Aripiprazole Treatment Research Articles

Oral and Long-acting Injectable Aripiprazole in Severe Mental Illness and Substance Use Disorder Comorbidity: An Updated Systematic Review.

Co-occurrence of substance use disorders is frequent in patients with mental health disorders is a condition known as "dual diagnosis". The use of substances worsens the prognosis and lowers the quality of life of psychiatric patients. It also increases the risk of hospitalization and suicide rate. To assess the effects of aripiprazole therapy on substance use and other psychiatric outcomes in dually diagnosed patients. We performed a systematic review conducted on 3 databases PUBMED, SCOPUS, and Web of Science, selecting original studies and analyzing the impact of aripiprazole therapy on dually diagnosed patients. Six hundred and fifty-five articles were founded and, after removing duplicates (n = 274) and applying the exclusion criteria, 12 articles were included in our systematic review. 12 studies were included, among which 6 were Randomized Controlled Trials. The Most frequent psychiatric diagnosis were schizoaffective disorders, schizophrenia, and bipolar disorders. Alcohol and cocaine use disorders were the most used substances. Eleven studies showed a clinical improvement after aripiprazole treatment. 8 studies evaluated craving and found a significant reduction after treatment with aripiprazole. No definitive conclusions can be drawn on substance usage and maintenance of abstinence. The present findings suggest aripiprazole may be associated with reducing substance craving and improving depression, psychosis, and schizoaffective disorders in dually diagnosed patients.

Aripiprazole dose associations with metabolic adverse effect: Results from a longitudinal study

ObjectiveWeight gain, blood lipids and/or glucose dysregulation can follow aripiprazole treatment onset. Whether aripiprazole dosage is associated with an increase in these metabolic parameters remains uncertain. The present study investigates aripiprazole dose associations with weight change, blood glucose, lipids, and blood pressure. Methods422 patients taking aripiprazole for a minimum of three weeks to one year were selected from PsyMetab and PsyClin cohorts. Associations between aripiprazole dose and metabolic outcomes were examined using linear mixed-effect models. ResultsAripiprazole dose was associated with weight change when considering its interaction with treatment duration (interaction term: −0.10, p < 0.001). This interaction resulted in greater weight gain for high versus low doses at the beginning of the treatment, this result being overturned at approximately five months, with greater weight increase for low versus high doses thereafter. LDL and HDL cholesterol levels were associated with aripiprazole dose over five months independently of treatment duration, with an average of 0.06 and 0.02 mmol/l increase for each 5 mg increment, respectively (p = 0.033 and p = 0.016, respectively). Furthermore, mean dose increases were associated with greater odds (+30 % per 5 mg increase) of clinically relevant weight gain (i.e., ≥7 %) over one year (p = 0.025). ConclusionAripiprazole dose was associated with one-year weight changes when considering its interaction with treatment duration. Increasing its dose could lead to metabolic worsening over the first five months of treatment, during which minimum effective doses should be particularly preferred.

Integrative Genetic Variation, DNA Methylation, and Gene Expression Analysis of Escitalopram and Aripiprazole Treatment Outcomes in Depression: A CAN-BIND-1 Study.

Little is known about the interplay between genetics and epigenetics on antidepressant treatment (1) response and remission, (2) side effects, and (3) serum levels. This study explored the relationship among single nucleotide polymorphisms (SNPs), DNA methylation (DNAm), and mRNA levels of four pharmacokinetic genes, CYP2C19, CYP2D6, CYP3A4, and ABCB1, and its effect on these outcomes. The Canadian Biomarker Integration Network for Depression-1 dataset consisted of 177 individuals with major depressive disorder treated for 8 weeks with escitalopram (ESC) followed by 8 weeks with ESC monotherapy or augmentation with aripiprazole. DNAm quantitative trait loci (mQTL), identified by SNP-CpG associations between 20 SNPs and 60 CpG sites in whole blood, were tested for associations with our outcomes, followed by causal inference tests (CITs) to identify methylation-mediated genetic effects. Eleven cis-SNP-CpG pairs (q<0.05) constituting four unique SNPs were identified. Although no significant associations were observed between mQTLs and response/remission, CYP2C19 rs4244285 was associated with treatment-related weight gain (q=0.027) and serum concentrations of ESCadj (q<0.001). Between weeks 2-4, 6.7% and 14.9% of those with *1/*1 (normal metabolizers) and *1/*2 (intermediate metabolizers) genotypes, respectively, reported ≥2 lbs of weight gain. In contrast, the *2/*2 genotype (poor metabolizers) did not report weight gain during this period and demonstrated the highest ESCadj concentrations. CITs did not indicate that these effects were epigenetically mediated. These results elucidate functional mechanisms underlying the established associations between CYP2C19 rs4244285 and ESC pharmacokinetics. This mQTL SNP as a marker for antidepressant-related weight gain needs to be further explored.

