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Predicting treatment dropout after antidepressant initiation.

ABSTRACT: Antidepressants exhibit similar efficacy, but varying tolerability, in randomized controlled trials. Predicting tolerability in real-world clinical populations may facilitate personalization of treatment and maximize adherence. This retrospective longitudinal cohort study aimed to determine the extent to which incorporating patient history from electronic health records improved prediction of unplanned treatment discontinuation at index antidepressant prescription. Clinical data were analyzed from individuals from health networks affiliated with two large academic medical centers between March 1, 2008 and December 31, 2014. In total, the study cohorts included 51,683 patients with at least one International Classification of Diseases diagnostic code for major depressive disorder or depressive disorder not otherwise specified who initiated antidepressant treatment. Among 70,121 total medication changes, 16,665 (23.77%) of them were followed by failure to return; maximum risk was observed with paroxetine (27.71% discontinuation), and minimum with venlafaxine (20.78% discontinuation); Mantel-Haenzel ?2 (8?df)?=?126.44, p?=?1.54e-23 <1e-6. Models incorporating diagnostic and procedure codes and medication prescriptions improved per-medication Areas Under the Curve (AUCs) to a mean of 0.69 [0.64-0.73] (ranging from 0.62 for paroxetine to 0.80 for escitalopram), with similar performance in the second, replication health system. Machine learning applied to coded electronic health records facilitates identification of individuals at high-risk for treatment dropout following change in antidepressant medication. Such methods may assist primary care physicians and psychiatrists in the clinic to personalize antidepressant treatment on the basis not solely of efficacy, but of tolerability.

SUBMITTER: Pradier MF

PROVIDER: S-EPMC7026064 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Predicting treatment dropout after antidepressant initiation.

Pradier Melanie F MF McCoy Thomas H TH Hughes Michael M Perlis Roy H RH Doshi-Velez Finale F

Translational psychiatry 20200206 1

Antidepressants exhibit similar efficacy, but varying tolerability, in randomized controlled trials. Predicting tolerability in real-world clinical populations may facilitate personalization of treatment and maximize adherence. This retrospective longitudinal cohort study aimed to determine the extent to which incorporating patient history from electronic health records improved prediction of unplanned treatment discontinuation at index antidepressant prescription. Clinical data were analyzed fr ...[more]

PMID: 32066733

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Project description:ImportanceThere is some evidence that men may be at higher risk of depression directly following the birth of their child and that approximately 1 in 10 men will experience depression in the year after birth, but less is known about men's antidepressant treatment during this time. Likewise, few direct comparisons have been made with antidepressant treatment in men who have not recently become fathers.ObjectivesTo determine whether recently having a child was associated with increased odds of antidepressant treatment in men.Design, setting, and participantsThis cohort study used UK primary care electronic health records from the IQVIA Medical Research Database. Participants included men aged 15 to 55 years who had had a child in the previous year, from January 2007 to December 2016, and compared with up to 5 men who did not have a child in the same calendar year. Data were analyzed from January 2022 to March 2023.ExposureA record of having a child in the previous year was identified through linked primary care records using a family identification number.Main outcomes and measuresThe main outcome was antidepressant initiation in the year after childbirth or in the year after this index date for men who did not have a child. Random-effects Poisson regression was used to determine associations of cohort, age group, social deprivation, history of antidepressant treatment, and calendar year with having an antidepressant prescription in the year after index date using prevalence risk rates (PPRs).ResultsAnalysis included 90 736 men who had had a child in the previous year and 453 632 men in the comparison cohort. Most men in the study (463 879 men [85.2%]) were aged between 25 and 44 years, and there were more men living in the least deprived areas (130 277 men [23.9%]) than the most deprived areas (72 268 men [13.3%]). Overall, 4439 men (4.9%) had at least 1 antidepressant prescription in the year after they had a child, compared with 26 646 men (5.9%) who did not have a child in the same year. However, after adjustment there was no difference in antidepressant treatment between groups (adjusted PRR [aPRR], 1.01; 95% CI, 0.98-1.04). In fathers, those who had recently received antidepressant treatment were much more likely to receive antidepressant treatment after childbirth compared with fathers with no history of antidepressant treatment (aPRR, 32.31; 95% CI, 30.37-34.38). Fathers living in the most deprived areas were 18% more likely to have an antidepressant prescription compared with fathers living in the least deprived areas (aPRR, 1.18; 95% CI, 1.07-1.30).Conclusions and relevanceThese findings suggest that recently having a child was not associated with an increase in antidepressant treatment among men, but previous antidepressant treatment in fathers was strongly associated with treatment after childbirth. Further research is needed to determine whether antidepressant treatment or experiencing depression can be a barrier to fatherhood and whether fatherhood is a barrier to receiving antidepressant treatment.

