Venlafaxine-Associated Rhabdomyolysis: A Literature Review.

PURPOSE: This systematic review aimed to investigate the clinical manifestations and characteristics of venlafaxine-associated rhabdomyolysis. METHODS: A systematic search was conducted in PubMed, Elsevier, Science Direct, Embase, Springer Link, Wiley Online Library, CNKI, and Wanfang databases from the date of database inception to January 2023. Previously reported cases of venlafaxine-associated rhabdomyolysis were identified, and relevant data from these cases were collected for descriptive statistical analysis. Cases that met the inclusion criteria were evaluated to determine the correlation between adverse reactions and venlafaxine. RESULTS: A total of 12 patients with venlafaxine-associated rhabdomyolysis were included. None of these patients had a history of muscle pain or discomfort. Of the 12 patients, 5 patients received venlafaxine at doses of ≤225 mg/d, whereas the remaining 7 patients received doses exceeding 225 mg/d. The main clinical symptoms included myalgia, muscle weakness, and renal injury. All 12 patients discontinued venlafaxine and received symptomatic care. CONCLUSIONS: Venlafaxine, used either as a monotherapy or in combination with other drugs, may be associated with rhabdomyolysis. Creatine kinase levels may normalize or significantly decrease after discontinuation of venlafaxine and symptomatic treatment.

Venlafaxine aggravating interstitial pneumonia: A case report.

A 70-year-old male taking venlafaxine for depression developed interstitial pneumonia and was admitted with shortness of breath and dyspnea. A computed tomography (CT) chest scan showed diffuse multiple lung lesions in both lungs, suggesting interstitial changes with inflammation or exudation. Compared with the CT chest scan 1 month earlier, there were significant progresses and new findings. The clinical diagnosis was interstitial pneumonia with pulmonary infection. The patient had been treated with fluvoxamine 100 mg/day, duloxetine 60 mg/day, venlafaxine 75 mg/day for depression over the past 4 months. The exacerbation of interstitial pneumonia was suspected to be related to venlafaxine. Wheezing improved slightly after discontinuation of venlafaxine and treatment in the respiratory ICU. However, the patient could not tolerate the ICU environment, therefore became agitated, irritable, and anxious. Finally the patient gave up treatment and was discharged. Three months after discharge, the patient died of a sudden of interstitial pneumonia. A Naranjo assessment score of 3 was obtained, indicating a possible correlation between the patient's adverse drug reaction and the suspect drug.

Are all antidepressants the same? The consumer has a point.

BACKGROUND: Although a large variety of antidepressants agents (AD) with different mechanisms of action are available, no significant differences in efficacy and safety have been shown. However, there have been few attempts to incorporate data on subjective experiences under different AD. METHOD: We conducted a qualitative and quantitative analysis of the posts from the website www.askapatient.com from different AD. We reviewed a random sample of 1000 posts. RESULT: After applying the inclusion and exclusion criteria, we included a final sample of 450 posts, 50 on each of the most used AD: sertraline, citalopram, paroxetine, escitalopram, fluoxetine, venlafaxine, duloxetine, mirtazapine, and bupropion. Bupropion, citalopram, and venlafaxine had the higher overall satisfaction ratings. Sertraline, paroxetine, and fluoxetine had high reports of emotional blunting, while bupropion very few. Overall satisfaction with AD treatment was inversely associated with the presence of the following side-effects: suicidality, irritability, emotional blunting, cognitive disturbances, and withdrawal symptoms. After adjusting for confounders, only emotional blunting was shown to be more frequently reported by users of serotonergic agents, as compared to non-serotoninergic agents. CONCLUSION: This research points out that the subjective experience of patients under treatment should be taken into consideration when selecting an AD as differences between agents were evident. In contrast to the more frequent treatment decisions, users might prefer receiving a non-serotoninergic agent over a serotonergic one due to their lower propensity to produce emotional blunting.

Anxiety exacerbation in a patient with chronic myeloid leukemia receiving dasatinib and venlafaxine.