Prenatal Immune Challenge Differentiates the Effect of Aripiprazole and Risperidone on CD200-CD200R and CX3CL1-CX3CR1 Dyads and Microglial Polarization: A Study in Organotypic Cortical Cultures.

Microglia are the primary innate immune cells of the central nervous system and extensively contribute to brain homeostasis. Dysfunctional or excessive activity of microglia may be associated with several neuropsychiatric disorders, including schizophrenia. Therefore, we examined whether aripiprazole and risperidone could influence the expression of the Cd200-Cd200r and Cx3cl1-Cx3cr1 axes, which are crucial for the regulation of microglial activity and interactions of these cells with neurons. Additionally, we evaluated the impact of these drugs on microglial pro- and anti-inflammatory markers (Cd40, Il-1β, Il-6, Cebpb, Cd206, Arg1, Il-10 and Tgf-β) and cytokine release (IL-6, IL-10). The research was executed in organotypic cortical cultures (OCCs) prepared from the offspring of control rats (control OCCs) or those exposed to maternal immune activation (MIA OCCs), which allows for the exploration of schizophrenia-like disturbances in animals. All experiments were performed under basal conditions and after additional stimulation with lipopolysaccharide (LPS), following the "two-hit" hypothesis of schizophrenia. We found that MIA diminished the mRNA level of Cd200r and affected the OCCs' response to additional LPS exposure in terms of this parameter. LPS downregulated the Cx3cr1 expression and profoundly changed the mRNA levels of pro- and anti-inflammatory microglial markers in both types of OCCs. Risperidone increased Cd200 expression in MIA OCCs, while aripiprazole treatment elevated the gene levels of the Cx3cl1-Cx3cr1 dyad in control OCCs. The antipsychotics limited the LPS-generated increase in the expression of proinflammatory factors (Il-1β and Il-6) and enhanced the mRNA levels of anti-inflammatory components (Cd206 and Tgf-β) of microglial polarization, mostly in the absence of the MIA procedure. Finally, we observed a more pronounced modulating impact of aripiprazole on the expression of pro- and anti-inflammatory cytokines when compared to risperidone in MIA OCCs. In conclusion, our data suggest that MIA might influence microglial activation and crosstalk of microglial cells with neurons, whereas aripiprazole and risperidone could beneficially affect these changes in OCCs.

Examining the Use of Oral Aripiprazole in Patients With Autism Spectrum Disorder: A Study of Retrospective Chart Review at a University Medical Center.

The purpose of this study was to examine the patterns of use of oral aripiprazole treatment in children and adolescents diagnosed with autism spectrum disorder (ASD) at a university medical center in Korea. We retrospectively reviewed the medical records of 164 outpatient children and adolescents diagnosed with ASD by child and adolescent psychiatrists. Patient demographic characteristics, clinical features, age and dose of aripiprazole treatment, associated adverse events, and concomitant medications, etc. were evaluated. Aripiprazole treatment was initiated at a mean age of 7.64 years, at a mean initial dose of 1.15 mg. Methylphenidate was often co-administered with aripiprazole. The most commonly reported adverse effects were increased appetite and weight gain, which in some cases led to discontinuation of medication. A follow-up study is warranted to evaluate the efficacy and safety of aripiprazole treatment in Korean children and adolescents diagnosed with ASD, and it is crucial to consider their clinical characteristics and response to treatment in the evaluation.

Cardiovascular risk associated with chronic treatment of paliperidone, olanzapine, risperidone and aripiprazole

