Toward a Definition of "No Meaningful Benefit" From Antidepressant Treatment: An Equipercentile Analysis With Cross-Trial Validation Across Multiple Rating Scales

J Clin Psychiatry. 2022 Jun 27;83(4):21m14239. doi: 10.4088/JCP.21m14239.

Abstract

Background: Many patients with major depressive disorder (MDD) who experience no meaningful benefit (NMB) from antidepressive treatment go undetected. However, there is a lack of consensus on the definition of NMB from antidepressants.

Methods: Equipercentile linking was used to identify a threshold for percent change in 17-item Hamilton Depression Rating Scale (HDRS-17) scores that equated with a Clinical Global Impressions-Improvement (CGI-I) score of 3 (minimally improved), a proxy for NMB, after 4 and 8 weeks of citalopram or escitalopram treatment, using data from the Pharmacogenomic Research Network Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS). The NMB threshold for the HDRS-17 was validated by equating a CGI-I rating of 3 with percent change values from the clinician- and patient-rated versions of the Quick Inventory of Depressive Symptomatology (QIDS-C and QIDS-SR) using data from PGRN-AMPS and phase 1 of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. This study was conducted between June 2021 and September 2021.

Results: In PGRN-AMPS, a 30% improvement in HDRS-17 score corresponded to a CGI-I rating of 3 at 4 and 8 weeks. The 30% improvement threshold was also observed for QIDS-C and QIDS-SR scores in both PGRN-AMPS and STAR*D. Similar results were observed for percent change in HDRS-17 and QIDS-based measures in lower- and higher-severity groups based on a median split of baseline total scores.

Conclusions: Improvement in depressive severity of ≤ 30%, as assessed using the HDRS-17, QIDS-C, and QIDS-SR, may validly define NMB from antidepressants during short-term treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Antidepressive Agents / therapeutic use
  • Citalopram / therapeutic use
  • Clinical Trials as Topic
  • Depressive Disorder, Major* / diagnosis
  • Depressive Disorder, Major* / drug therapy
  • Humans
  • Pharmacogenetics
  • Psychiatric Status Rating Scales
  • Treatment Outcome

Substances

  • Antidepressive Agents
  • Citalopram