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Antipsychotic medications appear to be effective for reducing challenging behaviour in the short-term among children with intellectual disabilities, but they carry a risk of significant side effects. Findings from this review must be interpreted with caution as studies were typically of low quality and most outcomes were based on a small number of studies. Further long-term, high-quality research is needed to determine the effectiveness and safety of psychotropic medication for reducing challenging behaviour.
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clinicaltrials.gov Identifiers: NCT00095823, NCT00095758, and NCT00105196.
Mean improvement in Montgomery-Asberg Depression Rating Scale total score was significantly greater with adjunctive aripiprazole versus adjunctive placebo for both between-class (-9.2 vs -6.2, P < .001) and within-class (-9.8 vs -6.6, P < .001) switch groups. Relative risks for response were 1.6 (95% CI = 1.3-2.1) for those who switched between classes and 1.7 (95% CI = 1.2-2.2) for those who switched within class.
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These equivalency estimates may be useful for clinical and research purposes. The source of the dose equivalency estimation is evidence-based and consistent across medication.
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The cognitive deficit was induced by infusion of the competitive NMDA receptor antagonist 3-(R)-2-carboxypiperazin-4-propyl-1-phosphonic acid (CPP) in the rat medial prefrontal cortex (mPFC). In vivo microdialysis was used to compare the effects of aripiprazole, olanzapine and haloperidol on CPP-induced glutamate (GLU) and serotonin (5-HT) release in the mPFC of conscious rats.
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The group presented with severe psychotic symptoms (mean baseline PANSS total score of 105.2), which were reduced rapidly (P < 0.0005). The between-group and group by time interaction terms were non-significant. Similar reductions were seen across all PANSS sub-scales. At Week 1 the mean PANSS Activation Scale score was reduced more with olanzapine than in the other groups (P < 0.002). Few instances of extrapyramidal symptoms occurred; all were sporadic and did not require treatment. Group body weight increased by 7.3% over the study. Vital signs remained unchanged.
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English-language literature cited in MEDLINE from January 1, 1968, to December 31, 2005, was searched with the keywords anxiety disorder, anxiety symptoms, generalized anxiety disorder, panic disorder, obsessive-compulsive disorder, posttraumatic stress disorder, social phobia, bipolar disorder, major depressive disorder, Hamilton Rating Scale for Anxiety, antipsychotics, typical antipsychotics, atypical antipsychotics, fluphenazine, haloperidol, perphenazine, pimozide, thiothixene, trifluoperazine, loxapine, molindone, chlorpromazine, mesoridazine, thioridazine, fluspirilene, penfluridol, pipothiazine, flupenthixol, clozapine, olanzapine, risperidone, quetiapine, ziprasidone, aripiprazole, amisulpride, and clinical trial. Randomized, double-blind, placebo-controlled trials and open-label studies with a minimum of 20 subjects with a DSM-III/IV or ICD-10 diagnosis of anxiety disorder and studies without a DSM-III/IV or ICD-10 diagnosis of anxiety disorder but with Hamilton Rating Scale for Anxiety (HAM-A) scores as an outcome were prioritized. Studies on bipolar disorder or major depressive disorder with the analysis of changes in anxiety symptoms were reviewed. Early studies on neurosis/ anxiety or anxious depression without a HAM-A component were also reviewed.
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In total, 737 patients were included in the safety database (aripiprazole n = 371; placebo n = 366). No suicides were reported. There were no treatment-emergent, suicide-related adverse events in the aripiprazole group; 2 patients in the placebo group had ≥ 1 adverse event related to suicide (both suicidal ideation). More placebo than aripiprazole patients > 25 years old experienced a 2-point (P < .01) or 1-point (P < .05) worsening of MADRS item 10 scores. For this age group, 2-point improvement in MADRS item 10 scores and 1-point improvement of IDS item 18 scores were significantly more common in aripiprazole patients than placebo patients (both P < .05).