IntroductionWeight gain, QT interval prolongation, and dyslipidemias associated with the chronic use of some antipsychotic medications can explain a higher prevalence of cardiovascular risk in these psychiatric population. The D’Agostino Index include some factors such as age, total cholesterol, high-density lipoproteins, systolic blood pressure increased, antihypertensive treatment, smoking, and diabetes, to estimate an individual’s risk (low, moderate or severe) of developing a cardiovascular event through a period of 10 years or throughout the patient’s lifetime.ObjectivesTo compare the degree of cardiovascular risk using the D’Agostino Index, among different antipsychotic medications.MethodsAn estimation of cardiovascular risk (low, moderate, or high) was performed with the D´Agostino index in a sample of 144 patients (82 men and 62 women) mean age 45,2 +/- 10.13. All patients were treated for at least one year at a therapeutic dose and adhered to their treatment regimen correctly. Subjects with some relevant pre-existing unstable heart disease were excluded. All patients previously provided informed consent and were of legal age. Clinical data on medical history, concomitant medications, and risk factors were collected. A completed physical exam, waist circumference, lab sample, a lifestyle scale, and an evaluation of vital signs in accordance with European Society of Hypertension were evaluated. Statistical analysis was carried out using the statistical software SPSS version 26.0. A significance level α=0.05 was considered throughout the study.ResultsThe four most consumed antipsychotics were risperidone 9.72% (n=14), paliperidone 25.7% (n=37), olanzapine 14.6% (n=21), and aripiprazole 34.7% (n=50). Descriptively, it was observed that the drugs most associated with moderate or high risks were paliperidone (37.8%) and olanzapine (33.3%), risperidone (28.6 %). Aripiprazol (22%) was the less associated compound with moderate/high cardiovascular risk.ConclusionsSubjects treated with olanzapine and paliperidone showed a higher association with cardiovascular risk. Predicting cardiovascular risk could provide individual benefits by enabling lifestyle modifications, pharmacological treatment changes, or closer monitoring to reduce cardiovascular risk.Disclosure of InterestA. Montejo Grant / Research support from: This study has been funded by the Instituto de Salud Carlos III (ISCIII) through the project PI19/1596 and co-funded by the European Union., C. Bermejo: None Declared, J. Matías: None Declared, T. Martín: None Declared, J. Matías-Polo: None Declared, Y. Santana: None Declared, J. López-López: None Declared, R. de Alarcón: None Declared, J. Acosta: None Declared

Functional neuroimaging biomarkers of anhedonia response to escitalopram plus adjunct aripiprazole treatment for major depressive disorder.

Identifying neuroimaging biomarkers of antidepressant response may help guide treatment decisions and advance precision medicine. To examine the relationship between anhedonia and functional neurocircuitry in key reward processing brain regions in people with major depressive disorder receiving aripiprazole adjunct therapy with escitalopram. Data were collected as part of the CAN-BIND-1 study. Participants experiencing a current major depressive episode received escitalopram for 8 weeks; escitalopram non-responders received adjunct aripiprazole for an additional 8 weeks. Functional magnetic resonance imaging (on weeks 0 and 8) and clinical assessment of anhedonia (on weeks 0, 8 and 16) were completed. Seed-based correlational analysis was employed to examine the relationship between baseline resting-state functional connectivity (rsFC), using the nucleus accumbens (NAc) and anterior cingulate cortex (ACC) as key regions of interest, and change in anhedonia severity after adjunct aripiprazole. Anhedonia severity significantly improved after treatment with adjunct aripiprazole.There was a positive correlation between anhedonia improvement and rsFC between the ACC and posterior cingulate cortex, ACC and posterior praecuneus, and NAc and posterior praecuneus. There was a negative correlation between anhedonia improvement and rsFC between the ACC and anterior praecuneus and NAc and anterior praecuneus. Eight weeks of aripiprazole, adjunct to escitalopram, was associated with improved anhedonia symptoms. Changes in functional connectivity between key reward regions were associated with anhedonia improvement, suggesting aripiprazole may be an effective treatment for individuals experiencing reward-related deficits. Future studies are required to replicate our findings and explore their generalisability, using other agents with partial dopamine (D2) agonism and/or serotonin (5-HT2A) antagonism.

Effects of aripiprazole on prolactin levels and differences in effectiveness in patients with schizophrenia: a post-hoc analysis of the real-world data of a multicenter study.

