Aripiprazole In Bipolar Disorder Research Articles

Gamma oscillations predict treatment response to aripiprazole in bipolar disorder

ObjectiveTreatment of Bipolar Disorder (BD) is a challenging issue. Aripiprazole monotherapy is a recommended option for the treatment of mania in BD. The electrophysiological markers of treatment response to aripiprazole could be potentially identified by quantitative Electroencephalography (qEEG). MethodsTwenty-four patients with BD were analysed retrospectively. Based on the percentage reduction in Young Mania Rating Scale, they were classified as responders (N = 14) and non-responders (N = 10) to aripiprazole monotherapy. Their resting-state qEEG recordings were examined. Spectral power across all frequency bands were calculated. Absolute powers for all frequency bands were compared between these groups. ResultsIndependent sample Mann-Whitney U test revealed that patients who did not respond to aripiprazole had greater gamma power than aripiprazole treatment responders. ConclusionsBased on the present findings, it can be proposed that excess in gamma power could be the electrophysiological biomarkers of unresponsiveness to aripiprazole treatment in BD.

Drug safety evaluation of aripiprazole in bipolar disorder

ABSTRACTIntroduction: Safety and tolerability of medications are key variables to inform treatment choice for patients with bipolar disorder (BD). This review focuses on the overall tolerability and safety profile of aripiprazole when used for its bipolar disorder indications, which include acute treatment of manic and mixed episodes and maintenance treatment of bipolar I disorder for the oral formulation, agitation associated with bipolar mania for the injectable immediate-release formulation, and maintenance treatment of bipolar I disorder for the long acting once-monthly (AOM) formulation.Areas covered: The authors reviewed aripiprazole safety in bipolar disorder according to product labeling. English language reports located through PubMed and information available on the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) websites, with a focus on the safety and tolerability of aripiprazole, were reviewed.Expert opinion: Compared to many other antipsychotics, aripiprazole has a relatively favorable tolerability profile, with a lower risk for weight gain, dyslipidemia, diabetes, and hyperprolactinemia. Compared to first-generation antipsychotics, and similar to most second-generation antipsychotics, aripiprazole has a reduced propensity for extrapyramidal side effects and a better cardiovascular safety.

EFFECTIVENESS OF A CLOZAPINE–ARIPIPRAZOLE COMBINATION IN TOURETTE SYNDROME AND BIPOLAR SPECTRUM DISORDER

Introduction Antipsychotic combination is a common strategy used in both bipolar disorder and schizophrenia, although just a few trials are available exploring its effectiveness. We report herein the case of a patient suffering from severe Tourette syndrome (TS) and bipolar spectrum disorder who benefited from a combination of clozapine and aripiprazole. Case report “Mr. FS,”a 39-year-old art-craft worker, had been suffering from TS since his early childhood. During the adolescence, TS was character-ized by mouth opening and shoulder rotation, complex motor tics, such as trunk-bending or gyrating, screaming, and complex phonic tics. He was treated with pimozide 8 mg/day, which led to a complete remission of tics for about 20 years, although the clinical picture was complicated by the onset of mood shifts associated with impulsive behaviors and obsessions (numerical obsessions, rituals of order and symmetry, disproportionate aggressiveness). In 2007, when he was 35, he visited us for a major depressive episode with suicidal thoughts, panic attacks, and agoraphobic avoidance. Paroxetine (20 mg/day) led to a fast improvement of mood and anxiety symptoms, albeit being ineffective on tics. Only transient responses were obtained with the association of various drugs (haloperidol, risperidone, olanzapine, amisulpiride) to paroxetine and mood stabilizers (valproic acid, 600 mg/day). After about 2 years of different combinations, a significant improvement was obtained with tetrabenazine 75 mg/day1 clozapine 25mg/day1valproic acid 600 mg/day and fluvoxamine 150 mg/day. This strategy had a good impact only on the affective and obsessive symptoms, while tics remained stable. Therefore, tetra-benazine, fluvoxamine, and valproic acid were tapered down. At the same time, aripiprazole (15 mg/day) was introduced, and, after about 1month, we observed a dramatic improve-ment of TS symptoms. The improvement is still maintained at 2-year follow-up, so that currently the patient, who is regularly taking clozapine 25 mg/day and aripiprazole 15 mg/day with no significant side effects, shows a good affective balance, with no impulsive behavior, obsessions, or tics. Discussion Clozapine is considered a standard treatment for schizophrenia and bipolar disorder, whereas it has been reported to exacerbate obsessions and tics, although this topic is controversial. The effectiveness of aripiprazole in bipolar disorder is well documented, and preliminary data do exist for its possible use in obsessive-compulsive (OCD) and related disorders. Conclusions Our case report highlights the possible usefulness of combining clozapine and aripiprazole in TS comorbid with bipolar spectrum disorders, perhaps due to the different and not overlapping pharmacological profile of these two antipsychotics. Aripiprazole has much higher affinity for D2 receptors than clozapine and, since it behaves as a 5-HT2A antagonist and 5-HT2C partial agonist, may have a robust anti-obsessional (and perhaps anti-tic) activity. Further controlled studies are necessary to investigate the benefits of antipsychotic polypharmacy in patients suffering from both bipolar and OCD spectrum disorders.