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The data for the treatment of late-life bipolar disorder are limited, but the available evidence shows efficacy for some commonly used treatments. Lithium, divalproex sodium, carbamazepine, lamotrigine, atypical antipsychotics, and antidepressants have all been found to be beneficial in the treatment of elderly patients with bipolar disorder. Although there are no specific guidelines for the treatment of these patients, monotherapy followed by combination therapy of the various classes of drugs may help with the resolution of symptoms. ECT and psychotherapy may be useful in the treatment of refractory disease. There is a need for more controlled studies in this age group before definitive treatment strategies can be enumerated.
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This retrospective cohort study used the OptumInsight commercial data set from January 2008 to June 2011. The index date was defined as the earliest date of prescription for the atypical antipsychotics aripiprazole, olanzapine, quetiapine, risperidone, and ziprasidone, from January 1, 2009, through June 30, 2010. Medical claims during a 2-year period (12 months before and 12 months after the index date) were used to identify relevant diagnostic codes from the International Classification of Diseases, Ninth Edition, Clinical Modification associated with the antipsychotic prescription. A logistic regression analysis was conducted to examine the predictors of use of atypical antipsychotics without a relevant diagnosis, that is, schizophrenia, bipolar, or major depressive disorder (MDD).
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Olanzapine induced a marked elevation in triglyceride and cholesterol levels and in liver transaminase enzymes after 12 weeks of treatment in a patient with schizophrenia. These changes were not seen in an earlier 10-week course of treatment with risperidone, and improved substantially 1 week after the patient stopped olanzapine and began treatment with aripiprazole. The patient did not exhibit weight gain or hyperglycemia with any of the medications. This case and a review of the literature suggest that olanzapine may have unique properties that affect hepatic enzyme pathways, independent of any effects on weight and glucose, that may lead to hyperlipidemia and transaminitis in some patients.
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Clozapine is the first choice antipsychotic medication for treatment-refractory schizophrenia; however, there are some disadvantages in using clozapine. A few reports have appeared concerning switching from clozapine to other antipsychotics for treatment-refractory schizophrenia. This report describes the case of a 58-year-old female patient with treatment-refractory schizophrenia who was successfully switched from clozapine 300 mg/day to aripiprazole 20 mg/day because of changes in consciousness. After the switch to aripiprazole, the patient's psychotic condition improved. As expected, we identified few successful cases of switches from clozapine in our search of the literature. Although controlled clinical trial data support use of clozapine in treatment-refractory schizophrenia, some patients cannot tolerate this agent or it may increase the risk of physical problems for some patients. In such situations, clinicians may want to consider prescribing a different antipsychotic or adding another antipsychotic and decreasing the dosage of clozapine.
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Aripiprazole has a low risk of extrapyramidal symptoms. Switching to aripiprazole has been reported to improve tardive dyskinesia caused by other medications. The authors report a case and review previous reports of dystonia and dyskinesia associated with aripiprazole.
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Hyperprolactinemia causes hypogonadotrophic hypogonadism. Hyperprolactinemia can be pre-existing in some patients with schizophrenia. Dopamine is the most important prolactin-inhibiting factor, and dopaminergic hyperactivity has been implicated in the pathophysiology of psychosis.
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Over 24 h, patients could receive up to three IM injections; the second and third administered > or = 2 and > or = 4 h, respectively, after the first, if deemed clinically necessary. Following IM treatment, oral aripiprazole or haloperidol was administered for 4 days. The primary efficacy measure was the mean change in PEC score from baseline at 2 h.
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In October 2015, we searched the Cochrane Central Register of Controlled Trials (CENTRAL), Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature (CINAHL) and seven other databases as well as two trial registers. We searched for records published in 1990 or later, as this was the year aripiprazole became available.
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From the evidence available, aripiprazole seems to be an antipsychotic effective and well tolerated in the treatment of women with psychotic disorders in pregnancy. However, further studies are needed to better establish the safety of aripiprazole during pregnancy, particularly as the risk of major malformtions and perinatal complications is concerned.
