Aripiprazole Treatment Research Articles

Tardive Oculogyric Crisis due to Aripiprazole treatment in an adolescent patient diagnosed with Bipolar Disorder

Antipsychotics usage in children and adolescents is becoming widespread. One of the extrapyramidal side effects associated with long-term antipsychotic drug use follow-up is an oculogyric crisis (OGC). OGC is defined as a dystonic reaction commonly observed after typical antipsychotic drug administration. However, there are rare cases which report OGC after atypical antipsychotic use. In this report, we present an adolescent with bipolar disorder who developed OGC after 2 years of aripiprazole and quetiapine use. To best of our knowledge, this case report has been the first case to present the clinical presentation of tardive OGC due to aripiprazole treatment in an adolescent patient. It is important to note that OGC might be observed in the acute phase and it might be as a result of chronic use detected during a clinical follow-up. Safety, tolerability and efficiency of aripiprazole in pediatric populations should be further analyzed in the future studies.

P.105 Adjunctive treatment of aripiprazole to olanzapine for weight reduction in patients with schizophrenia

In this article, introducing the method of radial basis function (RBF) into reproducing kernel particle method (RKPM), and the radial basis reproducing kernel particle method (RRKPM) is presented. The RRKPM has higher computational accuracy and better convergence than the RKPM. Then the RRKPM is used in elastic dynamic problem, and the weak form of integral is used to find the discretized governing equations. The penalty method is used to determine the essential boundary condition, and the two-point difference method is applied to discretizing the time. The RRKPM for elastic dynamic problem is constructed, and the accuracy and effectiveness of the RRKPM for elastic dynamic problem are verified by the numerical examples.

Impact of age and CYP2D6 genetics on exposure of aripiprazole and dehydroaripiprazole in patients using long-acting injectable versus oral formulation: relevance of poor and intermediate metabolizer status.

Tailoring medication dosing for the individual patient is complex, and many factors can influence drug exposure. We investigated the effect of age and CYP2D6 genotype on aripiprazole and dehydroaripiprazole exposure in patients using long-acting injectable (LAI) or oral aripiprazole. Matched data on serum concentration of aripiprazole and CYP2D6 genotype of patients using oral or LAI aripiprazole were included retrospectively from a therapeutic drug monitoring service. The patients were divided into the following CYP2D6 genotype-defined categories: poor metabolizers (PMs), intermediate metabolizers (IMs), normal metabolizers (NMs), and ultrarapid metabolizers (UMs). Linear mixed model analyses were used to evaluate the impact of CYP2D6 genotype on dose-adjusted serum concentrations of the active moiety of aripiprazole+dehydroaripiprazole in relation to age and formulation. We identified 635 patients (mean age = 40.1 years, 9.4% ≥ 65 years, 53.7% females) using LAI (n = 166) or oral formulation (n = 469). The genotype-predicted CYP2D6 phenotype subgroups were 2.4% UMs, 82.0% NMs, 8.0% IMs, and 7.2% PMs. Age did not significantly affect exposure of the active moiety of aripiprazole+dehydroaripiprazole in the LAI (p = 0.071) or oral (p = 0.14) subgroups. Compared with CYP2D6 NMs, PMs and IMs had significantly increased exposure of the active moiety of aripiprazole+dehydroaripiprazole in the LAI (1.7-fold higher, p < 0.001, and 1.5-fold higher, p < 0.001) and oral (1.7-fold higher, p < 0.001, and 1.6-fold higher, p < 0.001) subgroups. In conclusion, doses should be adjusted according to CYP2D6 genotype when initiating treatment with aripiprazole LAI or tablets, while advanced age do not affect the exposure of the active moiety of aripiprazole treatment regardless of formulation.

Aripiprazole causing false positive urine amphetamine drug screen in an adult patient with bipolar disorder

There has been only a few reports regarding aripiprazole causing false positive urine amphetamine drug screens, exclusively on children accidently ingesting aripiprazole.Herein, we present the first reported case of a 40 year old woman affected by Bipolar I Disorder, treated with aripirazole at therapeutic oral dose ranging from 15 mg/day to 30 mg/day, in the context of a depressive episode with mixed and psychotic features, showing a false positive urine amphetamine drug screen. We document the relationship between aripiprazole-dose, plasma concentration and amphetamines values in toxicologic urine examinations over time. Awareness of potential false positive urine amphetamine drug screens during aripiprazole treatment can condition therapeutic choices and prevent legal implications.

