Clinical efficacy and cognitive side effects of bifrontal versus right unilateral electroconvulsive therapy (ECT): a short-term randomised controlled trial in pharmaco-resistant major depression

BACKGROUND: In most studies right unilateral electroconvulsive therapy (ECT) has been shown to cause fewer cognitive side effects but less antidepressant efficacy compared with bi(fronto)temporal ECT at certain intensities. AIMS: To compare the short-term efficacy and side effects of right unilateral ECT and bifrontal ECT. METHODS: In a double-blind randomised controlled clinical trial, 92 patients diagnosed with pharmaco-resistant major depression received either six right unilateral ECT treatments (250% stimulus intensity of titrated threshold) or six bifrontal ECT (150% of threshold) treatments over a 3-week period. Concomitant psychotropic medications were continued during ECT treatments. The severity of depression and cognitive status was assessed prior to the first ECT and one day after the sixth ECT using the 21-item Hamilton Depression Rating Scale and the modified Mini Mental State Examination. RESULTS: Eight patients did not complete the course of the study due to minor side effects or withdrawal of consent. The mean Hamilton Depression score decreased from 27 to 17 points in both groups of 46 patients, resulting in 12 responders (primary endpoint defined as a decrease >50%) in each patient group (95% confidence interval for the odds ratio from 0.35 to 2.8). There was no reduction in the modified Mini Mental State score (mean score 86 of 100 points). CONCLUSIONS: Both bifrontal and right unilateral electrode placements in ECT were reasonably safe and moderately efficacious in reducing symptoms of pharmaco-resistant major depression.     

ACE polymorphism and response to electroconvulsive therapy in major depression

The angiotensin I-converting enzyme gene (ACE) has been repeatedly suggested as a major gene affecting affective disorders and their treatment, but the study results have been ambiguous so far. The primary purpose of this study was to compare the effects of the ACE genotype distributions and treatment response to electroconvulsive therapy (ECT) in patients with major depressive disorder (MDD). The association in ACE genotypes and the age at onset of depression was also analyzed and these gene distributions were also compared between patients and healthy controls. The study included 119 treatment-resistant MDD patients who were referred to ECT treatment, and 392 voluntary blood donors as controls. All participants were tested for their ACE genotype, and all study patients were evaluated both before and after treatment. The Montgomery–Åsberg Depression Scale (MADRS) was used as a primary efficacy evaluating method. The ACE genotype was not associated in treatment results for MDD. However, younger onset age of primary depression was associated with the I/D genotype in the whole patient group. The finding was partly gender dependent; in male patients the I allele carried a higher risk of earlier depression onset age, while in female patients the higher risk was seen only in the heterozygous I/D allele carriers. Distributions of these genotypes or alleles did not differ between patients and controls. The studied ACE genotype was not associated with ECT results but may be associated with age of onset of the illness in patients with MDD.     

Racial differences in the availability and use of electroconvulsive therapy for recurrent major depression

BackgroundBlack Americans with depression were less likely to receive electroconvulsive therapy (ECT) than whites during the 1970s and 80s. This pattern was commonly attributed to treatment of blacks in lower quality hospitals where ECT was unavailable. We investigated whether a racial difference in receiving ECT persists, and, if so, whether it arises from lesser ECT availability or from lesser ECT use within hospitals conducting the procedure.MethodsBlack or white inpatient stays for recurrent major depression from 1993 to 2007 (N = 419,686) were drawn from an annual sample of US community hospital discharges. The marginal disparity ratio estimated adjusted racial differences in the probabilities of (1) admission to a hospital capable of conducting ECT (availability), and (2) ECT utilization if treated where ECT is conducted (use).ResultsAcross all hospitals, the probability of receiving ECT for depressed white inpatients (7.0%) greatly exceeded that for blacks (2.0%). Probability of ECT availability was slightly greater for whites than blacks (62.0% versus 57.8%), while probability of use was markedly greater (11.8% versus 3.9%). The white versus black marginal disparity ratio for ECT availability was 1.07 (95% confidence interval 1.06–1.07) and stable over the period, while the ratio for use fell from 3.2 (3.1–3.4) to 2.5 (2.4–2.7).LimitationsDepressed persons treated in outpatient settings or receive no care are excluded from analyses.ConclusionsDepressed black inpatients continue to be far less likely than whites to receive ECT. The difference arises almost entirely from lesser use of ECT within hospitals where it is available.     

