mg). Optimization of treatment, at doses above 25 mg/day, cannot be the subject of evidence-based recommendations.

Pomaglumetad Methionil (LY2140023 Monohydrate) and Aripiprazole in Patients with Schizophrenia: A Phase 3, Multicenter, Double-Blind Comparison.

We tested the hypothesis that long-term treatment with pomaglumetad methionil would demonstrate significantly less weight gain than aripiprazole in patients with schizophrenia. In this 24-week, multicenter, randomized, double-blind, Phase 3 study, 678 schizophrenia patients were randomized to either pomaglumetad methionil (n = 516) or aripiprazole (n = 162). Treatment groups were also compared on efficacy and various safety measures, including serious adverse events (SAEs), discontinuation due to adverse events (AEs), treatment-emergent adverse events (TEAEs), extrapyramidal symptoms (EPS), and suicide-related thoughts and behaviors. The pomaglumetad methionil group showed significantly greater weight loss at Week 24 (Visit 12) compared with the aripiprazole group (−2.8 ± 0.4 versus 0.4 ± 0.6; P < 0.001). However, change in Positive and Negative Syndrome Scale (PANSS) total scores for aripiprazole was significantly greater than for pomaglumetad methionil (−15.58 ± 1.58 versus −12.03 ± 0.99; P = 0.045). The incidences of SAEs (8.2% versus 3.1%; P = 0.032) and discontinuation due to AEs (16.2% versus 8.7%; P = 0.020) were significantly higher for pomaglumetad methionil compared with aripiprazole. No statistically significant differences in the incidence of TEAEs, EPS, or suicidal ideation or behavior were noted between treatment groups. In conclusion, long-term treatment with pomaglumetad methionil resulted in significantly less weight gain than aripiprazole. This trial is registered with ClinicalTrials.gov NCT01328093.

P.2.f.026 An open clinical trial of adjunctive therapy with aripiprazole in patients with partial remission of major depressive disorder

P.2.f.026 An open clinical trial of adjunctive therapy with aripiprazole in patients with partial remission of major depressive disorder

Augmentation of Aripiprazole for Depressed Patients With an Inadequate Response to Antidepressant Treatment

Nonresponse or a partial response to 1 or more antidepressants is a common and significant problem in clinical practice. Adjunctive therapy with atypical antipsychotics is considered as 1 of the next treatment options for such inadequate responses. The present trial evaluated the efficacy and the safety of aripiprazole as an augmentation to ongoing antidepressant monotherapy for patients with major depressive disorder (MDD) who have previously exhibited an inadequate clinical response. This was a 6-week prospective, multicenter, open-label study with flexibly dosed adjunctive aripiprazole. The 86 participants with MDD showed inadequate responses to more than 8 weeks of standard antidepressant treatment. The primary outcome was the mean change in Montgomery-Asberg Depression Rating Scale total score from baseline to the end point (week 6). The mean daily dose of aripiprazole at the end point was 6.9 mg. The Montgomery-Asberg Depression Rating Scale total score was significantly decreased with adjunctive aripiprazole during the study period (by 14.0 points, P = 0.000). At the end point, the response rate was 52.3% and the remission rate was 39.8%. Adjunctive aripiprazole produced a significant response and remission from week 1 through the end point. The study completion rate was 73.9%, and adverse events included sedation (n = 11), akathisia (n = 9), headache (n = 6), tremor (n = 6), and increased appetite (n = 5). Of the discontinuations, only 5.7% were due to adverse events. Adjunctive aripiprazole in patients with MDD who had previously exhibited an inadequate response to standard antidepressant therapy was efficacious and well tolerated. A low daily dose of aripiprazole would be more acceptable in the clinical setting.

Aripiprazole: A dopamine modulator that mimics methylphenidate in producing faster antidepressant effects

Up to 60% of depressed patients do not respond to two months of pharmacotherapy, and late treatment responses are often correlated with poor outcomes and may be characterized as treatment-resistant depression (TRD). Previous studies have noted that the addition of a psychostimulant such as methylphenidate to the therapeutic regimen of patients with TRD or those depressed patients with comorbid fatigue, advanced age, or a major medical illness showed significant improvement within two weeks. One explanation for the benefit of methylphenidate in treating TRD is that it enhances the level of dopamine in the brain. Adjunctive low dose aripiprazole in patients with TRD has also become a common intervention. Several studies have focused on aripiprazole’s pharmacodynamic and pharmacokinetic profiles, but no definitive comments on its antidepressant effects. We hypothesize that a low dose of aripiprazole might play a role as a dopamine agonist similar to that of methylphenidate due to its partial dopamine D2 agonist and 30% intrinsic dopaminergic activity. In addition to its use in patients with TRD, adjunctive aripiprazole might work like methylphenidate in those depressed patients with fatigue, advanced age, or major illnesses. A new drug invention which combined an antidepressant with an adequate dose of aripiprazole should be considered. The neurobiological basis for this combination in treating TRD awaits further study.

