SynthesisPsychopharmacology2024
Venlafaxine's therapeutic reference range in the treatment of depression revised: a systematic review and meta-analysis.
Synthesis in Psychopharmacology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Trial
- Recurrent serotonin syndrome during low-dose venlafaxine treatment in a patient with reduced CYP2D6 activity.BMJ case reports · 2026Article
- Psychopharmacological Mechanisms of Antidepressant Withdrawal: Insights From Venlafaxine.Human psychopharmacology · 2026Review
- Physiologically Based Pharmacokinetic (PBPK) Modeling of Antidepressants: A Scoping Review of Existing Models, Applications, and Software Tools.Clinical pharmacokinetics · 2026Article
- Venlafaxine as Monotherapy and in Combination Regimens in Acute Rodent Nociception Experimental Models: A Review.International journal of molecular sciences · 2026Review
- Influence ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Pharmacogenetics of antidepressant response: a focused review on CYP2C19, CYP2D6, SLC6A4, and HTR2A polymorphisms.Frontiers in pharmacology · 2026Review
- Safety Profile and Suicidality Associated with the Use of Esketamine in the Treatment of Major Depressive Disorder in European Countries: An EudraVigilance Database Analysis.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Pharmacological Mechanism and Drug Research Prospects of Ginsenoside Rb1 as an Antidepressant.Antioxidants (Basel, Switzerland) · 2025Review
- Therapeutic Drug Monitoring for Individualized Antidepressant Treatment.Drug design, development and therapy · 2025Article
- Use of Exposure Data to Establish Causality in Drug-Adverse Event Relationships: An Example with Desvenlafaxine.Pharmaceuticals (Basel, Switzerland) · 2024Article
- Therapeutic reference range for duloxetine in the treatment of depression revised: A systematic review and meta-analysis.Neuroscience applied · 2024Review
Corrections and comments
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Authors and funding
12 authors at 9 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
introductionThe selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet.
objectivesWe performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression.
methodsFour databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal.
resultsHigh-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75-225 mg/day). The population-based concentration ranges (25-75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225-450 ng/ml for the AM and (ii) 144-302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140-600 ng/ml.
conclusionVEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN's dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.