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BioRxiv : the Preprint Server For... Nov 2023Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders...
UNLABELLED
Tourette disorder (TD) is poorly understood, despite affecting 1/160 children. A lack of animal models possessing construct, face, and predictive validity hinders progress in the field. We used CRISPR/Cas9 genome editing to generate mice with mutations orthologous to human variants in two high-confidence Tourette genes, and . Mice with human mutations in and exhibit cognitive and/or sensorimotor behavioral phenotypes consistent with TD. Sensorimotor gating deficits, as measured by acoustic prepulse inhibition, occur in both male and female TD models. mice show reduced prepulse inhibition only in females. Repetitive motor behaviors, common to mice and more pronounced in females, include vertical rearing and grooming. Sensorimotor gating deficits and rearing are attenuated by aripiprazole, a partial agonist at dopamine type II receptors. Unsupervised machine learning reveals numerous changes to spontaneous motor behavior and less predictable patterns of movement. Continuous fixed-ratio reinforcement shows TD mice have enhanced motor responding and reward learning. Electrically evoked striatal dopamine release, tested in one model, is greater. Brain development is otherwise grossly normal without signs of striatal interneuron loss. Altogether, mice expressing human mutations in high-confidence TD genes exhibit face and predictive validity. Reduced prepulse inhibition and repetitive motor behaviors are core behavioral phenotypes and are responsive to aripiprazole. Enhanced reward learning and motor responding occurs alongside greater evoked dopamine release. Phenotypes can also vary by sex and show stronger affection in females, an unexpected finding considering males are more frequently affected in TD.
SIGNIFICANCE STATEMENT
We generated mouse models that express mutations in high-confidence genes linked to Tourette disorder (TD). These models show sensorimotor and cognitive behavioral phenotypes resembling TD-like behaviors. Sensorimotor gating deficits and repetitive motor behaviors are attenuated by drugs that act on dopamine. Reward learning and striatal dopamine is enhanced. Brain development is grossly normal, including cortical layering and patterning of major axon tracts. Further, no signs of striatal interneuron loss are detected. Interestingly, behavioral phenotypes in affected females can be more pronounced than in males, despite male sex bias in the diagnosis of TD. These novel mouse models with construct, face, and predictive validity provide a new resource to study neural substrates that cause tics and related behavioral phenotypes in TD.
PubMed: 38077033
DOI: 10.1101/2023.11.28.569034 -
Cureus Nov 2023Oculogyric crisis (OGC) is a rare type of acute dystonia characterized by spasmodic upward deviation of the eyes lasting for a few minutes to several hours. It is...
Oculogyric crisis (OGC) is a rare type of acute dystonia characterized by spasmodic upward deviation of the eyes lasting for a few minutes to several hours. It is commonly seen with the administration of first-generation antipsychotics and rarely reported in patients taking second-generation antipsychotics. Although aripiprazole, a second-generation antipsychotic, is known for its low potential for extrapyramidal side effects (EPS), there are multiple case reports of it resulting in acute dystonia, especially OGC. In this paper, we report a case of aripiprazole-induced OGC in a 16-year-old female patient after a suicide attempt by taking 40 mg of aripiprazole and 5 g of acetaminophen. The necessary investigations were ordered, and the patient's dystonic symptoms resolved completely after administering parenteral diazepam and benztropine.
PubMed: 38054149
DOI: 10.7759/cureus.48267 -
Heliyon Nov 2023Adverse events (AEs) of antipsychotic drugs include neuroleptic malignant syndrome (NMS), which presents complex clinical symptoms, resulting in a fatal outcome. In this...
Adverse events (AEs) of antipsychotic drugs include neuroleptic malignant syndrome (NMS), which presents complex clinical symptoms, resulting in a fatal outcome. In this study, the association between antipsychotic drugs and NMS was comprehensively evaluated by cluster and association analyses using the Japanese Adverse Drug Event Report (JADER) database. The analyses were performed using 20 typical antipsychotics (TAPs) alongside 9 atypical antipsychotics (AAPs). The Standardised MedDRA Queries (SMQ) database was used to analyze NMS (SMQ code: 20000044). Reporting odds ratios (RORs) were used for AE signal detection. The relationship between antipsychotic drugs and AEs for NMS was investigated by performing hierarchical cluster analysis using Ward's method. Between April 2004 and September 2021, the total number of JADER reports was 705,294. RORs (95 % confidence interval) of NMS for haloperidol, chlorpromazine, risperidone, and aripiprazole were 12.1 (11.1-13.3), 6.3 (5.7-7.0), 6.2 (5.8-6.6), and 4.7 (4.4-5.1), respectively. Three clusters were formed, with characteristics as follows: Cluster 1 consisted of only TAPs, such as bromperidol and fluphenazine, whilst having a high reporting rate of hypotension, tachycardia, dyskinesia, and dystonia. Cluster 2 consisted of all AAPs alongside several TAPs, such as haloperidol and chlorpromazine, with higher reporting rates of disturbance of consciousness, extrapyramidal disorders (excluding dyskinesia and dystonia), and serotonin syndrome. Cluster 3 consisted of only perphenazine, whilst having a higher reporting rate of coma, leukocytosis, and Parkinsonism. The results of this study may therefore aid in the management of NMS using antipsychotic drugs.