Intramuscular Aripiprazole in the Acute Management of Psychomotor Agitation

To assess acute efficacy and safety of 9.75 mg of intramuscular (IM) injections of the atypical antipsychiatric aripiprazole in patients with schizophrenia or bipolar disorder and acute agitation. Open-label trial of IM injections of aripiprazole and 24-hour monitoring of clinical response in patients with major psychoses and acute agitation. Partial analysis of blood levels of the administered drug to correlate with clinical response. Acute psychiatric care wards in a single university hospital. A total of 201 acutely agitated patients (79 with schizophrenia and 122 with bipolar disorder I). Aripiprazole 9.75 mg IM injection. We evaluated clinical response using the Excitatory Component of the Positive and Negative Syndrome Scale (PANSS-EC), the Agitation/Calmness Evaluation Scale (ACES), and the Clinical Global Impressions scale (CGI). Assessments were conducted 30, 60, 90, and 120 minutes and 24 hours after the first injection for PANSS-EC and ACES, and 2, 4, 6, and 24 hours for CGI. Response was at least a 40% decrease in PANSS-EC scores. We measured serum aripiprazole and dehydroaripiprazole levels in a subsample. IM aripiprazole significantly improved clinical measures. PANSS-EC improved progressively, starting after 30 minutes. ACES improved after 90 minutes and continued thereafter. Effects were sustained, with steadily decreasing CGI scores, until the 24th hour. Response rate was 83.6% after 2 hours, but with repeat injections, it rose to over 90% with no differences among diagnostic groups. Although there were gender differences in the response to individual PANSS-EC items, the responses were similar overall. Neither clinical monitoring nor patient reporting revealed any side effects. No therapeutic window was identified, and levels did not correlate with any clinical measure. Aripiprazole was effective and safe in reducing acute agitation in patients with bipolar disorder or schizophrenia. Our results compare favorably to double-blind trials, probably due to higher expectations in trials involving no placebo arm. Absence of side effects could be related to the short observation time.

1654 – Efficacy of aripiprazole on behavioural symptoms in three young patients with severe acquired brain injury

The atypical antipsychotic drug aripirprazole has a partial agonist activity on the dopamine receptors. This characteristic makes aripiprazole different from other antipsychotic agents. In this paper, we aim to describe the use of this drug in the management of three young patients with acquired brain injury: a woman with Wilsons disease, a male with a rupture of an arteriovenous malformation and a male with severe traumatic brain injury. All patients presented behavioural symptoms. One of them presented frequent crises of psychomotor agitation with strong physical aggressive reaction, partial awareness and low frustration tolerance. The other two patients reported a prevalence of negative symptoms, as inactivity, apathy, lack of will and severe perseveration. They were referred to our Unit and were evaluated with a full functional assessment at the moment of admission and at the discharge, depending on their clinical picture. The evaluation included: MMSE (Mini Mental State Examination), LCF (Level of Cognitive Functioning), DRS (Disability Rating Scale) and FIM (Functional Independence Measure). The behavioural assessment was made with clinical interviews. After the introduction of aripiprazole, we found an improvement in the behavioural pattern, moreover neuropsychological and motor evaluation appeared not affected. These results suggest that the use of aripiprazole in patients with acquired brain injury is suitable for its efficacy in reducing psychotic and behavioural symptoms but also for its potential for not affecting motor and cognitive functioning.

EFFECTS OF ARIPIPRAZOLE AUGMENTATION IN TREATMENT-RESISTANT OBSESSIVE-COMPULSIVE DISORDER (A DOUBLE BLIND CLINICAL TRIAL)

Obsessive-compulsive disorder (OCD) is a chronic disorder with unknown etiology. Failure in OCD treatmentcompulsive is common and finding effective augmentations in treatment of OCD will benefit patients. Antipsychotic augmentation is a common strategy for treatment resistant OCD. This trial evaluated the efficacy of adding aripiprazole in patients whose OCD was insufficiently responsive to an adequate SSRI treatment. Thirty-nine adult outpatients, who met the DSM-IV-TR criteria for OCD and had treatment resistant OCD were evaluated in a double-blind randomized clinical trial. The patients received either aripiprazole 10 mg/day or placebo, for 12 weeks. Data were analyzed using intention-to-treat analysis with last observation carried forward. All statistical tests were two-sided, and were considered statistically significant at P < 0.05. A significant reduction in total scores of Y-BOCS (P < 0.0001) was found in the aripiprazole group. Aripiprazole was generally well tolerated. There was no significant difference between the two groups in terms of observed side effects. Results of the present study indicate that aripiprazole could be an effective augmentation medicine in treatment resistant OCD.

