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EBioMedicine Jun 2024Response to antipsychotic drugs (APD) varies greatly among individuals and is affected by genetic factors. This study aims to demonstrate genome-wide associations...
BACKGROUND
Response to antipsychotic drugs (APD) varies greatly among individuals and is affected by genetic factors. This study aims to demonstrate genome-wide associations between copy number variants (CNVs) and response to APD in patients with schizophrenia.
METHODS
A total of 3030 patients of Han Chinese ethnicity randomly received APD (aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone, haloperidol and perphenazine) treatment for six weeks. This study is a secondary data analysis. Percentage change on the Positive and Negative Syndrome Scale (PANSS) reduction was used to assess APD efficacy, and more than 50% change was considered as APD response. Associations between CNV burden, gene set, CNV loci and CNV break-point and APD efficacy were analysed.
FINDINGS
Higher CNV losses burden decreased the odds of 6-week APD response (OR = 0.66 [0.44, 0.98]). CNV losses in synaptic pathway involved in neurotransmitters were associated with 2-week PANSS reduction rate. CNV involved in sialylation (1p31.1 losses) and cellular metabolism (19q13.32 gains) associated with 6-week PANSS reduction rate at genome-wide significant level. Additional 36 CNVs associated with PANSS factors improvement. The OR of protective CNVs for 6-week APD response was 3.10 (95% CI: 1.33-7.19) and risk CNVs was 8.47 (95% CI: 1.92-37.43). CNV interacted with genetic risk score on APD efficacy (Beta = -1.53, SE = 0.66, P = 0.021). The area under curve to differ 6-week APD response attained 80.45% (95% CI: 78.07%-82.82%).
INTERPRETATION
Copy number variants contributed to poor APD efficacy and synaptic pathway involved in neurotransmitter was highlighted.
FUNDING
National Natural Science Foundation of China, National Key R&D Program of China, China Postdoctoral Science Foundation.
PubMed: 38870545
DOI: 10.1016/j.ebiom.2024.105195 -
PCN Reports : Psychiatry and Clinical... Dec 2023Jitteriness/anxiety syndrome is a recognized adverse effect observed during the initiation or change of dose in antidepressant treatment. Managing patients who develop...
BACKGROUND
Jitteriness/anxiety syndrome is a recognized adverse effect observed during the initiation or change of dose in antidepressant treatment. Managing patients who develop this syndrome remains a challenge. While escitalopram is a widely used antidepressant known to cause these symptoms, this report explores vortioxetine as a therapeutic alternative.
CASE PRESENTATION
Three distinct clinical scenarios were observed in patients who manifested jitteriness/anxiety syndrome while on escitalopram treatment for depression. Patient A was initiated on escitalopram and experienced an initial alleviation in depressive symptoms, but 3 months later displayed mood elevation, talkativeness, and increased activity, which disturbed his daily life. A transition to vortioxetine subsequently resolved the mood elevation. Patient B exhibited elevated mood, hyperactivity, irritability, and talkativeness just 6 days post-initiation of treatment with escitalopram. After the discontinuation of escitalopram and unsuccessful trials with aripiprazole, lurasidone, and lamotrigine, her depressive mood intensified, culminating in suicidal ideation. Starting vortioxetine led to a consistent improvement of her symptoms, and she resumed work and was emotionally stable. Patient C was initially diagnosed with bipolar disorder and faced a relapse into depression despite undergoing various treatments. After 2 weeks on escitalopram, she exhibited irritability and self-harm urges. Three months later, after being re-diagnosed with depressive disorders with anxious distress, vortioxetine was administered, which significantly reduced her depressive symptoms and allowed her to continue her education.
CONCLUSION
Vortioxetine presents as a promising therapeutic alternative that is worth considering for patients with escitalopram-induced jitteriness/anxiety syndrome.
PubMed: 38868737
DOI: 10.1002/pcn5.158 -
The Mental Health Clinician Jun 2024Aripiprazole has been linked to the development of impulse control problems (ICPs), most commonly gambling. Aripiprazole's effect on serotonergic and dopaminergic...
Aripiprazole has been linked to the development of impulse control problems (ICPs), most commonly gambling. Aripiprazole's effect on serotonergic and dopaminergic pathways has had mixed results on drinking behaviors. A male patient receiving outpatient psychiatric care presented with ongoing symptoms of depression on his current regimen of mirtazapine and gabapentin. Aripiprazole was chosen for augmentation after multiple failed trials of alternative medications. Within 3 weeks the patient discontinued the medication due to escalating binge-drinking behavior. This behavior resolved within 3 days after discontinuing aripiprazole. Individuals who engage in binge drinking demonstrate consistent impulse control deficits that are unrelated to the rewarding effects of alcohol. Aripiprazole may be related to this patient's return to binge drinking from an ICP standpoint rather than driven by alcohol cravings as other psychosocial factors remained stable throughout this time.
PubMed: 38835817
DOI: 10.9740/mhc.2024.06.212 -
Haloperidol-induced painless legs and moving toe syndrome in a schizophrenia patient: a case report.Future Science OA 2024Painless legs and moving toe syndrome (PoLMT) is a rare syndrome characterized by involuntary movements of the toe without pain. The exact etiology of the patient's...