To investigate the effect of aripiprazole on prolactin levels in patients with schizophrenia and analyze whether varying baseline prolactin levels affect the effectiveness and safety of aripiprazole, in a real-life diagnostic and therapeutic setting in a post-hoc analysis. In this post-hoc analysis, patients with schizophrenia in the acute phase were divided into an elevated-prolactin group and a normal-prolactin group. After 8 weeks of aripiprazole treatment, changes in the proportion of patients with an abnormal prolactin level were analyzed in both groups, and the efficacy and safety of aripiprazole were compared between the two groups. The elevated-prolactin group had more women, a longer duration of disease, and lower Positive and Negative Syndrome Scale (PANSS) total and subscale scores at baseline compared with the normal-prolactin group (all P < 0.05), and there was no significant difference in the proportion of patients with prior use of antipsychotic medication between the two groups. Regardless of previous antipsychotic use, patients in both groups developed hyperprolactinemia (23/168 [13.7%] in those who had taken antipsychotics vs. 43/375 [11.4%] in those who had not). After 8 weeks of aripiprazole treatment, the proportion of patients with abnormal prolactin in the elevated-prolactin group significantly decreased with prolonged treatment (P < 0.001), and aripiprazole had no significant effect on the normal-prolactin group (P = 0.250). Normal-prolactin group showed better efficacy than the elevated-prolactin group, and the differences in efficacy between the two groups was observed from week 4 to the endpoint (all p<0.05). In total, 87.2% (68/78) patients experienced mild to moderate adverse events in the elevated-prolactin group, which was significantly more frequent compared with the normal-prolactin group 71.0% (365/514). In this real-world study, for patients with acute schizophrenia, aripiprazole was effective in lowering the proportion of patients with abnormal prolactin levels, while it had no significant effect on patients with normal baseline prolactin. After adjusting for factors such as sex, age, prior antipsychotic drugs use history and disease severity, effectiveness and safety of aripiprazole in patients with normal baseline prolactin was significantly better than that in patients with elevated baseline prolactin.

Therapeutic Dosage of Antipsychotic Drug Aripiprazole Induces Persistent Mitochondrial Hyperpolarisation, Moderate Oxidative Stress in Liver Cells, and Haemolysis.

Aripiprazole has fewer metabolic side effects than other antipsychotics; however, there are some severe ones in the liver, leading to drug-induced liver injury. Repeated treatment with aripiprazole affects cell division. Since this process requires a lot of energy, we decided to investigate the impact of aripiprazole on rat liver cells and mitochondria as the main source of cellular energy production by measuring the mitochondrial membrane potential, respiration, adenosine triphosphate (ATP) production, oxidative stress, antioxidative response, and human blood haemolysis. Here, we report that mitochondrial hyperpolarisation from aripiprazole treatment is accompanied by higher reactive oxygen species (ROS) production and increased antioxidative response. Lower mitochondrial and increased glycolytic ATP synthesis demand more glucose through glycolysis for equal ATP production and may change the partition between the glycolysis and pentose phosphate pathway in the liver. The uniform low amounts of the haemolysis of erythrocytes in the presence of aripiprazole in 25 individuals indicate lower quantities of the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH+H+), which is in accordance with a decreased activity of glucose 6-phosphate dehydrogenase and the lower dehydrogenase activity upon aripiprazole treatment. The lower activity of glucose 6-phosphate dehydrogenase supports a shift to glycolysis, thus rescuing the decreased mitochondrial ATP synthesis. The putative reduction in NADPH+H+ did not seem to affect the oxidised-to-reduced glutathione ratio, as it remained equal to that in the untreated cells. The effect of aripiprazole on glutathione reduction is likely through direct binding, thus reducing its total amount. As a consequence, the low haemolysis of human erythrocytes was observed. Aripiprazole causes moderate perturbations in metabolism, possibly with one defect rescuing the other. The result of the increased antioxidant enzyme activity upon treatment with aripiprazole is increased resilience to oxidative stress, which makes it an effective drug for schizophrenia in which oxidative stress is constantly present because of disease and treatment.

Comparative effectiveness of aripiprazole and olanzapine on neurocognitive profile of patients with schizophrenia.

Schizophrenia causes significant neurocognitive impairment. Treatment with antipsychotics leads to improvement in psychopathology and neurocognitive functions. To see comparative effectiveness of aripiprazole and olanzapine on neurocognitive profile of patients with schizophrenia. This was a comparative, prospective, and interventional study. Patients with schizophrenia as per the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), were assessed on Brief Psychiatric Rating Scale (BPRS), Positive and Negative Syndrome Scale (PANSS), and neuropsychological tests at baseline. Patients were randomly assigned to aripiprazole (10-30 mg per day, orally) and olanzapine (5-20 mg per day, orally) groups on the basis of computer-generated random table number. Patients were reassessed at 10 weeks. A total of 40 patients completed the study duration of 10 weeks. At baseline, the majority of patients showed significant impairment in one or more domains of neurocognition. Both aripiprazole and olanzapine led to improvement in psychiatric symptoms as well as neurocognitive profile. Aripiprazole treatment leads to significant improvement in mental speed as compared to olanzapine. A highly significant decrease in the value of the Stroop effect indicates improvement (P = 0.000**) with aripiprazole and visual-spatial constructive ability (P < 0.001). The olanzapine group showed highly significant improvement in performance of category fluency (P < 0.01) and verbal fluency (P < 0.01). The study concludes that aripiprazole and olanzapine have strong potential to improve specific domains of neurocognitive profile.

