Clinically relevant drug interactions in anxiety disorders

Muscatello, Maria Rosaria Anna; Spina, Edoardo; Bandelow, Borwin; Baldwin, David S.

doi:10.1002/hup.2217

Cited by 37 publications

(23 citation statements)

References 134 publications

(151 reference statements)

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“…Prescribers frequently substitute one SSRI for another if the first is ineffective or poorly tolerated, and non-pharmacokinetic/pharmacologic factors often drive prescribing habits. If the use of potentially interacting drugs cannot be avoided, adverse clinical consequences may be minimized with individualized dose adjustments guided by clinical response or monitoring plasma drug concentrations, but that approach is used minimally in practice [24]. …”

Section: Discussionmentioning

confidence: 99%

Co-Prescription Trends in a Large Cohort of Subjects Predict Substantial Drug-Drug Interactions

et al. 2015

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Pharmaceutical prescribing and drug-drug interaction data underlie recommendations on drug combinations that should be avoided or closely monitored by prescribers. Because the number of patients taking multiple medications is increasing, a comprehensive view of prescribing patterns in patients is important to better assess real world pharmaceutical response and evaluate the potential for multi-drug interactions. We obtained self-reported prescription data from NHANES surveys between 1999 and 2010, and confirm the previously reported finding of increasing drug use in the elderly. We studied co-prescription drug trends by focusing on the 2009-2010 survey, which contains prescription data on 690 drugs used by 10,537 subjects. We found that medication profiles were unique for individuals aged 65 years or more, with ≥98 unique drug regimens encountered per 100 subjects taking 3 or more medications. When drugs were viewed by therapeutic class, it was found that the most commonly prescribed drugs were not the most commonly co-prescribed drugs for any of the 16 drug classes investigated. We cross-referenced these medication lists with drug interaction data from Drugs.com to evaluate the potential for drug interactions. The number of drug alerts rose proportionally with the number of co-prescribed medications, rising from 3.3 alerts for individuals prescribed 5 medications to 11.7 alerts for individuals prescribed 10 medications. We found 22% of elderly subjects taking both a substrate and inhibitor of a given cytochrome P450 enzyme, and 4% taking multiple inhibitors of the same enzyme simultaneously. By examining drug pairs prescribed in 0.1% of the population or more, we found low agreement between co-prescription rate and co-discussion in the literature. These data show that prescribing trends in treatment could drive a large extent of individual variability in drug response, and that current pairwise approaches to assessing drug-drug interactions may be inadequate for predicting real world outcomes.

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Section: Discussionmentioning

confidence: 99%

Co-Prescription Trends in a Large Cohort of Subjects Predict Substantial Drug-Drug Interactions

et al. 2015

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“…Pooling several clinical trials, it was found that quetiapine was better than placebo in both the maintenance and treatment of GAD [64]. Although not as strong as for monotherapy, there are also some studies that support quetiapine as an adjunctive therapy [65].…”

Section: Antipsychoticsmentioning

confidence: 99%

“…In particular, an Agency for Health Care, Research and Quality (AHRQ) review found that they may be beneficial in both obsessive-compulsive disorder (OCD) and post-traumatic stress disorder (PTSD). It found that studies of both risperidone and quetiapine have shown significant effects when used as augmentation to treatment with SSRIs [64]. In head to head studies of augmentation treatment, there was no significant difference between olanzapine and risperidone with an SSRI, while quetiapine has been shown to have better efficacy than ziprasidone as an adjuvant [64].…”

Section: Antipsychoticsmentioning

confidence: 99%

Pharmacological Management of Anxiety Disorders in the Elderly

Crocco

Jaramillo

Cruz-Ortiz

et al. 2017

Curr Treat Options Psych

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Opinion Statement Anxiety disorders are common in the elderly. Additionally, anxiety symptoms often accompany co-morbid psychiatric, medical, as well as neurodegenerative diseases in the older population. Anxiety in the elderly, often accompanied by depression, can lead to worsening physical, cognitive and functional impairments in this vulnerable population. Antidepressants are considered first line treatment. Both SSRIs and SNRIs are efficacious and well-tolerated in the elderly. Some SSRIs are strong inhibitors of the cytochrome P450 hepatic pathway whereas others have less potential for drug interaction. Those antidepressants with more favorable pharmacokinetic profiles should be considered first-line in the treatment of anxiety. Mirtazapine and vortioxetine are also considered safe treatment options. Buspirone may have benefit, but lacks studies in elderly populations. Although tricyclic/tetracyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) may be effective in the elderly, their side effect and safety profiles are suboptimal and thus are not recommended in late-life. Benzodiazepines and beta blockers should generally be avoided when treating anxiety in the elderly. There is not enough evidence to support the use of antipsychotics or mood stabilizers given their risk of problems in both the long and short term. In addition, antipsychotics have a black box warning for increased mortality in elderly patients with dementia.

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“…FVX is extensively metabolized to 11 metabolites, but all of them are devoid of any significant pharmacological activity [8,9] . Most importantly, this antidepressant has a potent inhibitory effect on the activity of CYP1A2 and CYP2C19, while it is also considered a moderate inhibitor of CYP2C9 and CYP3A4 and a weak inhibitor of CYP2D6 [10,11] . Taking into account that CYP2D6 is the same metabolic pathway involved in the biotransformation of ATX, the aim of the present study was to investigate whether FVX influences its pharmacokinetics.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Potential Pharmacokinetic Interaction between Atomoxetine and Fluvoxamine in Healthy Volunteers

Todor

Popa²,

Neag

et al. 2016

Pharmacology

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Background/Aims: Attention deficit hyperactivity disorder (ADHD) is frequently associated with other psychiatric pathologies. Therefore, the present study investigated a possible pharmacokinetic interaction between atomoxetine (ATX), a treatment option for ADHD, and an antidepressant, namely, fluvoxamine (FVX). Methods: Designed as an open-label, non-randomized clinical trial, the study included 2 periods. In period 1 (reference), each subject received ATX 25 mg (single-dose), whereas in period 2 (test), all subjects were given a combination of ATX 25 mg + FVX 100 mg, following a 6-day pretreatment regimen with the enzymatic inhibitor. Non-compartmental methods were employed to determine the pharmacokinetic parameters of ATX and its main active metabolite (glucuronidated form), 4-hydroxyatomoxetine-O-glucuronide. Results: The results revealed significant differences between the study periods for C_max, AUC_0-t and AUC_0-_∞ values corresponding to ATX and its metabolite. Small, but statistically significant increases in AUC values were reported for both parent drug (1,583.05 ± 1,040.29 vs. 2,111.55 ± 1,411.59 ng*h/ml) and 4-hydroxyatomoxetine-O-glucuronide (5,754.71 ± 1,235.5 vs. 6,293.17 ± 1,219.34 ng*h/ml) after combined treatment of ATX and the enzymatic inhibitor. Conclusion: FVX had a modest effect on the pharmacokinetics of ATX and 4-hydroxyatomoxetine-O-glucuronide. The presence or absence of any clinical consequences associated with this pharmacokinetic drug-drug interaction needs to be established in future studies.

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Clinically relevant drug interactions in anxiety disorders

Cited by 37 publications

References 134 publications

Co-Prescription Trends in a Large Cohort of Subjects Predict Substantial Drug-Drug Interactions

Co-Prescription Trends in a Large Cohort of Subjects Predict Substantial Drug-Drug Interactions

Pharmacological Management of Anxiety Disorders in the Elderly

Evaluation of the Potential Pharmacokinetic Interaction between Atomoxetine and Fluvoxamine in Healthy Volunteers

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