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Evidence supports the benefit of risperidone and aripiprazole for challenging and repetitive behaviors in children with ASDs. Evidence also supports significant adverse effects of these medications. Insufficient strength of evidence is present to evaluate the benefits or adverse effects for any other medical treatments for ASDs, including serotonin-reuptake inhibitors and stimulant medications.
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A 33-year-old, white, nonverbal, profoundly intellectually impaired woman (IQ <20-25), residing in a state-run facility, exhibited worsening aggressive behaviors associated with AD. These behaviors were characterized by a history of self-injurious behavior (eg, slapping and scratching herself); property destruction, including breaking windows; and head butting of staff and peers. Additional diagnoses included a seizure disorder, hyperprolactinemia, and osteoporosis. At the time of admission, her drug regimen included 3 atypical antipsychotic agents: risperidone, clozapine, and aripiprazole. Antipsychotic agents have been reported to lower the seizure threshold, and elevated prolactin levels have been associated with risperidone use. Aripiprazole and clozapine were discontinued on admission, and risperidone was discontinued one month later following increased behavioral deterioration. Buspirone was considered an appropriate replacement medication, as it has not been associated with elevated prolactin levels or a lowered seizure threshold, and was initiated at 15 mg/day. Significant reductions in aggression were noted following titration to a total daily dose of 90 mg.
Our search yielded 214 citations, however only open-label or randomized-controlled trials (RCT) with ≥25% of their subjects having an IQ≥71 were included in our review. Eleven original studies met our inclusion parameters for review; eight studies for the meta-analysis. These studies, although limited in methodological rigor, and the meta-analytic results suggest that SGAs provide improvement in behavioral symptoms associated with AD and HFA. The majority of the studies reported weight gain as a potentially concerning adverse effect.
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We report on two cases in which monotherapy of the selective serotonin reuptake inhibitor and sigma-1 receptor agonist fluvoxamine was effective in ameliorating the akathisia of patients with schizophrenia treated with the antipsychotic drug aripiprazole.
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This study assessed the metabolic effects of aripiprazole and pimozide in pediatric Tourette syndrome, a neurodevelopmental condition characterized by multiple motor and phonic tics. Patients receiving aripiprazole (n = 25) or pimozide (n = 25) were compared with medication-free patients (n = 25). Body mass index, glycemia, triglyceridemia, and cholesterolemia were monitored at baseline and 12 and 24 months after commencing treatment. The aripiprazole group demonstrated significant increases in cholesterolemia. The pimozide group demonstrated significant increases in glycemia. Both groups demonstrated elevations in triglyceridemia not significantly different from those in unmedicated control subjects. The effect of aripiprazole on cholesterol was apparent after 12 months, but leveled off during year 2 of treatment. Longitudinal studies are required to evaluate the full extent of glycemic alterations with pimozide. Both agents appear relatively safe for use in pediatric Tourette syndrome. These findings will help guide medication selection in patients with specific medical vulnerabilities.
Thirty-nine healthy middle-aged Korean subjects were enrolled (mean age, 52.7 years; mean height, 167 cm; mean weight, 67.6 kg); 33 participants completed the study (29 male subjects and 4 female subjects). The 90% CIs of the geometric means ratio (test drug/reference drug) of Cmax, AUC0-last, and AUC0-∞ values were 0.95 to 1.14, 0.98 to 1.09, and 0.97 to 1.08, respectively. All of the subjects who experienced adverse events recovered without sequelae, and no serious adverse events were observed.
Determining the most appropriate frequency of SGA use in children and adolescents will ultimately depend on decisive clarification of risks and benefits. The currently available literature highlights large international differences in the frequency of use. These differences may reflect fundamental dissimilarities in the therapeutic stance adopted toward ADHD and CD by physicians practicing in different countries.
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This study adds to a previous report indicating beneficial effects of adjunctive aripiprazole in treatment of bipolar I depression. Double-blind, placebo-controlled investigations are needed to confirm these findings.