Long-term Effects of Aripiprazole Treatment during Adolescence on Cognitive Function and Dopamine D2 Receptor Expression in Neurodevelopmentally Normal Rats.

ObjectiveThis study aimed to investigate the long-term effects of aripiprazole treatment during adolescence on behavior, cognitive function, and dopamine D2 receptor (D2R) expression in adult rats.MethodsAdolescent male Sprague-Dawley rats were injected intraperitoneally with aripiprazole, risperidone, or vehicle control for 3 weeks (postnatal day 36–56). After a 2-week washout period, locomotion, anxiety, and spatial working memory were evaluated in adulthood (postnatal day 71–84), using an open field test, elevated plus maze, and Y-maze, respectively. In addition, we assessed D2R levels in the dorsolateral and medial prefrontal cortex (PFC), dorsal and ventral striatum, and hippocampus using western blot analysis.ResultsSpontaneous alternation performance (SAP) in the Y-maze, a measure of spatial working memory, differed significantly among the 3 groups (F = 3.89, p = 0.033). A post-hoc test confirmed that SAP in the aripiprazole group was significantly higher than that in the risperidone group (post-hoc test p = 0.013). D2R levels in the medial PFC (F = 8.72, p = 0.001) and hippocampus (F = 13.54, p < 0.001) were different among the 3 groups. D2R levels in the medial PFC and hippocampus were significantly lower in the aripiprazole-treated rats than that in the risperidone-treated rats (post-hoc test p = 0.025 and p < 0.001, respectively) and controls (post-hoc test p < 0.001, all).ConclusionThis study showed that aripiprazole treatment in adolescence could influence cognitive function and dopaminergic neurotransmission into early adulthood.

Differences of Fasting Blood Glucose Level in People with Schizophrenia between Before and After Getting Aripiprazole Treatment.

BACKGROUND:Schizophrenia is a serious disorder of the brain and mind. People with schizophrenia are at high risk of developing type diabetes, due to overall poor physical health, poor health care, unhealthy lifestyles, and side effects of antipsychotic drugs. However, atypical antipsychotics have their deficiencies, because they can be associated with worsening cardiovascular risk factors such as weight gain, hyperglycemia and hyperlipidemia.AIM:Difference in fasting blood glucose levels in people with schizophrenia between before and after receiving aripiprazole treatment.METHODS:This research was conducted in November 2017-September 2018. This research was first conducted in Indonesia, especially North Sumatra. This research is a numerical comparative analytical study paired with an experimental design approach. The number of samples is 44 people. Blood samples are taken in schizophrenia patients before getting the drug, before meals and before activities, assessed fasting blood glucose levels before being treated with aripiprazole and after drug administration for 6 weeks. Data analysis used was a paired test for differences in fasting blood glucose levels in people with schizophrenia between before and after receiving aripiprazole treatment.RESULTS:Based on the demographic characteristics found the research subjects based on the most age group were 31-40 years age group of 30 subjects (68.2%), based on the highest level of education was high school by 26 subjects (59.1%), based on the most marital status was by status not married for 24 subjects (54.5%). It was found that the average blood glucose level before being given aripiprazole in schizophrenic patients was 89.23 ± 7.13. It was found that the average blood glucose level after being given aripiprazole in schizophrenic patients was 86.5 ± 10.1. It was found that there were no differences in blood glucose levels before and after being given aripiprazole in schizophrenic patientsCONCLUSION:There was no difference in blood glucose levels before and after being given aripiprazole in schizophrenic patients with p-value (0.078).

Role of Endocannabinoid System in the Peripheral Antinociceptive Action of Aripiprazole.