Comparison of the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depressive disorder

Only two-thirds of depressive patients respond to antidepressant treatment. In recent years, addition of an atypical antipsychotic drug to ongoing treatment with an antidepressant has been considered effective and well-tolerated. In the present study, we compared the efficacy between paroxetine and sertraline augmented with aripiprazole in patients with refractory major depression. Twenty-four patients who met the DSM-IV criteria for major depressive disorder who did not at least two different classes of antidepressants were enrolled in the study. Nine were male and thirteen were female, and their ages ranged from 28 to 66 (mean±SD=39±12) years. Patients were prescribed paroxetine (n=11) or sertraline (n=13) for 4weeks. Then, those whose scores on the 17-item Hamilton Rating Scale for Depression (HAMD17) decreased below 50% received adjunctive therapy of aripiprazole for 4weeks. Although the use of either combination treatment decreased the HAMD17 scores compared to the respective monotherapy, there was no significant difference in HAMD17 scores between the paroxetine plus aripiprazole group and sertraline plus aripiprazole group. Aripiprazole augmentation therapy with paroxetine or sertraline was equally effective and tolerated in patients with refractory major depressive order.

Efficacy of adjunctive aripiprazole in patients with major depressive disorder who showed minimal response to initial antidepressant therapy

To evaluate the efficacy of adjunctive aripiprazole in patients with minimal response to prior antidepressant therapy (ADT). Pooled data from three randomized, double-blind, placebo-controlled studies assessing the efficacy of adjunctive aripiprazole to ADT in patients with major depressive disorder who had a minimal response [< 25% reduction on the Montgomery-Åsberg Depression Rating Scale (MADRS)] to an 8-week prospective ADT. During the 6-week, double-blind adjunctive phase, response was defined as at least 50% reduction in the MADRS score and remission as at least 50% reduction in MADRS score and a MADRS score ≤ 10. Rates were examined using analysis of covariance and Cochran-Mantel-Haenszel tests. Kaplan-Meier curves were used to calculate time to response and remission. Of 1038 patients, 72% (n=746) exhibited a minimal response to ADT (ADT minimal responder). Time to response and remission were significantly shorter for ADT minimal responders receiving aripiprazole+ADT versus adjunctive placebo+ADT. ADT minimal responders on aripiprazole+ADT showed significantly greater improvements in MADRS score at endpoint compared with minimal responders on placebo+ADT (-10.3 vs. -6.5, P<0.0001). In addition, ADT minimal responders exhibited significantly higher response rates with aripiprazole+ADT than placebo+ADT (36 vs. 19%, respectively, P<0.0001) and higher remission rates (24 vs. 12%, respectively, P<0.0001). The numbers needed to treat with aripiprazole+ADT were six for response and eight for remission. Aripiprazole augmentation had a rapid and clinically meaningful effect in ADT minimal responders.

Acute changes in values of serum high-sensitive C-reactive protein levels during switching of antipsychotics to aripiprazole in patients with schizophrenia

Acute changes in values of serum high-sensitive C-reactive protein levels during switching of antipsychotics to aripiprazole in patients with schizophrenia

Aripiprazole in patients with autistic spectrum disorders: a review and case reports

Background: Although a significant amount of literature regarding use of aripiprazole (APZ) in autistic spectrum disorders (ASDs) has benne published, APZ is not approved for use in autism or ASDs in countries other than the United States. Even in the United States, approved use of APZ is limited to the patients with autism in children and adolescents. This review and case reports focus on the available evidence and clinical experience regarding the use of APZ in patients with ASDs including adults Methods: A literature review was conducted, using the PubMed search term ‘aripiprazole’and(‘autistic spectrum disorder’, ‘pervasive developmental disorders’ or ‘Asperger’s disorder’). Results: In previous reports, APZ can target symptoms such as anxiety, depression, aggression, and irritability. Compared with other antipsychotics, APZ also causes fewer adverse events that can lead to drug discontinuation. The case reports supported the literature review: APZ has moderate sedative, antidepressant, and antianxiety effects, when used to treat ASDs. None of the patients experienced adverse reactions (e.g., extrapyramidal symptoms,weight gain, and sedation). Conclusion: APZ reduces aggression in ASDs and improves qualitative deficits in interpersonal interactions and motivation. APZ also causes fewer adverse events. APZ may be associated with favorable treatment compliance,and may improve treatment of ASDs.

