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Psychopharmacology Sep 2023The long-term effectiveness of olanzapine and aripiprazole in real clinical conditions at flexible doses in patients after hospital discharge has not been evaluated yet.
Comparison between olanzapine and aripiprazole treatment for 104 weeks after hospital discharge in schizophrenia spectrum disorders: a multicenter retrospective cohort study in a real-world setting.
RATIONALE
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.
OBJECTIVES
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 104 weeks after the hospital discharge were compared using a Cox proportional hazards model and adjusted for possible confounders.
RESULTS
The Kaplan-Meier survival curves revealed that the continuation of olanzapine at 26 (P = 0.001) and 52 weeks (P = 0.018) was significantly higher than that of aripiprazole but not at 104 weeks. 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 104 weeks (hazard ratio: 0.438, 95% confidence interval: 0.246-0.780, P = 0.005). Aripiprazole was better than olanzapine in tolerability at 104 weeks (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.
CONCLUSION
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 104 weeks, due reduced tolerability of long-term olanzapine treatment.
Topics: Humans; Aripiprazole; Olanzapine; Schizophrenia; Retrospective Studies; Patient Discharge; Benzodiazepines; Piperazines; Quinolones; Antipsychotic Agents; Hospitals
PubMed: 37460628
DOI: 10.1007/s00213-023-06407-6 -
Therapeutic Advances in... 2023Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic...
Oral and long-acting injectable antipsychotic discontinuation and relationship to side effects in people with first episode psychosis: a longitudinal analysis of electronic health record data.
BACKGROUND
Discontinuation of treatment in people with first episode psychosis (FEP) is common, but the extent to which this is related to specific adverse effects of antipsychotic medications is unclear.
OBJECTIVES
To investigate whether antipsychotic discontinuation is associated with the prescription of particular antipsychotics and particular adverse effects.
DESIGN
Retrospective cohort study.
METHODS
We assembled de-identified electronic health record (EHR) data from 2309 adults with FEP who received care from the South London and Maudsley NHS Foundation Trust between 1st April 2008 and 31st March 2019. Associations between antipsychotic medications, clinician-recorded side effects and treatment discontinuation were investigated across a mean follow-up period of 34.2 months using Cox regression.
RESULTS
The mean age of patients was 26.7 years and 1492 (64.6%) were male. Among first prescribed antipsychotic medications, discontinuation occurred earlier with haloperidol [hazard ratio (HR) = 2.78, 95% CI = 1.69-4.60] and quetiapine (HR = 1.43, 95% CI = 1.16-1.80) than with olanzapine. Discontinuation occurred sooner when there was evidence of extrapyramidal symptoms (HR = 1.33, 95% CI = 1.08-1.64) or sexual dysfunction (HR = 1.59, 95% CI = 1.03-2.46). Among antipsychotics prescribed at any point during treatment, lurasidone (HR = 1.40, 95% CI = 1.10-1.78) and aripiprazole (HR = 1.09, 95% CI = 1.01-1.19) were associated with earlier discontinuation than olanzapine. Conversely, clozapine (HR = 0.55, 95% CI = 0.41-0.73) and paliperidone 1-monthly (PP1M) long-acting injectable (HR = 0.80, 95% CI = 0.68-0.94) were associated with later discontinuation. Unexpectedly, for antipsychotics prescribed at any stage of treatment, sedation (HR = 0.89, 95% CI = 0.81-0.97), weight gain (HR = 0.73, 95% CI = 0.64-0.83), and multiple side effects (HR = 0.83, 95% CI = 0.76-0.90) were associated with later discontinuation.
CONCLUSION
Earlier treatment discontinuation associated with sexual or extrapyramidal side effects could be related to their rapid onset and poor tolerability. Later treatment discontinuation associated with clozapine and PP1M could be related to the relative efficacy of these treatments. These findings merit consideration when selecting antipsychotic therapy for people with FEP.
PubMed: 38107162
DOI: 10.1177/20451253231211575 -
Psychological Medicine Dec 2023Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Despite unclear evidence to support the long-term use of antipsychotics to treat challenging (problem) behaviours in people with autism in the absence of a psychiatric disorder, this practice is common.
METHODS
We conducted a systematic review and meta-analysis of all randomised controlled trials (RCTs) involving antipsychotics for people with autism of all ages, irrespective of the outcomes assessed. We searched seven databases and hand-searched ten relevant journals. Two authors independently screened titles, abstracts and full papers and extracted data using the Cochrane Handbook template. We conducted meta-analyses of outcomes and the rate of adverse events.