Recently, we demonstrated that the antipsychotic dopaminergic and serotoninergic agonist aripiprazole induced peripheral antinociception. However, the mechanism underlying this effect has not been fully established. Here, our aim was to identify possible relationships between this action of aripiprazole and the endocannabinoid system. All drugs were given locally into the right hind paw of male Swiss mice weighing 30-35 g in a volume of 20 µL. The hyperalgesia was induced by intraplantar injection of prostaglandin E2 (2 μg). Aripiprazole was injected 10 minutes before the measurement, and an irreversible inhibitor of anandamide hydrolase (MAFP), an inhibitor for monoacylglycerol lipase (JZL184), and an anandamide reuptake inhibitor (VDM11) were given 10 minutes before the aripiprazole. Nociceptive thresholds were measured using an algesimetric apparatus in the third hour after prostaglandin E2 injection. Data were analyzed by ANOVA and Bonferroni tests. The antinociceptive effect induced by aripiprazole (100 μg) was blocked by cannabinoid 1 or 2 receptor antagonists AM251 (40 μg [P < .01], 80 μg [P < .0001], and 160 μg [P < .0001]) and AM630 (100 μg [P < .0001], 200 μg [P < .0001], and 400 μg [P < .0001]), respectively. The peripheral antinociception induced by aripiprazole (25 μg) was enhanced by administration of the inhibitor of fatty acid amide hydrolase (MAFP, 0.5 μg [P < .0001]) or monoacylglycerol lipase (JZL184, 4 μg [P < .0001]). Moreover, a similar enhancement was observed with the anandamide reuptake inhibitor (VDM11, 2.5 μg [P < .0001]). These results provide evidence for the involvement of the endocannabinoid system in peripheral antinociception induced by aripiprazole treatment.

The Difference of Fasting Blood Sugar of Male Patients with Schizophrenia Treated with Flexible Dose between Aripiprazole and Risperidone in Medan, Indonesia.

BACKGROUND:Life expectancy among schizophrenic patients is 20% shorter than the general population. Currently, long-term use of antipsychotic drugs can induce metabolic symptoms, including weight gain, glucose intolerance, high blood glucose.AIM:This research aimed to investigate the fasting blood sugar level of a male patient with schizophrenia treated with flexible dose.METHODS:This research is an experimental study, unpaired numerical comparative analytic with non-probability consecutive sampling by recruiting 50 research subjects of men with male patients with schizophrenia. Every 25 people were treated with aripiprazole, and another 25 subjects were treated with risperidone. The flexible dose on how doses are equated with bioequivalent doses between aripiprazole and risperidone was applied. Sampling was carried out in the inpatient and outpatient clinic of the psychiatric hospital Prof. Dr M. Ildrem Medan, North Sumatra, Indonesia, in a span of 6 months from January 2018 to July 2018. The diagnostic test used a Mini structured interview system International Statistical Classification of Diseases-10 (Mini-ICD 10) and the statistical analysis was involving Mann Whitney U Test.RESULTS:This research showed the mean of fasting blood sugar level in week 8 in the group receiving treatment with aripiprazole was 88.96 with a standard deviation of 4.33 and in the group receiving risperidone treatment was 102.80 with a standard deviation of 2.92. The results of the analysis using unpaired t-test in the two groups showed a significant difference in fasting blood sugar levels for men with schizophrenia in the group receiving aripiprazole treatment and the group receiving risperidone treatment in week 8 with a value of p < 0.001 (p < 0.05).CONCLUSION:This research revealed that based on the equivalence of risperidone and aripiprazole dosage given to the male patients with schizophrenia, the treatment using risperidone can significantly increase the fasting blood sugar level compared to the aripiprazole treatment in week 8.

Add-on atypical anti-psychotic treatment alleviates auditory verbal hallucinations in patients with chronic post-traumatic stress disorder

Auditory verbal hallucinations are common symptoms of post traumatic distress disorder. Previous studies have demonstrated alterations in the salience network (SN) in patients with post traumatic distress disorder and that hyperactivity of the SN is associated with AVHs in patients with psychosis. Patients with post traumatic distress disorder may benefit from aripiprazole; however, studies investigating the effect of aripiprazole on AVHs and activity in the SN in patients with post traumatic distress disorder are scarce. Therefore, we conducted an outcomes analysis using functional magnetic resonance imaging to explore the effects of add-on aripiprazole treatment on AVHs and brain functional connectivity in patients with post traumatic distress disorder. AVHs were alleviated by add-on aripiprazole treatment (Auditory Hallucination Rating Scale [AHRS] score reduced by ≥ 50%) in 22.7% of patients. Functional activity in the SN was obviously decreased in patients in whom AHRS scores were reduced ≥ 50% following add-on aripiprazole treatment compared to patients in whom AHRS scores were reduced by <50%. The decrease in functional connectivity within the SN was significantly correlated with the reduction in total AHRS scores. Although this study was associated with several limitations, the findings suggest that add-on aripiprazole treatment can alleviate AVHs in patients with post traumatic distress disorder by reducing activity in the SN.

