Abstract
Valproic acid and the antidepressants doxepin and venlafaxine are frequently used psychotropic drugs. In the literature, an influence of valproic acid on serum levels of antidepressants has been described, although studies have focused on amitriptyline. The authors assessed their therapeutic drug monitoring (TDM) database for patients receiving a combination of doxepin or venlafaxine and valproic acid and compared these samples with matched controls without valproic acid comedication in terms of the serum concentration of antidepressants. The mean dose-corrected serum concentration of doxepin+N-doxepin in 16 patients who received valproic acid comedication was higher (2.171±1.482 ng/ml/mg) than that in the matched controls (0.971±0.857 ng/ml/mg, P<0.003). We also found a significant correlation between valproic acid serum level and dose-corrected doxepin+N-doxepin serum level (Spearman's ρ r=0.602, P<0.014). The mean dose-corrected serum level of venlafaxine+O-desmethylvenlafaxine in 41 patients who received valproic acid comedication did not differ significantly from that of the matched controls (P<0.089), but there was a significant difference between both groups in the dose-corrected serum level of O-desmethylvenlafaxine (1.403±0.665 vs. 1.102±0.444, P<0.017). As a consequence, if a combination of valproic acid with doxepin or venlafaxine is administered, cautious dosing is advisable and TDM should be performed.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Adult
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Aged
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Antidepressive Agents / administration & dosage
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Antidepressive Agents / adverse effects
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Antidepressive Agents / pharmacokinetics
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Antidepressive Agents / therapeutic use*
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Biotransformation / drug effects
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Cyclohexanols / administration & dosage
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Cyclohexanols / adverse effects
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Cyclohexanols / pharmacokinetics
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Cyclohexanols / therapeutic use*
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Depression / blood
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Depression / drug therapy*
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Dose-Response Relationship, Drug
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Doxepin / administration & dosage
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Doxepin / adverse effects
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Doxepin / pharmacokinetics
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Doxepin / therapeutic use*
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Drug Interactions
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Drug Monitoring*
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Drug Therapy, Combination / adverse effects
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Female
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GABA Agents / administration & dosage
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GABA Agents / adverse effects
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GABA Agents / pharmacokinetics
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GABA Agents / therapeutic use
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Germany
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Histamine Antagonists / administration & dosage
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Histamine Antagonists / adverse effects
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Histamine Antagonists / pharmacokinetics
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Histamine Antagonists / therapeutic use
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Hospitals, University
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Humans
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Male
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Middle Aged
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Retrospective Studies
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Selective Serotonin Reuptake Inhibitors / administration & dosage
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Selective Serotonin Reuptake Inhibitors / adverse effects
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Selective Serotonin Reuptake Inhibitors / pharmacokinetics
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Selective Serotonin Reuptake Inhibitors / therapeutic use
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Valproic Acid / administration & dosage
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Valproic Acid / adverse effects
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Valproic Acid / pharmacokinetics
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Valproic Acid / therapeutic use*
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Venlafaxine Hydrochloride
Substances
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Antidepressive Agents
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Cyclohexanols
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GABA Agents
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Histamine Antagonists
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Serotonin Uptake Inhibitors
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Doxepin
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Valproic Acid
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Venlafaxine Hydrochloride