Up to 70% of patients with treatment-resistant schizophrenia do not respond to clozapine. Pharmacological augmentation to clozapine has been studied with unimpressive results. The authors examined ...the use of ECT as an augmentation to clozapine for treatment-refractory schizophrenia.
In a randomized single-blind 8-week study, patients with clozapine-resistant schizophrenia were assigned to treatment as usual (clozapine group) or a course of bilateral ECT plus clozapine (ECT plus clozapine group). Nonresponders from the clozapine group received an 8-week open trial of ECT (crossover phase). ECT was performed three times per week for the first 4 weeks and twice weekly for the last 4 weeks. Clozapine dosages remained constant. Response was defined as ≥40% reduction in symptoms based on the psychotic symptom subscale of the Brief Psychiatric Rating Scale, a Clinical Global Impressions (CGI)-severity rating <3, and a CGI-improvement rating ≤2.
The intent-to-treat sample included 39 participants (ECT plus clozapine group, N=20; clozapine group, N=19). All 19 patients from the clozapine group received ECT in the crossover phase. Fifty percent of the ECT plus clozapine patients met the response criterion. None of the patients in the clozapine group met the criterion. In the crossover phase, response was 47%. There were no discernible differences between groups on global cognition. Two patients required the postponement of an ECT session because of mild confusion.
The augmentation of clozapine with ECT is a safe and effective treatment option. Further research is required to determine the persistence of the improvement and the potential need for maintenance treatments.
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.
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).
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.
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.
Electroconvulsive therapy (ECT) is an effective treatment for major depression. Optimising efficacy and minimising cognitive impairment are goals of ongoing technical refinements.
To compare the ...efficacy and cognitive effects of a novel electrode placement, bifrontal, with two standard electrode placements, bitemporal and right unilateral in ECT.
This multicentre randomised, double-blind, controlled trial (NCT00069407) was carried out from 2001 to 2006. A total of 230 individuals with major depression, bipolar and unipolar, were randomly assigned to one of three electrode placements during a course of ECT: bifrontal at one and a half times seizure threshold, bitemporal at one and a half times seizure threshold and right unilateral at six times seizure threshold.
All three electrode placements resulted in both clinically and statistically significant antidepressant outcomes. Remission rates were 55% (95% CI 43-66%) with right unilateral, 61% with bifrontal (95% CI 50-71%) and 64% (95% CI 53-75%) with bitemporal. Bitemporal resulted in a more rapid decline in symptom ratings over the early course of treatment. Cognitive data revealed few differences between the electrode placements on a variety of neuropsychological instruments.
Each electrode placement is a very effective antidepressant treatment when given with appropriate electrical dosing. Bitemporal leads to more rapid symptom reduction and should be considered the preferred placement for urgent clinical situations. The cognitive profile of bifrontal is not substantially different from that of bitemporal.
We examined whether electroconvulsive therapy (ECT) plus medications (“STABLE + PHARM” group) had superior HRQOL compared with medications alone (“PHARM” group) as continuation strategy after ...successful acute right unilateral ECT for major depressive disorder (MDD). We hypothesized that scores from the Medical Outcomes Study Short Form-36 (SF-36) would be higher during continuation treatment in the “STABLE + PHARM” group versus the “PHARM” group. The overall study design was called “Prolonging Remission in Depressed Elderly” (PRIDE). Remitters to the acute course of ECT were re-consented to enter a 6 month RCT of “STABLE + PHARM” versus “PHARM”. Measures of depressive symptoms and cognitive function were completed by blind raters; SF-36 measurements were patient self-report every 4 weeks.
Participants were 120 patients >60 years old. Patients with dementia, schizophrenia, bipolar disorder, or substance abuse were excluded. The “PHARM” group received venlafaxine and lithium. The “STABLE + PHARM” received the same medications, plus 4 weekly outpatient ECT sessions, with additional ECT session as needed. Participants were mostly female (61.7%) with a mean age of 70.5 ± 7.2 years. “STABLE + PHARM” patients received 4.5 ± 2.5 ECT sessions during Phase 2. “STABLE + PHARM” group had 7 point advantage (3.5–10.4, 95% CI) for Physical Component Score of SF-36 (P < 0.0001), and 8.2 point advantage (4.2–12.2, 95% CI) for Mental Component Score (P < 0.0001). Additional ECT resulted in overall net health benefit. Consideration should be given to administration of additional ECT to prevent relapse during the continuation phase of treatment of MDD.