Project description:ImportanceTreatment with antidepressants has been associated with hip fracture. This association could restrict the treatment options, especially in older patients.ObjectiveTo investigate the association between antidepressant drug treatment and hip fracture starting 1 year before the initiation of treatment.Design, setting, and participantsIn this nationwide cohort study, 204 072 individuals in the Prescribed Drugs Register of Sweden's National Board of Health and Welfare aged 65 years or older who had a prescription of antidepressants filled between July 1, 2006, and December 31, 2011, were matched by birth year and sex to 1 control participant who was not prescribed antidepressants (for a total of 408 144 people in the register). Outcome data were collected from 1 year before to 1 year after the index date (date of prescription being filled). Data analysis was performed from July 1, 2005, to December 31, 2012.ExposuresFirst filled prescription of an antidepressant drug.Main outcomes and measuresIncident hip fractures occurring in the year before and year after initiation of antidepressant therapy were registered. Associations were investigated using multivariable conditional logistic regression models and flexible parametric models.ResultsOf the 408 144 people in the register who were included in the study, 257 486 (63.1%) were women, with a mean (SD) age of 80.1 (7.2) years. Antidepressant users sustained more than twice as many hip fractures than did nonusers in the year before and year after the initiation of therapy (2.8% vs 1.1% and 3.5% vs 1.3%, respectively, per actual incidence figures). In adjusted analyses, the odds ratios were highest for the associations between antidepressant use and hip fracture 16 to 30 days before the prescription was filled (odds ratio, 5.76; 95% CI, 4.73-7.01). In all separate analyses of age groups, of men and women, and of individual antidepressants, the highest odds ratios were seen 16 to 30 days before initiation of treatment, and no clear dose-response relationship was seen.Conclusions and relevanceThe present study found an association between antidepressant drug use and hip fracture before and after the initiation of therapy. This finding raises questions about the association that should be further investigated in treatment studies.

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Project description:Single-nucleotide polymorphisms (SNPs) in the FKBP5, GRIK4, and HTR2A genes have been shown to be associated with response to citalopram treatment in the STAR(*)D sample, but only associations with FKBP5 have so far been tested in the Munich Antidepressant Response Signature (MARS) project. Response and remission of depressive symptoms after 5 weeks of antidepressant treatment were tested against 82 GRIK4 and 37 HTR2A SNPs. Association analysis was conducted in about 300 depressed patients from the MARS project, 10% of whom had bipolar disorder. The most predictive SNPs from these two genes and rs1360780 in FKBP5 were then genotyped in a total of 387 German depressed in-patients to analyze potential additive and interactive effects of these variants. We could not replicate previous findings of the Sequenced Treatment Alternatives to Relieve Depression (STAR(*)D) study in our sample. Although not statistically significant, the effect for the best GRIK4 SNP of STAR(*)D (rs1954787, p=0.076, p(corrected)=0.98) seemed to be in the same direction. On the other hand, the nominally significant association with the top HTR2A SNPs of STAR(*)D (rs7997012, allelic, p=0.043, p(corrected)=0.62) was with the opposite risk allele. The GRIK4 SNP (rs12800734, genotypic, p=0.0019, p(corrected)=0.12) and the HTR2A SNP (rs17288723, genotypic, p=0.0011, p(corrected)=0.02), which showed the strongest association with remission in our sample, had not been reported previously. Associations across all genetic markers within the GRIK4 (genotypic, p=0.022) or HTR2A (genotypic, p=0.012) locus using the Fisher's product method (FPM) were also significant. In all 374 patients, the best predictive model included a main effect for GRIK4 rs12800734 and two significant interactions between GRIK4 rs12800734 and FKBP5 rs1360780, and GRIK4 rs12800734 and HTR2A rs17288723. This three SNP model explained 13.1% of the variance for remission after 5 weeks (p=0.00051 for the model). Analyzing a sub-sample of 194 patients, plasma ACTH (p=0.002) and cortisol (p=0.021) responses of rs12800734 GG (GRIK4) carriers, who also showed favorable treatment response, were significantly lower in the second combined dexamethasone (dex)/corticotrophin-releasing hormone (CRH) test before discharge compared with the other two genotype groups. Despite large differences in ethnicity and design compared with the STAR(*)D study, our results from the MARS study further support both independent and interactive involvement of GRIK4, HTR2A and FKBP5 in antidepressant treatment response.

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Predicting treatment dropout after antidepressant initiation.

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Predicting treatment dropout after antidepressant initiation.

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