-
Heliyon May 2024- Cocaine use disorder (CUD) is a complex disease. Several studies have shown the efficacy of multitarget drugs used to treat CUD. Here we compare the efficacy of...
PURPOSE
- Cocaine use disorder (CUD) is a complex disease. Several studies have shown the efficacy of multitarget drugs used to treat CUD. Here we compare the efficacy of mirtazapine (MIR), pindolol (PIN), fluoxetine (FLX), risperidone (RIS), trazodone (TRZ), ziprasidone (ZPR), ondansetron (OND), yohimbine (YOH), or prazosin (PRZ), to reduce long-term cocaine-induced locomotor activity and the expression of cocaine-induced locomotor sensitization in rats.
METHODS
- The study consists of four experiments, which were divided into four experimental phases. Induction (10 days), cocaine withdrawal (30 days), expression (10 days), and post-expression phase (10 days). Male Wistar rats were daily dosed with cocaine (10 mg/kg; i.p.) during the induction and post-expression phases. During drug withdrawal, the MIR, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ were administered 30 min before saline. In the expression, the multitarget drugs were administered 30 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min.During the agonism phase, in experiment four, 8-OH-DPAT, DOI, CP-809-101, SR-57227A, or clonidine (CLO) was administered 30 min before MIR and 60 min before cocaine. After each administration, locomotor activity for each animal was recorded for 30 min.
RESULTS
-MIR, FLX, RIS, ZPR, OND, or PRZ attenuated the cocaine-induced locomotor activity and cocaine locomotor sensitization. PIN, TRZ, and YOH failed to decrease cocaine locomotor sensitization. At the optimal doses used, PIN, FLX, RIS, TRZ, ZPR, OND, YOH, or PRZ failed to attenuate long-term cocaine locomotor activation. MIR generated a decrease in cocaine-induced locomotor activity of greater magnitude and duration than the other multitarget drugs evaluated.
CONCLUSION
- At the optimal doses of multitarget drugs evaluated, MIR was the multitarget drug that showed the greatest long-term cocaine-induced behavior effects compared to other multitarget drugs.
PubMed: 38726128
DOI: 10.1016/j.heliyon.2024.e29979 -
Therapeutic Advances in Drug Safety 2024Antidepressants are widely used to manage depression and other psychiatric diseases. A previous study revealed that hepatotoxicity was the main adverse event related to...
BACKGROUND
Antidepressants are widely used to manage depression and other psychiatric diseases. A previous study revealed that hepatotoxicity was the main adverse event related to antidepressants. Therefore, drug-induced liver injury (DILI) caused by antidepressants deserves more attention.
OBJECTIVES
To investigate DILI adverse events reported due to antidepressant use in the United States Food and Drug Administration Adverse Events Reporting System (FAERS) database.
RESEARCH DESIGN
A disproportionality analysis of spontaneously reported adverse events was conducted to assess the association between antidepressant drugs and DILI.
METHODS
FAERS data from 1 January 2004 to 31 December 2021 were compiled and analyzed using the reporting odds ratio (ROR) and information component (IC).
RESULTS
As per the FAERS database, of the 324,588 cases that were administered antidepressants, 10,355 were identified as cases with DILI. Among the identified 42 antidepressants, nefazodone ( = 47, ROR = 7.79, IC = 2.91), fluvoxamine ( = 29, ROR = 4.69, IC = 2.20), and clomipramine ( = 24, ROR = 3.97, IC = 1.96) had the highest ROR for cholestatic injury; mianserin ( = 3, ROR = 21.46, IC = 3.99), nefazodone ( = 264, ROR = 18.67, IC = 3.84), and maprotiline ( = 15, ROR = 5.65, IC = 2.39) for hepatocellular injury; and nefazodone ( = 187, ROR = 12.71, IC = 0.48), clomipramine ( = 35, ROR = 2.07, IC = 0.26), and mirtazapine ( = 483, ROR = 1.96, IC = 0.94) for severe drug-related hepatic disorders. Only nefazodone elicited hepatic failure signals ( = 48, ROR = 18.64, IC = 4.16). There are limited reports on the adverse reactions of relatively new antidepressant drugs, such as milnacipran, viloxazine, esketamine, and tianeptine, and those not approved by the Food and Drugs Administration, such as reboxetine and agomelatine.