Acute effects of electroconvulsive therapy on lymphocyte natural killer cell activity in patients with major depression

BACKGROUND: Major depression has been associated with a reduction in lymphocyte natural killer cell activity (NKCA). The effects of biological treatment of depression on the immune system have not been systematically investigated. The present study addresses the acute effects of electroconvulsive therapy (ECT) on NKCA. METHODS: Thirteen patients undergoing ECT for major depression were studied. NKCA at four different effector:target (E:T) ratios (E:T = 50:1; 25:1; 12.5:1 and 6.25:1, respectively) was assessed serially in relation to the first ECT session prior to and up to 1 h following treatment (-30', -10', -3' before ECT and +3', +10', +30' and +60' following ECT). On several patients, NKCA data were also available in relation to the sixth ECT session. Comparisons between mean NKCA values for each of the E:T ratios at the different time points were made using ANOVA. RESULTS: There were significant changes in NKCA values with time at E:T=25:1 (P < 0.05). Mean NKCA values for the 30 min following ECT were significantly higher than the mean NKCA values for the 30 min preceding ECT for all four E:T ratios used (P < 0.05). Differences in NKCA values between ECT no. 1 and ECT no. 6 were small and not statistically significant. CONCLUSION: ECT is associated with a significant albeit transient increase in NKCA. The clinical implications of these findings are unknown at the present time. LIMITATIONS: A small number of patients has been investigated, particularly for the sixth ECT session. No control group for ECT was available. No correlations with clinical outcome variables have been obtained.     

Evidence for increased genetic risk load for major depression in patients assigned to electroconvulsive therapy

Electroconvulsive therapy (ECT) is the treatment of choice for severe and treatment‐resistant depression; disorder severity and unfavorable treatment outcomes are shown to be influenced by an increased genetic burden for major depression (MD). Here, we tested whether ECT assignment and response/nonresponse are associated with an increased genetic burden for major depression (MD) using polygenic risk score (PRS), which summarize the contribution of disease‐related common risk variants. Fifty‐one psychiatric inpatients suffering from a major depressive episode underwent ECT. MD‐PRS were calculated for these inpatients and a separate population‐based sample (n = 3,547 healthy; n = 426 self‐reported depression) based on summary statistics from the Psychiatric Genomics Consortium MDD‐working group (Cases: n = 59,851; Controls: n = 113,154). MD‐PRS explained a significant proportion of disease status between ECT patients and healthy controls (p = .022, R² = 1.173%); patients showed higher MD‐PRS. MD‐PRS in population‐based depression self‐reporters were intermediate between ECT patients and controls (n.s.). Significant associations between MD‐PRS and ECT response (50% reduction in Hamilton depression rating scale scores) were not observed. Our findings indicate that ECT cohorts show an increased genetic burden for MD and are consistent with the hypothesis that treatment‐resistant MD patients represent a subgroup with an increased genetic risk for MD. Larger samples are needed to better substantiate these findings.     

