Neuropsychopharmacology Reports最新文献

Aim: Yokukansan is one of the most frequently used herbal medicines that can improve the behavioral and psychological symptoms of dementia. In this exploratory study, we investigated whether yokukansan affects the steady-state blood concentrations of donepezil, risperidone, and the major metabolites of both drugs in a real-world clinical setting.

Methods: A non-randomized, open-label, single-arm study examining drug-drug interactions was conducted. Fifteen dementia patients taking donepezil for at least 4 weeks and eight schizophrenia patients taking risperidone for at least 2 weeks were orally administered 2.5 g of yokukansan three times a day before or between meals, and blood samples were collected before and 8 weeks after starting co-treatment with yokukansan. Plasma concentrations of donepezil, risperidone, and each metabolite were measured using high-performance liquid chromatography-tandem mass spectrometry and compared before and after the 8-week administration of yokukansan.

Results: The plasma concentrations of donepezil and its metabolites (6-O-desmethyl-donepezil, 5-O-desmethyl-donepezil, and donepezil-N-oxide), risperidone, and its metabolite paliperidone did not differ before and after the 8-week treatment with yokukansan.

Conclusions: The findings of this study show that the concomitant use of yokukansan may have little clinical impact on the steady-state blood levels of donepezil and risperidone in patients with dementia or schizophrenia.

Neurodegenerative diseases (NDs) such as Alzheimer disease (AD) and Parkinson disease (PD) are group of diseases affecting the central nervous system (CNS) characterized by progressive neurodegenerations and cognitive impairment. Findings from different studies highlighted the beneficial and detrimental effects of serum uric acid on the development and progression of NDs. Therefore, this mini-review aims to discuss the beneficial and detrimental effects of uric on NDs. The neuroprotective effect of uric acid is mainly related to the antioxidant effect of uric acid which alleviates oxidative stress-induced neurodegeneration in AD and PD. However, long-term effect of hyperuricemia prompts for the development and progression of cognitive impairment. Hyperuricemia is associated with cognitive impairment and dementia, and gout increases dementia risk. In addition, hyperuricemia can cause cerebral vascular injury which is a risk factor for vascular dementia and cognitive impairment. Taken together, the relationship between uric acid and NDs risk remains conflicting. Hence, preclinical and clinical studies are indicated in this regard.

Background: In patients with schizophrenia, violent behavior is a clinically important factor that prevents their discharge. Clozapine is an effective antipsychotic medication for treatment-resistant schizophrenia, and its usefulness for aggressive behavior has also been suggested.

Case presentation: We present the case of a 38-year-old male patient diagnosed with schizophrenia who was successfully treated with clozapine after recurrent violent behavior. He was diagnosed with schizophrenia during his adolescence. He was hospitalized for treatment in his teens, but his hallucinations and delusions persisted even after discharge. In his 30s, he became noticeably emotionally unstable, and despite being treated for an adequate period with sufficient doses of several antipsychotics, his symptoms did not improve. This led to repeated hospitalizations triggered by violent behavior toward his parents and siblings within the home. During his fourth hospitalization, clozapine was initiated due to multiple incidents of violence toward nursing staff secondary to hallucinations and delusions. As the dose of clozapine was gradually increased with therapeutic drug monitoring, the patient's hostility, uncooperativeness, and suspiciousness markedly improved, and his aggressive behavior disappeared. He was discharged to a facility on day 194 after starting clozapine and has continued outpatient visits.

Conclusion: Clozapine was suggested to be effective for aggressive behavior in patients with treatment-resistant schizophrenia and should be actively considered. In such cases, regular measurement of blood concentration is useful for adjusting the dosage of clozapine.

Background: Neuroleptic malignant syndrome (NMS) is a rare and potentially life-threatening condition that may arise at any point during treatment and is often associated with adverse reactions to dopamine-blocking agents. This syndrome is normally characterized by features such as muscle rigidity, alteration in consciousness, autonomic instability, and leukocytosis.

Aim: The aim of this study is to investigate a borderline intellectual functioning (BIF) case in which NMS with insidious disease progression and long prodromal symptoms was developed.

Case presentation: The investigated patient was a 38-year-old female diagnosed with bipolar disorder and a variety of corresponding disorders. The patient exhibited gastrointestinal symptoms and restlessness in the weeks leading up to the study, subsequent to the administration of elevated doses of haloperidol, risperidone, and lithium. In addition, she was hospitalized for restlessness and aggressiveness in the summer of 2023. Furthermore, due to her chief complaint, she received parenteral haloperidol twice in the emergency room, subsequently experiencing fever, altered consciousness, generalized rigidity, and dysphagia. Moreover, the patient's initial creatine phosphokinase (CPK) level was 2550 IU/L, and she was hospitalized in an intensive care unit with the diagnosis of NMS for 8 days.