NCT01028508
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.
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.
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.
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.
Remission of illness in patients with major depressive disorder (MDD) is achieved in less than half of patients initially treated with medication. Electroconvulsive therapy (ECT) is another treatment ...option. We report the speed of response and remission rates in a cohort of depressed patients who received a course of acute-phase ECT in the initial phase of an ongoing multicenter randomized trial of continuation ECT versus pharmacotherapy.
Patients with MDD according to DSM-IV criteria received bilateral ECT 3 times weekly. Prior to each treatment, a 24-item Hamilton Rating Scale for Depression (HAM-D-24) score was obtained by a clinical rater. Sustained response was defined as a > or = 50% reduction in baseline HAM-D-24 score for at least 2 and all subsequent measurement occasions. Remission was defined as HAM-D-24 scores of < or = 10 for at least the last 2 consecutive assessments. Data were collected from May 1997 through November 2000.
Of the 253 patients who entered the study, 86% (N = 217) completed the acute course of ECT. Sustained response occurred in 79% of the sample, and remission occurred in 75% of the sample (N = 253); 34% (85/253) of patients achieved remission at or before ECT #6 (week 2), and 65% (164/253) achieved remission at or before ECT #10 (weeks 3-4). Over half (54%; 136/253) had an initial first response by ECT #3 (end of week 1).
ECT was associated with rapid response and remission in a high percentage of patients. ECT warrants early consideration in treatment algorithms for patients with MDD.
To compare the relative efficacy of electroconvulsive therapy (ECT) in psychotic and nonpsychotic patients with unipolar major depression.
The outcome of an acute ECT course in 253 patients with ...nonpsychotic (n = 176) and psychotic (n = 77) unipolar major depression was assessed in the first phase of an ongoing National Institute of Mental Health-supported four-hospital collaborative study of continuation treatments after successful ECT courses. ECT was administered with bilateral electrode placement at 50% above the titrated seizure threshold. The remission criteria were rigorous: a score <or=10 on the 24-item Hamilton Rating Scale for Depression (HRSD) after 2 consecutive treatments, and a decrease of at least 60% from baseline.
The overall remission rate was 87% for study completers. Among these, patients with psychotic depression had a remission rate of 95% and those with nonpsychotic depression, 83%. Improvement in symptomatology, measured by the HRSD, was more robust and appeared sooner in the psychotic patients compared with the nonpsychotic patients.
Bilateral ECT is effective in relieving severe major depression. Remission rates are higher and occur earlier in psychotic depressed patients than in nonpsychotic depressed patients. These data support the argument that psychotic depression is a distinguishable nosological entity that warrants separate treatment algorithms.
Abstract Introduction Patients with Major Depressive Disorder (MDD) referred for electroconvulsive therapy (ECT) have poorer Health Related Quality of Life (HRQOL), compared with other patients with ...MDD, but ECT is associated with significant and durable improvement in HRQOL. However, no prior research has focused exclusively on elderly patients with MDD receiving ECT. Methods HRQOL data from 240 depressed patients over the age of 60 was measured with the Medical Outcomes Study Short Form 36 (SF-36). The SF-36 was measured before and after a course of acute ECT. Predictors of change in HRQOL scores were identified by generalized linear modeling. Results At baseline, participants showed very poor HRQOL. After treatment with ECT, the full sample showed marked and significant improvement across all SF-36 measures, with the largest gains seen in dimensions of mental health. Across all participants, the Physical Component Summary (PCS) score improved by 2.1 standardized points (95% CI, 0.61,3.56), while the Mental Component Summary (MCS) score improved by 12.5 points (95% CI, 7.2,10.8) Compared with non-remitters, remitters showed a trend toward greater improvement in the PCS summary score of 2.7 points (95%CI, -0.45, 5.9), while the improvement in the MCS summary score was significantly greater (8.5 points, 95% CI, 4.6,12.3) in the remitters than non-remitters. Post-ECT SF-36 measurements were consistently and positively related to baseline scores and remitter/non-remitter status or change in depression severity from baseline. Objective measures of cognitive function had no significant relationships to changes in SF-36 scores. Limitations This study's limitations include that it was an open label study with no comparison group, and generalizability is limited to elderly patients. Discussion ECT providers and elderly patients with MDD treated with ECT can be confident that ECT will result in improved HRQOL in the short-term. Attaining remission is a key factor in the improvement of HRQOL. Acute changes in select cognitive functions were outweighed by improvement in depressive symptoms in determining the short term HRQOL of the participants treated with ECT.
