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PubMed2005

Efficacy of aripiprazole against hostility in schizophrenia and schizoaffective disorder: data from 5 double-blind studies.

OBJECTIVE: The objective was to determine the effects of aripiprazole on hostility. METHOD: A total of 1476 patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder were the subjects in 5 short-term, double-blind studies comparing aripiprazole with placebo; 3 of these studies also included a comparison with haloperidol. The studies were conducted between December 1993 and January 2001. The Positive and Negative Syndrome Scale (PANSS) was the principal outcome measure in these studies. To determine the effect of aripiprazole on hostility, post hoc analyses of the hostility item from the PANSS were conducted for the first 4 weeks of treatment. RESULTS: Aripiprazole was superior to placebo and not significantly different from haloperidol in reducing hostility. CONCLUSION: Aripiprazole is an effective treatment for hostility in patients with schizophrenia or schizoaffective disorder.

Adolescent↗
PubMedDate not supplied

Aripiprazole: a review of its pharmacology and clinical use.

Atypical antipsychotics generally have a lower propensity for extrapyramidal side-effects (EPSE), hyperprolactinaemia and tardive dyskinesia than that associated with typical antipsychotics but may still produce troublesome side-effects, such as weight gain, cardiac rhythm changes and impaired glucose tolerance. Aripiprazole is a new atypical antipsychotic with a unique receptor binding profile that combines partial agonist activity at D2 and 5HT1A receptors with potent antagonism at 5HT2A receptors. Clinical studies in acute schizophrenic relapse, chronic schizophrenia and acute mania show it is robustly more effective than placebo. Once-daily aripiprazole 15-30 mg is as effective as haloperidol 10 mg/day and risperidone 6 mg/day in short-term treatment of schizophrenia and more effective than haloperidol 7-10 mg/day in maintenance of response in chronic schizophrenia. Aripiprazole appears to be well tolerated, with most studies suggesting a frequency of adverse effects similar to placebo. Aripiprazole seems not to cause significant EPSE, hyperprolactinaemia, excessive weight gain or cardiac rhythm disturbance. Limited data suggest that aripiprazole is not associated with impaired glucose tolerance.

Antipsychotic Agents↗
PubMed2005

Characterisation of olanzapine-induced weight gain and effect of aripiprazole vs olanzapine on body weight and prolactin secretion in female rats.

RATIONALE: Atypical antipsychotic drug (APD)-induced weight gain causes non-compliance, increasing the risk of relapse and medical complications. OBJECTIVES: In an animal model, we assessed body weights, food intake, body fat/lean body mass contents and blood serum levels of glucose and lipids in female rats treated with olanzapine (Experiment 1). Also, we investigated the effect of aripiprazole vs olanzapine treatment on weight gain (WG) and plasma prolactin secretion in two strains (Wistar and Sprague-Dawley) and in two housing conditions (singly and group housed; Experiment 2). METHODS: In Experiment 1, Wistar females received either vehicle or olanzapine (5.0 mg kg(-1), p.o.) twice daily for 14 days. In Experiment 2, female rats (Wistar or Sprague-Dawley), housed singly or in groups, received either vehicle, aripiprazole (2.0-8.0 mg kg(-1), p.o.), or olanzapine (1.0-10 mg kg(-1), p.o.) twice daily for 7 days. Body weights and food intake were assessed daily. Body composition and blood assays were analyzed at the end of the treatment. RESULTS: WG induced by chronic olanzapine treatment was characterised by hyperphagia, increased body fat, and serum free fatty acid content and reduced lean tissue and serum glucose content. Subchronic aripiprazole treatment resulted in rapid and robust WG similar to those observed with olanzapine. In spite of similar effects on body weight, aripiprazole and olanzapine stimulated markedly different patterns of prolactin secretion. Body weight changes and prolactin secretion induced by these APDs were significantly modulated by housing and by strain. CONCLUSION: Assessment of body weight in the present model may not have predictive validity, and other measures may be needed to differentiate between WG-inducing and weight-neutral drugs.

Animals↗
PubMed2005

Aripiprazole's low intrinsic activities at human dopamine D2L and D2S receptors render it a unique antipsychotic.

