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The American Journal of Geriatric... Sep 2022Nonadherence to antidepressants interferes with optimal treatment of late-life depression. This analysis examines clinical and treatment factors predicting medication... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Nonadherence to antidepressants interferes with optimal treatment of late-life depression. This analysis examines clinical and treatment factors predicting medication nonadherence in difficult-to-treat late-life depression.
METHODS
Secondary analysis of data from a clinical trial of antidepressant pharmacotherapy for Major Depressive Disorder in 468 adults aged 60+ years. All participants received venlafaxine XR for 12 weeks. Nonremitters were randomized to augmentation with either aripiprazole or placebo for 12 additional weeks. Medication adherence was assessed 14 times over 24 weeks. The analyses examined sociodemographic, clinical, and treatment factors that may predict antidepressant nonadherence during early (weeks 1-6), late (weeks 7-12), and augmentation (weeks 13--24) treatment.
RESULTS
Poor cognitive function and early response were predictive of early nonadherence. Poor cognitive function and prior nonadherence were predictive of late nonadherence. Living alone was associated with nonadherence both late and during augmentation treatment.
CONCLUSION
Future studies should consider the role of early response and cognitive function to improve antidepressant adherence, particularly among older adults who live alone.
Topics: Aged; Antidepressive Agents; Depression; Depressive Disorder, Major; Humans; Medication Adherence; Venlafaxine Hydrochloride
PubMed: 35393165
DOI: 10.1016/j.jagp.2022.03.002 -
Evidence-based Mental Health Nov 2022Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants.
BACKGROUND
Studies report an increased risk of self-harm or suicide in people prescribed mirtazapine compared with other antidepressants.
OBJECTIVES
To compare the risk of serious self-harm in people prescribed mirtazapine versus other antidepressants as second-line treatments.
DESIGN AND SETTING
Cohort study using anonymised English primary care electronic health records, hospital admission data and mortality data with study window 1 January 2005 to 30 November 2018.
PARTICIPANTS
24 516 people diagnosed with depression, aged 18-99 years, initially prescribed a selective serotonin reuptake inhibitor (SSRI) and then prescribed mirtazapine, a different SSRI, amitriptyline or venlafaxine.
MAIN OUTCOME MEASURES
Hospitalisation or death due to deliberate self-harm. Age-sex standardised rates were calculated and survival analyses were performed using inverse probability of treatment weighting to account for baseline covariates.
RESULTS
Standardised rates of serious self-harm ranged from 3.8/1000 person-years (amitriptyline) to 14.1/1000 person-years (mirtazapine). After weighting, the risk of serious self-harm did not differ significantly between the mirtazapine group and the SSRI or venlafaxine groups (HRs (95% CI) 1.18 (0.84 to 1.65) and 0.85 (0.51 to 1.41) respectively). The risk was significantly higher in the mirtazapine than the amitriptyline group (3.04 (1.36 to 6.79)) but was attenuated after adjusting for dose.
CONCLUSIONS
There was no evidence for a difference in risk between mirtazapine and SSRIs or venlafaxine after accounting for baseline characteristics. The higher risk in the mirtazapine versus the amitriptyline group might reflect residual confounding if amitriptyline is avoided in people considered at risk of self-harm.
CLINICAL IMPLICATIONS
Addressing baseline risk factors and careful monitoring might improve outcomes for people at risk of serious self-harm.
Topics: Humans; Mirtazapine; Cohort Studies; Venlafaxine Hydrochloride; Depression; Amitriptyline; Electronic Health Records; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Suicide; United Kingdom
PubMed: 35246454
DOI: 10.1136/ebmental-2021-300355 -
Journal of Addiction MedicineThe botanical product kratom produces opioid-like effects at high doses and is sometimes used for opioid replacement by individuals with opioid use disorder....
The botanical product kratom produces opioid-like effects at high doses and is sometimes used for opioid replacement by individuals with opioid use disorder. Mitragynine, a major alkaloid contained in kratom leaves, has been shown to inhibit multiple cytochromes P450 (CYPs) in vitro, including CYP2D6 and CYP3A. As such, kratom may precipitate pharmacokinetic drug interactions when co-consumed with certain medications. We present a case of a patient taking 150 mg venlafaxine (CYP2D6/3A substrate), 300 mg quetiapine (CYP3A substrate), and a high amount of kratom (~90 g) daily. The patient presented to the emergency department with serotonin syndrome and corrected electrocardiogram abnormalities that may have been secondary to supratherapeutic exposure to venlafaxine and/or quetiapine. The patient's symptoms resolved after discontinuation of venlafaxine and quetiapine. He was amenable to medication therapy for kratom discontinuation and successfully completed an at-home induction with buprenorphine/naloxone. This case report adds to the literature about potential pharmacokinetic kratom-drug interactions and suggests that buprenorphine/naloxone can facilitate recovery from kratom use disorder.
