Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Venlafaxine in Geriatric Depression: Phase 1 of the PRIDE Study

Am J Geriatr Psychiatry. 2020 Mar;28(3):304-316. doi: 10.1016/j.jagp.2019.10.003. Epub 2019 Oct 12.


Objective: There is limited information regarding the tolerability of electroconvulsive therapy (ECT) combined with pharmacotherapy in elderly adults with major depressive disorder (MDD). Addressing this gap, we report acute neurocognitive outcomes from Phase 1 of the Prolonging Remission in Depressed Elderly (PRIDE) study.

Methods: Elderly adults (age ≥60) with MDD received an acute course of 6 times seizure threshold right unilateral ultrabrief pulse (RUL-UB) ECT. Venlafaxine was initiated during the first treatment week and continued throughout the study. A comprehensive neurocognitive battery was administered at baseline and 72 hours following the last ECT session. Statistical significance was defined as a two-sided p-value of less than 0.05.

Results: A total of 240 elderly adults were enrolled. Neurocognitive performance acutely declined post ECT on measures of psychomotor and verbal processing speed, autobiographical memory consistency, short-term verbal recall and recognition of learned words, phonemic fluency, and complex visual scanning/cognitive flexibility. The magnitude of change from baseline to end for most neurocognitive measures was modest.

Conclusion: This is the first study to characterize the neurocognitive effects of combined RUL-UB ECT and venlafaxine in elderly adults with MDD and provides new evidence for the tolerability of RUL-UB ECT in an elderly sample. Of the cognitive domains assessed, only phonemic fluency, complex visual scanning, and cognitive flexibility qualitatively declined from low average to mildly impaired. While some acute changes in neurocognitive performance were statistically significant, the majority of the indices as based on the effect sizes remained relatively stable.

Trial registration: NCT01028508.

Keywords: Major depressive disorder; electroconvulsive therapy; geriatric; memory; neuropsychology.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Aged
  • Combined Modality Therapy / adverse effects
  • Depressive Disorder, Major / drug therapy*
  • Depressive Disorder, Major / therapy
  • Electroconvulsive Therapy*
  • Female
  • Humans
  • Male
  • Neurocognitive Disorders / chemically induced
  • Neurocognitive Disorders / epidemiology*
  • Neuropsychological Tests
  • Treatment Outcome
  • Venlafaxine Hydrochloride / adverse effects*
  • Venlafaxine Hydrochloride / therapeutic use


  • Venlafaxine Hydrochloride

Associated data