INTRODUCTION: Tyrosine kinase inhibitor (TKI) use leads to near-normal life expectancy in patients with chronic myeloid leukemia (CML); unfortunately for some patients, adverse drug effects (ADEs) and medication burden associated with TKI therapy can lead to decreased quality of life. Additionally, TKIs have drug interactions that may negatively impact patients' management of co-morbidities or lead to increased ADEs. CASE REPORT: A 65-year-old female with a history of anxiety treated and controlled with venlafaxine experienced increased and resistant anxiety and insomnia after starting dasatinib for CML. MANAGEMENT AND OUTCOME: On dasatinib, the patient experienced worsening anxiety and insomnia. The stress of a new leukemia diagnosis, drug interactions, and ADEs from dasatinib were considered possible causes. Dose adjustments to dasatinib and venlafaxine were made to control the patient's symptoms. However, the patient's symptoms did not resolve. After being on dasatinib for 2.5 years, the patient discontinued TKI therapy due to being in a deep molecular remission and given ongoing challenges managing anxiety. Within 4 months of stopping dasatinib, the patient reported an improvement in anxiety and overall emotional wellbeing. She continues to feel better and remains in a complete molecular remission 20 months off treatment. DISCUSSION: This case demonstrates a possible previously unknown drug interaction with dasatinib as well as a possible rarely reported ADE of dasatinib. Additionally, it highlights the difficulties patients with psychiatric disorders may face on TKI therapy and challenges providers may have in identifying rare psychiatric ADEs, thus emphasizing the need for documentation of these types of cases.

Adherence, acceptability and tolerability of venlafaxine extended release at dose of 300 mg/day in patients with major depressive disorder.

Adherence to antidepressants is essential for good outcomes when treating depressive disorders.

Pharmacist assessment of drug-gene interactions and drug-induced phenoconversion in major depressive disorder: a case report.

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.

Venlafaxine-related galactorrhea in an adolescent female: A case report.

Hyperprolactinemia with galactorrhea is a well-documented adverse effect of some psychotropic medications. While advanced practice psychiatric nurses are likely familiar with hyperprolactinemia with galactorrhea as an adverse effect of antipsychotics, they may be less familiar with hyperprolactinemia with galactorrhea associated with antidepressants, an adverse effect that is far less common. Advanced practice psychiatric nurses must be able to identify hyperprolactinemia and galactorrhea in patients and must be able to evaluate and manage antidepressant-related hyperprolactinemia with galactorrhea. Thus, this case report describes hyperprolactinemia with galactorrhea in a teenage female prescribed venlafaxine for the treatment of major depressive disorder and posttraumatic stress disorder. To our knowledge, this is the first case report that describes galactorrhea related to a reuptake inhibitor (SNRI) in an adolescent.

Impact of Venlafaxine on Platelet Count and Activity-Case Report and Narrative Review.

Venlafaxine (VEN) is considered to be one of the most effective antidepressants. It belongs to the group of serotonin (5-HT) and noradrenaline (NA) reuptake inhibitors (SNRIs). NA and 5-HT have receptors on the surface of platelets and are involved in platelet aggregation. In this case study, we present the case of a patient treated for one of the types of myeloproliferative neoplasm (MPN), essential thrombocythemia (ET), in whom VEN was added to pharmacotherapy during the treatment of a severe episode of depression with psychotic symptoms. We observed a gradual reduction in platelet count when increasing the dose of VEN. We also present a narrative review of literature about the effect of VEN on platelet counts and activity. We conclude that, in the group of patients taking VEN, attention should be paid to the rare adverse effect of a decrease in the number of platelets.

Influence of Different Antidepressants on Ocular Surface in Patients With Major Depressive Disorder.

