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Pharmacogenomics Jul 2019Antidepressant response could be from 42 to 50% genetically determined. Venlafaxine (VEN) was the sixth most-prescribed antidepressant in the USA in 2017. Therefore, we... (Review)
Review
Antidepressant response could be from 42 to 50% genetically determined. Venlafaxine (VEN) was the sixth most-prescribed antidepressant in the USA in 2017. Therefore, we reviewed studies which focused on the pharmacogenetics of VEN and found that there is a lack of guidelines for pharmacogenetic testing for VEN. Within investigated genetic polymorphisms, few of them can be indicated as potential predictors of VEN efficacy and tolerance. However, additional pharmacogenetic studies of VEN should be performed to reproduce already obtained results or explain contradictory ones. The individualization of pharmacotherapy is a key issue in providing patients with the highest possible quality of treatment, therefore pharmacogenetic studies should be one of the components of therapy optimization.
Topics: Antidepressive Agents; Cytochrome P-450 CYP2D6; Depressive Disorder, Major; Genotype; Humans; Pharmacogenetics; Polymorphism, Genetic; Venlafaxine Hydrochloride
PubMed: 31368838
DOI: 10.2217/pgs-2019-0031 -
The Lancet. Psychiatry Jul 2019Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Depression is the single largest contributor to non-fatal health loss worldwide. Second-generation antidepressants are the first-line option for pharmacological management of depression. Optimising their use is crucial in reducing the burden of depression; however, debate about their dose dependency and their optimal target dose is ongoing. We have aimed to summarise the currently available best evidence to inform this clinical question.
METHODS
We did a systematic review and dose-response meta-analysis of double-blind, randomised controlled trials that examined fixed doses of five selective serotonin reuptake inhibitors (SSRIs; citalopram, escitalopram, fluoxetine, paroxetine, and sertraline), venlafaxine, or mirtazapine in the acute treatment of adults (aged 18 years or older) with major depression, identified from the Cochrane Central Register of Controlled Trials, CINAHL, Embase, LILACS, MEDLINE, PsycINFO, AMED, PSYNDEX, websites of drug licensing agencies and pharmaceutical companies, and trial registries. We imposed no language restrictions, and the search was updated until Jan 8, 2016. Doses of SSRIs were converted to fluoxetine equivalents. Trials of antidepressants for patients with depression and a serious concomitant physical illness were excluded. The main outcomes were efficacy (treatment response defined as 50% or greater reduction in depression severity), tolerability (dropouts due to adverse effects), and acceptability (dropouts for any reasons), all after a median of 8 weeks of treatment (range 4-12 weeks). We used a random-effects, dose-response meta-analysis model with flexible splines for SSRIs, venlafaxine, and mirtazapine.
FINDINGS
28 554 records were identified through our search (24 524 published and 4030 unpublished records). 561 published and 121 unpublished full-text records were assessed for eligibility, and 77 studies were included (19 364 participants; mean age 42·5 years, SD 11·0; 7156 [60·9%] of 11 749 reported were women). For SSRIs (99 treatment groups), the dose-efficacy curve showed a gradual increase up to doses between 20 mg and 40 mg fluoxetine equivalents, and a flat to decreasing trend through the higher licensed doses up to 80 mg fluoxetine equivalents. Dropouts due to adverse effects increased steeply through the examined range. The relationship between the dose and dropouts for any reason indicated optimal acceptability for the SSRIs in the lower licensed range between 20 mg and 40 mg fluoxetine equivalents. Venlafaxine (16 treatment groups) had an initially increasing dose-efficacy relationship up to around 75-150 mg, followed by a more modest increase, whereas for mirtazapine (11 treatment groups) efficacy increased up to a dose of about 30 mg and then decreased. Both venlafaxine and mirtazapine showed optimal acceptability in the lower range of their licensed dose. These results were robust to several sensitivity analyses.
INTERPRETATION
For the most commonly used second-generation antidepressants, the lower range of the licensed dose achieves the optimal balance between efficacy, tolerability, and acceptability in the acute treatment of major depression.
FUNDING
Japan Society for the Promotion of Science, Swiss National Science Foundation, and National Institute for Health Research.