Aripiprazole is the first clinically approved atypical antipsychotic agent having dopamine D2 receptor partial agonist activities. To evaluate aripiprazole's agonist and antagonist properties, we established a Chinese hamster ovary cell line expressing high and low densities of the long and short isoforms of human dopamine D2 receptors, then compared its properties with 7-{3-[4-(2,3-dimethylphenyl)piperazinyl]propoxy}-2(1H)-quinolinone (OPC-4392), S(-)-3-(3-hydroxyphenyl)-N-n-propylpiperidine ((-)-3-PPP), and terguride (other partial agonists) using forskolin-stimulated cAMP accumulation as an index. In cells expressing high receptor densities, all partial agonists predominantly behaved as agonists. However, in cells expressing low receptor densities, the partial agonists showed significantly lower maximal effects than dopamine. Aripiprazole showed the lowest intrinsic activities. In addition, all compounds blocked the action of dopamine with a maximum effect equal to that of each compound alone. Aripiprazole's low intrinsic activities may account for the clinical finding that, unlike the other partial agonists, it is substantially active against both positive and negative symptoms of schizophrenia.

Animals↗
PubMed2005

Treatment of residual anxiety symptoms with adjunctive aripiprazole in depressed patients taking selective serotonin reuptake inhibitors.

BACKGROUND: Depression and anxiety are common disorders and have substantially overlapping symptom complexes. Not surprisingly, treatment approaches are similar for both conditions with the selective serotonin reuptake inhibitors (SSRIs) as the initial therapy of choice. However, after first line treatments have been deployed, residual symptoms are often problematic. Augmentation strategies to address these difficulties are an area of active investigation. This study assessed aripiprazole as adjunctive therapy to SSRIs for patients with persistent anxiety symptoms complicating a depression or anxiety disorder. METHODS: Ten patients who had been receiving SSRIs for at least 6 weeks, but still had clinically significant anxiety symptoms, were enrolled in an open label, flexibly-dosed study of adjunctive aripiprazole. Clinical status was assessed with the Hamilton Anxiety Rating Scale (HAM-A), Montgomery Asberg Rating Scale (MADRS), and Sheehan Disability Scale (SDS). RESULTS: Eighty percent of the subjects had a greater than 50% reduction of symptoms on these outcome measures by week 2 of therapy, and continued with further decrements in symptoms throughout the course of the study. CONCLUSIONS: The results of this trial provide preliminary evidence that aripiprazole may be an effective adjunctive treatment in individuals on SSRIs with residual symptoms of anxiety or depression. More rigorous double-blind studies are warranted to confirm and elucidate the potential role of aripiprazole in these conditions.

Adult↗
PubMed2004

Aripiprazole: a new atypical antipsychotic with a different pharmacological mechanism.

Aripiprazole is a new atypical antipsychotic with a mode of action that is distinct from currently available antipsychotic drugs. In phase III comparative clinical studies, aripiprazole 15-30 mg/day was at least as effective as haloperidol and risperidone in short term treatment of acute exacerbation of schizophrenia but superior to haloperidol in long term maintenance therapy. Consistent with an atypical profile, aripiprazole is effective against positive, negative and cognitive symptoms of schizophrenia and has a favourable side effect profile with the incidence of extrapyramidal symptoms (EPS) comparable to placebo. It is also devoid of side effects such as clinically significant hyperprolactinaemia, hypercholesterolaemia and cardiotoxicity, and has a low propensity for weight gain. Symptom relief is achieved without significant sedation. These clinical data suggest its usefulness in psychosocial rehabilitation, as well as in long-term prevention of schizophrenic relapse. Recent results from a multicentre, open-label study in a general psychiatric setting provide the first evidence that aripiprazole is also effective under naturalistic conditions. However, only post-marketing experience will show whether the positive results of these controlled trials can be replicated in everyday practice.

Antipsychotic Agents↗
PubMed2006

Using aripiprazole to resolve antipsychotic-induced symptomatic hyperprolactinemia: a pilot study.