PURPOSE: Several studies have previously reported the association between dry eye and depression along with the treatment of depression. The aim of this study was to investigate the effects of different antidepressant drugs on tear parameters in patients with major depressive disorder. METHODS: We recruited 132 patients who were using different antidepressants and 58 healthy controls. Venlafaxine, duloxetine, escitalopram, and sertraline were used by 34, 28, 36, and 34 patients, respectively. The participants filled out and completed the Beck Depression Scale. We recorded Schirmer test, tear breakup time (TBUT) and corneal staining values of the participants. The Ocular Surface Disease Index was completed by the participants. In addition, we evaluated the tear meniscus parameters by using anterior segment optical coherence tomography. RESULTS: All conventional dry eye tests and tear meniscus parameters were significantly lesser in the depression group than in the control group (Schirmer test, 11.41 ± 6.73 mm and 22.53 ± 4.98 mm; TBUT, 5.29 ± 2.92 seconds and 13.38 ± 1.72; Corneal staining, tear meniscus area, 0.026 ± 0.012 mm2 and 0.11 ± 0.025 mm2; tear meniscus depth, 182.75 ± 78.79 µm and 257.48 ± 90.1 µm; tear meniscus height, 290.3 ± 133.63 µm and 459.78 ± 180.26 µm, in patients and controls, respectively). The tear parameters of the duloxetine group were lowest among the drug groups and Schirmer test, and TBUT of the venlafaxine group was statistically significantly different from the duloxetine group (P = 0.028 and P = 0.017, respectively). Ocular Surface Disease Index score of the depression group was significantly higher than the control group (31.12 ± 21.15 and 17.43 ± 11.75 in depression and control group, respectively.). CONCLUSIONS: We found that the usage of selective serotonin reuptake inhibitors and serotonin noradrenaline reuptake inhibitors affects the ocular surface by a mechanism other than the anticholinergic system. Besides serotonin blockage, the noradrenaline blockade of serotonin noradrenaline reuptake inhibitors may increase the dry eye findings on the ocular surface.

Antidepressant use in pregnancy and severe cardiac malformations: Danish register-based study.

OBJECTIVE: Studies restricted to live births may underestimate severe teratogenic effects. We address the limitation by including data from both prenatal and postnatal diagnoses of cardiac malformations. DESIGN: Register-based study. SETTING: Denmark. POPULATION: 364 012 singleton pregnancies from 2007 to 2014. METHODS: We used data from five nationwide registries. Exposure to antidepressants was measured using redeemed prescriptions. MAIN OUTCOME MEASURES: Pregnancies with cardiac malformations that end in miscarriage, termination, stillbirth, postnatal death or cardiac surgery <1 year of birth were classified as severe cardiac malformations (SCM). Propensity scores with adjusted prevalence ratios (PRs) were calculated. RESULTS: SCM were reported in 972 of 364 012 pregnancies overall and in 16 of 4105 exposed. For venlafaxine, the PR for SCM was 2.13 (95% confidence interval [CI] 0.89-5.13), 1.73 (95% CI 1.08-2.77) for other cardiac malformations, and there was a cluster of hypoplastic left heart syndromes (HLHS) (crude PR 17.4 [95% CI 6.41-47.2]), none of which ended in a live birth. For HLHS, the absolute risk increase was 4.4/1000 and the number needed to harm was 225. For selective serotonin reuptake inhibitors, the PRs were 1.09 (95% CI 0.52-2.30) and 1.38 (95% CI 1.00-1.92) for SCM and other cardiac malformations, respectively. CONCLUSIONS: Pregnancy exposure to venlafaxine is associated with an increased risk of severe cardiac malformations but with a low absolute risk. Potential mechanisms include direct effects or confounding by indication. Venlafaxine exposure is a marker for risk pregnancies for which fetal echocardiography may be considered. TWEETABLE ABSTRACT: Exposure to venlafaxine is associated with an increased risk of cardiac malformations but with a low absolute risk.

Venlafaxine vs. fluoxetine in postmenopausal women with major depressive disorder: an 8-week, randomized, single-blind, active-controlled study.