PubMed: 38034668
DOI: 10.1016/j.heliyon.2023.e21891 -
Saudi Pharmaceutical Journal : SPJ :... Dec 2023This study aimed to investigate the prescribing pattern of antipsychotic medications for schizophrenia using the British National Formulary total daily dose (TDD) online...
This study aimed to investigate the prescribing pattern of antipsychotic medications for schizophrenia using the British National Formulary total daily dose (TDD) online tool. We analysed data from the electronic medical records at King Khalid University Hospital (KKUH) of 272 patients diagnosed with schizophrenia who were prescribed both typical and atypical antipsychotic medications. The results showed that aripiprazole was the most commonly prescribed antipsychotic drug, followed by haloperidol then risperidone. The TDD online tool was used to calculate the TDD of each prescribed antipsychotic medication. Most patients were prescribed doses within the recommended range for each medication, although some were prescribed doses above or below the recommended range. Moreover, a high recommended TDD was associated with the combined use of antipsychotics rather than monotherapy. Additionally, high TDD levels were associated with the following antipsychotics: haloperidol, olanzapine, paliperidone, and quetiapine. Our findings highlight the importance of using evidence-based tools such as the TDD online tool to guide prescribing practices and ensure optimal dosing of antipsychotic medications for patients with schizophrenia.
PubMed: 38033746
DOI: 10.1016/j.jsps.2023.101837 -
Scientific Reports Nov 2023Autism spectrum disorder is a significant concern worldwide, particularly in Middle Eastern countries. Aripiprazole, a psychiatric medicine that works as a partial...
Autism spectrum disorder is a significant concern worldwide, particularly in Middle Eastern countries. Aripiprazole, a psychiatric medicine that works as a partial agonist at D receptors, is often used for autism-related behavior issues in children. Monitoring the therapy of aripiprazole could enhance the safety and effectiveness of treatment for autistic individuals. The purpose of this study was to develop a highly sensitive and environmentally friendly method for analysis of aripiprazole in plasma matrix. To achieve this, water-soluble N-carbon quantum dots were produced from a natural green precursor, guava fruit, and used in fluorescence quenching spectroscopy to determine the presence of aripiprazole. The synthesized dots were analyzed and characterized using transmission electron microscopy and Fourier transform infrared spectroscopy, and they showed a strong fluorescence emission peak at 475 nm. The proposed method was validated according to ICH M10 guidelines and was shown to be highly sensitive, allowing for nanoscale determination of aripiprazole in plasma matrix. Additionally, the method was compared to a previously reported spectrophotometric method, and it was found to be more sensitive and consistent with the principles of green analytical chemistry.
Topics: Child; Humans; Aripiprazole; Quantum Dots; Carbon; Autism Spectrum Disorder; Spectrometry, Fluorescence
PubMed: 38030673
DOI: 10.1038/s41598-023-47392-2 -
Therapeutic Advances in... 2023This review presents a comprehensive guide for optimizing medication management in older adults with depression within an outpatient setting. Medication optimization... (Review)
Review
This review presents a comprehensive guide for optimizing medication management in older adults with depression within an outpatient setting. Medication optimization involves tailoring the antidepressant strategy to the individual, ensuring the administration of appropriate medications at optimal dosages. In the case of older adults, this process necessitates not only adjusting or changing antidepressants but also addressing the concurrent use of inappropriate medications, many of which have cognitive side effects. This review outlines various strategies for medication optimization in late-life depression: (1) Utilizing the full dose range of a medication to maximize therapeutic benefits and strive for remission. (2) Transitioning to alternative classes (such as a serotonin and norepinephrine reuptake inhibitor [SNRI], bupropion, or mirtazapine) when first-line treatment with selective serotonin reuptake inhibitors [SSRIs] proves inadequate. (3) Exploring augmentation strategies like aripiprazole for treatment-resistant depression. (4) Implementing measurement-based care to help adjust treatment. (5) Sustaining an effective antidepressant strategy for at least 1 year following depression remission, with longer durations for recurrent episodes or severe presentations. (6) Safely discontinuing anticholinergic medications and benzodiazepines by employing a tapering method when necessary, coupled with counseling about the benefits of stopping them. Additionally, this article explores favorable medications for depression, as well as alternatives for managing anxiety, insomnia, allergy, overactive bladder, psychosis, and muscle spasm in order to avoid potent anticholinergics and benzodiazepines.