Aripiprazole disrupts cellular synchrony in the suprachiasmatic nucleus and enhances entrainment to environmental light-dark cycles in mice.

Many patients with psychiatric conditions, such as bipolar disorder and major depressive disorder, frequently experience disruptions in their sleep-wake cycles. Several case studies and clinical trials have shown that the administration of aripiprazole, a commonly prescribed antipsychotic drug, alleviates the symptoms of circadian sleep disorders in these patients. This improvement may be attributed to the effects of aripiprazole on the circadian central clock, specifically the hypothalamic suprachiasmatic nucleus (SCN), which regulates various circadian physiological rhythms, including the sleep-wake cycle, in mammals. To examine whether aripiprazole facilitates adaptation to changes in the light-dark cycle, we orally administered aripiprazole to mice and subjected them to jet-lag experiments. Mice receiving aripiprazole were more rapidly entrained to 6 h advanced light-dark cycles. Moreover, we examined the effect of aripiprazole on the cellular rhythms of SCN slice cultures and found that aripiprazole disrupted cellular synchronization in the SCN, thereby accelerating the damping of the SCN rhythm at the population level. Adenosine 3'5' monophosphate (cAMP) assay using a bioluminescence indicator revealed that intracellular cAMP level in the SCN increased following aripiprazole treatment. However, this increase was blocked by pre-treatment with the serotonin 1A receptor (5-HT1AR) antagonist. Based on these findings, we propose that aripiprazole modulates intracellular signaling, including 5-HT1AR-mediated cAMP signaling, and desynchronizes SCN neurons, ultimately leading to enhanced entrainment to phase advanced light-dark cycles in mice. These findings indicate that the improvement in sleep symptoms reported in patients with psychiatric disorders receiving aripiprazole may be due to modulation of the circadian clock. Our study provides novel insights into the potential clinical applications of aripiprazole in patients with various circadian sleep disorders.

Dynamics of mental state and prolactin levels in patients with chronic schizophrenia during aripiprazole therapy

Introduction. Although scientific literature demonstrates a relationship between prolactin levels, the efficacy of aripiprazole therapy, and negative symptoms in patients with schizophrenia, many questions regarding these problems remain controversial.Objective to study dynamics of clinical and hormonal parameters in patients with chronic schizophrenia during aripiprazole therapy.Materials and methods: 60 patients with schizophrenia were studied: 42 male (70%) and 18 female (30%), aged 20 to 65 years (mean age 52.84±17.40 years) on inpatient aripiprazole treatment with the mean daily dosage of 15.33±4.52 mg. Comparative analysis of prolactin parameters was carried out taking into account the following factors: effectiveness of therapy, age, duration of the disease, severity of negative symptoms (according to the PANSS scores). Responders included patients with a reduction in total PANSS score of 20% and more.Results: the effectiveness of aripiprazole monotherapy after switching from previous antipsychotic treatment in patients with chronic schizophrenia was noted in 71.7% of patients. The effectiveness of therapy does not depend on the background values of the hormone: at high rates, prolactin levels decrease, and at low rates, they increase. Meanwhile, a certain pattern was revealed between the dynamics of scores of the negative PANSS scale and the level of prolactin: responders with high background levels showed the decrease of prolactin levels given the decline of the PANSS scores, and in responders with low values, the hormone levels increased. In non-responders, low background scores of the negative scale and their slight changes during therapy were accompanied by an increase in prolactin levels. The data obtained in relation to non-responder patients who showed negative correlations between the levels of prolactin, age, dosage of the drug and the duration of the disease require a more careful attitude to the appointment of aripiprazole due to the likelihood of a decrease in their prolactin levels to abnormally low values.

Comparison between olanzapine and aripiprazole treatment for 104weeks after hospital discharge in schizophrenia spectrum disorders: a multicenter retrospective cohort study in a real-world setting.

