Influence of resistance to antidepressant pharmacotherapy on short-term response to electroconvulsive therapy

BACKGROUND: Few studies assessing the influence of resistance to antidepressant pharmacotherapy on the response to subsequent electroconvulsive therapy (ECT) are found in the literature. Results are somewhat conflicting and may not be applicable to the population of depressed patients in The Netherlands. The aim of this study is to assess the influence of medication resistance on the short-term response to ECT in a population of severely depressed inpatients in The Netherlands, where ECT is an exceptional treatment, often used as a final treatment option. METHODS: We reviewed the records of 41 consecutive inpatients with major depression according to DSM-III-R criteria and rated each patients' antidepressant pharmacotherapy prior to ECT. We examined the extent to which medication resistance was related to short-term response to ECT. RESULTS: When a reduction of at least 50% on the Hamilton Rating Scale for Depression (HRSD) post-ECT compared to pre-ECT (partial remission) is used as response criterion, medication resistant patients and patients without established medication resistance were equally likely to respond to subsequent ECT. When a post-ECT HRSD score < or = 7 (full remission) is used as response criterion, medication resistant patients were less likely to respond to subsequent ECT (8/29=27.6%) than patients who did not receive adequate antidepressant pharmacotherapy prior to ECT (6/12=50.0%), although the difference in response rate was not statistically significant. LIMITATIONS: This study has a retrospective nature and a relatively small sample size. CONCLUSION: Antidepressant medication resistance does not seem to have an influence on the short-term response to subsequent ECT. However, when the number of patients achieving full remission is concerned, a substantial percentage of antidepressant medication resistant patients respond to ECT, although their response rate was nearly half compared to that of patients without prior adequate treatment with antidepressants. This difference in response rate was not statistically significant. ECT seems to be an effective treatment for both patients with and without prior adequate treatment with antidepressants in this Dutch population.     

Does power matter with ECT?

BACKGROUND: To assess the incidence of depressed inpatients requiring high output ECT and the response of this group compared with a group requiring standard output ECT. METHODS: We reviewed the records of 59 consecutive inpatients that were treated with bilateral ECT between January 2001 and January 2004. Diagnosis of major depression was based on DSM IV criteria. Response and remission to ECT (respectively defined as a 50% reduction in score and a score of < or = 7 on the Hamilton Rating Scale for Depression; HRSD) of both groups were compared. RESULTS: Of the 59 patients, 13 (22%) required high output ECT. These patients needed significantly more ECT treatments than patients in the standard dose group (16.4+/-7.1 versus 10.4+/-4.5; p=0.01). In total, 31 of 46 patients (67%) requiring standard output ECT and 11 of the 13 patients (85%) requiring high output ECT responded to ECT. This difference is not significant. LIMITATIONS: This study has a retrospective nature and a rather homogenous sample. CONCLUSION: In this study 1 in 5 of the depressed inpatients needs a high dose energy of bilateral ECT to induce an adequate seizure. The efficacy of ECT in these patients is similar to that in the standard dose group. Considering these facts, high output ECT devices should be available for use in routine clinical practice.     

Influence of episode duration of major depressive disorder on response to electroconvulsive therapy

BACKGROUND: Longer duration of major depressive episode is supposed to decrease response to electroconvulsive therapy (ECT). Most studies on the subject are dated and their population differs from ours, therefore their results may not be applicable to our population of severely depressed inpatients. METHODS: We reviewed the records of 56 consecutive inpatients with major depressive disorder according to DSM-III-R criteria and assessed each patient's episode duration. We examined whether episode duration has an effect on response to ECT. RESULTS: Episode duration has no significant effect on response to ECT, according to both a reduction on the Hamilton Rating Scale for Depression (HRSD) of at least 50% and a post-treatment HRSD score 相似文献   

First admissions for depression: is the 'no-treatment interval' a critical predictor of time to remission?

BACKGROUND: This study aimed to replicate findings that length of episode prior to adequate antidepressant treatment (the 'no-treatment interval') and premorbid neuroticism predict time to remission from the institution of adequate treatment for depression. METHODS: Eighty-three inpatients meeting ICD-10 criteria for a depressive illness were entered into an 18-month prospective follow-up study of illness course. Subjects were assessed using the Schedules for Clinical Assessment in Neuropsychiatry, Maudsley Personality Inventory (MPI) and the Hamilton Rating Scale for Depression (HRSD). Remission was defined as an HRSD score of < 8 for 2 consecutive weeks. RESULTS: Twenty-two patients (27%) remained depressed 12 months after the onset of adequate treatment. Significantly longer times to remission were predicted by a longer no-treatment interval and higher premorbid neuroticism scores. LIMITATIONS: Adequate antidepressant treatment was commenced prior to admission in half the cases, requiring a retrospective assessment of illness course prior to study entry. Twenty-four patients (29%) had not remitted at the time of completion of the MPI. CONCLUSIONS: These results replicate previous findings identifying a longer time to treatment and higher neuroticism scores as predictors of chronicity in depression.     

