[Show abstract][Hide abstract] ABSTRACT: Although electroconvulsive therapy (ECT) is the most effective acute antidepressant intervention, sustained response rates are low. It has never been systematically assessed whether psychotherapy, continuation ECT, or antidepressant medication is the most efficacious intervention to maintain initial treatment response.
In a prospective, randomized clinical trial, 90 inpatients with major depressive disorder (MDD) were treated with right unilateral ultra-brief acute ECT. Electroconvulsive therapy responders received 6 months guideline-based antidepressant medication (MED) and were randomly assigned to add-on therapy with cognitive-behavioral group therapy (CBT-arm), add-on therapy with ultra-brief pulse continuation electroconvulsive therapy (ECT-arm), or no add-on therapy (MED-arm). After the 6 months of continuation treatment, patients were followed-up for another 6 months. The primary outcome parameter was the proportion of patients who remained well after 12 months.
Of 90 MDD patients starting the acute phase, 70% responded and 47% remitted to acute ECT. After 6 months of continuation treatment, significant differences were observed in the three treatment arms with sustained response rates of 77% in the CBT-arm, 40% in the ECT-arm, and 44% in the MED-arm. After 12 months, these differences remained stable with sustained response rates of 65% in the CBT-arm, 28% in the ECT-arm, and 33% in the MED-arm.
These results suggest that ultra-brief pulse ECT as a continuation treatment correlates with low sustained response rates. However, the main finding implicates cognitive-behavioral group therapy in combination with antidepressants might be an effective continuation treatment to sustain response after successful ECT in MDD patients.
[Show abstract][Hide abstract] ABSTRACT: In this article, we will introduce interpersonal psychotherapy as an effective short-term treatment strategy in major depression. In IPT, a reciprocal relationship between interpersonal problems and depressive symptoms is regarded as important in the onset and as a maintaining factor of depressive disorders. Therefore, interpersonal problems are the main therapeutic targets of this approach. Four interpersonal problem areas are defined, which include interpersonal role disputes, role transitions, complicated bereavement, and interpersonal deficits. Patients are helped to break the interactions between depressive symptoms and their individual interpersonal difficulties. The goals are to achieve a reduction in depressive symptoms and an improvement in interpersonal functioning through improved communication, expression of affect, and proactive engagement with the current interpersonal network. The efficacy of this focused and structured psychotherapy in the treatment of acute unipolar major depressive disorder is summarized. This article outlines the background of interpersonal psychotherapy, the process of therapy, efficacy, and the expansion of the evidence base to different subgroups of depressed patients.
European Archives of Psychiatry and Clinical Neuroscience 09/2012; · 3.36 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Discrepancies between scores on the Hamilton Depression Rating Scale (HAMD) and the Beck Depression Inventory (BDI), as well as differences regarding their sensitivity to detect change, have been reported. This study investigates discrepancies and their potential prediction on the basis of demographic, personality, and clinical factors in depressed inpatients and analyzes the sensitivity to change. The HAMD and the BDI were administered to 105 inpatients with major depressive disorder randomized to 5weeks of either interpersonal psychotherapy or clinical management. Personality was assessed with the NEO Five-Factor Inventory. Low extraversion and high neuroticism were associated with relatively higher endorsement of depressive symptoms on the BDI compared with the HAMD. The HAMD presented a greater reduction of symptom scores than the BDI. Patients with high BDI scores, high HAMD scores or both revealed the greatest change, possibly due to a statistical effect of regression to the mean. Restricted by sample size, analyses were not differentiated by treatment condition. Regression to the mean cannot be tested directly, but it might be considered as a possible explanation. The HAMD and the BDI should be regarded as two complementary rather than redundant or competing instruments as the discrepancy is associated with personality characteristics. Attributing large effect sizes solely to effective treatment and a sensitive measure may be misleading.
[Show abstract][Hide abstract] ABSTRACT: The only psychotherapy specifically designed and evaluated for the treatment of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), has never been directly compared to another depression-specific psychological method.