OBJECTIVE: To assess the effectiveness of substituting aripiprazole for other antipsychotic drugs taken by stable schizophrenic patients suffering from antipsychotic agent-induced symptomatic hyperprolactinemia. METHODS: Seven female schizophrenic patients with symptomatic hyperprolactinemia (167.6+/-58.0 microg/L) were recruited to take part in an 8-week open label trial of aripiprazole (10-20 mg/day) as a replacement for amisulpride or risperidone. Efficacy was assessed via PANSS and CGI-I scores. Serum prolactin levels were measured at baseline, week 4, and week 8. Data were collected from November, 2004 to May, 2005. RESULTS: At the end of weeks 4, serum prolactin levels were normalized (8.8+/-5.5 microg/L) and hyperprolactinemic symptoms were resolved in all patients. However, aripiprazole treatment was discontinued within 6 weeks for 2 of the 7 subjects due to aggravated auditory hallucinations. CONCLUSION: Results from this admittedly small-scale open-label study indicate that switching to aripiprazole may be useful for resolving antipsychotic-induced hyperprolactinemia and associated symptoms.

Adolescent↗
PubMed2002

The antipsychotic aripiprazole is a potent, partial agonist at the human 5-HT1A receptor.

Aripiprazole, 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butyloxy]-3,4-dihydro-2(1H)-quinolinone, a novel antipsychotic with partial agonist activity at dopamine D2 receptors, bound with high affinity to recombinant human 5-HT(1A) receptors (h5-HT(1A)) in Chinese hamster ovary cell membranes and displayed potent, partial agonism at 5-HT(1A) receptors in a guanosine-5'-O-(3-[(35)S]thio)-triphosphate ([(35)S]GTP gamma S)-binding assay that was blocked completely by a selective 5-HT(1A) receptor antagonist. An interaction with 5-HT(1A) receptors may contribute to the overall efficacy of aripiprazole against symptoms of schizophrenia, including anxiety, depression, cognitive and negative symptoms, and to its favorable side-effect profile. Combined with previous studies demonstrating the potent partial agonism of aripiprazole at dopamine D2 receptors, this study suggests aripiprazole is the first dopamine-serotonin system stabilizer.

Animals↗
PubMed2004

[Aripiprazole: a new atypical antipsychotic drug].

Aripiprazole is an atypical antipsychotic agent with an intrinsic dopamineagonist activity of 30 %. Aripiprazole exerts additional partial agonist action on 5-HT (1A) receptors and has antagonist properties at 5-HT (2A) receptors. Controlled studies demonstrated an effectiveness in acute relapse of schizophrenic psychosis, chronical schizophrenic and schizoaffective disorders. Aripiprazole was effective in the treatment of productive psychotic and negative symptoms. Compared to other antipsychotics aripiprazole demonstrated a favourable profile of side effects: only slight changes of body weight, mild extrapyramidal symptoms, no prolactin elevation and no significant changes in QTc interval. The efficacy in the long term treatment of schizophrenia seems to be similar to other antipsychotics (e. g. olanzapine). The first evaluations of studies with patients with bipolar disorders showed a significant efficacy in the treatment of mania.

Antipsychotic Agents↗
PubMed2004

Aripiprazole for maladaptive behavior in pervasive developmental disorders.

OBJECTIVE: The aim of this study was to obtain preliminary data regarding the effectiveness and tolerability of aripiprazole in the treatment of children and adolescents with a pervasive developmental disorder (PDD). METHOD: Five youths (mean age, 12.2 years; range, 5-18 years) meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) criteria for a PDD received a naturalistic, open-label trial of aripiprazole (mean dosage, 12.0 mg/day; range, 10-15 mg/day) for a minimum of 8 weeks (mean duration, 12 weeks; range, 8-16 weeks). RESULTS: All 5 patients were judged to be responders, as determined by a Clinical Global Impressions-Improvement (CGI-I) scale rating of "much improved" or "very much improved." Aripiprazole was well tolerated. No extrapyramidal symptoms or clinically significant changes in heart rate or blood pressure occurred during the short-term trials. Two of 5 patients experienced mild somnolence. Two subjects lost weight, 2 subjects had no change, and 1 subject gained weight (mean change, -8.2 lbs; range, -30 to +1 lb). The weight loss was likely the result of the discontinuation of atypical antipsychotics that had led to significant weight gain. CONCLUSIONS: This case series describes the effectiveness of aripiprazole in the treatment of maladaptive behaviors in 5 patients with a PDD. No significant adverse effects emerged during these short-term trials. Additional research is needed to support these preliminary findings.