Maternal aripiprazole exposure interacts with 7-dehydrocholesterol reductase mutations and alters embryonic neurodevelopment

Mutations in both copies in the gene encoding 7-dehydrocholesterol reductase (DHCR7) cause Smith–Lemli–Opitz Syndrome (SLOS), which is characterized by a toxic elevation in 7-dehydrocholesterol (7-DHC). Aripiprazole (ARI) exposure, independent of genetic mutations, also leads to elevation of 7-DHC. We investigated the combined effect of a single-copy Dhcr7+/− mutation and maternal ARI exposure on the developing offspring brain. We generated a time-pregnant mouse model where WT and Dhcr7+/− embryos were maternally exposed to ARI or vehicle (VEH) from E12 to E19 (5 mg/kg). Levels of cholesterol, its precursors, ARI and its metabolites were measured at P0. We found that ARI and its metabolites were transported across the placenta and reached the brain of offspring. Maternal ARI exposure led to decreased viability of embryos and increased 7-DHC levels, regardless of maternal or offspring Dhcr7 genotype. In addition, Dhcr7+/− pups were more vulnerable to maternal ARI exposure than their WT littermates, and maternal Dhcr7+/− genotype also exacerbated offspring response to ARI treatment. Finally, both 7-DHC levels and 7-DHC/cholesterol ratio is the highest in Dhcr7+/− pups from Dhcr7+/− mothers exposed to ARI, underscoring a potentially dangerous interaction between maternal genotype×embryonic genotype×treatment. Our findings have important clinical implications. SLOS patients should avoid drugs that increase 7-DHC levels such as ARI, trazodone and haloperidol. In addition, treatment with 7-DHC elevating substances might be potentially unsafe for the 1–1.5% of population with single-allele disruptions of the DHCR7 gene. Finally, prenatal and parental genetic testing for DHCR7 should be considered before prescribing sterol-interfering medications during pregnancy.

阿立哌唑治疗双相抑郁：国内文献的循证医学评价

阿立哌唑治疗双相抑郁：国内文献的循证医学评价

Clinical Usefulness of Aripiprazole Treatment in a Girl with Prader-Willi Syndrome and Psychosis

Clinical Usefulness of Aripiprazole Treatment in a Girl with Prader-Willi Syndrome and Psychosis

Effectiveness of aripiprazole once-monthly in schizophrenia patients pretreated with oral aripiprazole: a 6-month, real-life non-interventional study

BackgroundIn this study, the treatment of schizophrenia patients with aripiprazole once-monthly (AOM) was evaluated under real-life conditions in a naturalistic setting.MethodsThis multicenter, prospective, non-interventional study included 242 patients (age = 43.1 ± 15.1 years, 55.0% male) who were monitored during 6 months of AOM treatment. Endpoints included measurements of psychopathology (Brief Psychiatric Rating Scale, BPRS) and severity of illness scales (Clinical Global Impressions-Severity, CGI-S, and -Improvement, CGI-I). Furthermore, treatment-related adverse events (TRAEs) were recorded.ResultsAt baseline, the mean BPRS total score was 54.1 ± 15.6, the mean CGI-S was 4.8 ± 0.8 and the most frequent illness category was ‘markedly ill’ (41.7%). Patients had been pretreated with oral aripiprazole for a mean duration of 9.7 months (SD: 22.3) and 87.9% were deemed by their clinician as “clinically stable” and for a mean of 5.9 months. The difference in global BPRS after 6 months was − 13.8 (SD: 16.0; 95% CI: [− 15.9; − 11.7]; p < 0.001). The proportion of patients with high CGI-S scores decreased and the proportion of patients with low scores increased significantly (p < 0.001, respectively). BPRS scores improved numerically especially well in younger patients ≤35 years, CGI-S scores decreased significantly more in this population. TRAEs were rare, with low incidences of extrapyramidal symptoms (2.9%) or weight increase (0.4%).ConclusionsTreatment with AOM showed satisfying effectiveness in outpatients with further improvement of psychopathology after oral aripiprazole treatment for a considerable duration and even after having achieved clinically judged “stability”. Our findings indicate a robust therapeutic effect of AOM and substantiate previous results from randomized controlled trials under real-world routine conditions.