Thirty patients with early-onset chronic depression were randomized to 22 sessions of CBASP or Interpersonal Psychotherapy (IPT) provided in 16 weeks. Primary outcome was the score on the 24-item Hamilton Rating Scale for Depression (HRSD) assessed posttreatment by an independent blinded evaluator. Secondary endpoints were, among others, remission (HRSD≤8) rates and the Beck Depression Inventory (BDI). The study included a prospective naturalistic 12-month follow-up.
Intent-to-treat analyses of covariance (ANCOVA) revealed that there was no significant difference in posttreatment HRSD scores between the CBASP and the IPT condition, but in self-rated BDI scores. We found significantly higher remission rates in the CBASP (57%) as compared to the IPT (20%) group. One year posttreatment, no significant differences were found in the self-reported symptom level (BDI) using ANCOVA.
The study used only a small sample size and no placebo control. The generalizability of the results may be limited to patients with a preference for psychological treatment.
While the primary outcome was not significant, secondary measures showed relevant benefits of CBASP over IPT. We found preliminary evidence that in early-onset chronic depression, an approach specifically designed for this patient population was superior to a method originally developed for the treatment of acute depressive episodes. Long-term results suggest that chronically depressed patients may need extended treatment courses.
Journal of affective disorders 03/2011; 129(1-3):109-16. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Efficacy and cognitive outcome of ECT is depending on electrode placement, pulse width and electrical dosage. Several studies showed that high-dosage right unilateral ECT (RULECT) had a better antidepressant effects than low-dosage RULECT and less cognitive side effect than bilateral stimulation. In this prospective, randomized, double-blind trial, we examined the efficacy and cognitive side effects of RULECT with three different (high dose) stimulus intensities (4×, 7× and 10× above the seizure threshold (ST)).
41 patients with treatment resistant unipolar or bipolar depression were randomized to one of the three stimulation intensities. For stimulation, we used an ultrabrief pulse (0.3 ms). Primary outcome measures were reduction of the Hamilton Depression Rating Scale (HDRS), Beck Depression Inventory (BDI) and the response rate (50% reduction of the HDRS) in the three groups. For cognitive side effects, a neuropsychological test battery was assessed.
All three groups responded significantly to 9 ECTs (p < 0.005), but there were no statistical significant differences in the response rates between the three intensity groups. Besides of the Verbal Learning Memory Recognition Test (VLMT), which showed significant impairments in the high dose intensity groups, no differences could be shown between the three study groups in all neuropsychological tests.
A RULECT with ultrabrief pulse stimulation and 4× ST intensity is effective and from good tolerability. Higher intensity dosages seem to be associated with more cognitive side effects during a course of acute ECT treatment.
Journal of Psychiatric Research 02/2011; 45(2):174-8. · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Using standard self-evaluation questionnaires, numerous studies have found that subjective memory improves shortly after electroconvulsive therapy (ECT). This change covaries strongly with depression severity and is not associated with objective amnestic effects or treatment parameters. We examined subjective evaluations of ECT's cognitive effects using a novel interview that directly inquired about global impact, in contrast to the standard method of inquiring about specific aspects of cognition.
We conducted a prospective, randomized, double-masked trial comparing the effects of pulse width (0.3 vs 1.5 milliseconds) and electrode placement (right unilateral vs bilateral) on cognitive outcomes. Subjective evaluations were obtained before and during the week after the randomized ECT course, using the Cognitive Failures Questionnaire, the Squire Memory Complaint Questionnaire, and the novel Global Self-Evaluation of Memory. An extensive neuropsychological battery was administered at these time points.
Cognitive Failures Questionnaire and Squire Memory Complaint Questionnaire scores improved at post-ECT relative to pre-ECT, strongly covaried with depression severity (24-item Hamilton Depression Rating Scale scores) but not with objective amnestic deficits or treatment parameters. In contrast, the treatment conditions differed in post-ECT Global Self-Evaluation of Memory scores, and these scores were associated with objective amnestic effects.
