Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with Major Depressive Disorder: Systematic review and meta-analysis

Wagner, Stefanie; Engel, Alice; Engelmann, Jan; Herzog, David P.; Dreimüller, Nadine; Müller, Marianne B.; Tadić, André; Lieb, Klaus

doi:10.1016/j.jpsychires.2017.07.003

Cited by 62 publications

(47 citation statements)

References 43 publications

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“…The present study successfully replicated the findings of previous major studies, which demonstrated a significant relationship between early improvement within the first weeks of antidepressant treatment and later remission rate in patients with MDD. [ 6 ] Specifically, a similar association was found in patients with MDD and high level of anxiety symptoms. The results showed that patients who achieved the early improvement of the depressive symptoms in week 2 after antidepressant treatment also obtained the sustained relief of symptoms and improved quality of life during weeks 2 to 6.…”

supporting

confidence: 56%

Antidepressant treatment strategy with an early onset of action improves the clinical outcome in patients with major depressive disorder and high anxiety: a multicenter and 6-week follow-up study

Liao

Wang

et al. 2020

Chinese Medical Journal

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supporting

confidence: 56%

Antidepressant treatment strategy with an early onset of action improves the clinical outcome in patients with major depressive disorder and high anxiety: a multicenter and 6-week follow-up study

Liao

Wang

et al. 2020

Chinese Medical Journal

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“…Early improvement, defined as a decrease of depression severity of ≥20% in the first 2 weeks of treatment, is one of the best investigated and most reliable predictors for response to antidepressant treatment ( 35 , 36 ). The sensitivity (true positive rate) of early improvement on remission was high in our study (i.e., 89 out of 100 remitter were early improver at day 14; sensitivity: 89%), but the specificity (true negative rate) was low (i.e., only 34 out of 100 non-remitter showed a non-improvement at day 14 or in other words 66 out of 100 early improver became non-remitter after 8 weeks of treatment and were false positives).…”

Section: Discussionmentioning

confidence: 99%

“…A promising clinical marker for treatment response prediction is an early improvement of depressive symptoms, mostly defined as a ≥20% reduction in sum scores of depressive rating scales between baseline and day 14 ( 34 , 35 ). In a recent meta-analysis including data from 14,799 patients, we showed that patients with an early improvement of depressive symptomatology after 2 weeks of antidepressant treatment had an 8-/6.5-fold increased likelihood to become responder/remitter at treatment end as compared to non-improver ( 36 ). However, although early improvement shows a high sensitivity, it has only a low specificity (true negative rate) meaning that many early improvers become later non-responders (37%) or non-remitters (67%) ( 36 ).…”

Section: Introductionmentioning

confidence: 99%

“…In a recent meta-analysis including data from 14,799 patients, we showed that patients with an early improvement of depressive symptomatology after 2 weeks of antidepressant treatment had an 8-/6.5-fold increased likelihood to become responder/remitter at treatment end as compared to non-improver ( 36 ). However, although early improvement shows a high sensitivity, it has only a low specificity (true negative rate) meaning that many early improvers become later non-responders (37%) or non-remitters (67%) ( 36 ). The low specificity of the prediction of early improvement, therefore, asks for additional markers (e.g., biological markers), which could be combined with the early improvement marker to improve the specificity of prediction of treatment outcome.…”

Section: Introductionmentioning

confidence: 99%

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BDNF Plasma Levels and BDNF Exon IV Promoter Methylation as Predictors for Antidepressant Treatment Response