PubMed: 38022834
DOI: 10.1177/20451253231212327 -
Pharmacology & Therapeutics Jan 2024Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core impairments: impaired communication, impaired reciprocal social interaction,... (Review)
Review
Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by three core impairments: impaired communication, impaired reciprocal social interaction, and restricted, repetitive, and stereotypical behavior patterns. Spectrum refers to the heterogeneity of presentation, severity of symptoms, and medical comorbidities associated with ASD. Among the most common underlying medical conditions are attention-deficit/hyperactivity disorder (ADHD), anxiety, depression, epilepsy, digestive disorders, metabolic disorders, and immune disorders. At present, in the absence of an objective and accurate diagnosis of ASD, such as a blood test, pharmacological management remains a challenge. There are no approved medications to treat the core symptoms of the disorder and behavioral interventions are typically used as first line treatment. Additionally, psychotropic drugs with different mechanisms of action have been approved to reduce associated symptoms and comorbidities, including aripiprazole, risperidone, and haloperidol for irritability and aggression, methylphenidate, atomoxetine, clonidine, and guanfacine for ADHD, and melatonin for sleep disturbances. The purpose of this review is to emphasize that it is imperative to develop objective, personalized diagnostic kits in order to tailor and individualize treatment strategies, as well as to describe the current pharmacological management options available in clinical practice and new prospects that may be helpful in managing ASD's core symptoms.
Topics: Child; Humans; Autism Spectrum Disorder; Autistic Disorder; Psychotropic Drugs; Attention Deficit Disorder with Hyperactivity; Methylphenidate
PubMed: 38008401
DOI: 10.1016/j.pharmthera.2023.108564 -
Journal of Clinical Medicine Nov 2023Schizophrenia (SZ) is among the twenty most disabling diseases worldwide. Subjective quality of life, well-being, and satisfaction are core elements to achieving... (Review)
Review
Schizophrenia (SZ) is among the twenty most disabling diseases worldwide. Subjective quality of life, well-being, and satisfaction are core elements to achieving personal recovery from the disorder. Long-acting injectable second-generation antipsychotics (SGA-LAIs) represent a valid therapeutic option for the treatment of SZ as they guarantee good efficacy and adherence to treatment. The aim of this rapid review is to summarize the evidence on the efficacy of SGA-LAIs in improving subjective quality of life, well-being, and satisfaction. The PubMed database was searched for original studies using SGA, LAI, risperidone, paliperidone, aripiprazole, olanzapine, SZ, and psychosis as keywords. Twenty-one studies were included: 13 clinical trials, 7 observational studies, and 1 post hoc analysis. It has been shown that SGA-LAIs bring an improvement to specific domains of subjective and self-rated quality of life, well-being, or satisfaction in prospective observational studies without a control arm and in randomized controlled trials versus placebo. The superiority of SGA-LAIs as compared with oral equivalents and haloperidol-LAI has been reported by some randomized controlled and observational studies. Although promising, the evidence is still limited because of the lack of studies and several methodological issues concerning the choice of the sample, the evaluation of the outcome variables, and the study design. New methodologically sound studies are needed.
PubMed: 38002600
DOI: 10.3390/jcm12226985 -
Antioxidants (Basel, Switzerland) Oct 2023Aripiprazole has fewer metabolic side effects than other antipsychotics; however, there are some severe ones in the liver, leading to drug-induced liver injury. Repeated...
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.
PubMed: 38001783
DOI: 10.3390/antiox12111930 -
BMC Psychiatry Nov 2023Oculogyric crisis (OGC) is a rare focal dystonia of the ocular muscles that not only interferes with patients' medication adherence but also negatively affects the...
BACKGROUND
Oculogyric crisis (OGC) is a rare focal dystonia of the ocular muscles that not only interferes with patients' medication adherence but also negatively affects the course and prognosis of the primary disease. Early detection and treatment of OGC can improve patients' medication adherence and quality of life.
CASE PRESENTATION
This paper reports a case of a 19-year-old Asian female with a diagnosis of schizophrenia who was treated intermittently with atypical antipsychotics aripiprazole or risperidone for 2 years, with improvement of psychotic symptoms during the course of medication, and then developed double eye rolling and staring with irritability when treated with risperidone 4 mg/d or 6 mg/d. Then, we changed the medication to clozapine, and the patient's psychotic symptoms were controlled and stable. The symptoms of double eye rolling and gaze disappeared.
CONCLUSION
Oculogyric crisis (OGC) is a rare focal dystonia of the oculogyric muscle. This case provides clinicians with a basis for the early recognition and management of oculogyric crisis during the use of atypical antipsychotics (risperidone).
Topics: Humans; Female; Young Adult; Adult; Risperidone; Quality of Life; Antipsychotic Agents; Clozapine; Dystonic Disorders
PubMed: 38001400
DOI: 10.1186/s12888-023-05379-3