Influence of the CYP2D6 Isoenzyme in Patients Treated with Venlafaxine for Major Depressive Disorder: Clinical and Economic Consequences

• Published in: PloS one Vol. 9; no. 11; p. e90453
• Main Authors: Sicras-Mainar, Antoni, Guijarro, Pablo, Armada, Beatriz, Blanca-Tamayo, Milagrosa, Navarro-Artieda, Ruth
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 04.11.2014; Public Library of Science (PLoS)
• Subjects: Adolescent; Adult; Aged; Ambulatory care; Antidepressants; Antidepressive Agents, Second-Generation - economics; Antidepressive Agents, Second-Generation - pharmacology; Antidepressive Agents, Second-Generation - therapeutic use; Breast cancer; Cancer therapies; Cost analysis; Costs; CYP2D6 protein; Cytochrome; Cytochrome P-450 CYP2D6 - physiology; Cytochrome P-450 CYP2D6 Inhibitors - economics; Cytochrome P-450 CYP2D6 Inhibitors - pharmacology; Cytochrome P-450 CYP2D6 Inhibitors - therapeutic use; Cytochrome P450; Demographic variables; Demographics; Depressive Disorder, Major - drug therapy; Depressive Disorder, Major - economics; Drug dosages; Drug metabolism; Drug Synergism; Drug Therapy, Combination; Drugs; Enzymes; Female; Health care; Health Care Costs; Hospitals; Humans; Inhibitors; Isoenzymes - physiology; Male; Medical diagnosis; Medical records; Medicine and Health Sciences; Mental depression; Mental disorders; Metabolism; Metabolites; Middle Aged; Mortality; Observational studies; Patients; Population; Primary care; Regression analysis; Regression models; Remission; Retrospective Studies; Statistical analysis; Substrate inhibition; Substrates; Therapy; Treatment Outcome; Venlafaxine; Venlafaxine Hydrochloride - economics; Venlafaxine Hydrochloride - pharmacology; Venlafaxine Hydrochloride - therapeutic use; Young Adult; Spain
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0090453

Antidepressant drugs are the mainstay of drug therapy for sustained remission of symptoms. However, the clinical results are not encouraging. This lack of response could be due, among other causes, to factors that alter the metabolism of the antidepressant drug. to evaluate the impact of concomitant administration of CYP2D6 inhibitors or substrates on the efficacy, tolerability and costs of patients treated with venlafaxine for major depressive disorder in clinical practice. We designed an observational study using the medical records of outpatients. Subjects aged ≥ 18 years who started taking venlafaxine during 2008-2010 were included. Three study groups were considered: no combinations (reference), venlafaxine-substrate, and venlafaxine-inhibitor. The follow-up period was 12 months. The main variables were: demographic data, comorbidity, remission (Hamilton <7), response to treatment, adverse events and costs. The statistical analysis included logistic regression models and ANCOVA, with p values <0.05 considered significant. A total of 1,115 subjects were recruited. The mean age was 61.7 years and 75.1% were female. Approximately 33.3% (95% CI: 30.5 to 36.1) were receiving some kind of drug combination (venlafaxine-substrate: 23.0%, and venlafaxine-inhibitor: 10.3%). Compared with the venlafaxine-substrate and venlafaxine-inhibitor groups, patients not taking concomitant drugs had a better response to therapy (49.1% vs. 39.9% and 34.3%, p<0.01), greater remission of symptoms (59.9% vs. 50.2% and 43.8%, p<0.001), fewer adverse events (1.9% vs. 7.0% and 6.1%, p<0.05) and a lower mean adjusted cost (€2,881.7 vs. €4,963.3 and €7,389.1, p<0.001), respectively. All cost components showed these differences. The patients treated with venlafaxine alone showed a better response to anti-depressant treatment, greater remission of symptoms, a lower incidence of adverse events and lower healthcare costs.