Antidepressant medications have a variety of effects on sleep, apart from their antidepressant effects. It is unknown whether electroconvulsive therapy (ECT) has effects on perceived sleep in ...depressed patients. This secondary analysis examines the effects of ECT on perceived sleep, separate from its antidepressant effects.
Elderly patients with major depressive disorder, as defined by DSM-IV, received open-label high-dose, right unilateral ultrabrief pulse ECT, combined with venlafaxine, as part of participating in phase 1 of the National Institute of Mental Health-supported study Prolonging Remission in Depressed Elderly (PRIDE). Phase 1 of PRIDE participant enrollment period extended from February 2009 to August 2014. Depression severity was measured with the Hamilton Depression Rating Scale-24 item (HDRS₂₄), and measures of insomnia severity were extracted from the HDRS₂₄. Participants were characterized at baseline as either "high-insomnia" or "low-insomnia" subtypes, based upon the sum of the 3 HDRS₂₄ sleep items as either 4-6 or 0-3, respectively. Insomnia scores were followed during ECT and were adjusted for the sum of all the HDRS₂₄ non-sleep items. Generalized linear models were used for longitudinal analysis of insomnia scores.
Two hundred forty patients participated, with 48.3% in the high-insomnia and 51.7% in the low-insomnia group. Although there was a reduction in the insomnia scores in the high-insomnia group, only 12.4% of them experienced remission of insomnia after a course of ECT, despite an increase in utilization of sleep aids across the course of ECT, from 8.6% to 23.2%. The degree of improvement in insomnia symptoms paralleled the degree of improvement in non-insomnia symptoms. A "low" amount of improvement on the sum of the HDRS non-insomnia items (HDRS-sleep) was accompanied by a "low" amount of improvement in insomnia scores (change of -1.6 ± 1.2, P < .0001), while a "high" amount of improvement on the sum of the HDRS non-insomnia items was accompanied by a "higher" amount of improvement in insomnia scores (change of -3.1 ± 1.6, P < .0001). After adjustment for non-insomnia symptoms, there was no change in insomnia in the low-insomnia group.
We found that ECT, combined with venlafaxine, has a modest anti-insomnia effect that is linked to its antidepressant effect. Most patients will have some degree of residual insomnia after ECT, and will require some consideration of whether additional, targeted assessment and treatment of insomnia is warranted.
ClinicalTrials.gov Identifier: NCT01028508.
The authors compared the clinical and cognitive effects of bifrontal electrode placement with standard bitemporal electrode placement in the treatment of patients with major depression.
Forty-eight ...patients with unipolar or bipolar depression were treated with a course of bifrontal or bitemporal ECT. The Hamilton Rating Scale for Depression and the standardized Mini-Mental State were administered at baseline and repeated during the course of treatment.
Forty-seven of the 48 patients who completed the course of treatment met remission criteria by the 12th treatment. There were no differences between the patients given bifrontal ECT and those given bitemporal ECT in the number of treatments required to reach remission criteria. The standardized Mini-Mental State scores of the patients given bitemporal ECT worsened more after treatment than did those of the patients given bifrontal ECT.
Bifrontal electrode placement was as efficacious as bitemporal placement and resulted in less cognitive impairment. A study of the two placements with more cognitive measures is indicated.
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