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JAMA Psychiatry Dec 2020Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks.
IMPORTANCE
Antidepressants are commonly used during pregnancy, but limited information is available about individual antidepressants and specific birth defect risks.
OBJECTIVE
To examine associations between individual antidepressants and specific birth defects with and without attempts to partially account for potential confounding by underlying conditions.
DESIGN, SETTING, AND PARTICIPANTS
The population-based, multicenter case-control National Birth Defects Prevention Study (October 1997-December 2011) included cases with selected birth defects who were identified from surveillance systems; controls were randomly sampled live-born infants without major birth defects. Mothers of cases and controls participated in an interview after the expected delivery date. The data were analyzed after the completion of the National Birth Defects Prevent Study's data collection.
EXPOSURES
Self-reported antidepressant exposure was coded to indicate monotherapy exposure to antidepressants.
MAIN OUTCOMES AND MEASURES
We used multivariable logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals for associations between maternal antidepressant use and birth defects. We compared early pregnancy antidepressant-exposed women with those without antidepressant exposure and, to partially account for confounding by underlying maternal conditions, those exposed to antidepressants outside of the birth defect development critical period.
RESULTS
This study included 30 630 case mothers of infants with birth defects and 11 478 control mothers (aged 12-53 years). Early pregnancy antidepressant use was reported by 1562 case mothers (5.1%) and 467 control mothers (4.1%), for whom elevated aORs were observed for individual selective serotonin reuptake inhibitors (SSRIs) and selected congenital heart defects (CHD) (eg, fluoxetine and anomalous pulmonary venous return: aOR, 2.56; 95% CI, 1.10-5.93; this association was attenuated after partially accounting for underlying conditions: aOR, 1.89; 95% CI, 0.56-6.42). This pattern was observed for many SSRI-CHD combinations. Associations between SSRIs and non-CHD birth defects often persisted or strengthened after partially accounting for underlying conditions (eg, citalopram and diaphragmatic hernia: aOR, 5.11; 95% CI, 1.29-20.24). Venlafaxine had elevated associations with multiple defects that persisted after partially accounting for underlying conditions (eg, anencephaly and craniorachischisis: aOR, 9.14; 95% CI, 1.91-43.83).
CONCLUSIONS AND RELEVANCE
We found some associations between maternal antidepressant use and specific birth defects. Venlafaxine was associated with the highest number of defects, which needs confirmation given the limited literature on venlafaxine use during pregnancy and risk for birth defects. Our results suggest confounding by underlying conditions should be considered when assessing risk. Fully informed treatment decision-making requires balancing the risks and benefits of proposed interventions against those of untreated depression or anxiety.
Topics: Abnormalities, Drug-Induced; Adolescent; Adult; Bupropion; Case-Control Studies; Child; Female; Humans; Middle Aged; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors; Venlafaxine Hydrochloride; Young Adult
PubMed: 32777011
DOI: 10.1001/jamapsychiatry.2020.2453 -
Journal of Clinical Pharmacology Jun 2023Depression is common in pregnant women. However, the rate of antidepressant treatment in pregnancy is significantly lower than in nonpregnant women. Although some... (Review)
Review
Depression is common in pregnant women. However, the rate of antidepressant treatment in pregnancy is significantly lower than in nonpregnant women. Although some antidepressants may cause potential risks to the fetus, not treating or withdrawing the treatment is associated with relapsing and adverse pregnancy outcomes such as preterm birth. Pregnancy-associated physiologic changes can alter pharmacokinetics (PK) and may impact dosing requirements during pregnancy. However, pregnant women are largely excluded from PK studies. Dose extrapolation from the nonpregnant population could lead to ineffective doses or increased risk of adverse events. To better understand PK changes during pregnancy and guide dosing decisions, we conducted a literature review to catalog PK studies of antidepressants in pregnancy, with a focus on maternal PK differences from the nonpregnant population and fetal exposure. We identified 40 studies on 15 drugs, with most data from patients taking selective serotonin reuptake inhibitors and venlafaxine. Most of the studies have relatively poor quality, with small sample sizes, reporting concentrations at delivery only, a large amount of missing data, and not including times and adequate dose information. Only four studies collected multiple samples following a dose and reported PK parameters. In general, there are limited data available regarding PK of antidepressants in pregnancy and deficiencies in data reporting. Future studies should provide accurate information on drug dosing and timing of dose, PK sample collection, and individual-level PK data.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Premature Birth; Antidepressive Agents; Venlafaxine Hydrochloride; Selective Serotonin Reuptake Inhibitors; Fetus