Topics: Analgesics, Opioid; Buprenorphine, Naloxone Drug Combination; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP3A; Drug Interactions; Humans; Male; Mitragyna; Quetiapine Fumarate; Venlafaxine Hydrochloride
PubMed: 35165231
DOI: 10.1097/ADM.0000000000000968 -
Basic & Clinical Pharmacology &... Apr 2022Venlafaxine (VEN), a first-line antidepressant, and Zuojin Pill (ZJP), a common herbal medicine consisting of Rhizoma Coptidis and Fructus Evodiae, are high likely...
Venlafaxine (VEN), a first-line antidepressant, and Zuojin Pill (ZJP), a common herbal medicine consisting of Rhizoma Coptidis and Fructus Evodiae, are high likely co-administered in China. ZJP could significantly inhibit VEN pharmacokinetics in vitro and in rats through suppression of CYP2D6 activity. To date, however, no clinical study has demonstrated the clinical relevance. Here, the VEN pharmacokinetics at a single dose of VEN with or without co-administration of ZJP was compared. ZJP had a weak herb-drug interactions (HDI) on the pharmacokinetics of VEN. The geometric means of C and AUC of VEN increased by 36.7% and 34.6%, respectively, and the corresponding 90% confidence intervals (CIs) of geometric mean ratios (GMRs) exceed outside bioequivalent range of 0.80-1.25. However, the corresponding 90% CIs of GMRs of these parameters for ODV were within the range. Since ODV exposure (AUC), approximately 3.4-fold higher than that of VEN, hardly changed, the systemic exposure of VEN active moiety (VEN + ODV) with ZJP increased slightly (≤8.5%) compared with that of VEN alone. In addition, the incidence of VEN-related side effects, especially gastrointestinal relevance, was significantly reduced with ZJP. Therefore, rational concomitant use of VEN and ZJP might have low risk of HDI and be promising in clinical practice.
Topics: Animals; Antidepressive Agents; Drugs, Chinese Herbal; Herb-Drug Interactions; Humans; Rats; Venlafaxine Hydrochloride
PubMed: 35132786
DOI: 10.1111/bcpt.13713 -
BMC Psychiatry Jan 2022Response to antidepressant therapy is highly variable among individuals. Pharmacogenomic (PGx) testing presents an opportunity to guide drug selection while optimizing...
BACKGROUND
Response to antidepressant therapy is highly variable among individuals. Pharmacogenomic (PGx) testing presents an opportunity to guide drug selection while optimizing therapy outcomes and/or decreasing the risk for toxicity.
CASE PRESENTATION
A patient with multiple comorbidities, including severe major depressive disorder (MDD), experienced adverse drug events and undesirable response to multiple antidepressant medications (i.e., bupropion, escitalopram, and venlafaxine). A clinical pharmacist assessed significant drug-gene, drug-drug, and drug-drug-gene interactions as well as other clinical factors to provide recommendations for antidepressant therapy optimization.
CONCLUSION
This case highlights the importance of PGx testing and the key role of pharmacists in identifying and mitigating drug-related problems and optimizing drug therapy in patients with MDD.
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Pharmacists; Pharmacogenetics; Venlafaxine Hydrochloride
PubMed: 35057765
DOI: 10.1186/s12888-021-03659-4 -
Romanian Journal of Ophthalmology 2021We report a case of bilateral and acute angle closure after a single dose of antidepressant venlafaxine in a 40-year-old woman with no previous pathologies, who asked...
We report a case of bilateral and acute angle closure after a single dose of antidepressant venlafaxine in a 40-year-old woman with no previous pathologies, who asked for consultation for blurred vision and pain in the left eye. Initial evaluation included visual acuity, slit lamp biomicroscopy and intraocular pressure (IOP) measurement using Goldmann's applanation tonometer. Gonioscopy and fundus examination were also performed in both eyes. Examination and IOP supported the diagnosis of acute glaucoma in the left eye. The patient's evolution was satisfactory after bilateral peripheral iridotomy was performed with Nd-YAG laser, as described in the cases reported in the international literature. The pathophysiology of angle closure and its relationship with venlafaxine intake were also discussed.
Topics: Adult; Female; Glaucoma, Angle-Closure; Gonioscopy; Humans; Intraocular Pressure; Iris; Laser Therapy; Venlafaxine Hydrochloride
PubMed: 35036652
DOI: 10.22336/rjo.2021.56 -
The International Journal of... Apr 2022Venlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter...
BACKGROUND
Venlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter (NET) remained to be determined. Paroxetine is generally considered as a selective 5-HT reuptake inhibitor but exhibits some affinity for NET. Atomoxetine is a NET inhibitor but also has some affinity for the 5-HT reuptake transporter (SERT).
METHODS
This study examined the effects of forced titration of venlafaxine from 75 to 300 mg/d, paroxetine from 20 to 50 mg/d, or atomoxetine from 25 to 80 mg/d in 32 patients with major depressive disorder. Inhibition of SERT was estimated using the depletion of whole-blood 5-HT. Inhibition of NET was assessed using the attenuation of the systolic blood pressure produced by i.v. injections of tyramine.