The long-term effectiveness of olanzapine and aripiprazole in real clinical conditions at flexible doses in patients after hospital discharge has not been evaluated yet. This study was a multicenter retrospective cohort study. Patients with schizophrenia (n = 398) were prescribed olanzapine (n = 303) or aripiprazole (n = 95) at hospital discharge. The continuation of olanzapine or aripiprazole at 26, 52, or 104weeks after the hospital discharge were compared using a Cox proportional hazards model and adjusted for possible confounders. The Kaplan-Meier survival curves revealed that the continuation of olanzapine at 26 (P = 0.001) and 52weeks (P = 0.018) was significantly higher than that of aripiprazole but not at 104weeks. Olanzapine was better than aripiprazole in efficacy at 26 (hazard ratio: 0.321, 95% confidence interval: 0.159-0.645, P = 0.001), 52 (hazard ratio: 0.405, 95% confidence interval: 0.209-0.786, P = 0.008), and 104weeks (hazard ratio: 0.438, 95% confidence interval: 0.246-0.780, P = 0.005). Aripiprazole was better than olanzapine in tolerability at 104weeks (hazard ratio: 4.574, 95% confidence interval: 1.415-14.787, P = 0.011). Rates after two years continuation of olanzapine and aripiprazole were not significantly different in patients with less than five years' duration of illness, but olanzapine was more commonly maintained for more than two years in those patients who had been ill for over five years' due to its greater efficacy. Olanzapine treatment showed better continuation rates at 26 and 52 after hospital discharge than aripiprazole, whereas maintenance with the two antipsychotics did not differ significantly at 104weeks, due reduced tolerability of long-term olanzapine treatment.

Efficacy of transcutaneous electrical acupoint stimulation for patients with first-episode schizophrenia: An 8-week, preliminary, randomized controlled trial

Combination therapy with antipsychotics has been investigated for treating schizophrenia, and has shown clear advantages among non-invasive therapies. Transcutaneous electrical acupoint stimulation (TEAS) is a novel non-invasive treatment with definite efficacy in treating mental disorders. The current study aimed to investigate the efficacy of TEAS in further improving the psychotic symptoms in patients with first-episode schizophrenia (FES) being treated with pharmacological drugs.This 8-week, preliminary, sham-controlled, randomized clinical trial was conducted in patients with FES to compare the efficacy of TEAS and sham TEAS in combination with aripiprazole treatment. The primary outcome was a change in the Positive and Negative Syndrome Scale (PANSS) score after ending the intervention (Week 8).A total of 49 participants completed the whole treatment cycle. The linear mixed-effects regression for PANSS indicated a significant time × group interaction (F(2, 116)=9.79, p <0.001). The PANSS score differed by 8.77 points (95% CI, -2.07 to -15.47 points; p=.01) between the TEAS group and the sham TEAS group after 8 weeks of treatment; this difference was significant.This study indicates that 8 weeks of TEAS combined with aripiprazole treatment can effectively treat FES. Thus, TEAS is an effective combination therapy to improve the psychiatric symptoms of FES.

Evidence of the Dysbiotic Effect of Psychotropics on Gut Microbiota and Capacity of Probiotics to Alleviate Related Dysbiosis in a Model of the Human Colon.

Growing evidence indicates that non-antibiotic therapeutics significantly impact human health by modulating gut microbiome composition and metabolism. In this study, we investigated the impact of two psychotropic drugs, aripiprazole and (S)-citalopram, on gut microbiome composition and its metabolic activity, as well as the potential of probiotics to attenuate related dysbiosis using an ex vivo model of the human colon. After 48 h of fermentation, the two psychotropics demonstrated distinct modulatory effects on the gut microbiome. Aripiprazole, at the phylum level, significantly decreased the relative abundances of Firmicutes and Actinobacteria, while increasing the proportion of Proteobacteria. Moreover, the families Lachnospiraceae, Lactobacillaceae, and Erysipelotrichaceae were also reduced by aripiprazole treatment compared to the control group. In addition, aripiprazole lowered the levels of butyrate, propionate, and acetate, as measured by gas chromatography (GC). On the other hand, (S)-citalopram increased the alpha diversity of microbial taxa, with no differences observed between groups at the family and genus level. Furthermore, a probiotic combination of Lacticaseibacillus rhamnosus HA-114 and Bifidobacterium longum R0175 alleviated gut microbiome alterations and increased the production of short-chain fatty acids to a similar level as the control. These findings provide compelling evidence that psychotropics modulate the composition and function of the gut microbiome, while the probiotic can mitigate related dysbiosis.