Tolerability profile of aripiprazole in patients with Tourette syndrome

Over the last few years, aripiprazole has been proposed as a potentially useful medication for tics in patients with Tourette syndrome (TS). Aripiprazole has been associated with fewer adverse effects compared with other atypicals; however, little is known about its tolerability profile in the TS population. This study assessed the prevalence and characteristics of adverse effects resulting from the use of aripiprazole in a retrospective chart review of 29 patients with TS. Six patients (20.7%) discontinued aripiprazole because of the severity of specific adverse effects. The most commonly reported adverse effects were sedation (n = 9, 30%) and sleep problems (n = 5, 17%). In the majority of cases, adverse effects were not severe. There were no differences in demographic or clinical variables between the patients who did or did not experience adverse effects. The discontinuation rate of 20.7% suggests that aripiprazole is safe and reasonably well tolerated for use in TS. The prevalence of adverse effects appears to increase with treatment duration.

A 64-week, multicenter, open-label study of aripiprazole effectiveness in the management of patients with schizophrenia or schizoaffective disorder in a general psychiatric outpatient setting.

ObjectiveTo evaluate the overall long-term effectiveness of aripiprazole in patients with schizophrenia in a general psychiatric practice setting in Taiwan.MethodsThis was a prospective, open-label, multicenter, post-market surveillance study in Taiwanese patients with a Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder requiring a switch in antipsychotic medication because current medication was not well tolerated and/or clinical symptoms were not well controlled. Eligible patients were titrated to aripiprazole (5-30 mg/day) over a 12-week switching phase, during which their previous medication was discontinued. Patients could then enter a 52-week, long-term treatment phase. Aripiprazole was flexibly dosed (5-30 mg/day) at the discretion of the treating physicians. Efficacy was assessed using the Clinical Global Impression scale Improvement (CGI-I) score, the Clinical Global Impression scale Severity (CGI-S) score, The Brief Psychiatry Rating Scale (BPRS), and the Quality of Life (QOL) scale, as well as Preference of Medicine (POM) ratings by patients and caregivers. Safety and tolerability were also assessed.ResultsA total of 245 patients were enrolled and switched from their prior antipsychotic medications, and 153 patients entered the 52-week extension phase. In all, 79 patients (32.2%) completed the study. At week 64, the mean CGI-I score was 3.10 and 64.6% of patients who showed response. Compared to baseline, scores of CGI-S, QOL, and BPRS after 64 weeks of treatment also showed significant improvements. At week 12, 65.4% of subjects and 58.9% of caregivers rated aripiprazole as better than the prestudy medication on the POM. The most frequently reported adverse events (AEs) were headache, auditory hallucinations and insomnia. A total of 13 patients (5.3%) discontinued treatment due to AEs. No statistically significant changes were noted with respect to fasting plasma glucose, lipid profile, body weight, and body mass index after long-term treatment with aripiprazole.ConclusionsAlthough the discontinuation rate was high, aripiprazole was found to be effective, safe and well tolerated in the long-term treatment of Taiwanese patients with schizophrenia who continued to receive treatment for 64 weeks.

Differential add-on effects of aripiprazole in resolving hyperprolactinemia induced by risperidone in comparison to benzamide antipsychotics