Adolescent↗
PubMed2004

Aripiprazole possibly worsens psychosis.

Aripirazole is a novel antipsychotic that functions as a partial agonist at the dopamine D2 receptor and, thus, might theoretically worsen psychosis. We report a series of four clinical cases of exacerbation of psychosis related to initiation of aripiprazole therapy. Cases 1 and 2 demonstrated the worsening of psychosis following initiation of aripiprazole (15-30 mg daily) while tapering off the previous atypical antipsychotic. Cases 3 and 4 demonstrated worsening of psychosis following the addition of aripiprazole (15-30 mg daily) to an atypical antipsychotic. In two out of the four cases, discontinuation of arpiprazole resulted in improvement of psychotic symptoms. Although the cases presented are suggestive of a relationship between initiation of aripiprazole therapy and worsening of psychosis, further research is needed to clarify any potential association.

Adult↗
PubMed2005

Aripiprazole as an augmentor of selective serotonin reuptake inhibitors in depression and anxiety disorder patients.

More than half of anxiety and depression patients treated with an adequate course of antidepressants fail to fully improve. We retrospectively examined whether treatment-resistant depression and anxiety disorder patients responded to and tolerated augmentation with the atypical antipsychotic, aripiprazole. We report on patients with depression and anxiety disorders, including panic disorder, generalized anxiety disorder, social anxiety and post-traumatic stress disorder, who had an incomplete response to a variety of selective serotonin reuptake inhibitors (SSRIs) and who received augmentation with aripiprazole. The primary outcome measure was the Clinical Global Impression of Improvement (CGI-I). In the intent-to-treat analysis, the mean+/-SD CGI-S was 3.8+/-1.3 at endpoint. Fifty-nine percent of subjects received CGI-I ratings of 1 or 2, 'much improved' or 'very much improved,' in terms of their depression and anxiety symptoms at the end of 12 weeks. Several patients showed an early (weeks 1-5), as well as sustained, response to augmentation with doses of aripiprazole between 15 and 30 mg/day. The results suggest that aripiprazole may be effective as an augmentation for patients with persistent depressive and anxiety disorders despite initial SSRI treatment. Because this is a retrospective case review, further prospective studies are required to confirm these findings.

Adult↗
PubMed2005

Aripiprazole in schizophrenia with cocaine dependence: a pilot study.

The debilitation of schizophrenia (SCHZ) worsens markedly with comorbid cocaine dependence (CD) and alcohol abuse. To date, no medications have conclusively demonstrated effects against both SCHZ and CD (SCHZ + CD) simultaneously. Because of its dopamine-modulating properties, we hypothesized that aripiprazole would alleviate cocaine craving in patients with SCHZ + CD. We conducted a prospective, 8-week, open-label trial in poorly compliant SCHZ + CD subjects. Each received aripiprazole as their sole neuroleptic agent at a maximum dose of 15 mg/d. The Brief Psychiatric Rating Scale (BPRS) and the Brief Substance Craving Scale (BSCS) measured psychosis and subjective cocaine and alcohol cravings. Urine tests for cocaine provided data on actual use. Of 10 male subjects entered, 6 (60%) completed the 8-week trial. In those cases, positive urine tests dropped significantly (P < 0.001) after 2 weeks, when aripiprazole had reached steady state. Mean cocaine craving scores declined significantly (P = 0.026) as did mean alcohol craving scores (P = 0.006). Declining psychosis scores were associated with declining cocaine craving (r = 0.87, P < 0.01) and alcohol craving (r = 0.88, P < 0.01), respectively. This experience suggests possible aripiprazole effects in lowering both desire for and the use of cocaine in comorbid SCHZ subjects. These data suggest double-blind, randomized, comparison study in this severely ill, comorbid patient group.