BACKGROUND: In the population of postmenopausal patients with major depressive disorder (MDD), the superiority of serotonin-norepinephrine reuptake inhibitors (SNRIs) over selective serotonin reuptake inhibitors (SSRIs) has not yet been definitively proven. Consequently, a direct comparison of the efficacy of SSRIs and SNRIs in the treatment of postmenopausal depression could provide relevant data. The aim of this study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of postmenopausal MDD. METHODS: This was an 8-week, multicenter, randomized, single-blind, active-controlled trial conducted at a psychiatric hospital (Beijing Anding Hospital) and a general hospital (Beijing Chaoyang Hospital) between April 2013 and September 2017. The primary outcome measure was improving depressive symptoms (Hamilton Depression Rating Scale (HAMD-24) score). The secondary outcomes included the change of HAMD-24 anxiety/somatization factor score and Clinical Global Impressions-Improvement (CGI-I) response rate. Safety was assessed by treatment-emergent adverse events (TEAEs) and laboratory tests. Efficacy was analyzed by using the full analysis set (FAS) following the modified intention-to-treat (mITT) principle. The primary endpoint measurements were analyzed using a mixed-effect model for repeated measures (MMRM) model with patients as a random-effect factor, treatment group as the independent variable, time as a repeated measure, and baseline covariates, using a first-order ante dependence covariance matrix. RESULTS: A total of 184 women were randomized. The full analysis set (FAS) included 172 patients (venlafaxine, n = 82; fluoxetine, n = 90). Over the 8-week study period, the reduction in HAMD-24 scores was significant (P < 0.001) in both groups, while a significantly greater decline from baseline was observed in the venlafaxine group compared with the fluoxetine group (least-squares mean difference [95% CI]: - 2.22 [- 7.08, - 0.41]), P = 0.001). The baseline-to-week-8 least-squares mean change of the anxiety/somatization factor scores, CGI-I response rate were greater in the venlafaxine group than in the fluoxetine group (all P < 0.05). The most frequent TEAEs (≥5%) in both groups were nausea, somnolence, dizziness, headache, and dry mouth. There was no significant difference in the incidence of adverse events between the two groups. CONCLUSION: Venlafaxine was well tolerated and compared to fluoxetine, it led to a greater improvement in the treatment of postmenopausal MDD. TRIAL REGISTRATION: Clinical Trials. gov #NCT01824433 . The trial was registered on April 4, 2013.

The Effect of Venlafaxine on Electrocardiogram Intervals During Treatment for Depression in Older Adults.

PURPOSE/BACKGROUND: Venlafaxine is a commonly used antidepressant with both serotonergic and noradrenergic activity. There are concerns that it may prolong the corrected QT interval (QTc), and older adults may be at higher risk for this adverse effect, especially at higher dosages of the medication. METHODS/PROCEDURES: In this secondary analysis of a prospective clinical trial, we measured changes in QTc and other electrocardiogram (ECG) parameters in 169 adults 60 years or older with a major depressive disorder treated acutely with venlafaxine extended release up to 300 mg daily. We examined the relationship of venlafaxine dosage and ECG parameters, as well as the relationship between serum levels of venlafaxine and ECG parameters. FINDINGS/RESULTS: Venlafaxine exposure was not associated with an increase in QTc. Heart rate increased with venlafaxine treatment, whereas the PR interval shortened, and QRS width did not change significantly. The QTc change from baseline was not associated with venlafaxine dosages or serum concentrations. Age, sex, cardiovascular comorbidities, and depression remission status did not predict changes in QTc with venlafaxine. IMPLICATIONS/CONCLUSIONS: Venlafaxine treatment did not prolong QTc or other ECG parameters, even in high dosages in older depressed adults. These findings indicate that venlafaxine does not significantly affect cardiac conduction in most older patients.

Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Venlafaxine in Geriatric Depression: Phase 1 of the PRIDE Study.