Topics: Depressive Disorder, Major; Dose-Response Relationship, Drug; Double-Blind Method; Humans; Mirtazapine; Randomized Controlled Trials as Topic; Serotonin Agents; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 31178367
DOI: 10.1016/S2215-0366(19)30217-2 -
CMAJ : Canadian Medical Association... Apr 2021
Topics: Administration, Intravenous; Animals; Antidepressive Agents, Second-Generation; Drug Overdose; Glucose; Humans; Hypoglycemia; Venlafaxine Hydrochloride
PubMed: 33875464
DOI: 10.1503/cmaj.78409 -
The Primary Care Companion For CNS... Feb 2021
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Urinary Retention; Venlafaxine Hydrochloride
PubMed: 34000145
DOI: 10.4088/PCC.20l02702 -
European Journal of Paediatric... Mar 2017During pregnancy, the developing fetal brain may be exposed to a range of psychotropic medications. The serotonin-noradrenergic reuptake inhibitor venlafaxine is one... (Review)
Review
During pregnancy, the developing fetal brain may be exposed to a range of psychotropic medications. The serotonin-noradrenergic reuptake inhibitor venlafaxine is one such drug, when used as a maternal antidepressant. Here we review the discontinuation phenomenon that may follow in exposed neonates following birth. Adults who abruptly stop taking venlafaxine can experience withdrawal symptoms. Venlafaxine and its metabolites cross the placenta and so the newborn can be exposed to this risk, as well as potential toxicity. Several case reports document features of encephalopathy following birth in exposed neonates. It is suggested that a possible combination of partial toxicity together with withdrawal may lead to these symptoms - a discontinuation syndrome. The underlying neurobiology is not yet established. Common symptoms and signs seen in affected neonates include poor feeding, jitteriness, respiratory distress and myoclonic seizure-like activity. Onset is typically between birth and day 4 of life with resolution by 2-21 days of life. Electroencephalography does not necessarily correlate with clinical seizures, or response to anticonvulsants. In limited follow-up data, no long-term consequences of this discontinuation syndrome are reported. We suggest where it is not possible for mothers to be switched from venlafaxine to other antidepressant drugs, that their infants are observed closely for 2-4 days following delivery. In symptomatic neonates, following exclusion of other causes, supportive care including breastfeeding may be sufficient for management. Clinicians should be vigilant to venlafaxine discontinuation as a cause for encephalopathy or paroxysmal episodes in exposed neonates.
Topics: Antidepressive Agents; Brain Diseases; Female; Humans; Infant, Newborn; Pregnancy; Prenatal Exposure Delayed Effects; Seizures; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride
PubMed: 27931774
DOI: 10.1016/j.ejpn.2016.11.003 -
Prescrire International Apr 2016Venlafaxine is a serotonergic and noradrenergic antidepressant. It shares the same serotonergic adverse effects as the "selective" serotonin reuptake inhibitor (SSRI)... (Review)
Review
Venlafaxine is a serotonergic and noradrenergic antidepressant. It shares the same serotonergic adverse effects as the "selective" serotonin reuptake inhibitor (SSRI) antidepressants while in addition provoking noradrenergic adverse effects, in particular cardiovascular disorders, yet offers no demonstrated advantages over SSRIs in terms of efficacy. Several cohort studies using data from a UK database have shown that venlafaxine overdoses are more frequently fatal than SSRI overdoses. Several meta-analyses of more than 70 published and unpublished randomised clinical trials, including about 7000 patients in total, have shown that treatment discontinuation due to adverse effects is more common with venlafaxine than with SSRI antidepressants. Venlafaxine can provoke dose-dependent blood pressure elevation, sometimes requiring treatment discontinuation. Exposure to venlafaxine during the second and third trimesters of pregnancy increases the risk of pre-eclampsia and eclampsia. A cohort study in about 50 elderly patients and analysis of several hundred reported suicide attempts by venlafaxine overdose demonstrated a risk of QT interval prolongation, which can lead to torsades de pointes, an unusual and potentially fatal type of ventricular tachycardia. Large British and Danish cohort studies found no increased risk of sudden cardiac death with venlafaxine compared with other antidepressants. However, since only 3.5% and 7% of the patients were using venlafaxine, the statistical power of these studies was relatively low. In practice, the data available as of mid-2015 from clinical trials and epidemiological studies confirm the harms foreseeable from venlafaxine's pharmacological properties: a higher risk of cardiovascular adverse effects and of fatal overdoses than with most SSRI antidepressants. Since venlafaxine and SSRI antidepressants have similar and limited efficacy, venlafaxine is best avoided. An SSRI anti-depressant is a more reasonable option, with the exception of citalopram and escitalopram which also expose patients to more cardiovascular adverse effects.
