Neurocognitive Outcomes From Phase II of the PRIDE Study: Excellent Tolerability
Out on PubMed, from the PRIDE Study Group, is this study:
Longitudinal Neurocognitive Effects of Combined Electroconvulsive Therapy (ECT) and Pharmacotherapy in Major Depressive Disorder in Older Adults: Phase 2 of the PRIDE Study.
Am J Geriatr Psychiatry. 2021 May 17:S1064-7481(21)00293-1. doi: 10.1016/j.jagp.2021.04.006. Online ahead of print.PMID: 34074611
The abstract is copied below:
Objective: There is limited information regarding neurocognitive outcomes of right unilateral ultrabrief pulse width electroconvulsive therapy (RUL-UB ECT) combined with pharmacotherapy in older adults with major depressive disorder. We report longitudinal neurocognitive outcomes from Phase 2 of the Prolonging Remission in Depressed Elderly (PRIDE) study.
Method: After achieving remission with RUL-UB ECT and venlafaxine, older adults (≥60 years old) were randomized to receive symptom-titrated, algorithm-based longitudinal ECT (STABLE) plus pharmacotherapy (venlafaxine and lithium) or pharmacotherapy-only. A comprehensive neuropsychological battery was administered at baseline and throughout the 6-month treatment period. Statistical significance was defined as a p-value of less than 0.05 (two-sided test).
Results: With the exception of processing speed, there was statistically significant improvement across most neurocognitive measures from baseline to 6-month follow-up. There were no significant differences between the two treatment groups at 6 months on measures of psychomotor processing speed, autobiographical memory consistency, short-term and long-term verbal memory, phonemic fluency, inhibition, and complex visual scanning and cognitive flexibility.
Conclusion: To our knowledge, this is the first report of neurocognitive outcomes over a 6-month period of an acute course of RUL-UB ECT followed by one of 2 strategies to prolong remission in older adults with major depression. Neurocognitive outcome did not differ between STABLE plus pharmacotherapy versus pharmacotherapy alone over the 6-month continuation treatment phase. These findings support the safety of RUL-UB ECT in combination with pharmacotherapy in the prolonging of remission in late-life depression.
Keywords: Electroconvulsive therapy; major depression; neurocognitive adverse effects.
BRIEF SUMMARY
There is limited longitudinal information regarding the neurocognitive outcomes of right unilateral
ultrabrief pulse width electroconvulsive therapy (RUL-UB ECT) in combination with pharmacotherapy
in older adults with major depressive disorder. Addressing this information gap, we report neurocognitive outcomes from Phase 2 of the Prolonging Remission in Depressed Elderly (PRIDE) study. Following remission from an acute course of ECT plus venlafaxine, older adults were randomized to receive one of two prolonging remission strategies: symptom-titrated, algorithm-based longitudinal ECT (STABLE) in combination with pharmacotherapy (venlafaxine and lithium) or only pharmacotherapy. Study participants completed neuropsychological assessments at baseline and throughout the 6-month continuation treatment period. There were no differences in neurocognitive outcome between STABLE plus pharmacotherapy versus pharmacotherapy alone over the 6-month continuation treatment phase.
CONCLUSION
This is the first report of the long-term outcomes in older adults with depression of an acute course of RUL-UB ECT + VLF, followed by one of two prolonging remission strategies (STABLE+VLF+Li versus VLF+Li). Our key finding is that neurocognitive function improved over the 6-month follow-up period. Regardless of which prolonging remission strategy was used, patients demonstrated recovery of the mild-to-moderate neurocognitive impairments they experienced after the acute course of RUL-UB ECT + VLF. For the group as a whole, performance on most neurocognitive measures returned to the average range. While processing speed remained mildly impaired, this could be related to either the ECT or pharmacotherapy treatment, or depression itself, but this did not differ between the prolonging remission strategies. This result supports the long term safety of RUL-UB ECT + VLF in the acute treatment of depression in the older adult population, followed by VLF+Li, with or without STABLE in the prolonging of remission. Importantly, the two prolonging remission strategies were relatively similar and showed no divergence at the 6-month time point in their neurocognitive outcomes. This is despite the fact that the STABLE+VLF+Li arm, relative to the VLF+Li arm, involved the continued provision of additional ECT sessions. Moreover, in combination with our previously reported data that the additional ECT sessions (STABLE) were associated with significant sustained mood improvement, these current data suggest that the STABLE remission strategy conferred antidepressant benefit without added cognitive adverse effects.
This is likely the last major paper to come out of the PRIDE Study. The main conclusion of the paper is that there is good cognitive tolerability of RUL-UBP ECT, with resolution of the (relatively minor) acute effects, even when patients get some additional continuation ECT.
This is the first report of the long-term outcomes in older adults with depression of an acute course of RUL-UB ECT + VLF, followed by one of two prolonging remission strategies (STABLE+VLF+Li versus VLF+Li). Our key finding is that neurocognitive function improved over the 6-month follow-up period. Regardless of which prolonging remission strategy was used, patients demonstrated recovery of the mild-to-moderate neurocognitive impairments they experienced after the acute course of RUL-UB ECT + VLF. For the group as a whole, performance on most neurocognitive measures returned to the average range. While processing speed remained mildly impaired, this could be related to either the ECT or pharmacotherapy treatment, or depression itself, but this did not differ between the prolonging remission strategies. This result supports the long term safety of RUL-UB ECT + VLF in the acute treatment of depression in the older adult population, followed by VLF+Li, with or without STABLE in the prolonging of remission. Importantly, the two prolonging remission strategies were relatively similar and showed no divergence at the 6-month time point in their neurocognitive outcomes. This is despite the fact that the STABLE+VLF+Li arm, relative to the VLF+Li arm, involved the continued provision of additional ECT sessions. Moreover, in combination with our previously reported data that the additional ECT sessions (STABLE) were associated with significant sustained mood improvement, these current data suggest that the STABLE remission strategy conferred antidepressant benefit without added cognitive adverse effects.
This is likely the last major paper to come out of the PRIDE Study. The main conclusion of the paper is that there is good cognitive tolerability of RUL-UBP ECT, with resolution of the (relatively minor) acute effects, even when patients get some additional continuation ECT.
My strong preference is to refer to cognitive effects as a tolerability, not a safety, issue.
One regret I have about the PRIDE Phase I study design is that the addition of venlafaxine required us to report the excellent acute antidepressant results as the result of "RUL-UBP ECT + venlafaxine," when the likely reality was that ECT was responsible for 99% of the effect.
Let me take this opportunity to give kudos to the entire PRIDE team for your tireless work and commitment; I am very proud of the contributions we have made together to the ECT literature.
Dr Kellner,
ReplyDeleteThis was a well conceived, executed and practical study that will inform the field for decades. Thank you for your stewardship
-Vaughn McCall