Hyperprolactinemia is associated with typical antipsychotic agents and atypical antipsychotics such as risperidone and amisulpride. This study investigates the effects of 8-week adjunctive treatment with aripiprazole in patients with hyperprolactinemia induced by risperidone in comparison to benzamide antipsychotics (amisulpride and sulpiride). Aripiprazole was administered to 24 patients with antipsychotic-induced hyperprolactinemia. The doses of pre-existing antipsychotics were fixed, while the aripiprazole dose was 5–20 mg/day during the 8-week study period. Serum prolactin levels were measured at weeks 4 and 8. Symptoms and side effects were assessed using the Positive and Negative Syndrome Scale (PANSS), Arizona Sexual Experience Scale, Abnormal Involuntary Movement Scale, Simpson–Angus Scale, Barnes Akathisia Scale, and metabolic measures at weeks 2, 4 and 8. Mean (standard error) prolactin levels decreased from 77.0 ± 13.3 ng/mL to 18.3 ± 2.1 ng/mL ( p < 0.001 vs. baseline), from 144.9 ± 24.4 ng/mL to 127.5 ± 21.7 ng/mL ( p = 0.099 vs. baseline) and 71.4 ± 24.6 ng/mL to 43.3 ± 14.7 ng/mL ( p = 0.106 vs. baseline) for those taking risperidone, amisulpride, and sulpiride, respectively. For those who took risperidone before the study started, 14 of 15 (93.3%) patients had normalized prolactin levels, while only 1 of 10 (10%) taking benzamide antipsychotics had normalized prolactin levels. The PANSS score improved significantly, and aripiprazole had no significant influence on metabolic measures or scales of movement side effects. Adjunctive aripiprazole treatment reversed effectively hyperprolactinemia induced by risperidone, but was less effective for that induced by benzamide antipsychotics. Trial registration: clinicaltrials.gov Identifier: NCT00541554.

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

Aim: To evaluate the efficacy and safety of the augmentation of clozapine with aripiprazole in patients with treatment-resistant 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 CGI-Severity 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.

Assessment of safety, tolerability and effectiveness of adjunctive aripiprazole to lithium/valproate in bipolar mania: a 46-week, open-label extension following a 6-week double-blind study

Objective:This study evaluated the long-term tolerability and effectiveness of aripiprazole adjunctive to lithium or valproate in partial responders with bipolar mania.Methods:Completers of a 6-week double-blind comparison of adjunctive aripiprazole versus placebo in bipolar mania partially responsive to lithium or valproate monotherapy could enter a 46-week extension treatment with open-label adjunctive aripiprazole plus lithium (ARI + LI) or valproate (ARI + VAL). Safety, efficacy and functioning were assessed.Clinical trial registration:CN138-134LT: Study of Aripiprazole in Patients With Bipolar I Disorder; ID number: NCT00257972; registry: www.clinicaltrials.govResults:In total, 283 (ARI + LI n = 108; ARI + VAL n = 175) patients entered and 146 (ARI + LI n = 55; ARI + VAL n = 91) completed the 46-week, open-label extension. Frequently reported adverse events (AEs) that occurred with ARI + LI vs. ARI + VAL were: tremor (17.0% vs. 12.1%), akathisia (6.6% vs. 8.6%), headache (6.6% vs. 4.0%), insomnia (9.4% vs. 10.3%), depression (7.5% vs. 9.2%) and weight increase (11.3% vs. 8.6%). Extrapyramidal symptom-related AEs occurred in 24 (22.6%) ARI + LI- and 38 (21.8%) ARI + VAL-treated patients, with eight discontinuations. The majority of new-onset events of akathisia and insomnia occurred early. Mean (SE) weight change from double-blind endpoint to Week 46 (LOCF) was 2.3 (0.6) kg with ARI + LI and 2.0 (0.4) kg with ARI + VAL. Significant improvements from baseline over the 52 weeks (LOCF) occurred with ARI + LI and ARI + VAL on mean (95%CI) YMRS total score (−16.5 [−18.1; −14.8] and −17.6 [−18.9; −16.3], both p < 0.001 vs. baseline) and MADRS total score (−1.7 [−3.3; −0.1], p < 0.05 vs. baseline vs. −2.7 [−4.0; −1.4], p < 0.001 vs. baseline). Over the 46-week extension, continued aripiprazole provided continued YMRS improvement with ARI + LI (−2.9) and ARI + VAL (−3.3), while mean MADRS total changes were +1.1 and +1.0, respectively, and LIFE-RIFT changes were 0.2 and −0.5, respectively.Conclusions:Long-term aripiprazole adjunctive to lithium/valproate in bipolar mania was safe and well tolerated. Improvements in manic symptoms and functioning were maintained. Aripiprazole, adjunctive to either lithium or valproate, appeared to be equally safe and effective combinations for the treatment of bipolar disorder.Limitations:As an open-label extension study with a low completion rate, a conservative interpretation of the findings is warranted. Additionally, the study population was not randomly selected but chosen at the discretion of the investigator, and patients did not maintain therapeutic levels of their mood stabiliser consistently.