Topics: Depressive Disorder; Dose-Response Relationship, Drug; Drug Overdose; Female; Humans; Hypertension; Long QT Syndrome; Pre-Eclampsia; Pregnancy; Serotonin and Noradrenaline Reuptake Inhibitors; Torsades de Pointes; Venlafaxine Hydrochloride
PubMed: 27186622
DOI: No ID Found -
JAMA Feb 2023Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years.... (Review)
Review
IMPORTANCE
Menopause, due to loss of ovarian follicular activity without another pathological or physiological cause, typically occurs between the ages of 45 years and 56 years. During the menopausal transition, approximately 50% to 75% of women have hot flashes, night sweats, or both (vasomotor symptoms) and more than 50% have genitourinary symptoms (genitourinary syndrome of menopause [GSM]).
OBSERVATIONS
Vasomotor symptoms typically last more than 7 years and GSM is often chronic. Efficacious treatments for women with bothersome vasomotor symptoms or GSM symptoms include hormonal and nonhormonal options. Systemic estrogen alone or combined with a progestogen reduces the frequency of vasomotor symptoms by approximately 75%. Oral and transdermal estrogen have similar efficacy. Conjugated equine estrogens (CEE) with or without medroxyprogesterone acetate (MPA) were the only hormonal treatments for which clinical trials were designed to examine cardiovascular events, venous thromboembolism, and breast cancer risk. Compared with placebo, the increased risk of stroke and venous thromboembolism associated with CEE (with or without MPA) and breast cancer (with use of CEE plus MPA) is approximately 1 excess event/1000 person-years. Low-dose CEE plus bazedoxifene is not associated with increased risk of breast cancer (0.25%/year vs 0.23%/year with placebo). Bioidentical estrogens approved by the US Food and Drug Administration (with identical chemical structure to naturally produced estrogens, and often administered transdermally) also are available to treat vasomotor symptoms. For women who are not candidates for hormonal treatments, nonhormonal approaches such as citalopram, desvenlafaxine, escitalopram, gabapentin, paroxetine, and venlafaxine are available and are associated with a reduction in frequency of vasomotor symptoms by approximately 40% to 65%. Low-dose vaginal estrogen is associated with subjective improvement in GSM symptom severity by approximately 60% to 80%, with improvement in severity by 40% to 80% for vaginal prasterone, and with improvement in severity by 30% to 50% for oral ospemifene.
CONCLUSIONS AND RELEVANCE
During the menopausal transition, approximately 50% to 75% of women have vasomotor symptoms and GSM symptoms. Hormonal therapy with estrogen is the first-line therapy for bothersome vasomotor symptoms and GSM symptoms, but nonhormonal medications (such as paroxetine and venlafaxine) also can be effective. Hormone therapy is not indicated for the prevention of cardiovascular disease.
Topics: Female; Humans; Estrogen Replacement Therapy; Estrogens; Estrogens, Conjugated (USP); Hot Flashes; Medroxyprogesterone Acetate; Menopause; Neoplasms; Paroxetine; Venlafaxine Hydrochloride; Venous Thromboembolism; Sweating; Female Urogenital Diseases; Autonomic Nervous System Diseases
PubMed: 36749328
DOI: 10.1001/jama.2022.24140 -
Pharmacotherapy Jun 2023This report highlights the effects of discontinuing venlafaxine on thyroid function in an older adult with previously well-managed Hashimoto thyroiditis and sleep apnea.
STUDY OBJECTIVE
This report highlights the effects of discontinuing venlafaxine on thyroid function in an older adult with previously well-managed Hashimoto thyroiditis and sleep apnea.
DESIGN
Concurrent intervention.
CASE STUDY
Setting Community-based psychiatry practice Patient - 66 year old female Intervention Over 8 months, a 66-year-old patient slowly reduced the venlafaxine dose. She was treated simultaneously for sleep apnea. Measurements Clinical data including venlafaxine and levothyroxine dosing, thyroid hormone laboratory values, subjective complaints, and objective electrocardiographic (ECG) findings were aggregated and analyzed.
MAIN RESULTS
As venlafaxine dose was decreased over time, the patient complained of bounding heart palpitations shown to be premature ventricular contractions, and wide and narrow complex ventricular tachycardia on ECG. Thyroid-stimulating hormone decreased from a baseline value of 0.791 uIU/mL to a nadir of 0.18 uIU/mL during venlafaxine dosage reduction from 225 mg/day to 155 mg/day. Cardiac symptoms subsided following levothyroxine dosage reduction.