PubMed: 37317494
DOI: 10.1002/jcph.2282 -
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 -
CMAJ : Canadian Medical Association... Apr 2021
Topics: Adolescent; Antidepressive Agents, Second-Generation; Cardiopulmonary Bypass; Decontamination; Drug Overdose; Electrocardiography; Female; Gastric Lavage; Humans; Long QT Syndrome; Seizures; Suicide, Attempted; Venlafaxine Hydrochloride
PubMed: 33846207
DOI: 10.1503/cmaj.201318-f -
CNS Drugs Sep 2023Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories.... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Although one of the major presentations of vestibular migraine is dizziness with/without unsteady gait, it is still classified as one of the migraine categories. However, in contrast to ordinary migraine, vestibular migraine patients have distinct characteristics, and the detailed treatment strategy for vestibular migraine is different and more challenging than ordinary migraine treatment. Currently, there is no conclusive evidence regarding its management, including vestibular migraine prophylaxis.
AIM
The objective of this current network meta-analysis (NMA) was to compare the efficacy and acceptability of individual treatment strategies in patients with vestibular migraine.
METHODS
The PubMed, Embase, ScienceDirect, ProQuest, Web of Science, ClinicalKey, Cochrane Central, and ClinicalTrials.gov databases were systematically searched for randomized controlled trials (RCTs), with a final literature search date of 30 December 2022. Patients diagnosed with vestibular migraine were included. The PICO of the current study included (1) patients with vestibular migraine; (2) intervention: any active pharmacologic or non-pharmacologic intervention; (3) comparator: placebo-control, active control, or waiting list; and (4) outcome: changes in migraine frequency or severity. This NMA of RCTs of vestibular migraine treatment was conducted using a frequentist model. We arranged inconsistency and similarity tests to re-examine the assumption of NMA, and also conducted a subgroup analysis focusing on RCTs of pharmacological treatment for vestibular migraine management. The primary outcome was changes in the frequency of vestibular migraines, while the secondary outcomes were changes in vestibular migraine severity and acceptability. Acceptability was set as the dropout rate, which was defined as the participant leaving the study before the end of the trial for any reason. Two authors independently evaluated the risk of bias for each domain using the Cochrane risk-of-bias tool.
RESULTS
Seven randomized controlled trials (N = 828, mean age 37.6 years, 78.4% female) and seven active regimens were included. We determined that only valproic acid (standardized mean difference [SMD] -1.61, 95% confidence interval [CI] -2.69, -0.54), propranolol (SMD -1.36, 95% CI -2.55, -0.17), and venlafaxine (SMD -1.25, 95% CI -2.32, -0.18) were significantly associated with better improvement in vestibular migraine frequency than the placebo/control groups. Furthermore, among all the investigated pharmacologic/non-pharmacologic treatments, valproic acid yielded the greatest decrease in vestibular migraine frequency among all the interventions. In addition, most pharmacologic/non-pharmacologic treatments were associated with similar acceptability (i.e. dropout rate) as those of the placebo/control groups.
CONCLUSIONS
The current study provides evidence that only valproic acid, propranolol, and venlafaxine might be associated with beneficial efficacy in vestibular migraine treatment.
TRIAL REGISTRATION
CRD42023388343.
Topics: Adult; Female; Humans; Male; Migraine Disorders; Network Meta-Analysis; Propranolol; Valproic Acid; Venlafaxine Hydrochloride
PubMed: 37676473
DOI: 10.1007/s40263-023-01037-0 -
Pharmacotherapy Nov 2021To compare associations between individual antidepressants and newborn outcomes. (Comparative Study)
Comparative Study
OBJECTIVE
To compare associations between individual antidepressants and newborn outcomes.
DESIGN
Retrospective cohort study.
SETTING
Deliveries in a large, US medical system.
