-
The Medical Letter on Drugs and... Aug 2023
Topics: Humans; Anxiety Disorders
PubMed: 37516898
DOI: 10.58347/tml.2023.1682a -
The International Journal of... Oct 2019About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant... (Randomized Controlled Trial)
Randomized Controlled Trial
Efficacy and Safety of Fixed-Dose Esketamine Nasal Spray Combined With a New Oral Antidepressant in Treatment-Resistant Depression: Results of a Randomized, Double-Blind, Active-Controlled Study (TRANSFORM-1).
BACKGROUND
About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants and are considered to have treatment-resistant depression.
METHODS
This Phase 3, double-blind, multicenter study enrolled adults with moderate-to-severe depression and nonresponse to ≥2 antidepressants in the current depression episode. Eligible patients (N = 346) were randomized (1:1:1) to twice-weekly nasal spray treatment (esketamine [56 or 84 mg] or placebo) plus a newly initiated, open-label, oral antidepressant taken daily for 4 weeks. The primary efficacy endpoint was change from baseline to day 28 in the Montgomery-Asberg Depression Rating Scale total score, performed by blinded, remote raters. Based on the predefined statistical testing sequence, esketamine 84 mg/antidepressant had to be significant for esketamine 56 mg/antidepressant to be formally tested.
RESULTS
Statistical significance was not achieved with esketamine 84 mg/antidepressant compared with antidepressant/placebo (least squares [LS] means difference [95% CI]: -3.2 [-6.88, 0.45]; 2-sided P value = .088). Although esketamine 56 mg/antidepressant could not be formally tested, the LS means difference was -4.1 [-7.67, -0.49] (nominal 2-sided P value = .027). The most common (>20%) adverse events reported for esketamine/antidepressant were nausea, dissociation, dizziness, vertigo, and headache.
CONCLUSIONS
Statistical significance was not achieved for the primary endpoint; nevertheless, the treatment effect (Montgomery-Asberg Depression Rating Scale) for both esketamine/antidepressant groups exceeded what has been considered clinically meaningful for approved antidepressants vs placebo. Safety was similar between esketamine/antidepressant groups and no new dose-related safety concerns were identified. This study provides supportive evidence for the safety and efficacy of esketamine nasal spray as a new, rapid-acting antidepressant for patients with treatment-resistant depression.
TRIAL REGISTRATION
ClinicalTrials.gov identifier: NCT02417064.
Topics: Administration, Intranasal; Administration, Oral; Adolescent; Adult; Antidepressive Agents; Citalopram; Delayed-Action Preparations; Depressive Disorder, Treatment-Resistant; Double-Blind Method; Drug Therapy, Combination; Duloxetine Hydrochloride; Female; Humans; Ketamine; Male; Middle Aged; Sertraline; Treatment Outcome; Venlafaxine Hydrochloride; Young Adult
PubMed: 31290965
DOI: 10.1093/ijnp/pyz039 -
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 -
Expert Opinion on Drug Metabolism &... May 2020: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A... (Meta-Analysis)
Meta-Analysis
: Pregnancy-related physiological changes exert a crucial impact on the pharmacokinetics of antidepressants; however, the current evidence presents inconsistencies. A clearer understanding of pregnancy-related effects on antidepressant disposition may facilitate the development of guidelines for appropriate dose adjustments during the course of pregnancy based on therapeutic drug monitoring.: We systematically reviewed studies comparing antidepressant levels in the same individuals during pregnant and non-pregnant states. Using dose-adjusted plasma concentration measurements, we estimated alteration ratios between the 3rd trimester and baseline (before or after pregnancy). Additionally, we performed a meta-analysis for changes in dose-adjusted concentrations to estimate mean differences.: Data for several antidepressants display clear alteration patterns during pregnancy. On the basis of the alteration ratios trimipramine, fluvoxamine, and nortriptyline show a prominent decrease in dose-adjusted levels, especially in the 3rd trimester. Clomipramine, imipramine, citalopram, and paroxetine show smaller decreases in dose-adjusted concentrations in the third trimester. For escitalopram, venlafaxine and fluoxetine, changes are considered negligible. For sertraline, there was a tendency toward increased dose-adjusted concentrations in pregnancy. Available evidence suffers from major limitations and factors affecting pharmacokinetics have been insufficiently addressed. Further research is required to promote knowledge on pregnancy effects on antidepressant pharmacokinetics.