OBJECTIVE: There is limited information regarding the tolerability of electroconvulsive therapy (ECT) combined with pharmacotherapy in elderly adults with major depressive disorder (MDD). Addressing this gap, we report acute neurocognitive outcomes from Phase 1 of the Prolonging Remission in Depressed Elderly (PRIDE) study. METHODS: Elderly adults (age ≥60) with MDD received an acute course of 6 times seizure threshold right unilateral ultrabrief pulse (RUL-UB) ECT. Venlafaxine was initiated during the first treatment week and continued throughout the study. A comprehensive neurocognitive battery was administered at baseline and 72 hours following the last ECT session. Statistical significance was defined as a two-sided p-value of less than 0.05. RESULTS: A total of 240 elderly adults were enrolled. Neurocognitive performance acutely declined post ECT on measures of psychomotor and verbal processing speed, autobiographical memory consistency, short-term verbal recall and recognition of learned words, phonemic fluency, and complex visual scanning/cognitive flexibility. The magnitude of change from baseline to end for most neurocognitive measures was modest. CONCLUSION: This is the first study to characterize the neurocognitive effects of combined RUL-UB ECT and venlafaxine in elderly adults with MDD and provides new evidence for the tolerability of RUL-UB ECT in an elderly sample. Of the cognitive domains assessed, only phonemic fluency, complex visual scanning, and cognitive flexibility qualitatively declined from low average to mildly impaired. While some acute changes in neurocognitive performance were statistically significant, the majority of the indices as based on the effect sizes remained relatively stable.

The Course of Adverse Events in Venlafaxine XR Treatment in Generalized Anxiety Disorder.

PURPOSE: The time course of adverse events is an important factor for patient management. Clinicians are better able to prepare patients for specific adverse events, which leads to better treatment adherence. METHODS: Adverse events were followed longitudinally for 6 months during the open-label phase of a relapse prevention trial with 264 patients with generalized anxiety disorder. Adverse events were assessed at each treatment visit using a 21-item checklist. Logistic regression modeling, continuation ratio modeling, and hierarchical linear modeling were used to determine whether adverse events led to early attrition and whether adverse events decreased in enrolled patients over time. FINDINGS: Adverse events were found to have decreased highly significantly during treatment. A highly significant race effect was found in that whites had a significantly higher adverse event rate than did nonwhites. Early attrition rates were predicted by presence of nausea and fatigue, late attrition by dizziness, nervousness, and sexual dysfunction. IMPLICATIONS: Our findings provide information for clinicians on the course of adverse events over treatment, useful to prepare patients for treatment adherence.

Pharmacokinetic correlates of venlafaxine: associated adverse reactions.

To address the potential correlation between plasma concentrations of venlafaxine (VEN), its active metabolite O-desmethylvenlafaxine (ODVEN) and the active moiety, AM, (ODVEN + VEN) and adverse drug reactions (ADR) in a large naturalistic sample of in- and outpatients. We compared plasma concentrations of VEN, ODVEN and AM and dose-adjusted (C/D) levels as well the ODVEN/VEN ratios between patients complaining ADRs, following the Udvalg for Kliniske Undersogelser side effect rating scales (UKU) (n = 114) and patients without ADRs (control group, n = 688) out of a naturalistic database. We also investigated potential pharmacokinetic correlates of the four UKU categories by comparing patients complaining ADRs with those who did not. Based on previous literature we applied different ODVEN/VEN ratio values as cut-offs to split our sample into two groups at a time and compare frequencies of ADRs between the groups. No differences for demographic and pharmacokinetic variables including plasma and C/D concentrations as well as ODVEN/VEN ratios were observed between study groups. Neither the comparisons between females and males nor between elderly and non-elderly patients revealed significant differences (p > 0.05 in all cases). No differences were also reported exploring the patients complaining ADRs from the 4 UKU categories separately. After applying various ODVEN/VEN cut-offs, groups did not display differences in frequencies of ADRs (p > 0.05 in all cases). Our findings do not demonstrate a direct link between venlafaxine metabolism measures and ADRs. Therefore, additional dimensions are needed to be considered in future trials aiming to disentangle the involved aspects of ADRs in patients receiving venlafaxine.