Painless legs and moving toe syndrome (PoLMT) is a rare syndrome characterized by involuntary movements of the toe without pain. The exact etiology of the patient's PoLMT is unknown. We present a case of PoLMT in 45-year-old woman with a history of haloperidol intake for 10 months. Haloperidol was discontinued, and aripiprazole (15 mg) was initiated. After this switch, a reduction in movement was observed in the third and fourth toes; however, the second toe showed no discernible change.
PubMed: 38817384
DOI: 10.2144/fsoa-2023-0207 -
Scientific Reports May 2024The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial...
The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.
Topics: Humans; Aripiprazole; COVID-19; Male; Female; Antipsychotic Agents; Middle Aged; Retrospective Studies; Aged; SARS-CoV-2; COVID-19 Drug Treatment; Adult; Aged, 80 and over
PubMed: 38811612
DOI: 10.1038/s41598-024-60297-y -
Brain Sciences Apr 2024Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse,... (Review)
Review
BACKGROUND
Up to 34% of patients with schizophrenia are resistant to several treatment trials. Lack of continuous and adequate treatment is associated with relapse, rehospitalization, a lower effect of antipsychotic therapy, and higher risk of side effects. Long-acting injectables antipsychotics (LAI APs) enhance compliance and improve clinical outcomes and quality of life in patients with schizophrenia, and thus it may be advisable to administer two LAI APs at the same time in cases of treatment-resistant schizophrenia. The purpose of this review is to summarize the available literature regarding the combined use of two LAI APs in patients with schizophrenia or other psychotic spectrum disorders.
METHODS
An extensive literature search for relevant articles regarding any combination of two long-acting injectable antipsychotics has been performed from inception up to 9 February 2024, on PubMed, Scopus and APA PsycInfo, according to the PRISMA statement. Only studies reporting combination of two LAI APs and its clinical outcome in patients with schizophrenia and related disorders were selected.
RESULTS
After the selection process, nine case reports, four case series and two observational retrospective studies were included in the final analysis. All patients treated with dual LAI APs reported a good response, and no new or unexpected adverse effects due to the combination of two LAIs were reported. Different drug combinations were used, and the most frequent association resulted in aripiprazole monohydrate + paliperidone palmitate once monthly (32 times).
CONCLUSIONS
Our review highlights that the treatment regimen with two concurrent LAI APs is already widely used in clinical practice and is recognized as providing a promising, effective, and relatively safe therapeutic strategy for treating the schizophrenia spectrum disorders.
PubMed: 38790412
DOI: 10.3390/brainsci14050433 -
Prague Medical Report 2024Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder,... (Review)
Review
Second-generation antipsychotics (SGAs), also known as atypical antipsychotics, are a newer class of antipsychotic drugs used to treat schizophrenia, bipolar disorder, and related psychiatric conditions. The plasma concentration of antipsychotic drugs is a valid measure of the drug at its primary target structure in the brain, and therefore determines the efficacy and safety of these drugs. However, despite the well-known high variability in pharmacokinetics of these substances, psychiatric medication is usually administered in uniform dosage schedules. Therapeutic drug monitoring (TDM), as the specific method that can help personalised medicine in dose adjustment according to the characteristics of the individual patient, minimizing the risk of toxicity, monitoring adherence, and increasing cost-effectiveness in the treatment, thus seems to be an elegant tool to solve this problem. Non-response to therapeutic doses, uncertain adherence to medication, suboptimal tolerability, or pharmacokinetic drug-drug interactions are typical indications for TDM of SGAs. This review aims to summarize an overview of the current knowledge and evidence of the possibilities to tailor the dosage of selected SGAs using TDM, including the necessary pharmacokinetic parameters for personalised pharmacotherapy.
Topics: Humans; Drug Monitoring; Antipsychotic Agents; Schizophrenia
PubMed: 38761044
DOI: 10.14712/23362936.2024.10 -
RSC Advances May 2024Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer...
Therapeutic deep eutectic solvents (THEDSs) are the best exemplification of green alternative formulations of active pharmaceutical ingredients (APIs) that offer superlative properties of APIs. Previously, THEDESs of risperidone, fentanyl and levofloxacin with capric acid (CA) were developed by our group. These APIs share cyclic tertiary amine nuclei. Herein, DESs of two drugs bearing cyclic tertiary amine nucleus, namely, droperidol and aripiprazole, in the presence of CA, were investigated as model drugs. Comprehensive analyses were conducted using liquid-state 1D and 2D NMR and differential scanning calorimetry (DSC) to elucidate the regiochemistry and thermodynamic mechanisms bringing about those THEDESs. Everted gut sac technique was used to study the flux of the developed THEDESs. 1D and 2D NMR techniques analyses revealed the importance of cyclic tertiary amine nuclei in forming interactions with CA. This was confirmed by the downfield shift of the protons proximal to the tertiary amine groups compared to the individual drugs. Diffusion NMR analysis (DOSY) showed a significant reduction in the diffusion coefficient of CA in the mixed system compared with CA in isolation. Thermal analysis of the two drugs revealed that the drugs have a low tendency to recrystallise upon melting but rather vitrify from a melt to form an amorphous solid. Interestingly, the superior absorption and flux of the THEDES formulation of droperidol was demonstrated using the ERIS. Collectively, this work provides a green method to attain liquid formulations of APIs with enhanced pharmacokinetic features.
PubMed: 38716106
DOI: 10.1039/d4ra01469c -
Frontiers in Neuroscience 2024
PubMed: 38707592
DOI: 10.3389/fnins.2024.1371195