Clinical use of aripiprazole in patients with schizophrenia: A real-life setting results from the German Postmarketing Surveillance Study

When aripiprazole (ABILIFY®) received its approval in Germany for the treatment of schizophrenia, a hospital-based postmarketing surveillance study was initiated in order to gain further insights concerning safety and efficacy of the antipsychotic under real-life conditions. Efficacy was rated by using standard CGI, GAF, and SF-12 instruments, whereas safety was evaluated according to the reports on adverse effects. Data from 799 patients with schizophrenia from 122 psychiatric hospitals returned for evaluation. Eighty percent of the patients were treated for 4 weeks with 10–30 mg/day aripiprazole (mean modal dose 15 mg/day). Within the observation period significant improvements of CGI, GAF, and SF-12 ratings was observed. Aripiprazole was tolerated well by the patients. Most frequent adverse effects were insomnia, irritability, restlessness, nausea and vomiting, in general being moderate to mild and corresponding to the known tolerability profile of aripiprazole. The results demonstrate that the administration of aripiprazole can result in an improvement of the symptoms of schizophrenia within 4 weeks in a real-life hospital-based in- and outpatient setting.

Effectiveness of aripiprazole in a patient with presumed idiopathic Parkinson's disease and chronic paranoid schizophrenia

SEVERAL CASES OF the coexistence of schizophrenia and idiopathic Parkinson's disease (IPD) have been reported and the management of concurrent psychosis and parkinsonism has been considered as quite difficult as even atypical antipsychotics may worsen parkinsonism; conversely L-dopa may worsen psychosis.1, 2 To my knowledge, this is the first case report of successful treatment with aripiprazole in a schizophrenic patient with comorbid IPD. A 71-year-old woman with chronic schizophrenia was admitted to our department. She was diagnosed with schizophrenia at age 28. She had auditory hallucinations with voices conversing with each other and persecutory delusions but did not have mood symptoms. After brief admission at age 48, her condition was stable on thioridazine 40 mg/day and sulpiride 200 mg/day. However, at age 61, she noted the resting tremor of her left arm. She discontinued all antipsychotics for several years. But, thereafter, she experienced resting tremor of the right extremities, rigidity and postural instability. At age 69, she was diagnosed as having IPD and L-dopa/carbidopa was commenced. The treatment improved parkinsonism but exacerbated her psychosis. In addition she complained of various side-effects such as nausea and consequently discontinued it after 3 months. On admission, she had no obvious cognitive deficits (the Mini-Mental State Examination = 28/30). The results of laboratory tests and the findings of cranial magnetic resonance were normal. In 123I-metaiodobenzylguanidine myocardial scintigraphy, the average count per pixel in heart to mediastinum (H/M) ratio was decreased [H/M (early) = 1.854, H/M (late) = 1.350]. Her score on the Brief Psychiatric Rating Scale (BPRS) was 79, her stage on the Hoehn–Yahr scale was IV, and her activities-of-daily-living (ADL) rating on the Barthel index was 35. However, after she started taking aripiprazole 6 mg/day, we sometimes saw her walking by herself. Therefore, we gradually increased aripiprazole over 4 weeks to 18 mg/day. Then, her psychosis gradually improved and she wanted to be more mobile. She underwent physical therapy with successful discharge after 3 months. Her psychotic symptoms, motor function and ADL all improved without antiparkinsonian medications (BPRS = 37, Hoehn–Yahr stage = III, Barthel index = 65). She continues to do well on aripiprazole 6 months post-discharge. The number of schizophrenic patients with comorbid IPD will increase in aging patients with schizophrenia. This case suggests that aripiprazole may be useful in treating such patients (especially when L-dopa cannot be administered due to its side-effects) because aripiprazole, a dopamine D2 partial agonist, theoretically may improve hypodopaminergic activity in the nigrostriatal pathway in patients with IPD. In addition, the present patient was able to undergo physical therapy safely because aripiprazole rarely induces sedation and orthostatic hypotension due to extremely weak antagonism at α1 and H1 receptors. However, several case reports of aripiprazole in patients with psychosis associated with IPD indicate that aripiprazole worsens motor function,3, 4 partly because aripiprazole appears to bind to D2 receptors by competing with dopamine replenished by L-dopa because the binding affinity to dopamine D2 receptors of aripiprazole is higher than that of dopamine.5 It is necessary to note this when administering aripiprazole with L-dopa.

Trial of aripiprazole in the treatment of first‐episode schizophrenia

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. 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. 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. Aripiprazole is an effective and well-tolerated antipsychotic agent in patients with first-episode schizophrenia. Further investigations with larger samples are needed.