Conclusions: This case study highlights the necessity of being attentive about prodromal symptoms of NMS and emergent interventions.

Aim: COVID-19 can lead to encephalopathy and loss of consciousness. This double-blinded randomized clinical trial conducted in Tehran, Iran, aimed to assess the potential effectiveness of modafinil in patients with COVID-19-related encephalopathy.

Methods: Nineteen non-intubated COVID-19 patients with encephalopathy were randomized into two groups: a treatment group receiving crushed modafinil tablets and a placebo group receiving starch powder. Modafinil was administered at a dose of 100 mg every 2 h, reaching a peak dosage of 400 mg. The level of consciousness was assessed using the Glasgow Coma Score (GCS) at multiple time points on the day of medication administration. The trial was registered under IRCT20170903036041N3 on 23/5/2021.

Results: The average age in the modafinil and placebo groups was 75.33 and 70 years, respectively. No significant differences were observed between the two groups in terms of chronic conditions, clinical symptoms, or laboratory data. GCS scores were similar between the groups at baseline (p-value = 0.699). After four doses of modafinil, GCS scores were slightly higher in the treatment group, but this difference was not statistically significant (p-value = 0.581). GCS scores after each round of drug administration didn't significantly differ between the treatment and placebo groups (p-value = 0.908).

Conclusion: Modafinil exhibited a slight improvement in the level of consciousness among COVID-19 patients with encephalopathy, although this improvement did not reach statistical significance when compared to the control group. Further research with larger sample sizes and longer treatment durations is recommended to explore modafinil's potential benefits in managing altered consciousness in COVID-19 patients.

Aim: The aim of the study was to identify the clinical significance of anxiety in those with depression, the Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) defined criteria for an anxious distress specifier for major depressive disorder (MDD). The Clinically Useful Depression Outcome Scale (CUDOS) supplemented with questions for the DSM-5 anxious distress specifier (CUDOS-A) is a self-report instrument to assess the clinical significance of anxiety in addition to assess symptoms and the severity of depression. This study aimed to evaluate the psychometric properties of the Japanese version of the CUDOS-A.

Methods: An observational, prospective study was conducted with 131 MDD outpatients and 200 healthy controls. The Japanese version of the CUDOS-A, along with other measures, was administered to assess depressive symptoms, anxiety, social function, and biological rhythm. Reliability and validity analyses were performed, including internal consistency, test-retest reliability, convergent validity, and contrasted-groups validity.

Results: The Japanese version of the CUDOS-A demonstrated excellent internal consistency (Cronbach's alpha = 0.96) and test-retest reliability (ICC = 0.78). Significant positive correlations were found between the CUDOS-A and measures of depression, anxiety, social function, and biological rhythm (all, p < 0.001), supporting its convergent validity. The CUDOS-A effectively differentiated between patients with MDD and healthy controls (p < 0.001), indicating good contrasted-groups validity.

Conclusions: The Japanese version of the CUDOS-A is a useful measure for research and for clinical practice, enabling the efficient assessment of anxious distress in individuals with depression.

Aim: Behavioral psychological symptoms of dementia (BPSD) are sometimes difficult to treat due to severe psychiatric symptoms such as delusions of poisoning and violent behavior. Moreover, in cases of parental neglect, the management of these psychiatric symptoms becomes more difficult. Therefore, home-visiting doctors sometimes have to manage patients with BPSD and severe psychiatric symptoms, and a new approach is needed. In this case report, the effect of blonanserin transdermal patch on these patients is to be highlighted.

Methods: The patient is a 91-year-old woman diagnosed with Alzheimer's disease. She had severe BPSD such as delusion of robbery and violent behavior, and refused oral medications including memantine and yokukansan. Then she was treated with blonanserin transdermal patch (20 mg/day). The severity of psychiatric symptoms of BPSD was assessed over time using the Neuropsychiatric Inventory (NPI) score. Moreover, the patient's cognitive function was also assessed over time by Mini-Mental State Examination (MMSE).

Results: After the introduction of blonanserin patch, the patient's psychiatric symptoms were stabilized markedly, and both NPI and MMSE scores improved. The patient was able to stay at home calmly and was mentally well stabilized to the extent that she did not require hospitalization. No apparent side effects were admitted.