RESULTS
We included 39 papers based on 21 primary RCTs that recruited 1482 people with autism. No RCT assessed any psychiatric disorder outcome, such as psychoses or bipolar disorder. A meta-analysis of ten placebo-controlled RCTs showed a significantly improved Aberrant Behaviour Checklist-Irritability score in the antipsychotic group with an effect size of -6.45 [95% confidence interval (CI) -8.13 to -4.77] (low certainty). Pooled Clinical Global Impression data on 11 placebo-controlled RCTs showed an overall effect size of 0.84 (95% CI 0.48 to 1.21) (moderate certainty). There was a significantly higher risk of overall adverse effects ( = 0.003) and also weight gain ( < 0.00001), sedation ( < 0.00001) and increased appetite ( = 0.001) in the antipsychotic group.
CONCLUSIONS
There is some evidence for risperidone and preliminary evidence for aripiprazole to significantly improve scores on some outcome measures among children with autism but not adults or for any other antipsychotics. There is a definite increased risk of antipsychotic-related different adverse effects.
Topics: Child; Humans; Antipsychotic Agents; Aripiprazole; Risperidone; Psychotic Disorders; Autism Spectrum Disorder; Randomized Controlled Trials as Topic
PubMed: 37539448
DOI: 10.1017/S003329172300212X -
International Journal of Circumpolar... Dec 2023This nationwide retrospective cross-sectional study examines the prevalence of antipsychotic polypharmacy (APP) and demographic, forensic, and clinical factors...
This nationwide retrospective cross-sectional study examines the prevalence of antipsychotic polypharmacy (APP) and demographic, forensic, and clinical factors associated with its practice among Greenlandic forensic psychiatric patients. We collected data from electronic patient files, court documents, and forensic psychiatric assessments. We defined APP as two or more concurrent prescriptions of antipsychotic medication. The study population of 74 patients had a mean age of 41.4 years, and 61 were men. All included patients had either schizophrenia or another ICD-10 F2-diagnosis. We used unpaired t-tests and Chi or Fisher's exact test. The prevalence of APP was 35% ( = 26), and there was a significant association between APP and a prescription of clozapine (Chi, = 0.010), olanzapine (Fisher's test, = 0.003), and aripiprazole (Fisher's test, = 0.013). Furthermore, we found a significant association between APP and prescription of a first-generation antipsychotic (FGA) (Chi, = 0.011). Despite recommendations in guidelines, the use of APP is common practice. The majority of forensic psychiatric patients suffer from severe psychiatric disorders, often with other comorbidities, including substance use disorder. The severity and complexity in mental health render forensic psychiatric patients at high risk of APP treatment. Further knowledge on APP use is crucial to secure and further improve the psychopharmacological treatment for this group of patients.
Topics: Male; Humans; Adult; Female; Antipsychotic Agents; Polypharmacy; Retrospective Studies; Cross-Sectional Studies; Clozapine
PubMed: 37300837
DOI: 10.1080/22423982.2023.2218654 -
International Immunopharmacology May 2024The prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Inflammatory cytokines and the kynurenine...
BACKGROUND
The prevalence of depression is higher in patients with inflammatory bowel disease (IBD) than in the general population. Inflammatory cytokines and the kynurenine pathway (KP) play important roles in IBD and associated depression. Aripiprazole (ARP), an atypical antipsychotic, shows various anti-inflammatory properties and may be useful in treating major depressive disorder. This study aimed to evaluate the protective effects of ARP on TNBS-induced colitis and subsequent depression in rats, highlighting the role of the KP.
MATERIAL AND METHODS
Fifty-six male Wistar rats were used, and all groups except for the normal and sham groups received a single dose of intra-rectal TNBS. Three different doses of ARP and dexamethasone were injected intraperitoneally for two weeks in treatment groups. On the 15th day, behavioral tests were performed to evaluate depressive-like behaviors. Colon ulcer index and histological changes were assessed. The tissue levels of inflammatory cytokines, KP markers, lipopolysaccharide (LPS), nuclear factor-kappa-B (NF-κB), and zonula occludens (ZO-1) were evaluated in the colon and hippocampus.
RESULTS
TNBS effectively induced intestinal damages and subsequent depressive-like symptoms in rats. TNBS treatment significantly elevated the intestinal content of inflammatory cytokines and NF-κB expression, dysregulated the KP markers balance in both colon and hippocampus tissues, and increased the serum levels of LPS. However, treatment with ARP for 14 days successfully reversed these alterations, particularly at higher doses.
CONCLUSION
ARP could alleviate IBD-induced colon damage and associated depressive-like behaviors mainly via suppressing inflammatory cytokines activity, serum LPS concentration, and affecting the NF-κB/kynurenine pathway.