Delusional depression. Phenomenology, Neuroendocrine function, and tricyclic antidepressant response

The authors studied clinical variables, family history, cortisol secretion, and 4-week tricyclic antidepressant response in 13 delusional and 12 non-delusional, hospitalized depressives. Comparison in these parameters between the two groups revealed more family history of depression but less of alcoholism, greater frequency of cortisol hypersecretion, and poorer response to tricyclics in the delusional group. This lack of complete response was found despite full remission of delusions in 84.6% of the delusional subjects. The clinical and theoretical implications of these findings are discussed.     

Post-seizure EEG fractal dimension of first ECT predicts antidepressant response at two weeks.

BACKGROUND: Duration of seizure by itself is an insufficient criterion for a therapeutically adequate seizure in ECT. Therefore, measures of seizure EEG other than its duration need to be explored as indices of seizure adequacy and predictors of treatment response. We measured the EEG seizure using a geometrical method-fractal dimension (FD) and examined if this measure predicted remission. METHODS: Data from an efficacy study on melancholic depressives (n = 40) is used for the present exploration. They received thrice or once weekly ECTs, each schedule at two energy levels - high or low energy level. FD was computed for early-, mid- and post-seizure phases of the ictal EEG. Average of the two channels was used for analysis. RESULTS: Two-thirds of the patients (n = 25) were remitted at the end of 2 weeks. As expected, a significantly higher proportion of patients receiving thrice weekly ECT remitted than in patients receiving once weekly ECT. Smaller post-seizure FD at first ECT is the only variable which predicted remission status after six ECTs. Within the once weekly ECT group too, smaller post-seizure FD was associated with remission status. CONCLUSIONS: Post-seizure FD is proposed as a novel measure of seizure adequacy and predictor of treatment response. CLINICAL IMPLICATIONS: Seizure measures at first ECT may guide selection of ECT schedule to optimize ECT. LIMITATIONS: The study examined short term antidepressant effects only. The results may not be generalized to medication-resistant depressives.     

A prospective follow-up study of ECT outcome in older depressed patients

BACKGROUND: This study examined the relationship between age and outcome of electroconvulsive therapy (ECT). METHOD: This was a naturalistic, prospective follow-up of 81 consecutive in-patients with primary major depression. ECT outcome was compared for three age groups - under 65, 65-74 and 75 years and over - on the Hamilton Rating Scale for Depression (HRSD), Global Assessment of Functioning scale (GAF) and clinical outcome rating scale. Assessments were performed pre-ECT, immediately post-ECT, 1-3 years later and, for patients suspected of having dementia, 5 years later. RESULTS: At post-ECT and follow-up, improvement on HRSD and clinical outcome ratings were comparable for patients in the three age groups. Improvements on GAF were also comparable post-ECT, but not between post-ECT and follow-up. At follow-up, 35.7% of the oldest group had dementia. Importantly, patients who did and did not develop dementia were clinically indistinguishable prior to ECT. The number and severity of common adverse events were similar pre- and post-ECT and were not associated with age. CONCLUSIONS: Depressive outcome and adverse effects of ECT are largely independent of age. Older patients receiving ECT appear to have a higher risk of developing dementia, possibly underpinned by cerebrovascular disease.     

"Side effects" of ECT are mainly depressive phenomena and are independent of age

BACKGROUND: The aetiology of reported side effects of electroconvulsive therapy (ECT) is unclear. We examined the interaction of depression and age on adverse neuropsychological and putative side effects of ECT. METHOD: Inpatients (N=81; median age 70 years) with major depression were assessed prospectively pre-ECT, immediately post-ECT and 1-3 years later. Patients were administered the Hamilton Rating Scale for Depression (HRSD), the Global Assessment of Functioning scale (GAF) and neuropsychological tests from the Wechsler Memory Scale. Side effects and total burden scores were rated pre- and post-treatment. RESULTS: HRSD and GAF scores improved with treatment after ECT, but the prevalence and total burden of side effects were unchanged. Side effect burden was related to depression level before and after ECT. Improvement in depression correlated with reduction in side effect burden. There was a significant decline in side effect burden after controlling for change in depression. Patients' scores on neuropsychological measures did not appear to change after ECT or between pre-ECT and follow-up. Re-analysis, allowing for age, chronicity of depression, medication use and development of dementia, did not alter the findings. LIMITATIONS: lack of a control group, lack of information on ECT technique, incomplete data sets and limited neuropsychological testing. CONCLUSIONS: ECT, an effective treatment for depression, does not cause significant side effects or neuropsychological impairment, which are more likely to be depressive phenomena. ECT appears to be safe for old (> or =65 years) and very old (> or =75 years) patients, who do not appear to be more susceptible to adverse effects.     