Conclusions: The blonanserin transdermal patch may be able to manage BPSD at home and is effective in patients who refuse oral medications. Home-visiting doctors may consider the use of blonanserin patches at home for patients with severe BPSD, manifesting as delusions of poisoning and refusing oral drugs.

Introduction: Catatonia, a psychomotor disorder characterized by diverse clinical signs, including stupor and mutism, remains elusive in its causes and a challenge to diagnose. Moreover, it is often underrecognized due to its resemblance to disorders of consciousness. However, when diagnosing catatonia, an antipsychotic medication may exacerbate the condition. The first-line treatment typically includes benzodiazepines and/or electroconvulsive therapy (ECT).

Case report: A 60-year-old woman with systemic lupus erythematosus (SLE) and epilepsy presented with catatonic stupor. Despite stable treatment, she experienced an acute deterioration in consciousness, requiring hospitalization. Her condition improved markedly following a benzodiazepine challenge, as documented on EEG. This improvement was short-lived, but a second benzodiazepine challenge restored her from E1V1M1 (stupor) to E4V5M6 within minutes, as documented by a video recording. The patient was treated with lorazepam 1.5 mg/day orally and did not experience further relapses.

Discussion: The diagnosis of catatonia had been based on her scores on the Bush-Francis Catatonia Rating Scale (BFCRS; Screening, 6/14; Severity, 19), despite meeting only two DSM-5 criteria for catatonia (stupor and mutism). The diagnosis was supported by EEG and video documentation, excluding other potential differential diagnoses such as nonconvulsive status epilepticus and encephalopathy. Additional quantitative EEG analyses indicated that benzodiazepine administration increased brainwide alpha and beta band power significantly, suggesting that the benzodiazepine normalized attention, consciousness, and long-range synchronization. This report additionally emphasizes the significance of video recordings in managing catatonia, and it helps in accurately tracking symptoms, documenting comprehensively, and improving patient understanding, which is crucial for treatment adherence.

Purpose: Alcohol is implicated in epileptogenesis and seizures attack. An increasing number of studies about alcohol and epilepsy have been published. We aimed to assess research trends and hot spots in the field of alcohol and epilepsy.

Patients and methods: Literature concerning alcohol and epilepsy was systemically searched through the Web of Science database. Collaborative maps were quantitatively analyzed by using the VOSviewer and CiteSpace tools.

Results: A total of 1578 papers about the field of alcohol and epilepsy were taken into analysis, which was written by 6840 authors from 2153 institutions in 85 countries, published in 676 journals, and cited 79 667 references from 10 750 journals. The United States was the leading country and had close ties with others. The University of Toronto was the most productive institution. Alcoholism-clinical and experimental research was the fastest-growing journal. Richard J. Bodnar was the author contributing the most literature. Analysis of keywords showed epilepsy, alcohol, seizures, alcohol withdrawal, and management were common themes.

Conclusion: The presented study conducted the first bibliometric analysis of the field of alcohol and epilepsy, which will provide insights into the latest progress, evolution paths, frontier research hot spots, and future research trends in the field.

Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable sensations. Herein, we present cases of BMS in which the remaining uncomfortable sensations improved with perospirone augmentation with clonazepam. Case 1: A 61-year-old man complained of a burning pain in his tongue, a sensation of dryness and discomfort as if his tongue was sticking to a palatal plate. With the diagnosis of BMS, psychopharmacotherapy was initiated with amitriptyline. At the dose of amitriptyline 50 mg, the pain lessened but uncomfortable sensations persisted. Further attempts to alleviate symptoms by combining aripiprazole with amitriptyline, aripiprazole with mirtazapine, or aripiprazole with clonazepam were limited; however, nearly all symptoms were relieved by a combination of perospirone 8.0 mg with clonazepam 1.5 mg. Case 2: A 51-year-old woman complained of a burning sensation along with oral dryness and crumb-like feeling on her tongue. She was diagnosed with BMS and began treatment with amitriptyline. Her burning sensation improved at the dose of 25 mg, but uncomfortable sensations persisted. Augmentation of amitriptyline with aripiprazole, aripiprazole either with valproate, mirtazapine, or clonazepam failed to produce a significant improvement. However, a regimen of perospirone 6.0 mg and clonazepam 1.5 mg relieved the crumb-like sensation and pain and culminated in a stabilized condition. The reported cases suggested that multiple approaches targeting the dopaminergic circuit in basal ganglia involving the serotoninergic and GABA systems, through the administration of perospirone with clonazepam is an effective adjunctive treatment for the remaining uncomfortable sensations in patients with BMS.