The Associations Between CYP2D6 Metabolizer Status and Pharmacokinetics and Clinical Outcomes of Venlafaxine: A Systematic Review and Meta-Analysis.

BACKGROUND: The association between CYP2D6 metabolizer status and clinical outcomes of venlafaxine was extensively investigated previously, but no widely accepted conclusion has been reached so far. To obtain a more precise estimation of the association, a systematic review by meta-analysis was conducted in the present study. METHODS: The PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Technology of Chongqing, and Wan Fang Database were searched for eligible studies up to August 2018. RESULTS: Fourteen related studies involving 1035 patients were finally included. Significant associations were found among 3 CYP2D6 phenotypes (NM, IM, and PM) and most pharmacokinetic parameters of venlafaxine. However, CYP2D6 phenotypes were not associated with Hamilton Depression Rating Scale response of venlafaxine. In addition, we also found no significant association between CYP2D6 phenotype and overall rate of adverse events. CONCLUSIONS: CYP2D6 metabolizer status had significant influence on venlafaxine pharmacokinetics, but insufficient evidence demonstrated that CYP2D6 metabolizer status was associated with its therapeutic effects and overall rate of adverse events, which provided further evidence regarding the relationship between CYP2D6 metabolizer status and venlafaxine.

QTc Time Correlates with Amitriptyline and Venlafaxine Serum Levels in Elderly Psychiatric Inpatients.

INTRODUCTION: Many antidepressants cause QT prolongation but the classification of cardiac risk of these drugs varies markedly in different published lists. This retrospective study analyzed the correlation of QTc time with amitriptyline and venlafaxine serum level in elderly psychiatric inpatients. METHODS: Elderly inpatients aged≥65 years for whom venlafaxine or amitriptyline serum level had been measured were selected retrospectively from a therapeutic drug monitoring database and screened for an electrocardiogram measurement at the time of blood withdrawal. The correlation of amitriptyline or venlafaxine serum levels with QTc time was examined by using Pearson's correlation analysis. RESULTS: Amitriptyline serum levels (n=11) correlated significantly with QTc time (r=0.918, p<0.001, CI 95%). Venlafaxine serum levels (n=27) also correlated significantly with QTc time (r=0.382, p<0.05, CI 95%). DISCUSSION: Amitriptyline and venlafaxine induce QT prolongation depending on drug concentrations in blood. Its extent, however, is very low when drug serum levels are within the therapeutic range. Future pharmacokinetic studies that correlate drug serum level and QT time should classify the cardiac risk of drugs based on the grade of the regression line in relation to the therapeutic range.

First indication of deleterious impacts in white-seabream larvae (Diplodus sargus) survival and behaviour following acute venlafaxine exposure.

Wastewater effluents are teeming with organisms, nutrients and chemical substances which water treatment processes fail to remove. Among these substances, pharmaceuticals such as antidepressants are a frequent occurrence, and have been reported to lead to severe effects in the physiology and behaviour of non-target marine species across taxa. Venlafaxine (VFX) is one of the most consistently prescribed substances for the treatment of human depressive disorders, acting as a serotonin and norepinephrine reuptake inhibitor. In the present study, the potential effects of this antidepressant on the survival and key behaviours (i.e. movement, aggression and foraging) of white seabream (Diplodus sargus) larvae were addressed. Larvae were submitted to an acute exposure of two different VFX treatments (low concentration, 10 µg L-1; and high concentration, 100 µg L-1) for a total of 48 h. Sampling took place after 24 and 48 h of exposure. Overall, results showed a significant effect of a two-day exposure to VFX in larvae of D. sargus. Survival was significantly reduced by exposure to a high concentration, but behavioural effects of antidepressant exposure were subtle: i.e. increased attack frequency and temporary modulation of capture success. Further research efforts should be directed towards evaluating the potential chronic effects of antidepressants in marine species, if we are to anticipate possible pressures on natural populations, and effectively advice policymakers towards the investment in new and more efficient methods of wastewater treatments.