POPULATION
Women who received at least one antidepressant prescription 3 months prior to conception through delivery.
METHODS
Eligible women had maternal characteristics and newborn outcomes extracted from medical record data. Exposure was defined by the timing of the prescription during pregnancy.
MAIN OUTCOME MEASURES
Newborn outcomes (any adaptation syndrome, neonatal intensive care unit (NICU) admission) were analyzed for each antidepressant and compared using standard statistics and multivariable regression compared to exposure to bupropion. Odds of outcomes based on timing of exposure were also explored.
RESULTS
A total of 3,694 women were analyzed. Rates of any adaptation syndrome (p < 0.001), NICU admission (p < 0.001), and transient tachypnea of newborn (TTN) (p = 0.006) were significantly different between drugs. Infants exposed to duloxetine had the highest rates of NICU admissions (39.6%) and adaptation syndromes (15.1%). Venlafaxine-exposed infants had the highest rates of TTN (18.2%). Controlling for maternal age, race, insurance, and gestational age at delivery, early pregnancy antidepressant exposure was associated with adaptation syndrome and NICU admission for both duloxetine (adjusted odds ratio (aOR) 2.31 [95% Confidence Interval (CI) 1.11-4.80] and aOR 2.47 [95% CI 1.40-4.34], respectively) and escitalopram (aOR 1.72 [95% CI 1.09-2.70] and aOR 1.64 [95% CI 1.21-2.22], respectively). Exposure in the third trimester was associated with any adaptation syndrome for citalopram, duloxetine, escitalopram, fluoxetine, sertraline, and venlafaxine and NICU admission for bupropion, citalopram, duloxetine, escitalopram, and fluoxetine.
CONCLUSION
Duloxetine and escitalopram appear to have the strongest associations with any adaptation syndrome and NICU admission whereas bupropion and sertraline tended to have among the lowest risks of these outcomes. These results can help providers and patients discuss choice of individual antidepressant drugs during pregnancy.
Topics: Antidepressive Agents; Bupropion; Citalopram; Duloxetine Hydrochloride; Escitalopram; Female; Fluoxetine; Humans; Infant, Newborn; Pregnancy; Prenatal Exposure Delayed Effects; Retrospective Studies; Sertraline; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 34587291
DOI: 10.1002/phar.2628 -
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 -
The American Journal of Managed Care Sep 2001The prevalence of depression and the high costs associated with its management have heightened interest in pharmacoeconomic evaluation of drug treatment, especially the... (Comparative Study)
Comparative Study Review
The prevalence of depression and the high costs associated with its management have heightened interest in pharmacoeconomic evaluation of drug treatment, especially the use of selective serotonin reuptake inhibitors (SSRIs) and the serotonin-norepinephrine reuptake inhibitor venlafaxine. A number of studies of venlafaxine in both inpatient and outpatient settings have revealed that extended-release venlafaxine has a lower expected cost than comparable treatment with SSRIs and tricyclic antidepressants (TCAs). When the relative cost effectiveness of immediate-release venlafaxine, SSRIs, and TCAs was assessed in the treatment of major depressive disorder in 10 countries, venlafaxine yielded a lower than expected cost compared with SSRIs and TCAs in all but 1 country. In comparing healthcare expenditures for depressed patients with and without anxiety, there was a pharmacoeconomic benefit to both immediate- or extended-release venlafaxine, regardless of the presence or absence of comorbid anxiety. A review of computerized administrative claims data from 9 US healthcare plans on resource use and the cost of venlafaxine instead of TCAs after switching from an SSRI showed that overall costs did not vary markedly between venlafaxine and TCAs. This led to the conclusion that although therapy with venlafaxine is more costly than TCA therapy, this increase may be offset by lower costs of other medical services. Such findings have enormous potential ramifications for practicing physicians in terms of venlafaxine's superior remission rate, lower likelihood of relapse, loss of fewer patients to adverse events or lack of efficacy, and flexibility in dosing that enables titration to achieve an optimal response.