Efficacy, safety and tolerability of aripiprazole in bipolar disorder: An updated systematic review and meta-analysis of randomized controlled trials

Numerous studies have investigated aripiprazole as a treatment for bipolar disorder (BD). therefore we conducted this comprehensive meta-analysis to investigate the efficacy and safety profile of aripiprazole in treating BD. Two authors conducted systematic searches of PubMed and ScienceDirect from inception until May 14th, 2017. Randomized controlled trials (RCTs) of people with BD who received aripiprazole were included. A total of 20 RCTs met the eligibility criteria, including two which investigated the efficacy of aripiprazole versus haloperidol (aripiprazole=340; haloperidol=337), three which compared aripiprazole versus lithium (aripiprazole=208; lithium=212), and 15 with multiple comparisons of aripiprazole versus a placebo (aripiprazole=1923; placebo=1499). Compared to a placebo, aripiprazole improved acute mania (Hedges' g: −0.299, p=0.001) and psychosis (Hedges' g: −0.296, p<0.001) in the acute mania state, but did not improve depressive symptoms (Hedges' g: −0.127, p=0.054) in the acute depressive state. Aripiprazole was associated with lower relapse rates in bipolar mania when used in combination versus a placebo in maintenance therapy (odds ratio: 0.522, p<0.029). Aripiprazole was also associated with higher levels of high density lipoprotein, lower dropout rates, but no difference in extrapyramidal symptoms in the maintenance phase versus a placebo or in comparison with other medications (haloperidol or lithium). Our results suggest that aripiprazole is effective and safe in treating bipolar mania. Further trials are necessary to evaluate the efficacy and tolerability versus other medications.

A clinical review of aripiprazole in bipolar depression and maintenance therapy of bipolar disorder

Background Bipolar disorder is a chronic, recurrent disorder with a significant negative impact on quality of life. Effective treatments are available for acute mania. In contrast, there is a lack of consensus on the treatment of acute bipolar depression and long treatment options for bipolar disorder require more study. Aripiprazole is FDA approved for the treatment of acute mania. This paper reviews current data on the efficacy of aripiprazole in the treatment of acute bipolar depression and in maintenance therapy of bipolar disorder. Methods PubMed and abstracts of recent conferences were searched for randomized, double-blind studies that investigated the efficacy of aripiprazole in acute bipolar depression or maintenance therapy of bipolar disorder. Results Two studies assessed the efficacy of aripiprazole monotherapy in the treatment of acute bipolar depression. These showed that although aripiprazole significantly reduced depressive symptoms early in treatment, the results were not significantly different from placebo at the primary end point of week 8. As to long-term treatment, aripiprazole was superior to placebo in delaying time to relapse for manic episodes, but not for depressive episodes after 26 and 100 weeks of maintenance therapy. Aripiprazole was as effective as lithium, and adjunctive aripiprazole with lithium or valproate was more effective than placebo plus lithium or valproate, in preventing a manic relapse. Reductions in manic and mixed relapse rates compared to placebo were achieved in a study combining aripiprazole with lamotrigine; however, the results were not statistically significant. Similar to other maintenance studies, depressive relapse rates were not significantly reduced compared to placebo. Limitations Negative findings for aripiprazole in the treatment of acute bipolar depression have been attributed to high study doses, rapid titration, and high placebo rates. A recent post-hoc analysis demonstrated that aripiprazole was more effective in patients with severe depressive symptoms, particularly for patients on a lower dose. Further research is needed to confirm this finding. The inability of aripiprazole to reduce the time to depressive relapse during maintenance therapy may be due to the recruitment of patients with an index manic episode and a consequent lower incidence of depressive relapses. Therefore, studies using a depression index episode are needed to appropriately evaluate relapse prevention. Conclusions Although aripiprazole has proven efficacy for acute mania and the prevention of mania, the evidence available thus far does not support the efficacy of aripiprazole for the treatment of acute bipolar depression and prevention of depressive relapse. Further studies with appropriate doses and a depressive index episode are needed to clarify the role of aripiprazole in bipolar disorder.

