A Novel Strategy for Continuation ECT in Geriatric Depression: Phase 2 of the PRIDE Study

Abstract

Objective: The randomized phase (phase 2) of the Prolonging Remission in Depressed Elderly (PRIDE) study evaluated the efficacy and tolerability of continuation ECT plus medication compared with medication alone in depressed geriatric patients after a successful course of ECT (phase 1).

Method: PRIDE was a two-phase multisite study. Phase 1 was an acute course of right unilateral ultrabrief pulse ECT, augmented with venlafaxine. Phase 2 compared two randomized treatment arms: a medication only arm (venlafaxine plus lithium, over 24 weeks) and an ECT plus medication arm (four continuation ECT treatments over 1 month, plus additional ECT as needed, using the Symptom-Titrated, Algorithm-Based Longitudinal ECT [STABLE] algorithm, while continuing venlafaxine plus lithium). The intent-to-treat sample comprised 120 remitters from phase 1. The primary efficacy outcome measure was score on the 24-item Hamilton Depression Rating Scale (HAM-D), and the secondary efficacy outcome was score on the Clinical Global Impressions severity scale (CGI-S). Tolerability as measured by neurocognitive performance (reported elsewhere) was assessed using an extensive test battery; global cognitive functioning as assessed by the Mini-Mental State Examination (MMSE) is reported here. Longitudinal mixed-effects repeated-measures modeling was used to compare ECT plus medication and medication alone for efficacy and global cognitive function outcomes.

Results: At 24 weeks, the ECT plus medication group had statistically significantly lower HAM-D scores than the medication only group. The difference in adjusted mean HAM-D scores at study end was 4.2 (95% CI=1.6, 6.9). Significantly more patients in the ECT plus medication group were rated "not ill at all" on the CGI-S compared with the medication only group. There was no statistically significant difference between groups in MMSE score.

Conclusions: Additional ECT after remission (here operationalized as four continuation ECT treatments followed by further ECT only as needed) was beneficial in sustaining mood improvement for most patients.

FIGURE 1.. Longitudinal Trajectory of Modeled Hamilton Depression Rating Scale (HAM-D) Score Least Squares Means in a Study of Continuation ECT in Geriatric Depression^a

^a The graph shows baseline-adjusted least squares 24-item HAM-D mean scores from a basic mixed-effects repeated-measures model (unstructured covariance), with difference in baseline-adjusted least squares treatment means at study end (week 24) (Δ)=3.9 (95% CI=1.3, 6.5, p=0.004). For the model containing baseline HAM-D score, site, and psychosis, Δ=4.2 (95% CI=1.6, 6.9, p=0.002, unstructured covariance). Treatment-by-site, treatment-by-psychosis, and treatment-by-baseline HAM-D score interaction terms were not significant. For the comparison of the trajectories of HAM-D mean scores over time (time as continuous) in a mixed-effects model (baseline-adjusted model, unstructured covariance): treatment-by time interaction, p=0.084; main effect of time, p=0.001; main effect of treatment, p=0.12; and baseline HAM-D score, p<0.001. For analyses by treatment: main effect of time for the ECT plus medication group, p<0.001; main effect of time for the medication only group, p=0.398.

FIGURE 2.. Time to Relapse for Patients in the ECT Plus Medication and Medication Only Treatment Arms in a Study of Continuation ECT in Geriatric Depression^a

^a The graph shows a Kaplan-Meier survival curve with probability of not relapsing over time. The “event” is relapse, with eight patients in the ECT plus medication arm relapsing compared with 12 in the medication only arm. The numbers in the box below the figure are the number of patients “at risk” of relapsing at the beginning of each time interval. Patients who have dropped out or relapsed in prior intervals are no longer “at risk” and are removed from the denominator when determining probability of not relapsing in that interval. Note that “not relapsing” is not equivalent to “remaining remitted” because not all patients who have not relapsed have HAM-D scores that meet the criteria for remission.

FIGURE 3.. Trajectories of 24-item Hamilton Depression Rating Scale (HAM-D) Scores for Individual Patients in the ECT Plus Medication Arm Who Had ECT During the Flexible Phase (Weeks 5–24) (N=21) in a Study of Continuation ECT in Geriatric Depression^a

^a The graph shows the number and timing of rescue ECT treatments given in the ECT plus medication arm for those requiring an ECT treatments beyond the four ECT treatments received in the fixed phase. Each line represents a patient who received rescue ECT treatments (N=21). Small circles indicate that the patient received one ECT treatment in a given week, and large circles indicate that a patient received two treatments in a given week. Discontinuation of a line indicates patient dropout. Note the steep declines in individual trajectories immediately following the small and large circles.