CONCLUSION
A significant association was observed between DILI and nefazodone. Duloxetine and clomipramine were associated with three DILI categories, except hepatic failure. The disproportionality analysis cannot conclude on a definite causal link between antidepressants and DILI. Additional research is required to assess new-generation antidepressants for their propensity to cause DILI.
PubMed: 38715707
DOI: 10.1177/20420986241244585 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024Mirtazapine blocks 5-hydroxytryptamine type (5-HT), 5-HT, 5-HT and histamine H receptors, similarly to olanzapine. This study aimed to investigate the efficacy and...
BACKGROUND
Mirtazapine blocks 5-hydroxytryptamine type (5-HT), 5-HT, 5-HT and histamine H receptors, similarly to olanzapine. This study aimed to investigate the efficacy and safety of mirtazapine plus granisetron and dexamethasone for carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic cancers.
METHODS
We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four institutions in Japan. Registered patients were moderately to highly emetogenic chemotherapy-naïve, and were scheduled to receive CBDCA at area under the curve (AUC) ≥ 4 mg/mL per minute. Patients received mirtazapine 15 mg/day orally at bedtime for four consecutive days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the delayed period (24-120 h).
RESULTS
Between July 2022 and July 2023, 52 patients were enrolled, and 48 patients were evaluated. CR rates in the delayed (24-120 h), overall (0-120 h), and acute periods (0-24 h) were 83.3%, 83.3%, and 100%, respectively. No grade 3 or higher treatment-related adverse events were observed except for one patient who had grade 3 dry mouth as evaluated by Common Terminology Criteria for Adverse Events version 5.0.
CONCLUSIONS
Prophylactic antiemetic therapy with mirtazapine plus granisetron and dexamethasone shows promising efficacy and an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic cancers receiving a CBDCA-based regimen at AUC ≥ 4 mg/mL per minute.
Topics: Humans; Granisetron; Male; Mirtazapine; Female; Dexamethasone; Middle Aged; Aged; Nausea; Vomiting; Prospective Studies; Carboplatin; Antiemetics; Thoracic Neoplasms; Adult; Antineoplastic Combined Chemotherapy Protocols; Aged, 80 and over; Japan; Drug Therapy, Combination
PubMed: 38678830
DOI: 10.1016/j.lungcan.2024.107801 -
Science Advances Apr 2024Serotonin [5-hydroxytryptamine (5-HT)] acts via 13 different receptors in humans. Of these receptor subtypes, all but 5-HTR have confirmed roles in native tissue and are...
Serotonin [5-hydroxytryptamine (5-HT)] acts via 13 different receptors in humans. Of these receptor subtypes, all but 5-HTR have confirmed roles in native tissue and are validated drug targets. Despite 5-HTR's therapeutic potential and plausible druggability, the mechanisms of its activation remain elusive. To illuminate 5-HTR's pharmacology in relation to the highly homologous 5-HTR, we screened a library of aminergic receptor ligands at both receptors and observe 5-HTR/5-HTR agonism by multicyclic drugs described as pan-antagonists at 5-HT receptors. Potent agonism by tetracyclic antidepressants mianserin, setiptiline, and mirtazapine suggests a mechanism for their clinically observed antimigraine properties. Using cryo-EM and mutagenesis studies, we uncover and characterize unique agonist-like binding poses of mianserin and setiptiline at 5-HTR distinct from similar drug scaffolds in inactive-state 5-HTR structures. Together with computational studies, our data suggest that these binding poses alongside receptor-specific allosteric coupling in 5-HTR and 5-HTR contribute to the agonist activity of these antidepressants.
Topics: Humans; Serotonin; Mianserin; Antidepressive Agents; Receptors, Serotonin; Signal Transduction
PubMed: 38630816
DOI: 10.1126/sciadv.adk4855 -
Clinical Psychopharmacology and... May 2024Very-late-onset schizophrenia-like psychosis (VLOSLP) is a condition in which psychotic symptoms emerge after the age of 60 years. Given its heterogeneous nature, VLOSLP...
