Dataset Information

Discontinuation and dose adjustment of metoprolol after metoprolol-paroxetine/fluoxetine co-prescription in Dutch elderly.

ABSTRACT: PURPOSE:Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug-drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly. METHODS:We performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (?60 years) who had ever been prescribed metoprolol and had a first co-prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co-prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI). RESULTS:Combinations of metoprolol-paroxetine/fluoxetine, metoprolol-citalopram, and metoprolol-mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol-citalopram, metoprolol-paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77-1.48; OR = 0.87, 95% CI:0.57-1.33, respectively). In comparison with metoprolol-mirtazapine, metoprolol-paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01-2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03-2.53). CONCLUSION:Paroxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.

SUBMITTER: Bahar MA

PROVIDER: S-EPMC6001522 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature

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Discontinuation and dose adjustment of metoprolol after metoprolol-paroxetine/fluoxetine co-prescription in Dutch elderly.

Bahar Muh Akbar MA Wang Yuanyuan Y Bos Jens H J JHJ Wilffert Bob B Hak Eelko E

Pharmacoepidemiology and drug safety 20180324 6

<h4>Purpose</h4>Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug-drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.<h4>Methods</h4>We performed a cohort study using the University of Groningen IADB ...[more]

PMID: 29575226

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Project description:PurposeTo compare treatment outcomes in patients with major depressive disorder treated with duloxetine, escitalopram, fluoxetine, paroxetine, or sertraline for up to 6 months.Patients and methodsData were taken from a 6-month prospective, observational study that included 1,549 major depressive disorder patients without sexual dysfunction in 12 countries. We report the overall results and those from Asian countries. Depression severity was measured using the Clinical Global Impression and the 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Clinical and functional remissions were defined as having a QIDS-SR16 <6, and as having a rating of <3 on all three Sheehan Disability Scale items and no reduced productivity, respectively. Mixed effects modeling with repeated measures analysis and generalized estimating equation models were used. Propensity scores were included in the models.ResultsThe mixed effects modeling with repeated measures regression models showed that the Clinical Global Impression rating during follow-up was significantly lower in those patients treated with duloxetine compared with escitalopram (0.40, 95% CI 0.25 to 0.56); fluoxetine (0.22, 95% CI 0.05 to 0.38); paroxetine (0.38, 95% CI 0.23 to 0.54); and sertraline (0.32, 95% CI 0.16 to 0.49). The QIDS-SR16 of duloxetine-treated patients was significantly lower than those treated with escitalopram (1.58, 95% CI 1.03 to 2.12); fluoxetine (1.48, 95% CI 0.90 to 2.06); paroxetine (1.53, 95% CI 1.00 to 2.07); and sertraline (1.19, 95% CI 0.61 to 1.78). The probability of clinical remission of the patients treated with escitalopram, fluoxetine, paroxetine, and sertraline was lower than those treated with duloxetine (OR 0.46, 95% CI 0.33 to 0.64; OR 0.42, 95% CI 0.29 to 0.61; OR 0.40, 95% CI 0.29 to 0.56; OR 0.50, 95% CI 0.35 to 0.71; respectively). The regression analysis of functional remission also showed more favorable results for duloxetine, with OR ranging from 0.43, 95% CI 0.31 to 0.60 for paroxetine to 0.49, 95% CI 0.35 to 0.70 for sertraline. The results for the Asian countries were generally consistent.ConclusionDuloxetine-treated patients had better 6-month outcomes in terms of depression severity and clinical and functional remission, compared with selective serotonin reuptake inhibitor-treated patients.

Project description:Purpose: To our knowledge, no study has examined in a structured way the extent of underprescription of clozapine in ambulatory patients with Non-Affective Psychotic Disorder (NAPD). In the Netherlands, psychiatric care for such patients is provided by Flexible Assertive Community Treatment (FACT) teams and by early intervention teams. In 20 FACT teams and 3 early intervention teams we assessed the proportion of patients who: use clozapine (type 1 patients), previously used this drug (type 2), have an unfulfilled indication for this drug, by type of indication (type 3), or were at least markedly psychotic, but had not yet received two adequate treatments with other antipsychotic drugs (type 4). We expected to find major differences between teams. To rule out that these differences are caused by differences in severity of psychopathology, we also calculated the proportions of patients who use clozapine given an indication at any time (number of type 1 patients divided by the sum of type 1, 2, and 3 patients). Materials and methods: The nurse practitioner of each team identified the patients already on clozapine. Next, using a highly-structured decision tree, the nurse practitioner and psychiatrist assessed whether the remaining patients had an indication for this drug. Indications were treatment-resistant positive symptoms, tardive dyskinesia, aggression and suicidality. The severity of positive symptoms was determined using the Clinical Global Impression-Schizophrenia Scale (CGI-SCH). Results: In the participating FACT-teams 2,286 NAPD patients were assessed. The range among teams in proportions was: type 1: 8.8-34.7% (mean: 23.0%), type 2: 0-8.2% (mean: 3.5%), type 3: 1.7-15.6% (mean: 6.9%), type 4: 1.8-16.3% (mean: 8.6%). The range in proportions of patients using this drug given an indication was 49.0-90.9% (mean: 68.8%). These figures were lower in early intervention teams. Conclusions: The proportion of patients in FACT-teams who have an unfulfilled indication for clozapine is 6.9%. There were considerable differences between teams with respect to this proportion. Almost a third of the outpatients had at any time an indication for clozapine. If one takes type 4 patients into account, this proportion may be higher. Registration number: NTR5135 http://www.trialregister.nl/trialreg/index.asp.

Dataset Information

Discontinuation and dose adjustment of metoprolol after metoprolol-paroxetine/fluoxetine co-prescription in Dutch elderly.

Publications

Discontinuation and dose adjustment of metoprolol after metoprolol-paroxetine/fluoxetine co-prescription in Dutch elderly.

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