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Psychopharmacology Feb 2024The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The 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.
OBJECTIVES
We 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.
METHODS
Four 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.
RESULTS
High-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.
CONCLUSION
VEN 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.
Topics: Humans; Antidepressive Agents; Depression; Desvenlafaxine Succinate; Norepinephrine; Reference Values; Serotonin; Venlafaxine Hydrochloride
PubMed: 37857898
DOI: 10.1007/s00213-023-06484-7 -
Marine Pollution Bulletin Jul 2023The assessment of exposure to the antidepressant venlafaxine and its major metabolite o-desmethylvenlafaxine in Holothuria tubulosa, Anemonia sulcata and Actinia equina...
Accumulation and metabolization of the antidepressant venlafaxine and its main metabolite o-desmethylvenlafaxine in non-target marine organisms Holothuria tubulosa, Anemonia sulcata and Actinia equina.
The assessment of exposure to the antidepressant venlafaxine and its major metabolite o-desmethylvenlafaxine in Holothuria tubulosa, Anemonia sulcata and Actinia equina is proposed. A 28-day exposure experiment (10 μg/L day) followed by a 52-day depuration period was conducted. The accumulation shows a first-order kinetic process reaching an average concentration of 49,125/54342 ng/g dw in H. tubulosa and 64,810/93007 ng/g dw in A. sulcata. Venlafaxine is considered cumulative (BCF > 2000 L/kg dw) in H. tubulosa, A. sulcata and A. equina respectively; and o-desmethylvenlafaxine in A. sulcata. Organism-specific BCF generally followed the order A. sulcata > A. equina > H. tubulosa. The study revealed differences between tissues in metabolizing abilities in H. tubulosa this effect increases significantly with time in the digestive tract while it was negligible in the body wall. The results provide a description of venlafaxine and o-desmethylvenlafaxine accumulation in common and non-target organisms in the marine environment.
Topics: Animals; Venlafaxine Hydrochloride; Desvenlafaxine Succinate; Holothuria; Aquatic Organisms; Antidepressive Agents; Sea Anemones
PubMed: 37207394
DOI: 10.1016/j.marpolbul.2023.115055 -
Environmental Science and Pollution... Feb 2024In this paper, we report a study concerning the quantification of new emerging pollutants in water as a request from the third European Watch List mechanism. The EU...
Determination of pollutants, antibiotics, and drugs in surface water in Italy as required by the third EU Water Framework Directive Watch List: method development, validation, and assessment.
In this paper, we report a study concerning the quantification of new emerging pollutants in water as a request from the third European Watch List mechanism. The EU Watch List compound was investigated by an internal method that was validated in terms of detection limits, linearities, accuracy, and precision in accordance with quality assurance criteria, and it was used to monitor several rivers from 11 Italian regions. The methodology developed was satisfactorily validated from 5 to 500 ng L for the emerging pollutants studied, and it was applied to different river waters sampled in Italy, revealing the presence of drugs and antibiotics. Rivers were monitored for 2 years by two different campaigns conducted in 2021 and 2022. A total of 19 emerging pollutants were investigated on 45 samples. The most detected analytes were O-desmethylvenlafaxine and venlafaxine. About azole compounds, sulfamethoxazole, fluconazole, and Miconazole were found. About antibiotics, ciprofloxacin and amoxicillin were found in three and one samples, respectively. Moreover, statistical analyses have found a significant correlation between O-desmethylvenlafaxine with venlafaxine, sulfamethoxazole with venlafaxine, and fluconazole with venlafaxine.
Topics: Water; Venlafaxine Hydrochloride; Desvenlafaxine Succinate; Water Pollutants, Chemical; Anti-Bacterial Agents; Fluconazole; Rivers; Italy; Sulfamethoxazole
PubMed: 38280169
DOI: 10.1007/s11356-024-32025-6