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.     

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.     

The effects of electro-convulsive therapy on the speed of information processing in major depression

BACKGROUND: This study investigates whether cognitive impairment is evident in inpatients diagnosed with Major Depression (MD) following electro-convulsive therapy (ECT), and if so, whether it is independent from depressive symptomatology. METHODS: Speed of information processing was measured using the inspection time (IT) task. IT was compared between twelve inpatients diagnosed with MD receiving ECT and twelve age-, gender-, verbal IQ-, and depression and anxiety severity matched control inpatients diagnosed with MD not receiving ECT, over four testing sessions (prior to ECT, following one ECT session, following the completion of an ECT block, and 4 to 6 weeks after the ECT block (follow-up)). RESULTS: The mean IT score for the inpatients diagnosed with MD who received ECT slowed significantly from the first ECT to immediately after the ECT block, and was significantly faster at follow-up. The mean IT score of the inpatients diagnosed with MD not receiving ECT gradually but significantly became faster over the entire equivalent time period. LIMITATIONS: Small sample sizes. CONCLUSIONS: ECT temporarily slows information processing speed in MD patients, independent of depression symptomatology.     

Short-term prognosis in primary and secondary major depression

Among inpatients treated without ECT, those with primary unipolar depression had significantly better outcomes at discharge than did those with secondary depression. This difference grew more striking during a 6-month follow-up; patients with secondary depression were clearly less likely to recover from the index depressive episode and had substantially higher symptom levels at the time of follow-up. In contrast, patients with DSM-III melancholia resembled depressed patients without melancholia on all outcome measures.     

Caregiver's distress is associated with delusions in Alzheimer's patients

Behavioral disturbances in Alzheimer's (AD) patients might be caused by environmental factors. The authors tested the hypothesis that delusions in AD might be a result of caregiver's distress. Participants were 22 delusional and 21 nondelusional mild AD patients and their caregivers. Those who cared for nondelusional patients, compared with the delusional patients' caregivers, reported higher levels of distress because of behavioral disturbances other than delusions. When patients were stratified into 2 groups according to median distress value, 64% of the delusional patients and 33% of the nondelusional patients showed a high level of caregiver's distress, chi2(1, N = 43) = 3.94, p = .047. Although final conclusions about the causal direction of the association cannot be drawn, these findings are consistent with the hypothesis that distressed caregivers might use inappropriate coping strategies that, in turn, might favor the development of delusions.     

Eeg sleep and affective psychosis

EEG sleep changes in delusional depression have been reported previously but no attempt has been made to examine sleep profiles among specific delusional subtypes. In 29 psychotically depressed patients, those patients with delusions of guilt or sin demonstrated both increased sleep discontinuity and decreased REM sleep, especially during the first REM period, while patients with somatic delusions showed increased REM activity, especially in the first REM period. The implications of these findings are discussed.     

TPH1 218A/C polymorphism is associated with major depressive disorder and its treatment response

The association between the tryptophan hydroxylase 1 (TPH1) 218A/C polymorphism and (1) severity of major depressive disorder (MDD) and (2) response to treatment was studied. There were three study populations, the first consisting of 119 treatment-resistant MDD inpatients treated with electro-convulsive therapy (ECT), and the second of 98 MDD open care patients treated with selective serotonin reuptake inhibitors (SSRI). In addition, there was a control population of 395 healthy blood donors. The first aim of the study was to compare the genotypes of the patient with those of the healthy controls and between patient populations. The second aim was to compare the genotypes of MDD patients achieving remission with basic SSRI treatment (MADRS < 8) with the genotypes of non-responders to ECT (defined as MADRS > 15). TPH1 218A/C polymorphism was associated with the risk of MDD. CC genotype was significantly more common in patients (including both ECT and SSRI treated patients) than in controls (38.2% and 26.8% respectively; p = 0.008), and its frequency was significantly higher in more severe forms of depression, i.e. in ECT treated patients compared with SSRI treated patients (42.0% and 33.7%, p = 0.026). CC genotype was also associated with lower probability of achieving remission. It was significantly more frequent among ECT non-responders than among SSRI remitters (53.1% and 23.3%, p = 0.049). In this Finnish population TPH1 218A/C polymorphism was associated with the risk of MDD and treatment response; CC genotype was associated with the increased risk of MDD and lower probability of responding treatment. Further studies with larger samples will be required to confirm the results.     