CONCLUSIONS
There was a direct relationship between antidepressant dosage reduction and levothyroxine dosage requirements. Cautious monitoring is recommended during venlafaxine deprescribing in patients with pre-existing thyroid disease.
Topics: Female; Humans; Aged; Thyroxine; Venlafaxine Hydrochloride; Deprescriptions; Hashimoto Disease
PubMed: 37052367
DOI: 10.1002/phar.2803 -
Psychopharmacology Sep 2022Major depression (MD) is one of the most common psychiatric disorders worldwide. Currently, the first-line treatment for MD targets the serotonin system but these drugs,... (Review)
Review
Major depression (MD) is one of the most common psychiatric disorders worldwide. Currently, the first-line treatment for MD targets the serotonin system but these drugs, notably the selective serotonin reuptake inhibitors, usually need 4 to 6 weeks before the benefit is felt and a significant proportion of patients shows an unsatisfactory response. Numerous treatments have been developed to circumvent these issues as venlafaxine, a mixed serotonin-norepinephrine reuptake inhibitor that binds and blocks both the SERT and NET transporters. Despite this pharmacological profile, it is difficult to have a valuable insight into its ability to produce more robust efficacy than single-acting agents. In this review, we provide an in-depth characterization of the pharmacological properties of venlafaxine from in vitro data to preclinical and clinical efficacy in depressed patients and animal models of depression to propose an indirect comparison with the most common antidepressants. Preclinical studies show that the antidepressant effect of venlafaxine is often associated with an enhancement of serotonergic neurotransmission at low doses. High doses of venlafaxine, which elicit a concomitant increase in 5-HT and NE tone, is associated with changes in different forms of plasticity in discrete brain areas. In particular, the hippocampus appears to play a crucial role in venlafaxine-mediated antidepressant effects notably by regulating processes such as adult hippocampal neurogenesis or the excitatory/inhibitory balance. Overall, depending on the dose used, venlafaxine shows a high efficacy on depressive-like symptoms in relevant animal models but to the same extent as common antidepressants. However, these data are counterbalanced by a lower tolerance. In conclusion, venlafaxine appears to be one of the most effective treatments for treatment of major depression. Still, direct comparative studies are warranted to provide definitive conclusions about its superiority.
Topics: Animals; Antidepressive Agents; Cyclohexanols; Depressive Disorder, Major; Humans; Serotonin; Selective Serotonin Reuptake Inhibitors; Venlafaxine Hydrochloride
PubMed: 35947166
DOI: 10.1007/s00213-022-06203-8 -
Human Psychopharmacology Jul 2015Venlafaxine is one of the most frequently prescribed antidepressants worldwide, despite its toxicity risk in overdose. Furthermore, the molecule has been recently... (Review)
Review
INTRODUCTION
Venlafaxine is one of the most frequently prescribed antidepressants worldwide, despite its toxicity risk in overdose. Furthermore, the molecule has been recently identified at the EU-wide level as one of the novel psychoactive substances. This paper aims at investigating the potential of misuse, taking into account both the existing literature and the analysis of the misusers' experiences as described in venlafaxine misuse web reports.
METHODS
A literature search was performed using PubMed, Embase, and Medline. Posts/threads relating to venlafaxine misuse issues were identified through Google® and Yahoo® English-language searches. Resulting websites' data were then qualitatively assessed, and information was collected on a range of issues, including dosage, drug intake modalities, untoward drug effects, and association with other recreational drugs.
RESULTS
A few literature case reports focusing on venlafaxine as a misusing drug were here identified. The molecule was here typically ingested or snorted at dosages up to 10-15 times higher than those clinically advised, obtaining MDMA/amphetamine-like stimulant and psychedelic effects. Polydrug misuse was commonly reported. Venlafaxine appeared to be widely available online for sale.
CONCLUSIONS
Physicians should carefully evaluate patients for history of drug dependence and observe them for signs of venlafaxine misuse.
Topics: Antidepressive Agents, Second-Generation; Databases, Bibliographic; Drug Overdose; Humans; Internet; Prescription Drug Misuse; Venlafaxine Hydrochloride
PubMed: 26216559
DOI: 10.1002/hup.2476