Aripiprazole in acute treatment of children and adolescents with autism spectrum disorder: a systematic review and meta-analysis.

BackgroundRecent randomized controlled trials indicated that aripiprazole was the effective treatment for children and adolescents with autism spectrum disorder (ASD).ObjectiveThis study systematically reviewed the efficacy, acceptability and tolerability of aripiprazole in treatment of ASD children and adolescents.Data sourcesElectronic search of databases including, Scopus, PubMed, CINAHL and Cochrane Controlled Trials Register was performed in July 2017.MethodsThe full-text versions of included trials were meticulously evaluated and extracted. The main efficacious outcomes consisted of pooled mean change scores of the standardized rating scales for ASD and the pooled response rate.ResultsA total of 408 randomized patients from eligible trials were included for synthesizing in this meta-analysis. The pooled mean change scores in aripiprazole-treated group for the Aberrant Behavior Checklist (ABC)-Irritability, ABC-Hyperactivity/noncompliance, ABC-Inappropriate speech and ABC-Stereotypic behavior were significantly greater than those of the placebo-treated group. Unfortunately, the significant difference between two groups was not found for ABC-Lethargy/social withdrawal. The overall pooled response rate of the aripiprazole-treated group was significantly higher than that of the placebo-treated group. The pooled overall discontinuation rate in aripiprazole-treated group was significantly better than that of placebo-treated group. The pooled discontinuation rates due to adverse events in aripiprazole-treated group significantly differed from the placebo-treated group (RR [95% CI] of 1.43 [0.65, 3.18], I2=0%).LimitationA small number of studies were gathered in this review.ConclusionAripiprazole has efficacy in the treatment of behavioral disturbances, including irritability, hyperactivity/noncompliance, inappropriate speech and stereotypic behavior found in ASD children and adolescents; however, it could not improve the lethargy/social withdrawal in such patients. The present evidence also indicates that it is safe, acceptable and tolerable in such treatment. As a small sample size, further well-defined and large sample size studies should be conducted to warrant those findings.

PMH40 - COST-MINIMISATION ANALYSIS OF SECOND GENERATION LONG ACTING INJECTABLES (RISPERIDONE , PALIPERIDONE, AND ARIPIPRAZOLE) FOR SCHIZOPHRENIA IN SPANISH MEDIUM-LONG TERM CARE PSYCHIATRIC UNITS

A cost-minimization analysis was performed from the perspective of the Spanish National Healthcare System (NHS) on second generation long acting antipsychotic injectables (LAI) in medium-long term care inpatient clinical wards from 15 different hospitals. The objective was to identify the most cost-saving LAI in clinical practice. Inclusion criteria were to have a diagnostic of schizophrenia spectrum disorder, to have a stable treatment for at least three months and hospital stay longer than five months. We evaluate the real dosing plan used with LAI in a previous multicentric, transversal and observational study. Afterwards we used a cost-minimization analysis to compare what LAI option is the most cost-saving option. We only consider drug treatment cost and administration cost, once hospitalization cost has none variation between options treatments in medium-long term psychiatric care units. Statistics test, ANOVA, was applied to compare the mean annual cost between the different LAI: Bonferroni-adjusted post hoc test was performed when necessary. We evaluated 371 patients dosing schedules that help very much to make a real economical evaluation: monthly aripiprazole treatment year cost is 4204 euros (n=80, SD: 240,9), monthly paliperidone is 6190 euros (n=168, SD: 2711,8), three months paliperidone is 5082,3 euros (n=61, SD:1852,5) and two weeks risperidone is 7067,8 euros (n=62, SD:2458,8). Monthly aripiprazole has a significant difference in cost when compared with monthly paliperidone (-1986 euros; p<0,0001), and two weeks risperidone (-2863 euros; p<0,0001) but the difference between three months paliperidone is not statistically significant (-878,2 euros; p=0,12). Three months paliperidone has a significant difference in cost when compared monthly paliperidone (-1107,8 euros; p=0,006) and risperidone (-1985,6 euros; p<0,0001). Monthly paliperidone versus risperidone (-877,8; p=0,049). Monthly aripiprazole is a cost-saving option to reduce economic burden of schizophrenia treatment in this group of patients followed by three months paliperidone.