RESULTS
All 3 medications significantly reduced 5-HT levels at the initiating regimens: venlafaxine and paroxetine by approximately 60% and atomoxetine by 16%. The 3 subsequent regimens of venlafaxine and paroxetine reduced 5-HT levels by over 90%, but the highest dose of atomoxetine only reached a 40% inhibition. Atomoxetine dose dependently inhibited the tyramine pressor response from the lowest dose, venlafaxine from 225 mg/d, and paroxetine left it unaltered throughout.
CONCLUSION
These results confirm that venlafaxine and paroxetine are potent SERT inhibitors over their usual therapeutic range but that venlafaxine starts inhibiting NET only at 225 mg/d, whereas paroxetine remains selective for SERT up to 50 mg/d. Atomoxetine dose dependently inhibits NET from a low dose but does not inhibit SERT to a clinically relevant degree.
Topics: Antidepressive Agents, Second-Generation; Atomoxetine Hydrochloride; Cyclohexanols; Depressive Disorder, Major; Humans; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Paroxetine; Serotonin; Selective Serotonin Reuptake Inhibitors; Tyramine; Venlafaxine Hydrochloride
PubMed: 34958348
DOI: 10.1093/ijnp/pyab086 -
Brazilian Journal of Biology = Revista... 2021The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse....
The present research was made to determine the micronuclei and cytotoxic capacity of the antidepressant venlafaxine in an in vivo acute and subchronic assays in mouse. In the first study, we administered once 5, 50, and 250 mg/kg of the drug, and included a negative and a daunorubicin treated group. Observations were daily made during four days. The subchronic assay lasted 5 weeks with daily administration of venlafaxine (1, 5, and 10 mg/kg) plus a negative and an imipramine administered groups. Observations were made each week. In the first assay results showed no micronucleated polychromatic erythrocytes (MNPE) increase, except with the high dose at 72 h. The strongest cytotoxic effect was found with 250 mg/kg at 72 h (a 51% cytotoxic effect in comparison with the mean control level). In the subchronic assay no MNPE increase was found; however, with the highest dose a significant increase of micronucleated normochromatic erythrocytes was observed in the last three weeks (a mean of 51% respect to the mean control value). A cytotoxic effect with the two high doses in the last two weeks was observed (a polychromatic erythrocyte mean decrease of 52% respect to the mean control value). Results suggest caution with venlafaxine.
Topics: Animals; Antineoplastic Agents; DNA Damage; Dose-Response Relationship, Drug; Erythrocytes; Mice; Micronucleus Tests; Venlafaxine Hydrochloride
PubMed: 34932628
DOI: 10.1590/1519-6984.251289 -
Medicine Dec 2021Drug-induced liver injury (DILI) is the leading cause of acute liver injury (ALI), market withdrawal of a drug, and rejection of applications for marketing licenses. The...
RATIONALE
Drug-induced liver injury (DILI) is the leading cause of acute liver injury (ALI), market withdrawal of a drug, and rejection of applications for marketing licenses. The incidence of DILI is very low, with a value between 1 and 19 per 100,000 patient years. All antidepressants may induce DILI even at low therapeutic doses. In this report, we present a case of ALI after venlafaxine administration.
PATIENT CONCERNS
A 27-year-old Chinese Han woman was admitted for depression. Several serum liver function indices in this patient were abnormal after antidepressant treatment. The Roussel Uclaf Causality Assessment Method (RUCAM) causality assessment score was 8, and the R value was 31.18.
DIAGNOSES
The patient was diagnosed with hepatocellular ALI, which was derived from venlafaxine-related adverse events.
INTERVENTIONS
First, all medications were stopped to block the progression of DILI. Then, a hepatoprotective strategy and proper psychological treatment were performed to recover the impaired hepatic function.
OUTCOMES
Liver function was fully recovered as indicated by liver function indices and ultrasound imaging.
LESSONS
The possibility of DILI should not be overlooked during the long-term use of antipsychotic drugs. In response, regular liver function monitoring should be performed in a timely manner to avoid missing diagnoses and delayed treatment. Furthermore, the necessary medical treatment needs to be conducted after the occurrence of ALI.
Topics: Adult; Adverse Drug Reaction Reporting Systems; Chemical and Drug Induced Liver Injury; Depression; Drug-Related Side Effects and Adverse Reactions; Female; Humans; Liver; Ultrasonography; Venlafaxine Hydrochloride
PubMed: 34889278
DOI: 10.1097/MD.0000000000028140 -
PLoS Medicine Nov 2021The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective...
BACKGROUND
The prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths.
METHODS AND FINDINGS
A population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates.
CONCLUSIONS
Based on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Cohort Studies; Congenital Abnormalities; Denmark; Duloxetine Hydrochloride; Female; Humans; Maternal Exposure; Middle Aged; Pregnancy; Risk Factors; Stillbirth; Sweden; Young Adult
PubMed: 34807906
DOI: 10.1371/journal.pmed.1003851