Aripiprazole in bipolar disorder: clinical strategies to maximize efficacy and tolerability

A number of double-blind, randomized, controlled trials have confirmed the clinical efficacy of aripiprazole in bipolar disorder and schizophrenia. Aripiprazole is the prototype of the 'third generation' atypical antipsychotics, or dopamine-serotonin- stabilizers and is characterized by a relatively low risk of inducing metabolic adverse effects, causing sedation and other side effects such as hyperprolactinemia. As a partial agonist at dopamine D2 receptors, aripiprazole acts as a functional antagonist in the mesolimbic dopamine pathway, where excessive dopamine activity is thought to cause positive symptoms, but acts as a functional agonist activity in the mesocortical pathway, where reduced dopamine activity is thought to be associated with negative symptoms and cognitive impairment. This presentation will review the available research data on the efficacy of aripiprazole in bipolar disorder and discuss how this data translate in the real world clinical practice and what the best strategies are to maximize the efficacy and tolerability of this medication.

Treatment of psychotic symptoms in bipolar disorder with aripiprazole monotherapy: a meta-analysis

BackgroundWe present a systematic review and meta-analysis of the available clinical trials concerning the usefulness of aripiprazole in the treatment of the psychotic symptoms in bipolar disorder.MethodsA systematic MEDLINE and repository search concerning clinical trials for aripiprazole in bipolar disorder was conducted.ResultsThe meta-analysis of four randomised controlled trials (RCTs) on acute mania suggests that the effect size of aripiprazole versus placebo was equal to 0.14 but a more reliable and accurate estimation is 0.18 for the total Positive and Negative Syndrome Scale (PANSS) score. The effect was higher for the PANSS-positive subscale (0.28), PANSS-hostility subscale (0.24) and PANSS-cognitive subscale (0.20), and lower for the PANSS-negative subscale (0.12). No data on the depressive phase of bipolar illness exist, while there are some data in favour of aripiprazole concerning the maintenance phase, where at week 26 all except the total PANSS score showed a significant superiority of aripiprazole over placebo (d = 0.28 for positive, d = 0.38 for the cognitive and d = 0.71 for the hostility subscales) and at week 100 the results were similar (d = 0.42, 0.63 and 0.48, respectively).ConclusionThe data analysed for the current study support the usefulness of aripiprazole against psychotic symptoms during the acute manic and maintenance phases of bipolar illness.

Efficacy and safety of aripiprazole in the treatment of bipolar disorder: a systematic review

BackgroundThe current article is a systematic review concerning the efficacy and safety of aripiprazole in the treatment of bipolar disorder.MethodsA systematic Medline and repositories search concerning the usefulness of aripiprazole in bipolar disorder was performed, with the combination of the words 'aripiprazole' and 'bipolar'.ResultsThe search returned 184 articles and was last updated on 15 April 2009. An additional search included repositories of clinical trials and previous systematic reviews specifically in order to trace unpublished trials. There were seven placebo-controlled randomised controlled trials (RCTs), six with comparator studies and one with add-on studies. They assessed the usefulness of aripiprazole in acute mania, acute bipolar depression and during the maintenance phase in comparison to placebo, lithium or haloperidol.ConclusionAripiprazole appears effective for the treatment and prophylaxis against mania. The data on bipolar depression are so far negative, however there is a need for further study at lower dosages. The most frequent adverse effects are extrapyramidal signs and symptoms, especially akathisia, without any significant weight gain, hyperprolactinaemia or laboratory test changes.

P.6.c.002 Aripiprazole in bipolar disorder and polysubstance use: a case report

P.6.c.002 Aripiprazole in bipolar disorder and polysubstance use: a case report

Aripiprazole: pharmacology and evidence in bipolar disorder

Aripiprazole is a psychotropic agent with a novel pharmacologic profile. The purpose of this article is to review the pharmacology, efficacy and safety of aripiprazole in bipolar disorder. The authors conducted a PubMed search of all English-language articles published between January 1995 and February 2007. The key search term was ‘aripiprazole’ combined with: ‘randomized controlled trial’, ‘pharmacology’, ‘pharmacokinetics’, ‘pharmacodynamics’, ‘depression’, ‘mania’, ‘maintenance’ and ‘bipolar disorder’. s and proceedings from national and international psychiatric meetings were also reviewed. The search was augmented with a manual review of relevant article reference lists. This review is limited to pivotal registration, as well as acute and maintenance, randomized controlled trials in bipolar disorder. Aripiprazole is established as efficacious in acute mania and in the maintenance treatment of bipolar disorder. Aripiprazole has a favorable safety and tolerability profile, with minimal propensity for clinically significant weight gain and metabolic disruption. Extrapyramidal side effects, such as akathisia, are reported and may be treatment limiting in some cases. The hazard risk for tardive dyskinesia in the bipolar population is unknown. Aripiprazole constitutes an alternative mood-stabilizing pharmacologic avenue in bipolar disorder; its comparative efficacy in long-term recurrence prevention and bipolar depression is a future research vista.