State-dependent effects of the D2 partial agonist aripiprazole on dopamine neuron activity in the MAM neurodevelopmental model of schizophrenia.

Aripiprazole is an antipsychotic drug characterized by partial agonist activity at D2 receptors to normalize both hyperdopaminergic and hypodopaminergic states. Traditional D2 antagonist antipsychotic drugs have been shown previously to reduce dopamine neuron activity through action on D2 autoreceptors to produce an overexcitation-induced cessation of cell firing, referred to as depolarization block. It is unclear whether aripiprazole reduces dopamine neuron activity via inhibition or, as seen following D2 antagonist administration, depolarization block. The impact of acute and repeated aripiprazole treatment was examined in the methylazoxymethanol acetate (MAM) rodent model to observe its effects on a hyperdopaminergic system, compared to normal rats. We found that administration of aripiprazole acutely or after 1 or 7 days of withdrawal from 21-day repeated treatment led to a decrease in the number of spontaneously active dopamine neurons in MAM rats but not in controls. This reduction was not reversed by apomorphine (100-200 µg/kg i.p. or 20 µg/kg i.v.) administration, suggesting that it was not due to depolarization block. In contrast, 1 h after induction of depolarization block of dopamine neurons by acute haloperidol treatment (0.6 mg/kg i.p.), aripiprazole (1 mg/kg, i.p.) reversed the depolarization block state. Therefore, aripiprazole rapidly reduced the hyperdopaminergic activity selectively in MAM rats. The reduction is unlikely due to depolarization block and persists following 7-day withdrawal from repeated treatment. Aripiprazole also removes haloperidol-induced depolarization block in MAM rats, which may underlie the acute psychotic state often observed with switching to this treatment.

Real-world effectiveness and safety of aripiprazole augmentation therapy in patients with major depressive disorder

Aims: Augmentation therapy is an option for patients with major depressive disorder who do respond sufficiently to adequate dosages of selective serotonin reuptake inhibitors or serotonin–norepinephrine reuptake inhibitors, but little is known about application of this strategy in everyday practice.Methods: This prospective, multi-center, observational study investigated the effectiveness and safety of aripiprazole augmentation in Japanese patients with inadequate response to conventional antidepressant therapy in real-world clinical practice. The primary endpoint was mean change in the (Japanese version) Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to study end. Safety was assessed by monitoring adverse events.Results: There were 1103 patients in the safety population and 1090 patients in the effectiveness population. Mean change in the MADRS total score at study end was –14.9 ± 12.3 (p < .001 vs baseline). The remission rate increased from 34.5% at Month 6 to 43.3% at Month 12, suggesting additional benefit with continued treatment. The type of primary antidepressant (paroxetine, fluvoxamine, sertraline, milnacipran, duloxetine, mirtazapine, or escitalopram) had no influence on the effectiveness of aripiprazole augmentation therapy. A baseline MADRS total score of <33 points and an elapsed time of <176 days from an episode of depression to the start of aripiprazole treatment increased the likelihood of achieving remission; 24.8% of patients experienced at least one adverse event, but no new safety signals were identified.Conclusions: Aripiprazole augmentation therapy appears to be effective and safe in Japanese patients with depression/depressive symptoms treated in everyday clinical practice, taking into account factors associated with achieving remission.

The effects of brexpiprazole and aripiprazole on body weight as monotherapy in patients with schizophrenia and as adjunctive treatment in patients with major depressive disorder: an analysis of short-term and long-term studies.