Topics: Animals; Male; Trinitrobenzenesulfonic Acid; Kynurenine; Rats, Wistar; Anti-Inflammatory Agents; Aripiprazole; Colitis; Depression; Rats; NF-kappa B; Cytokines; Signal Transduction; Colon; Hippocampus; Disease Models, Animal; Humans
PubMed: 38691917
DOI: 10.1016/j.intimp.2024.112158 -
Therapeutic Advances in... 2023Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising... (Review)
Review
Gradual, hyperbolic tapering has been proposed as a method to reduce the risk of withdrawal effects and potential relapse of an underlying condition by minimising disruption of existing equilibria. We applied hyperbolic tapering principles to long-acting aripiprazole to generate regimens for withdrawal in clinical practice. We derived thresholds for taper rates using existing studies and consensus. Using pharmacokinetic data for aripiprazole long-acting injectable antipsychotic (ALAI), we conducted modelling to examine the impact of abrupt cessation of long-acting injectable antipsychotic (LAI) medication and the effect of prolonging inter-dose interval on plasma aripiprazole levels and consequent D occupancy. We also modelled transitions from LAI medication to oral medication. Regimens were designed to afford a rate of reduction between 5 and 12.5 percentage points of D occupancy per month. Abrupt discontinuation of ALAI was shown to lead to a maximal D occupancy reduction of 16.8 percentage points per month; prolongation of the inter-dose interval of ALAI produced a slower reduction. Specifically, hyperbolic tapering was afforded by prolongation of a 400 mg ALAI inter-dose interval from 4 to 7 weeks, before reducing the dose to 300 mg ALAI. This could then be administered at up to 4-week (for 6% maximal D occupancy change), 6-week (9% change) or 7-week (11% change) intervals. Switching to oral medication - 5, 2.5 and 1.25 mg for the three regimens, respectively - is required for ALAI to complete full cessation to prevent too rapid a reduction in D occupancy. Oral medication should probably be maintained at a consistent dose for 3-6 months before further reductions to account for residual LAI being concurrently eliminated. Hyperbolic dose tapering is possible with ALAI through prolongation of the inter-dose interval and may reduce the risk of relapse compared to abrupt discontinuation of LAI medication.
PubMed: 37719449
DOI: 10.1177/20451253231198463 -
Molecular Psychiatry Apr 2024The intricate involvement of the serotonin 5-HT receptor (5-HTR) both in schizophrenia and in the activity of antipsychotic drugs is widely acknowledged. The currently...
The intricate involvement of the serotonin 5-HT receptor (5-HTR) both in schizophrenia and in the activity of antipsychotic drugs is widely acknowledged. The currently marketed antipsychotic drugs, although effective in managing the symptoms of schizophrenia to a certain extent, are not without their repertoire of serious side effects. There is a need for better therapeutics to treat schizophrenia for which understanding the mechanism of action of the current antipsychotic drugs is imperative. With bioluminescence resonance energy transfer (BRET) assays, we trace the signaling signature of six antipsychotic drugs belonging to three generations at the 5-HTR for the entire spectrum of signaling pathways activated by serotonin (5-HT). The antipsychotic drugs display previously unidentified pathway preference at the level of the individual Gα subunits and β-arrestins. In particular, risperidone, clozapine, olanzapine and haloperidol showed G protein-selective inverse agonist activity. In addition, G protein-selective partial agonism was found for aripiprazole and cariprazine. Pathway-specific apparent dissociation constants determined from functional analyses revealed distinct coupling-modulating capacities of the tested antipsychotics at the different 5-HT-activated pathways. Computational analyses of the pharmacological and structural fingerprints support a mechanistically based clustering that recapitulate the clinical classification (typical/first generation, atypical/second generation, third generation) of the antipsychotic drugs. The study provides a new framework to functionally classify antipsychotics that should represent a useful tool for the identification of better and safer neuropsychiatric drugs and allows formulating hypotheses on the links between specific signaling cascades and in the clinical outcomes of the existing drugs.
PubMed: 38561467
DOI: 10.1038/s41380-024-02531-7 -
Advanced Biomedical Research 2023Sexual desire and sexual activity are natural needs of human beings, which can be problematic and lead to various sexual disorders, if not used in the right way,...
BACKGROUND
Sexual desire and sexual activity are natural needs of human beings, which can be problematic and lead to various sexual disorders, if not used in the right way, including hypersexuality. The present study aimed to compare the effect of dialectical behavior therapy (DBT) and aripiprazole drug on marital instability in patients with hypersexuality.
MATERIALS AND METHODS
This experimental case--control Pretest--Posttest Control Group Design with follow up was done on 27 male and female patients with hypersexuality having at least a higher education degree selected from four hospitals and psychiatric centers including Khorshid Hospital, Asgariyeh Specialized Hospital, Farhangian Clinic and Imam Reza Medical Center in Isfahan and were randomly assigned to two groups of treatment (nine patients in every group) and one group of control (nine patients) after adjusting the age and gender. Pretest phase was done for both three groups using Marital Instability Index (MII). The first treatment group underwent DBT intervention for eight sessions of 2 hours (once a week), and the second experimental group was prescribed aripiprazole for 2 months. Afterwards, the posttest and follow-up were performed for all the three groups. The data were analyzed using SPSS 24 and multivariate analysis of covariance (MANCOVA).