Topics: Antidepressive Agents; Depression; Dose-Response Relationship, Drug; Female; Humans; Pregnancy; Pregnancy Complications; Pregnancy Trimester, Third
PubMed: 32238008
DOI: 10.1080/17425255.2020.1750598 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Aug 2022To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis.
METHODS
Databases of PubMed, Cochrane Library, EMBASE, Web of Science, PsycINFO, CBM, CNKI and Wanfang Data were searched for randomized controlled trials (RCT) related to antidepressants in treatment of children and adolescents with depression from inception to December 2021. Quality assessment and data extraction from the included RCTs were performed. Statistical analyses of efficacy and tolerability were conducted with Stata 15.1 software. Surface under the cumulative ranking (SUCAR) was used to rank the value of the antidepressants.
RESULTS
A total of 33 RCTs were included in 32 articles, involving 6949 patients. There are 13 antidepressants used in total, including amitriptyline, vilazodone, fluoxetine, selegiline, paroxetine, imipramine, desipramine, sertraline, nortriptyline, escitalopram, citalopram, venlafaxine and duloxetine. The results of network meta-analysis showed that the efficacy of duloxetine ( =1.95, 95% 1.41-2.69), fluoxetine ( =1.73, 95% 1.40-2.14), venlafaxine ( =1.37, 95% 1.04-1.80) and escitalopram ( =1.48, 95% : 1.12-1.95) were significantly higher than that of placebos (all <0.05); the probability cumulative ranks were duloxetine (87.0%), amitriptyline (83.3%), fluoxetine (79.0%), escitalopram (62.7%), etc. The results showed that the intolerability of patients receiving imipramine ( =0.15, 95% 0.08-0.27), sertraline ( =0.33, 95% 0.16-0.71), venlafaxine ( =0.35, 95% 0.17-0.72), duloxetine ( =0.35, 95% 0.17-0.73) and paroxetine ( =0.52, 95% 0.30-0.88) were significantly higher than that of placebos (all <0.05), and the probability cumulative ranks were imipramine (95.7%), sertraline (69.6%), venlafaxine (68.6%), duloxetine (68.2%), etc. Conclusion: Among 13 antidepressants, duloxetine, fluoxetine, escitalopram and venlafaxine are significantly better than placebo in terms of efficacy, but duloxetine and venlafaxine are less well tolerated.
Topics: Adolescent; Child; Humans; Venlafaxine Hydrochloride; Duloxetine Hydrochloride; Fluoxetine; Sertraline; Paroxetine; Amitriptyline; Imipramine; Depression; Escitalopram; Network Meta-Analysis; Depressive Disorder, Major; Antidepressive Agents
PubMed: 37202104
DOI: 10.3724/zdxbyxb-2022-0145 -
The British Journal of Psychiatry : the... Mar 2020There is strong research evidence to support the pharmacological treatment of post-traumatic stress disorder (PTSD) as a second line to trauma-focused psychological...
There is strong research evidence to support the pharmacological treatment of post-traumatic stress disorder (PTSD) as a second line to trauma-focused psychological interventions. Fluoxetine, paroxetine, sertraline and venlafaxine are the best-evidenced drugs, with lower-level evidence for other medications. It is important that prescribing for PTSD is evidence-based.
Topics: Evidence-Based Medicine; Fluoxetine; Humans; Paroxetine; Sertraline; Stress Disorders, Post-Traumatic; Venlafaxine Hydrochloride
PubMed: 32345407
DOI: 10.1192/bjp.2020.40 -
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