Topics: Antidepressive Agents, Second-Generation; Antidepressive Agents, Tricyclic; Anxiety; Cost-Benefit Analysis; Cyclohexanols; Depression; Drug Utilization Review; Humans; Managed Care Programs; Selective Serotonin Reuptake Inhibitors; United States; Venlafaxine Hydrochloride
PubMed: 11570029
DOI: No ID Found -
Psychiatria Danubina Mar 2011Dual-action antidepressants serotonin-norepinephrine reuptake inhibitors (SRNIs) are widely used to treat depression. Owing to its efficiency and safety, venlafaxine...
Dual-action antidepressants serotonin-norepinephrine reuptake inhibitors (SRNIs) are widely used to treat depression. Owing to its efficiency and safety, venlafaxine holds a prominent place in this group of depressants. Abrupt venlafaxine discontinuation involves a high risk of withdrawal syndrome. Mechanism of its development is similar to that of selective serotonin reuptake inhibitors (SSRIs), but of higher intensity. Venlafaxine withdrawal symptoms may include several somatic symptoms as well as several psychiatric symptoms. In some cases, symptoms may look like a stroke. A treatment option is re-inclusion of venlafaxine or a SSRI antidepressant. The paper presents the case of a 70-year-old patient who discontinued of her own accord to take venlafaxine, which she had been taking regularly at a daily dose of 225 mg for more than a year. A few hours after taking the last dose, withdrawal syndrome occurred with severe symptoms resembling a stroke. The patient was examined by a neurologist and the CT and laboratory parameters showed no irregularities. Diagnosis was made after psychiatric observation. Venlafaxine, 150 mg per day, was prescribed, the symptoms disappeared relatively quickly, and the patient fully recovered. Withdrawal syndrome is a real risk for each venlafaxine treated patient. The possibility of its occurrence should be always kept in mind and patients should be timely informed about it. In this way, the risk of venlafaxine withdraw syndrome could be reduced, unnecessary stress to patients prevented and the costs of medical treatment lowered.
Topics: Aged; Antidepressive Agents, Second-Generation; Cyclohexanols; Depressive Disorder, Major; Diagnosis, Differential; Dose-Response Relationship, Drug; Female; Humans; Hypertension; Ischemic Attack, Transient; Retreatment; Stroke; Substance Withdrawal Syndrome; Venlafaxine Hydrochloride
PubMed: 21448114
DOI: No ID Found -
International Journal of Molecular... Jul 2021Multiple sclerosis (MS) is a demyelinating, autoimmune disease that affects a large number of young adults. Novel therapies for MS are needed considering the efficiency...
Multiple sclerosis (MS) is a demyelinating, autoimmune disease that affects a large number of young adults. Novel therapies for MS are needed considering the efficiency and safety limitations of current treatments. In our study, we investigated the effects of venlafaxine (antidepressant, serotonin-norepinephrine reuptake inhibitor), risperidone (atypical antipsychotic) and febuxostat (gout medication, xanthine oxidase inhibitor) in the cuprizone mouse model of acute demyelination, hypothesizing an antagonistic effect on TRPA1 calcium channels. Cuprizone and drugs were administered to C57BL6/J mice for five weeks and locomotor activity, motor performance and cold sensitivity were assessed. Mice brains were harvested for histological staining and assessment of oxidative stress markers. Febuxostat and metabolites of venlafaxine (desvenlafaxine) and risperidone (paliperidone) were tested for TRPA1 antagonistic activity. Following treatment, venlafaxine and risperidone significantly improved motor performance and sensitivity to a cold stimulus. All administered drugs ameliorated the cuprizone-induced deficit of superoxide dismutase activity. Desvenlafaxine and paliperidone showed no activity on TRPA1, while febuxostat exhibited agonistic activity at high concentrations. Our findings indicated that all three drugs offered some protection against the effects of cuprizone-induced demyelination. The agonistic activity of febuxostat can be of potential use for discovering novel TRPA1 ligands.
Topics: Animals; Corpus Callosum; Cuprizone; Disease Models, Animal; Drug Evaluation, Preclinical; Febuxostat; Female; HEK293 Cells; Humans; Mice, Inbred C57BL; Motor Activity; Multiple Sclerosis; Neurotransmitter Agents; Risperidone; TRPA1 Cation Channel; Venlafaxine Hydrochloride; Mice
PubMed: 34281235
DOI: 10.3390/ijms22137183