RESULTS
The findings showed that DBT and aripiprazole had little effect on the problem of marital instability in patients with hypersexuality ( > 0.05); also, there was no significant difference between the effect of DBT and aripiprazole ( > 0.05).
CONCLUSION
DBT and the drug aripiprazole cannot have a significant effect on the marital instability in patients.
PubMed: 37694240
DOI: 10.4103/abr.abr_161_22 -
Diseases (Basel, Switzerland) May 2024Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can... (Review)
Review
BACKGROUND
Wernicke encephalopathy (WE) is an acute and potentially fatal neuropsychiatric disorder resulting from thiamine deficiency: its etiology and clinical presentation can be heterogeneous and arduously recognized, especially in children and adolescents.
CASE PRESENTATION
An 8-year-old girl arrived to the emergency room with ataxic gait, nystagmus, and mental confusion after a 10-day history of repeated severe vomiting; her recent clinical history was characterized by restricted nutrition due to a choking phobia, which caused substantial . Brain magnetic resonance imaging revealed a bilaterally increased T2 signal in the medial areas of the thalami and cerebral periaqueductal region. Diagnosis of WE based on clinical and neuroradiological findings was established and confirmed after labwork showing low serum thiamine. Following psychiatric evaluation, the patient was also diagnosed with avoidance-restrictive food intake disorder (ARFID), which required starting cognitive behavioral therapy and introducing aripiprazole. The patient displayed improvement of the radiological findings after one month and complete resolution of her neurological symptoms and signs.
CONCLUSIONS
Eating disorders like ARFID might forerun acute signs of WE; this possibility should be considered even in pediatric patients, especially when atypical neurological pictures or feeding issues come out.
PubMed: 38920544
DOI: 10.3390/diseases12060112 -
Psychiatry and Clinical Neurosciences Sep 2023This study identified discrepant therapeutic outcomes of antipsychotics.
AIM
This study identified discrepant therapeutic outcomes of antipsychotics.
METHODS
A total of 5191 patients with schizophrenia were enrolled, 3030 as discovery cohort, 1395 as validation cohort, and 766 as multi-ancestry validation cohort. Therapeutic Outcomes Wide Association Scan was conducted. Types of antipsychotics (one antipsychotic vs other antipsychotics) were dependent variables, therapeutic outcomes including efficacy and safety were independent variables.
RESULTS
In discovery cohort, olanzapine related to higher risk of weight gain (AIWG, OR: 2.21-2.86), liver dysfunction (OR: 1.75-2.33), sedation (OR: 1.76-2.86), increased lipid level (OR: 2.04-2.12), and lower risk of extrapyramidal syndrome (EPS, OR: 0.14-0.46); risperidone related to higher risk of hyperprolactinemia (OR: 12.45-20.53); quetiapine related to higher risk of sedation (OR = 1.73), palpitation (OR = 2.87), increased lipid level (OR = 1.69), lower risk of hyperprolactinemia (OR: 0.09-0.11), and EPS (OR: 0.15-0.44); aripiprazole related to lower risk of hyperprolactinemia (OR: 0.09-0.14), AIWG (OR = 0.44), sedation (OR: 0.33-0.47), and QTc prolongation (β = -2.17); ziprasidone related to higher risk of increased QT interval (β range: 3.11-3.22), nausea (OR: 3.22-3.91), lower risk of AIWG (OR: 0.27-0.46), liver dysfunction (OR: 0.41-0.38), and increased lipid level (OR: 0.41-0.55); haloperidol related to higher risk of EPS (OR: 2.64-6.29), hyperprolactinemia (OR: 5.45-9.44), and increased salivation (OR: 3.50-3.68). Perphenazine related to higher risk of EPS (OR: 1.89-2.54). Higher risk of liver dysfunction in olanzapine and lower risk of hyperprolactinemia in aripiprazole were confirmed in validation cohort, and higher risk of AIWG in olanzapine and hyperprolactinemia in risperidone were confirmed in multi-ancestry validation cohort.
CONCLUSION
Future precision medicine should focus on personalized side-effects.
Topics: Humans; Antipsychotic Agents; Aripiprazole; Hyperprolactinemia; Lipids; Olanzapine; Randomized Controlled Trials as Topic; Risperidone; Schizophrenia; Treatment Outcome
PubMed: 37210704
DOI: 10.1111/pcn.13567