et al. 2018

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Major problems of current antidepressant pharmacotherapy are insufficient response rates and difficulties in response prediction. We recently provided preliminary evidence in a small study that patients with major depressive disorder (MDD) with a hypomethylation of the CpG-87 site of the promoter IV region of the brain-derived neurotrophic factor (BDNF) gene are less likely to benefit from antidepressants. Here, we aimed at replicating this finding in a secondary analysis of 561 MDD patients (mean age 40.0 ± 11.9 years, 56% female) included into the Early Medication Change study (EMC). We measured BDNF exon IV promoter and p11 gene methylation at Baseline (BL) as well as BDNF-plasma-levels (pBDNF) at BL and day 14 and related them to treatment outcome. Although we were not able to replicate the predictor function of hypomethylation of the BDNF exon IV promoter, a subgroup of patients with severe depression (Hamilton Depression Rating Scale [HAMD-17] ≥ 25) (n = 199) and hypermethylation at CpG-87 of the BDNF exon IV promoter had significantly higher remission rates than patients without a methylation (p = 0.032). We also found that 421 (75%) of 561 patients showed an early improvement (≥ 20% HAMD-17 reduction after 2 weeks), which was associated with a 4.24-fold increased likelihood to remit at study end compared to the 140 patients without early improvement. However, specificity of response prediction of early improvement was low (34%) and false positive rate high (66%). The combination of early improvement with a pBDNF increase between BL and day 14, however, increased the specificity of response prediction from 34 to 76%, and the combination with methylation of the CpG-87 site of the BDNF exon IV promoter from 34 to 62%. Thus, the combined markers reduced false positives rates from 66 to 24% and 38%, respectively. Methylation at other sites or p11 promoter methylation failed to increase specificity of early improvement prediction. In sum, the results add to previous findings that BDNF, BDNF promoter methylation and the combination of clinical and biological markers may be interesting candidates for therapy response prediction which has to be confirmed in further studies.Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT00974155, identifier: NCT00974155

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“…Recent studies indicated that early improvement within 2 weeks of antidepressant treatment is a strong predictor of subsequent remission at 6–12 weeks [ 16 , 17 ], which supports the benefit of early clinical decision-making regarding subsequent treatment strategies. However, at least 20–30% of patients who did not exhibit early improvement also achieved remission after 4–12 weeks of treatment [ 18 , 19 ], which suggests that changing treatment options based on the early improvement status is premature.…”

Section: Introductionmentioning

confidence: 93%

Genetic Markers for Later Remission in Response to Early Improvement of Antidepressants

Kang

Kim

Yoo

et al. 2020

IJMS

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Planning subsequent treatment strategies based on early responses rather than waiting for delayed antidepressant action can be helpful. We identified genetic markers for later non-remission in patients exhibiting poor early improvement using whole-exome sequencing data of depressive patients treated in a naturalistic manner. Among 1000 patients, early improvement at 2 weeks (reduction in Hamilton Depression Rating Scale [HAM-D] score ≥ 20%) and remission at 12 weeks (HAM-D score ≤ 7) were evaluated. Gene- and variant-level analyses were conducted to compare patients who did not exhibit early improvement and did not eventually achieve remission (n = 126) with those who exhibited early improvement and achieved remission (n = 385). Genes predicting final non-remission in patients who exhibited poor early improvement (COMT, PRNP, BRPF3, SLC25A40, and CGREF1 in males; PPFIBPI, LZTS3, MEPCE, MAP1A, and PFAS in females; ST3GAL5 in the total population) were determined. Among the significant genes, variants in the PRNP (rs1800014), COMT (rs6267), BRPF3 (rs200565609), and SLC25A40 genes (rs3213633) were identified. However, interpretations should be made cautiously, as complex pharmacotherapy involves various genes and pathways. Early detection of poor early improvement and final non-remission based on genetic risk would be helpful for decision-making in a clinical setting.

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Early improvement as a resilience signal predicting later remission to antidepressant treatment in patients with Major Depressive Disorder: Systematic review and meta-analysis

Cited by 62 publications

References 43 publications

Antidepressant treatment strategy with an early onset of action improves the clinical outcome in patients with major depressive disorder and high anxiety: a multicenter and 6-week follow-up study

Antidepressant treatment strategy with an early onset of action improves the clinical outcome in patients with major depressive disorder and high anxiety: a multicenter and 6-week follow-up study

BDNF Plasma Levels and BDNF Exon IV Promoter Methylation as Predictors for Antidepressant Treatment Response

Genetic Markers for Later Remission in Response to Early Improvement of Antidepressants

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