In contrast to standard methods, direct questioning about global impact resulted in more negative views about ECT's cognitive effects, concordance with objective cognitive measures, and differences among treatment conditions. Patients may be more accurate in their assessment of ECT's adverse effects than had previously been suggested.
The journal of ECT 10/2010; 27(1):59-66. · 1.19 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Metabolic changes after electroconvulsive therapy (ECT) have been described in depressed patients, but results are heterogeneous. To determine the concentrations of N-acetyl-aspartate (NAA), choline-containing compounds, creatine + phosphocreatine (tCr), and glutamate in the left dorsolateral prefrontal cortex (DLPFC) and left anterior cingulum of depressed patients before and after ECT, we used proton magnetic resonance spectroscopy.
Metabolite concentrations in the DLPFC and anterior cingulum were determined in 25 patients with major depressive disorder (MDD) and 27 healthy control subjects using the point resolved spectroscopy sequence. Neuropsychological and clinical parameters were determined before and after nine sessions of right unilateral ultrabrief pulse ECT.
In the cingulum, baseline glutamate and NAA levels were decreased in depressed patients. High glutamate at baseline predicted a greater treatment response. After ECT, increased NAA levels were observed in responders to treatment and tCr levels were significantly decreased across all depressive patients. In the left DLPFC, NAA levels were significantly decreased in responders to ECT compared with nonresponders. Autobiographic memory was deteriorated in all patients after ECT.
Low glutamatergic state in depressive patients emphasizes the role of dysfunctional glutamatergic neurotransmission in the pathophysiology of MDD. The low NAA level at baseline in the patients supports neurodegenerative changes in MDD. N-acetyl-aspartate levels might serve as early surrogate marker for dynamic metabolic changes due to ECT, reflecting both neuroprotection and lowered neuronal viability. The tCr decrease in the cingulum suggests altered mitochondrial energy metabolism.
[Show abstract][Hide abstract] ABSTRACT: The Cognitive Behavioral Analysis System of Psychotherapy (CBASP) by James McCullough is the first psychotherapeutical approach specifically designed for chronic depression. Whereas its efficacy has recently been studied, empirical investigations on the underlying etiopathological hypotheses are missing. McCullough postulates that chronically depressed patients - particularly those with early onset - think preoperationally. This term was coined by J. Piaget and includes egocentrism in the views of self and others and incapacity for authentic interpersonal empathy. In accordance, empirical studies indicate a deficit in theory of mind (ToM) in depressed individuals.
Sixteen patients with early onset chronic depression were compared to sixteen matched healthy controls using three measurements: 1) the Movie for the Assessment of Social Cognition (MASC) as a new video-based theory of mind test, 2) self-rated questionnaires on empathy (Interpersonal Reactivity Index (IRI), and a scale assessing individual competence in relationships), and 3) a structured evaluation by the patients' therapists.
The groups did not differ in their theory of mind performance on any aspect assessed by the used test. However, patients rated their empathy in daily life as significantly inferior to healthy controls. In addition, the therapists assigned a considerable amount of preoperational behavior to their patients. No meaningful correlations between these three types of measurements were found. Limitations: Small sample size, no structural assessment of possible psychopathology in the control group, control group was not rated by clinicians concerning preoperational behaviors.
Lack of empathy exists in the daily life of early onset chronically depressed patients according to their own and their therapists' evaluation. However, a video-based test failed to pick up deficits in their theory of mind capacities. Further research is needed to investigate theory of mind deficits using real life interpersonal interactions demanding the patient's personal involvement.
Journal of affective disorders 08/2010; 124(3):262-9. · 3.76 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) has been found to exert modest to moderate therapeutic effects in major depression, but mechanism of action and its clinical relevance have not been clarified yet. Previous trials have reported patterns of symptomatology predicting response to rTMS. As most patients also received concomitant antidepressant medication these response patterns may rather refer to combined treatment than rTMS alone. Thus, this study aims to replicate previous findings and explore patterns of response in drug-free patients.