Very-late-onset schizophrenia-like psychosis (VLOSLP) is a condition in which psychotic symptoms emerge after the age of 60 years. Given its heterogeneous nature, VLOSLP remains a diagnostic and therapeutic dilemma. Here, we report a case of a 68-year-old patient with psychosis refractory to antipsychotics who was successfully treated with mirtazapine monotherapy. This case suggests that mirtazapine monotherapy may be effective for the treatment of patients with antipsychotic- refractory VLOSLP.
PubMed: 38627087
DOI: 10.9758/cpn.23.1103 -
Clinical Psychopharmacology and... May 2024Clozapine is the only approved drug for treatment-resistant schizophrenia, but the response to the drug is often inadequate. Augmentation with other antipsychotics,... (Review)
Review
Clozapine is the only approved drug for treatment-resistant schizophrenia, but the response to the drug is often inadequate. Augmentation with other antipsychotics, anticonvulsants, and antidepressants is recommended for such patients, but there is a lack of evidence regarding the most effective therapy. This network meta-analysis was conducted to evaluate the efficacy of pharmacological agents used in the augmentation strategies in patients who were partial/ non-responders to clozapine. Relevant data were extracted from 30 randomized controlled trials through searches of electronic databases (MEDLINE/PubMed, Embase, Cochrane, clinical trial registries). PRISMA guidelines were followed for the extraction, management, analysis, and reporting of the data. The outcome measure in this study was a reduction in symptom severity according to total PANSS/BPRS and was reported as the standardized mean difference with a 95% credible interval. Bayesian network meta-analysis with random effects model and uninformative priors was conducted, and the ranking probability of each intervention was done. Meta-regression was done to assess the effect of duration on the reduction in symptom severity scores. Mirtazapine (-5.2 [95%CrI: -7.7, -2.7]) and memantine (-2.1 [95%CrI: -4.0, -0.19]] were more efficacious than placebo for augmentation of clozapine in partial/non-responders and were the most effective adjunctive agents as per SUCRA scores. Both drugs did not cause a significant increase in frequency of adverse events compared to placebo. There was a significant effect of duration on the reduction in symptom severity. There was no evident publication bias. Mirtazapine and memantine may prove beneficial for augmentation of clozapine in non/partial responders to monotherapy.
PubMed: 38627071
DOI: 10.9758/cpn.23.1119 -
Behavioral Sciences (Basel, Switzerland) Mar 2024Self-induced bloodletting (SBL) is a very rare form of self-injury (SI) seen primarily in adolescents and young adults with personality and eating disorders. It can...
Successful Pharmacologic Treatment of Self-Bloodletting with Factitious Chronic Anemia (Lasthénie de Ferjol Syndrome) with High-Dose Serotonergic Medication: A Case Report.
Self-induced bloodletting (SBL) is a very rare form of self-injury (SI) seen primarily in adolescents and young adults with personality and eating disorders. It can result in complications like malaise, fatigue, or iron-deficiency anemia (Lasthénie de Ferjol syndrome, LFS), and poses a risk of accidental death or suicide. The condition often goes undetected due to patient concealment. There is no specific treatment established, and pharmacological strategies remain uncertain. We discuss the case of a 22-year-old female patient treated at our Psychiatry and Psychotherapy Department following a suicide attempt via SBL. She self-administered a venous cannula, losing 1.5 L of blood. Diagnosed with iron-deficiency anemia (LFS), she was initially treated with mirtazapine, risperidone, lithium, and later off-label high-dose clomipramine (300 mg/d). Clomipramine significantly reduced her SBL and suicidal thoughts, and her hemoglobin levels re-normalized under iron-substitution therapy. Despite improvement and later discharge, she attempted suicide by SBL again three months later, having stopped clomipramine due to adverse side effects. High-dose escitalopram was administered, leading to a decrease and eventual cessation of her SBL urges. This case demonstrates that patients with SBL/LFS can benefit from high-dose clomipramine or escitalopram. Despite its rarity, the consideration of high-dose serotonergic antidepressants is crucial in psychiatric diagnostics and treatment for patients affected by SBL/LFS.
