Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice

Trivedi, Madhukar H.; Rush, A. John; Wisniewski, Stephen R.; Nierenberg, Andrew A.; Warden, Diane; Ritz, Louise; Norquist, Grayson S.; Howland, Robert H; Lebowitz, Barry D.; McGrath, Patrick J.; Shores-Wilson, Kathy; Biggs, Melanie M.; Balasubramani, Goundappa K.; Fava, Maurizio

doi:10.1176/appi.ajp.163.1.28

Cited by 3,357 publications

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“…1 Identifying the most effective treatment for a given patient is a long and costly process that not only delays recovery, but also has a negative effect on long-term outcome. Predictors of response would therefore be of important significant clinical value.…”

Section: Introductionmentioning

confidence: 99%

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

et al. 2010

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Section: Introductionmentioning

confidence: 99%

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

et al. 2010

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“…STAR * D had no placebo arm; thus all participants received active treatment. In the overall sample, over 70% of participants had experienced two or more prior episodes of depression or a sustained episode during the two years before study entry, and about 60% had one or more comorbid psychiatric disorders (3). …”

Section: What Did Star*d Contribute To Pharmacogenetics Research?mentioning

confidence: 99%

“…Response rates for any single medication are about 50%. For only a minority of patients do symptoms fully remit after about six months of treatment and sometimes with trials of two or more medications (3). Tolerability and adverse events are common factors contributing to nonadherence and treatment discontinuation, which result in persisting symptoms and disability.…”

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confidence: 99%

Pharmacogenetics Studies in STAR*D: Strengths, Limitations, and Results

Laje

Perlis²,

Rush³

et al. 2009

Psychiatric Services

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Several lines of evidence support an important genetic contribution to the wide individual variation in therapeutic response to antidepressant medications. The Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study provided the largest cohort assembled to date of DNA from patients with nonpsychotic major depressive disorder, uniformly treated with citalopram and followed prospectively for up to 12 weeks. This pivotal study changed the face of pharmacogenetics research by increasing the sample size by an order of magnitude as well as by providing detailed prospective information about antidepressant response and tolerability. Several groups have identified markers in genes and tested the replication of previous findings of genes associated with outcome and side effects of antidepressant treatment. Variants in HTR2A, GRIK4, and KCNK2 were associated with citalopram treatment outcome. Replication was achieved in markers in the FKBP5 gene. Other findings in PDE11A and BDNF were not successfully replicated, and reports of potential confounders in previous associations with serotonin transporter variation (SLC6A4) were identified. Polymorphisms in pharmacokinetic genes involved in metabolism and transmembrane transport were also not associated with antidepressant response. Adverse events were also tested. Treatment-emergent suicidal ideation was associated with GRIK2, GRIA3, PAPLN, IL28RA, and CREB1. Sexual dysfunction was linked with variation in GRIN3A, GRIA1 GRIA3, and GRIK2. Reported and future findings of pharmacogenetics studies in STAR*D could help elucidate pathways involved in major depression and those pertinent to antidepressant outcome and side effects. Replication of these findings in independent samples could lead to the development of new treatments and to optimization of available treatments.

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“…About 20% of those receiving treatment do not achieve remission, while 50% have no response at all (Trivedi et al., 2006). Relapse rates increase with increases in the number of treatments required (Rush et al., 2006a).…”

Section: Introductionmentioning

confidence: 99%

Finding treatment-resistant depression in real-world data: How a data-driven approach compares with expert-based heuristics

et al. 2017

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BackgroundDepression that does not respond to antidepressants is treatment‐resistant depression (TRD). TRD definitions include assessments of treatment response, dose and duration, and implementing these definitions in claims databases can be challenging. We built a data‐driven TRD definition and evaluated its performance.MethodsWe included adults with depression, ≥1 antidepressant, and no diagnosis of mania, dementia, or psychosis. Subjects were stratified into those with and without proxy for TRD. Proxies for TRD were electroconvulsive therapy, deep brain, or vagus nerve stimulation. The index date for subjects with proxy for TRD was the procedure date, and for subjects without, the date of a randomly selected visit. We used three databases. We fit decision tree predictive models. We included number of distinct antidepressants, with and without adequate doses and duration, number of antipsychotics and psychotherapies, and expert‐based definitions, 3, 6, and 12 months before index date. To assess performance, we calculated area under the curve (AUC) and transportability.ResultsWe analyzed 33,336 subjects with no proxy for TRD, and 3,566 with the proxy. Number of antidepressants and antipsychotics were selected in all periods. The best model was at 12 months with an AUC = 0.81. The rule transported well and states that a subject with ≥1 antipsychotic or ≥3 antidepressants in the last year has TRD. Applying this rule, 15.8% of subjects treated for depression had TRD.ConclusionThe definition that best discriminates between subjects with and without TRD considers number of distinct antidepressants (≥3) or antipsychotics (≥1) in the last year.

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Evaluation of Outcomes With Citalopram for Depression Using Measurement-Based Care in STAR*D: Implications for Clinical Practice

Cited by 3,357 publications

References 68 publications

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

Interaction between serotonin transporter gene variants and life events predicts response to antidepressants in the GENDEP project

Pharmacogenetics Studies in STAR*D: Strengths, Limitations, and Results

Finding treatment-resistant depression in real-world data: How a data-driven approach compares with expert-based heuristics

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