In the Munich-Berlin Predictor Study data of 79 patients from two open clinical trials evaluating effects of high-frequency rTMS of the left dorsolateral prefrontal cortex were pooled. Previous models predicting the response to rTMS [Fregni, F., Marcolin, M.A., Myczkowski, M., Amiaz, R., Hasey, G., Rumi, D.O., Rosa, M., Rigonatti, S.P., Camprodon, J., Walpoth, M., Heaslip, J., Grunhaus, L., Hausmann, A., Pascual-Leone, A., 2006. Predictors of antidepressant response in clinical trials of transcranial magnetic stimulation. Int. J. Neuropsychopharmacol. 9, 641-654; Brakemeier, E.L., Luborzewski, A., Danker-Hopfe, H., Kathmann, N., Bajbouj, M., 2007. Positive predictors for antidepressive response to prefrontal repetitive transcranial magnetic stimulation (rTMS). J. Psychiatr. Res. 41, 395-403.] were systematically tested and new explorative regression analyses were conducted.
Of the 79 patients, 34.2% showed an antidepressant response. Previous models could not be validated. Explorative regression analysis revealed a significant model with therapy resistance, HAMD items 1 (depressed mood), and 2 (feelings of guilt) as negative and retardation as positive predictors.
No controlled study; specific statistical issues; sample size; differences concerning patient population and stimulation parameters between study sites.
In sum, this study does not confirm clinical valid and robust patterns being predictive for a response to rTMS in depression. The only exception is a high level of therapy resistance being associated with poor outcome. Future predictor studies should focus on large and homogenous samples of rTMS multicenter trials and include neurobiological variables.
Journal of Affective Disorders 06/2008; 108(1-2):59-70. · 3.30 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: While electroconvulsive therapy (ECT) in major depression is effective, cognitive effects limit its use. Reducing the width of the electrical pulse and using the right unilateral electrode placement may decrease adverse cognitive effects, while preserving efficacy.
In a double-masked study, we randomly assigned 90 depressed patients to right unilateral ECT at 6 times seizure threshold or bilateral ECT at 2.5 times seizure threshold, using either a traditional brief pulse (1.5 ms) or an ultrabrief pulse (0.3 ms). Depressive symptoms and cognition were assessed before, during, and immediately, two, and six months after therapy. Patients who responded were followed for a one-year period.
The final remission rate for ultrabrief bilateral ECT was 35 percent, compared with 73 percent for ultrabrief unilateral ECT, 65 percent for standard pulse width bilateral ECT, and 59 percent for standard pulse width unilateral ECT (all P's<0.05 after covariate adjustment). The ultrabrief right unilateral group had less severe cognitive side effects than the other 3 groups in virtually all primary outcome measures assessed in the acute postictal period, and during and immediately following therapy. Both the ultrabrief stimulus and right unilateral electrode placement produced less short- and long-term retrograde amnesia. Patients rated their memory deficits as less severe following ultrabrief right unilateral ECT compared to each of the other three conditions (P<0.001).
The use of an ultrabrief stimulus markedly reduces adverse cognitive effects, and when coupled with markedly suprathreshold right unilateral ECT, also preserves efficacy. (ClinicalTrials.gov number, NCT00487500.).
[Show abstract][Hide abstract] ABSTRACT: Methods used to evaluate subjective effects of electroconvulsive therapy (ECT) have relied on self-report about discrete aspects of memory. Although objective deficits are demonstrable, patients generally report improved memory after ECT. Patients have not been asked to evaluate the global impact of ECT on mood or memory. This study was undertaken to compare patients' evaluations of ECT outcomes using direct questioning about global impact compared with standard methods.
A prospective, naturalistic study was conducted in seven hospitals. Patients completed clinical and neurocognitive assessments before ECT, including the Cognitive Failures Questionnaire (CFQ), the Autobiographical Memory Interview-Short Form, and a novel interview assessing expectations about the impact of ECT on mood and memory (Global Self-Evaluation-Mood [GSE-Md], GSE-memory [GSE-My]). Follow-ups were conducted one and 24 weeks after ECT, and the GSE-Md and GSE-My evaluated perceived global impact at these time points.