Antidepressant efficacy of Sudarshan Kriya Yoga (SKY) in melancholia: a randomized comparison with electroconvulsive therapy (ECT) and imipramine

BACKGROUND: Sudarshan Kriya Yoga (SKY) is a procedure that involves essentially rhythmic hyperventilation at different rates of breathing. The antidepressant efficacy of SKY was demonstrated in dysthymia in a prospective, open clinical trial. This study compared the relative antidepressant efficacy of SKY in melancholia with two of the current standard treatments, electroconvulsive therapy (ECT) and imipramine (IMN). METHODS: Consenting, untreated melancholic depressives (n=45) were hospitalized and randomized equally into three treatment groups. They were assessed at recruitment and weekly thereafter for four weeks. RESULTS: Significant reductions in the total scores on Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HRSD) occurred on successive occasions in all three groups. The groups, however, did not differ. Significant interaction between the groups and occasion of assessment occurred. At week three, the SKY group had higher scores than the ECT group but was not different from the IMN group. Remission (total HRSD score of seven or less) rates at the end of the trial were 93, 73 and 67% in the ECT, IMN and SKY groups, respectively. No clinically significant side effects were observed. DISCUSSION: Within the limitations of the design (lack of double blind conditions), it can be concluded that, although inferior to ECT, SKY can be a potential alternative to drugs in melancholia as a first line treatment.     

Delusional depression. A one year follow-up

Fifty-two unipolar delusional depressives were matched to 52 unipolar nondelusional depressives on the basis of sex, age at index episode of depression and age at first episode of depression. In a one year follow-up after discharge from inpatient treatment, the delusional depressives had a poorer clinical course than the nondelusional depressives as manifested by significantly higher rates both of major depression or delusions lasting longer than 9 months and of being in a major depressive episode at the end of the follow-up period.     

Discontinuation of antidepressant drugs during electroconvulsive therapy: a controlled study

BACKGROUND: The concurrent use of antidepressant drugs with ECT is recommended by a recent ECT guideline. The study aimed to examine differential therapeutic and side effect responses when antidepressants are discontinued or not during ECT. METHODS: This study compared the effectiveness and side effect profile of unilateral ECT with antidepressant drugs (Group-1) or unilateral ECT with drug placebo (Group-2) in 30 major depressive disorder (DSM-IV) patients on antidepressants using a prospective randomised trial. Hamilton Rating Scale for Depression (HRSD), Montgomery Asberg Depression Rating Scale (MADRS), UKU scale, Columbia ECT side effect check list were used. The assessments were carried out before starting ECTs and at fixed intervals thereafter for four weeks. In addition, at six weeks a follow-up assessment was carried out using HRSD. ECTs were stopped after four weeks or earlier if patient obtained HRSD scores <8 and remained so for one week. RESULTS: Continuation of antidepressant drugs with ECT conferred no therapeutic advantage. Barring tricyclic antidepressant induced anticholinergic side effects, no differential side effect profile was noted. At follow-up none relapsed in Group-2 and the mean HRSD scores between the groups did not differ. Limitation: The antidepressant treatment prior to ECT was uncontrolled. In addition, the design was not strictly double-blind. CONCLUSION: The study failed to support an advantage with antidepressant continuation during an ECT course in major depressive disorder.     

Serial dexamethasone suppression tests in depressed patients treated only with electroconvulsive therapy

Several systematic studies have evaluated serial dexamethasone suppression tests (DST) in patients with major depression who were treated with antidepressant medications. DST changes were noted to parallel clinical improvement in most recovering patients. If serial DSTs are a valid state-related correlate of depressive pathophysiology, all types of effective antidepressant treatment should result in DST 'normalization'. However, no treatment modalities other than antidepressant medications have been studied serially with systematic assessments. To test whether serial DSTs reflect clinical progress in depressives treated solely with electroconvulsive therapy (ECT), we studied weekly DSTs and Hamilton Rating Scales for Depression (HRSD) in 22 drug-free depressed patients. We observed progressive DST 'normalization' in most patients and moderately high correlations between weekly DST and HRSD values throughout treatment. Most patients receiving ECT became DST suppressors. In most patients the DST appeared to reflect the severity of depressive pathophysiology, perhaps providing serial feedback to clinicians monitoring the progress of treatment with ECT.     

Why do people with delusions fail to choose more realistic explanations for their experiences? An empirical investigation

Delusions can be viewed as explanations of experiences,. By definition, the experiences are insufficient to merit the delusional explanations. So why have delusions been accepted rather than more realistic explanations? The authors report a study of alternative explanations in 100 individuals with delusions. Patients were assessed on the following criteria: symptom measures, the evidence for the delusions, the availability of alternative explanations, reasoning, and self-esteem. Three quarters of the patients did not report any alternative explanation for the experiences on which the delusions were based. These patients reported significantly more internal anomalous experiences and had a more hasty reasoning style than patients who did have alternative explanations available. Having doubt in a delusion, without an alternative explanation, was associated with lower self-esteem. Clinicians will need to develop plausible and compelling alternative accounts of experience in interventions rather than merely challenge patients' delusional beliefs.