Adult↗
PubMed2006

Aripiprazole and suicidality.

Cases of psychotic symptoms that worsen after treatment with aripiprazole have been described. We report the case of a 19-year-old patient who, although her psychotic symptoms did not worsen, attempted suicide after switching from risperidone to aripiprazole. The patient had not shown any aggressive behaviour towards herself or others in the 18 months before the introduction of aripiprazole, nor following its discontinuation (12 months). The observed time sequence, with the repetition 4 weeks later of high suicidal behaviour, led us to consider that this effect might possibly be linked to the aripiprazole treatment, which could have increased the risk of suicide in this patient.

Adult↗
PubMed2006

A case of Aripiprazole and extra pyramidal side effects.

This is a case report of a 56-year-old lady who was admitted to a psychiatric ward because she was showing a plethora of positive and negative symptoms of schizophrenia. She has a positive history of mental illness; her mother had a diagnosis of schizophrenia. The patient did not have any medical history of relevance and was not taking any medication. She was commenced on Aripiprazole and after 5 weeks developed disabling extra-pyramidal side effects. On discontinuation of Aripiprazole, the side effects subsided and disappeared quickly. According to the authors' knowledge, this is the first case of a patient developing extra-pyramidal side effects following treatment with Aripiprazole, not previously exposed to other antipsychotic, and with no co-morbid medical conditions. The authors suggest titrating Aripiprazole slowly.

Antipsychotic Agents↗
PubMed2006

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

Around 40-70% patients with treatment-resistant schizophrenia fail to respond to clozapine. Though combining antipsychotics is commonly practised with non-responders, there is little evidence for its use.We carried out a retrospective review of case notes of patients with treatment-resistant schizophrenia on clozapine-aripiprazole combination at our clozapine clinic. We report changes in psychotic symptoms, social function, weight, total cholesterol, serum glucose, HDL, CGI and GAF score pre- and post-aripiprazole augmentation. Clozapine-aripiprazole combination was associated with 22% reduction of clozapine dose. Eighteen out of 24 (75%) lost a mean weight of 5.05 kg. There was improvement in positive and negative symptoms, social functions, weight loss and a moderate increase in HDL. Our findings suggest that clozapine-aripiprazole is a safe and tolerable combination; however, control trials are needed to validate our findings.

Adult↗
PubMed2003

Aripiprazole in an adult with Asperger disorder.

OBJECTIVE: To report a case of aripiprazole-responsive adult Asperger disorder. CASE SUMMARY: A 34-year-old white man with lifelong, disabling Asperger disorder and a 20-year history of failed psychotherapeutic and pharmacologic interventions was prescribed aripiprazole, with dramatic symptomatic improvement. DISCUSSION: Multiple prior pharmacologic efforts over several years aimed predominantly at altering serotonin and dopamine neurotransmission resulted in treatment failure due to intolerable adverse effects, exacerbation of underlying symptoms, or nonresponse. Aripiprazole, with a complex profile of neurotransmitter affinities, has produced significant core symptom changes. Improved sociability; increased self-awareness; reduced rigidity, anxiety, and irritability; and reduced preoccupation with circumscribed esoteric interests are among the effects noted. CONCLUSIONS: Previously intractable Asperger disorder symptoms in a 34-year-old man were ameliorated with aripiprazole.

Adult↗
PubMed2003

Aripiprazole: efficacy and tolerability profile of a novel-acting atypical antipsychotic.

Aripiprazole, the latest atypical antipsychotic to come to clinical practice, has a proposed mechanism of action different to other agents, most notably in its partial agonist action at dopamine (D2) receptors and at serotonin (5HT1A) receptors. Placebo-controlled comparative trials of aripiprazole confirm efficacy for positive, negative and general psychopathology. Treatment-emergent adverse effects appear low. Aripiprazole is associated with low propensity for extrapyramidal side effects, an absence hyperprolactinemia and a low propensity for weight gain. Aripiprazole's clinical role will be determined by clinical experience, additional phase IV studies, and comparative information for this agent with respect to the efficacy and tolerability profiles of other atypical antipsychotic medications.

Antipsychotic Agents↗