LAMOTRIGINE INDUCED LEUCOPENIA IN A PATIENT WITH TYPE 2 BIPOLAR DISEASE

IntroductionLamotrigine(LTG) is a widely used medication for bipolar disorder(BD) maintenance treatment, bipolar depression, epilepsy, trigeminal neuralgia.1The well-known common side effects of LTG are rash,fatigue, gastrointestinal symptoms,dizziness,headache,insomnia.2While one of the most refrained side effects of LTG is Steven Johnson’s syndrome, there have been reports of blood dyscrasia,such as agranulocytosis, neutropenia, pancytopenia.3,4Unfortunately, the exact mechanism of the blood dyscrasias isn’t fully explained.Here we report a case of LTG-induced leucopenia in a patient with BD type 2 patient.We obtained the patient’s consent.ObjectivesWe report a case of a 56-year-old female patient, brought to the emergency unit with complaints of feeling unhappy, hopeless,having trouble sleeping and suicidal thoughts for two months.She attempted suicide a few days ago,had multiple suicide attempts in the last two years.She had 3 psychiatric hospitalizations due to depressive episodes and 1 hypomanic episode.Her mood was depressed.She had psychomotor retardation,no psychotic feature.Due to active suicidal ideation,we admitted her to the inpatient unit with the diagnosis of BD type 2.Routine blood tests were within the normal range.We increased quetiapine XR 300 mg and venlafaxine 300 mg,which she had already taken;discontinued her aripiprazole treatment and added LTG 25 mg/d. 8 after initiation of LTG,there was a decrease in white blood coun(WBC) from a baseline level of 5.18x109/L to 3x109/L,while neutrophil count decreased from 3.8x109/L to 1.15x109/L in 12 days.Her medical records showed no sign of leucopenia.No pathology was detected in the peripheral smear or ultrasonography performed with the haematology consultation.Considering leucopenia might be an adverse drug reaction associated with LTG, we discontinued LTG treatment on the 9th day of administration. 9 days after discontinuation WBC was up to 4.22x109/L,neutrophil count was 2.78x109/L. We started valproate 500 mg/d and on the 27th day of her stay, she was discharged with a euthymic mood, having no depressive symptoms or suicidal thoughts.Her last treatment was venlafaxine 225 mg, quetiapine XR 300 mg, quetiapine IR 100 mg, valproate 500 mg, lorazepam 1 mg daily.MethodsIt is a retrospective review.ResultsIn this LTG naive patient,the WBC values were within the normal range at admission.There was a significant temporal relationship between the initiation of the LTG and the decrease in WBC values.The absence of other factors in the laboratory tests and examinations,the rapid increase of WBC levels after the LTG was discontinued suggests the observed effect may be a side effect of LTG.ConclusionsBlood dyscrasies aren’t a very common side effect of LTG, but it might be helpful to see CBC, especially in older populations, on patients with polypharmacy regimens and with severe mental illness that may interfere with patient’s ability to express any subtle side effect.Disclosure of InterestNone Declared

Long-acting new generation antipsychotics in the maintenance treatment of bipolar disorders

IntroductionMaintaining remission, preventing from future episodes, better treatment adherence and improving the quality of life are main aims of long-term treatment in bipolar disorders (BD). In recent years, new generation long-acting injectable (LAI) antipsychotics have been frequently used in maintenance treatment for bipolar disorders.ObjectivesWe aimed to review socio-demographic and clinical characteristics of bipolar patients taking LAI treatment for maintenance treatment.MethodsClinical records of 56 bipolar patients who are on LAI treatment and followed in Mazhar Osman Mood Clinic (MOMC) of Selcuk University Medical Faculty were evaluated. Descriptive statistical analysis was performed with Statistical Package for the Social Sciences (SPSS).ResultsNearly half of the patients were male (n:29, 52%). 49,1% of the patients were married. The mean age was 37.1±12.2 years and the mean duration of education was 11.1±4.2 years. All of the patients were diagnosed with bipolar 1 disorder. Most of the patients (64,7%) was on aripiprazole LAI while remaining was receiving paliperidone LAI for maintenance treatment. We found a significant reduction in the number of manic episodes after long-acting treatment (p&lt;0.001), but we could not find any difference for depression. Ten of the patients discontinued the treatment due to the side effects, extrapyramidal side effects were the most common side effects. Eight of the patients were switched from paliperidone treatment to aripiprazole treatment due to side effects, especially hyperprolactinemia. Relapse was observed in 46,4% of the patients and there was no difference between aripiprazole and paliperidone in terms of relapse rate.ConclusionsLAI new generation antipsychotics are taking place in long-term treatment of bipolar disorder via improving treatment adherence. Side effect profile of aripiprazole and paliperidone are different. However, we could not find any difference between two drugs in terms of side effects and relapse rates. Small sample size and shorter duration of follow-up should be considered as limitations.Disclosure of InterestNone Declared

The Sapap3−/− mouse reconsidered as a comorbid model expressing a spectrum of pathological repetitive behaviours