Patients reported marked improvement after ECT on the CFQ, a traditional instrument assessing specific cognitive complaints. CFQ and depression severity scores were strongly correlated. On the GSE-My, patients reported a deleterious memory effect both one and 24 weeks after ECT. GSE-My, but not CFQ, scores were associated with treatment technique and long-term retrograde amnesia.
Characterization of patients' experience of cognitive side effects after ECT differs markedly depending on assessment method. Direct questioning about global impact revealed more negative views and associations with objective indices of cognitive impairment. This represents the first report of concordance between subjective and objective measures of the effects of ECT on memory.
[Show abstract][Hide abstract] ABSTRACT: Neuroimaging studies suggest a specific role of anterior cingulate cortex (ACC) and left dorsolateral prefrontal cortex (DLPFC) in major depression. Stimulation of the latter by means of repetitive transcranial magnetic stimulation (rTMS) as an antidepressant intervention has increasingly been investigated in the past. The objective of the present study was to examine in vivo neurochemical alterations in both brain regions in 17 patients with unipolar major depression before and after 10 days of high-frequency (20Hz) rTMS of the left DLPFC using 3-tesla proton magnetic resonance spectroscopy. Six out of seventeen patients were treatment responders, defined as a 50% reduction of the Hamilton depression rating scale. No neurochemical alterations in the ACC were detected after rTMS. As compared to the non-responders, responders had lower baseline concentrations of DLPFC glutamate which increased after successful rTMS. Correspondingly, besides a correlation between clinical improvement and an increase in glutamate concentration, an interaction between glutamate concentration changes and stimulation intensity was observed. Our results indicate that metabolic, state-dependent changes within the left DLPFC in major depressive disorder involve the glutamate system and can be reversed in a dose-dependent manner by rTMS.
Journal of Psychiatric Research 11/2007; 41(7):606-15. · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) is a brain stimulation technique which had recently been investigated as a putative antidepressant intervention. However, there is little agreement about clinically useful predictors of rTMS outcome. Therefore, the objective of the present study was to determine whether specific biographical, clinical, and psychopathological parameters are associated with the antidepressant response to rTMS in a large sample of 70 depressive patients. We performed a logistic regression analysis in 70 patients with major depressive disorder treated with rTMS of the left dorsolateral prefrontal cortex testing the predictive value of various domains of the depression syndrome as well as the variables episode duration, degree of treatment resistance, and CORE criteria. Response was defined as a 50% reduction of the initial Hamilton score (HAMD). After two weeks of treatment, 21% of the patients showed a response to rTMS. The binary logistic regression model correctly assigned 86.7% of the responders and 96.4% of the non-responders to their final response group. In the model, a high level of sleep disturbances was a significant predictor for treatment response to rTMS. Also, a low score of treatment resistance and a short duration of episode were positive predictors. These findings provide new evidence that especially pronounced sleep disturbances may be a significant clinical predictor of a response to rTMS. Prospective rTMS studies are necessary to validate the predictive value of the derived model.
Journal of Psychiatric Research 09/2007; 41(5):395-403. · 4.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Repetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex is a relatively non-invasive technique with putative therapeutic effects in major depression. However, the exact neurophysiological basis of these effects needs further clarification. Therefore, we studied the impact of ten daily sessions of left, dorsolateral prefrontal rTMS on motor cortical excitability, as revealed by transcranial magnetic stimulation-elicited motor-evoked potentials in 30 patients. As compared to the non-responders, responders (33%) showed changes in parameters pointing towards a reduced cortical excitability. These results suggest that repetitive transcranial magnetic stimulation of the dorsolateral, prefrontal cortex may have inhibitory effects on motor cortical neuronal excitability in patients with major depressive disorder. Furthermore, measurement of motor cortical excitability may be a useful tool for investigating and monitoring inhibitory brain effects of antidepressant stimulation techniques like rTMS.