The aim of this analysis was to explore the effects of brexpiprazole and aripiprazole on body weight when used as monotherapy to treat schizophrenia and as adjunctive treatment to antidepressant treatment (ADT) for major depressive disorder (MDD) in short-term (4/6 weeks) and long-term (≤52 weeks) studies. Body weight data were obtained from the clinical studies of each drug (brexpiprazole and aripiprazole), in schizophrenia and adjunctive treatment of MDD. Data were pooled and analyzed to assess the mean change in body weight and to determine the incidence of a clinically relevant change in body weight from baseline (≥7% increase or decrease, at any time) in each treatment group. The overall weight profiles for brexpiprazole and aripiprazole in the short-term and long-term treatment of schizophrenia, and MDD (adjunctive to ADT), were similar. In short-term schizophrenia studies, the mean weight increase was 1.2 kg for brexpiprazole and 0.6 kg for aripiprazole. In short-term MDD studies (adjunctive to ADT), the mean weight increase was 1.5 kg for brexpiprazole and 1.6 kg for aripiprazole. In the long-term schizophrenia studies, at week 52, the mean weight increase was 2.1 kg for brexpiprazole and 3.0 kg for aripiprazole. In long-term MDD studies (adjunctive to ADT), at week 52, the mean weight increase was 3.2 kg for brexpiprazole and 4.0 kg for aripiprazole. Clinically relevant increases or decreases in body weight were also similar for brexpiprazole and aripiprazole. Overall, in the treatment of schizophrenia, and in adjunctive treatment of MDD, brexpiprazole and aripiprazole have a similar effect on body weight over the course of 1 year.

Notes on Use of the Odds Ratio under the Sequential Parallel Comparison Design with Binary Outcomes

ABSTRACTWhen the patient response is dichotomous, the effects due to a treatment and other covariates are often not additive. Thus, the risk difference (RD) may vary between phases in the sequential parallel comparison design (SPCD). The weighted average of RD's over two phases in these cases is not a meaningful summary measure of the treatment effect. Since it is more common to encounter the binary data in which the treatment and other covariates effects are additive on the logit scale, we advocate use of the odds ratio (OR) to measure the treatment effect. Under the homogeneity assumption of OR, we show that the weighted-least-squares method can be easily employed to derive both point and interval estimators for the OR under the SPCD. When the OR varies between phases, we note that Woolf logit interval estimator can be applied to estimate the OR for each phase separately. We apply Monte Carlo simulation to evaluate the performance of these estimators in a variety of situations under the SPCD. We use the placebo-controlled trial employing the SPCD to assess the efficacy of a low dose of aripiprazole in treatment of patients with major depressive disorder to illustrate the use of estimators developed here.

COMT Val 108/158 Met polymorphism and treatment response to aripiprazole in patients with acute schizophrenia.

IntroductionThe COMT Val 108/158 Met polymorphism (rs4680) may affect treatment response to antipsychotics, as well as metabolism and dynamics of neurotransmitters during the treatment of schizophrenia. We investigated the effects of the COMT Val 108/158 Met polymorphism on treatment response to aripiprazole and plasma monoamine metabolite levels in patients with acute schizophrenia.Materials and methodsForty patients with schizophrenia were treated with aripiprazole for 6 weeks. We measured Positive and Negative Syndrome Scale (PANSS) and plasma levels of homovanillic acid (HVA) and plasma MHPG (3-methoxy-4-hydroxyphenethyleneglycol) at baseline and endpoint. The COMT Val 108/158 Met polymorphism was genotyped with the polymerase chain reaction and restriction fragment length polymorphism.ResultsThere were significant genotype–time interactions on PANSS total and general psychopathology scores, with Met/Met genotype showing greater improvement. The response rate to aripiprazole did not differ between COMT Val 108/158 Met genotype groups. We found a significant time effect on plasma MHPG levels, but no time effect on plasma HVA levels or time–genotype interactions in the plasma levels of HVA and MHPG. Although the responder rate did not differ among the 3 genotype groups.ConclusionOur results suggest that individuals with the Met/Met genotype had greater improvement in PANSS score after the treatment with aripiprazole. On the other hand, the Val 108/158 Met polymorphism may not induce changes in plasma levels of monoamine metabolites during aripiprazole treatment. Because of the small sample size, further studies are needed to confirm and to extend our results.