PubMed: 38540540
DOI: 10.3390/bs14030237 -
Comparative Medicine Feb 2024
PubMed: 38532261
DOI: 10.30802/AALAS-CM-24-000010 -
Neuropsychopharmacology Reports Jun 2024Burning mouth syndrome (BMS) is characterized by burning sensations in the oral region without corresponding abnormalities and is often accompanied by uncomfortable...
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.
Topics: Humans; Clonazepam; Middle Aged; Burning Mouth Syndrome; Male; Female; Drug Therapy, Combination; Isoindoles; Thiazoles; GABA Modulators
PubMed: 38500267
DOI: 10.1002/npr2.12425 -
JAMA Network Open Mar 2024Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Antipsychotic-induced akathisia (AIA) occurs in 14% to 35% of patients treated with antipsychotics and is associated with increased suicide and decreased adherence in patients with schizophrenia. However, no comprehensive review and network meta-analysis has been conducted to compare the efficacy of treatments for AIA.
OBJECTIVE
To compare the efficacy associated with AIA treatments.
DATA SOURCES
Three databases (MEDLINE, Web of Science, and Google Scholar) were systematically searched by multiple researchers for double-blind randomized clinical trials (RCTs) comparing active drugs for the treatment of AIA with placebo or another treatment between May 30 and June 18, 2023.
STUDY SELECTION
Selected studies were RCTs that compared adjunctive drugs for AIA vs placebo or adjunctive treatment in patients treated with antipsychotics fulfilling the criteria for akathisia, RCTs with sample size of 10 patients or more, only trials in which no additional drugs were administered during the study, and RCTs that used a validated akathisia score. Trials with missing data for the main outcome (akathisia score at the end points) were excluded.
DATA EXTRACTION AND SYNTHESIS
Data extraction and synthesis were performed, estimating standardized mean differences (SMDs) through pairwise and network meta-analysis with a random-effects model. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed.
MAIN OUTCOMES AND MEASURES
The primary outcome was the severity of akathisia measured by a validated scale at the last available end point.
RESULTS
Fifteen trials involving 492 participants compared 10 treatments with placebo. Mirtazapine (15 mg/d for ≥5 days; SMD, -1.20; 95% CI, -1.83 to -0.58), biperiden (6 mg/d for ≥14 days; SMD, -1.01; 95% CI, -1.69 to -0.34), vitamin B6 (600-1200 mg/d for ≥5 days; SMD, -0.92; 95% CI, -1.57 to -0.26), trazodone (50 mg/d for ≥5 days; SMD, -0.84; 95% CI, -1.54 to -0.14), mianserin (15 mg/d for ≥5 days; SMD, -0.81; 95% CI, -1.44 to -0.19), and propranolol (20 mg/d for ≥6 days; SMD, -0.78; 95% CI, -1.35 to -0.22) were associated with greater efficacy than placebo, with low to moderate heterogeneity (I2 = 34.6%; 95% CI, 0.0%-71.1%). Cyproheptadine, clonazepam, zolmitriptan, and valproate did not yield significant effects. Eight trials were rated as having low risk of bias; 2, moderate risk; and 5, high risk. Sensitivity analyses generally confirmed the results for all drugs except for cyproheptadine and propranolol. No association between effect sizes and psychotic severity was found.
CONCLUSIONS AND RELEVANCE
In this systematic review and network meta-analysis, mirtazapine, biperiden, and vitamin B6 were associated with the greatest efficacy for AIA, with vitamin B6 having the best efficacy and tolerance profile. Trazodone, mianserin, and propranolol appeared as effective alternatives with slightly less favorable efficacy and tolerance profiles. These findings should assist prescribers in selecting an appropriate medication for treating AIA.
Topics: Humans; Antipsychotic Agents; Biperiden; Cyproheptadine; Gallopamil; Mianserin; Mirtazapine; Network Meta-Analysis; Propranolol; Randomized Controlled Trials as Topic; Trazodone; Vitamin B 6; Akathisia, Drug-Induced
PubMed: 38451521
DOI: 10.1001/jamanetworkopen.2024.1527