Gender differences in electroconvulsive therapy: a retrospective chart review

BACKGROUND: There is a growing interest in gender differences of different psychiatric disorders, especially major depression. We sought a possible gender difference related to electroconvulsive therapy (ECT). METHODS: This retrospective study compared 20 male and 23 female depressed adult patients treated by ECT. We compared their findings on gender differences to those of 12 female and 4 male bipolar patients and 11 male and 19 female schizophrenic patients, all treated in the same ECT setting. RESULTS: Depressed female patients underwent significantly fewer antidepressant drug trials than males before being referred to ECT (t41=2.09, P<0.05). A similar gender difference was found in the treatment of patients suffering from schizophrenia: female patients underwent fewer pharmacological antipsychotic trials than males before being referred to ECT (t28=3.11, P<0.01). ECT was significantly more effective in female patients than in male patients suffering from schizophrenia (U=38, P<0.05). LIMITATIONS: This is a retrospective pilot study whose results are based on subjective evaluations. CONCLUSION: The findings of this study may support a gender difference both in referral and in the outcome of ECT. Clinical relevance: there might be a need to consider lowering the number of pre-ECT drug trials for depressed males and to consider ECT as a viable therapeutic option for schizophrenic females.     

Advances in gene therapy for neurogenetic diseases: a brief review

Journal of Molecular Medicine - Neurogenetic diseases are neurological conditions with a genetic cause (s). There are thousands of neurogenetic diseases, and most of them are incurable. The...     

Time dependent therapeutic effects of single electroconvulsive therapy (ECT) in endogenous depression.

The present study was addressed to test the hypothesis of time dependent effects of a single ECT in endogenous depression. In a randomized, prospective and double blind controlled comparison 12 patients received only one true modified ECT followed by five sham ECTs on alternate days. They responded as well as the control group of 12 patients who received six true ECTs on alternate days. The Hamilton Rating Scale for Depression and a global rating scale for depression were used to monitor therapeutic response. The therapeutic effects of ECT were time dependent developing during the second week of the study period.     

Cost-effectiveness of transcranial magnetic stimulation vs. electroconvulsive therapy for severe depression: a multi-centre randomised controlled trial

BACKGROUND: Electroconvulsive therapy (ECT) has a long history of use in treating depression. Repetitive transcranial magnetic stimulation (rTMS) has been introduced more recently to the treatment spectrum. Its cost-effectiveness has not been explored. METHOD: Forty-six right-handed people with severe depressive episodes referred for ECT were randomised to receive either ECT twice weekly or rTMS on consecutive weekdays. Health and other service use were recorded for retrospective periods of 3 months prior to initiation of treatment and during the 6 months following the end of allocated treatment. Costs were calculated for the treatment period and the subsequent 6 months, and comparisons made between groups after adjustment for any baseline differences. Cost-effectiveness analysis was conducted with incremental change on the 17-item Hamilton Rating Scale for Depression (HRSD) as the primary outcome measure, and quality-adjusted life years (based on SF6D-generated utility scores with societal weights) as secondary outcome, cost-effectiveness acceptability curves plotted. RESULTS: Based on the HRSD scores and other outcome measures, rTMS was not as effective as ECT. The cost of a single session of rTMS was lower than the cost of a session of ECT, but overall there were no treatment cost differences. In the treatment and 6-month follow-up periods combined, health and other service costs were not significantly different between the two groups. Informal care costs were higher for the rTMS group. Total treatment, service and informal care costs were also higher for the rTMS group. The cost-effectiveness acceptability curves indicated a very small probability that decision-makers would view rTMS as more cost-effective than ECT. LIMITATIONS: Small sample size, some sample attrition and a relatively short follow-up period of 6 months for a chronic illness. Productivity losses could not be calculated. CONCLUSIONS: ECT is more cost-effective than rTMS in the treatment of severe depression.     

Subsyndromal depression in adolescents after a brief psychotherapy trial: course and outcome