Symptom comorbidity is present amongst neuropsychiatric disorders with repetitive behaviours, complicating clinical diagnosis and impeding appropriate treatments. This is of particular importance for obsessive-compulsive disorder (OCD) and Tourette syndrome. Here, we meticulously analysed the behaviour of Sapap3 knockout mice, the recent rodent model predominantly used to study compulsive-like behaviours, and found that its behaviour is more complex than originally and persistently described. Indeed, we detected previously unreported elements of distinct pathologically repetitive behaviours, which do not form part of rodent syntactic cephalo-caudal self-grooming. These repetitive behaviours include sudden, rapid body and head/body twitches, resembling tic-like movements. We also observed that another type of repetitive behaviour, aberrant hindpaw scratching, might be responsible for the flagship-like skin lesions of this mouse model. In order to characterise the symptomatological nature of observed repetitive behaviours, we pharmacologically challenged these phenotypes by systemic aripiprazole administration, a first-line treatment for tic-like symptoms in Tourette syndrome and trichotillomania. A single treatment of aripiprazole significantly reduced the number of head/body twitches, scratching, and single-phase grooming, but not syntactic grooming events. These observations are in line with the high comorbidity of tic- and compulsive-like symptoms in Tourette, OCD and trichotillomania patients.

The effect of therapeutic drug monitoring of risperidone and aripiprazole on weight gain in children and adolescents: the SPACe 2: STAR (trial) protocol of an international multicentre randomised controlled trial

BackgroundAntipsychotic drugs are an important part of the treatment of irritability and aggression in children with an autism spectrum disorder (ASD). However, significant weight gain and metabolic disturbances are clinically relevant side effects of antipsychotic use in children. In the SPACe study, we showed positive correlations between both risperidone and aripiprazole plasma trough concentrations and weight gain over a 6-month period. The trial SPACe 2: STAR is designed as a follow-up study, in which we aim to research whether therapeutic drug monitoring in clinical practice can prevent severe weight gain, while retaining clinical effectiveness.MethodsSPACe 2: STAR is an international, multicentre, randomised controlled trial (RCT). One hundred forty children aged 6 to 18 who are about to start risperidone or aripiprazole treatment for ASD related behavioural problems will be randomised into one of two groups: a therapeutic drug monitoring (TDM) group, and a care as usual (CAU) group. Participants will be assessed at baseline and 4, 10, 24, and 52 weeks follow-up. In the TDM group, physicians will receive dosing advice based on plasma levels of risperidone and aripiprazole and its metabolites at 4 and 10 weeks. Plasma levels will be measured in dried blood spots (DBS). The primary outcome will be BMI z-score at 24 weeks after start of antipsychotic treatment. Among the secondary outcomes are effectiveness, metabolic laboratory measurements, levels of prolactin, leptin and ghrelin, extrapyramidal side effects, and quality of life.DiscussionThis will be the first RCT evaluating the effect of TDM of antipsychotic drugs in children and adolescents. Thus, findings from SPACe 2: STAR will be of great value in optimising treatment in this vulnerable population.Trial registrationClinicalTrials.gov Identifier: NCT05146245. EudraCT number: 2020–005450-18. Sponsor protocol name: SPACe2STAR. Registered 8 June 2021. Protocol Version 6, Protocol date: 18 august 2022.

Hemispheric lateralization of semantic processing before and after aripiprazole treatment in first-episode psychosis or ultra-high risk state

Whether aberrant language-related lateralization can be improved after antipsychotic treatment in drug-free patients with first-episode psychosis or ultra-high risk state is little known. We aimed to investigate the improvement in lateralization of semantic processing after antipsychotic treatment and associated clinical and cognitive changes. Twenty-one drug-free patients with first-episode psychosis or ultra-high risk state underwent functional magnetic resonance imaging with a semantic task, neuropsychological testing, and clinical assessments with the Positive and Negative Syndrome Scale before and after 6 weeks of aripiprazole treatment. A lateralization index of the region of interest, i.e., inferior frontal gyrus, was calculated and correlated with the behavioral indices of the semantic task, Positive and Negative Syndrome Scale scores, and language-related neuropsychological test scores. After treatment, the lateralization index of the inferior frontal gyrus was significantly increased, which was related to reduced activation of the right inferior frontal gyrus. The increase in the lateralization index was significantly associated with the increase in verbal fluency score. A higher baseline accuracy of the semantic task was associated with a higher post-treatment lateralization index of the inferior frontal gyrus and greater improvement of the total score and positive subscore of the Positive and Negative Syndrome Scale. Our findings indicated aripiprazole treatment significantly increased semantic processing-related lateralization in the inferior frontal gyrus in drug-free patients with first-episode psychosis or ultra-high risk state. A higher baseline accuracy might predict a higher post-treatment lateralization index and greater symptom improvement.