INTRODUCTION: Subsyndromal depression has been associated with an increased risk of the development of major depressive disorder (MDD). Since treatment trials of adolescent MDD often result in subsyndromal depression as the outcome, the long-term course of these youth would be useful to understand. METHODS: 107 adolescents with MDD participated in a clinical psychotherapy trial, of whom 99 were followed up for two years after acute treatment. Those with subsyndromal depression (2-3 symptoms) at the end of acute treatment were compared to those who were well (< or =1 symptom) and those who were still depressed (> or =4 symptoms) on presentation at intake, the end of treatment, and over the two-year follow-up. RESULTS: Of the 99 youth, at the end of acute treatment 26 were well, 18 were subsyndromal, and 55 were still depressed. A substantial proportion of the subsyndromally depressed youth were functionally impaired (38%), and showed a protracted time to recovery. The risk of recurrence was similar to those who were without depression at the end of acute treatment (46% vs. 44%). Recurrence was predicted by depressive symptom severity and family difficulties at the end of acute treatment. LIMITATIONS: A large proportion of the subsyndromal groups received open treatment that may have altered their course. Also, this was a referred sample, rather than an epidemiological one. CONCLUSIONS: In clinical samples treated with psychotherapy, subsyndromal depression poses a significant risk for functional impairment and protracted recovery. Depressive recurrence may be prevented by targeting reduction of symptom severity and of family difficulties.     

Value of the initial stimulus dose in right unilateral and bifrontal electroconvulsive therapy

BACKGROUND: The outcome of electroconvulsive therapy (ECT) is affected by the placement and dose of the stimulus. In general, the ECT dose can be selected either by the dose-titration method (on which the measured seizure threshold level is based), or the method of predetermined dose (e.g. the age-based dosing and the fixed high dose method). METHODS: Seizure thresholds were measured in 50 patients with right unilateral (RUL) and in 30 patients with experimental bifrontal (BF) ECT stimulus. The ECT dose (mC) of the age-based dosing was calculated by multiplying the age (years) by 5.0 (age method) or 2.5 (half-age method). The fixed high dose was set to 378 mC. RESULTS: The seizure thresholds had only a moderate correlation with the age of the patients. The methods based on the predetermined dose would have led us to give patients with the lowest seizure thresholds in the RUL ECT group very high stimulus doses, up to 12 (age method) or 15 (fixed high dose method) times the individual seizure threshold. In contrast, the RUL ECT patients with the highest seizure thresholds would have received low stimulus doses down to 1.5 times (half-age method) the initial seizure threshold. In the BF ECT group the-age based dose would have been similarly dependent on the initial seizure threshold level. CONCLUSION: The use of the dose-titration method is recommended, because it is the only method that allows for the individual selection of ECT stimulus dose relative to the seizure threshold.     

Stress reactivity following brief treatment for depression: differential effects of psychotherapy and medication

Psychotherapy and medication treatments are both effective in reducing depressive symptoms. However, only psychotherapy provides an enduring effect by reducing depressive vulnerability following treatment termination. This differential efficacy may reflect mode-specific effects on the longitudinal relationship between depression and stress. The current study examined posttreatment data from 153 outpatients enrolled in the Treatment of Depression Collaborative Research Program. Longitudinal analyses using the latent difference score (LDS) framework (a structural modeling technique that combines features of latent growth curve and cross-lagged regression models) evaluated the temporal relationship between severity of depression and frequency of stressful life events, assessed by interviewers at treatment termination and at 6, 12, and 18 months following treatment. Results supported a stress reactivity model in that stressful events led to elevations in the rate of depression change. Furthermore, multigroup LDS analysis indicated that this longitudinal stress reactivity occurred only for outpatients in the medication conditions. Results demonstrate that the enduring impact of psychotherapy involves the development of enhanced resiliency to stressful life events.     

Evaluating the effectiveness of a brief group cognitive behavioural therapy intervention for perinatal depression

Archives of Women's Mental Health - Little is known about the effectiveness of group cognitive behavioural therapy (CBT) in women with perinatal depression (PND) and psychiatric comorbidities....     

RGS4 polymorphism and response to electroconvulsive therapy in major depressive disorder

We studied the association between RGS4 (rs951436) polymorphism and treatment response in electroconvulsive therapy (ECT) as well as risk of treatment-resistant depression. The study sample consisted of 119 patients with major depressive disorder (MDD) and 384 healthy control subjects. RGS4 polymorphism was not associated with treatment response in ECT or risk of MDD. According to the present data, the impact of RGS4 genotype is not decisive in major depressive disorder. The results provide preliminary data on the impact of RGS4 polymorphism in treatment response in ECT.