Eva-Lotta Brakemeier

Cognitive behavioral analysis system of psychotherapy versus interpersonal psychotherapy for early-onset chronic depression: A randomized pilot study

BACKGROUND 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. METHODS 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. RESULTS 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. LIMITATIONS 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. CONCLUSIONS 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.

Abnormal Cingulate and Prefrontal Cortical Neurochemistry in Major Depression After Electroconvulsive Therapy

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Cognitive-Behavioral Therapy as Continuation Treatment to Sustain Response After Electroconvulsive Therapy in Depression: A Randomized Controlled Trial

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex and cortical excitability in patients with major depressive disorder.

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.

Self-Evaluation of the Cognitive Effects of Electroconvulsive Therapy

Objectives: 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 ECTs 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. Methods: 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. Results: 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. Conclusions: In contrast to standard methods, direct questioning about global impact resulted in more negative views about ECTs cognitive effects, concordance with objective cognitive measures, and differences among treatment conditions. Patients may be more accurate in their assessment of ECTs adverse effects than had previously been suggested.

Effects of 3 different stimulus intensities of ultrabrief stimuli in right unilateral electroconvulsive therapy in major depression: A randomized, double-blind pilot study

OBJECTIVE 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)). METHODS 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. RESULTS 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. CONCLUSION 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.

CBASP hilft chronisch depressiven Patienten

Chronische Depressionen sind schwer beeinträchtigende Störungen, die für die Patienten mit großem Leid verbunden sind und allgemein als äußerst schwer zu behandeln gelten. Das Cognitive Behavioral Analysis System of Psychotherapy (CBASP) ist bis dato das einzige psychotherapeutische Verfahren, welches speziell für diese Patientengruppe entwickelt wurde. Erste Studien belegen die Effektivität des integrativen Verfahrens bei chronischen Depressionen im ambulanten und stationären Setting.

CBASP als stationäres Behandlungskonzept der therapieresistenten chronischen Depression: Eine Pilotstudie zum Zusammenhang von Nebenwirkungen und Therapieerfolg

BACKGROUND Inpatient psychotherapy might trigger adverse effects among others due to short but intensive treatment. Thus, in this pilot study, certain adverse effects of the multidisciplinary inpatient Cognitive Behavioral Analysis System of Psychotherapy (CBASP) for treatment-resistant chronically depressed patients as well as their relationship to treatment outcome (response-, remission-, and relapse-rates) are examined. MATERIAL AND METHODS 50 patients with treatment-resistant and chronic depression completed the structured 12-weeks inpatient treatment program. Adverse effects were assessed by 1) deterioration of depressive symptoms (measured by the Hamilton Depression Rating Scale, HDRS) at discharge and 2) a self-report questionnaire measuring Adverse Effects of Inpatient Psychotherapy (ADEFIP), which were filled out 6 to 12 months after discharge by the patients. RESULTS After 12 weeks of treatment, 84% could be classified as responder, of whom 44% fulfilled the remission criterion. 16% were Non-Responder. According to HDRS, none of the patients showed objective deterioration of the depressive symptoms. Six months after discharge, 40% of the responders suffered from relapse. Concerning the ADEFIP, 66% of the patients reported transient deterioration of symptoms. These patients were less likely to achieve remission. Over 50% reported interpersonal conflicts with treatment team members or other patients without any relation to outcome. Finally, more than half of the patients reported significant changes in social relationships after discharge. These patients were less likely to relapse. Overall, 94% of the patients reported at least one of the in this study assessed adverse effects. CONCLUSIONS Despite some limitations, this pilot study suggests that the CBASP inpatient program could indeed cause adverse effects. However, only subjective transient deterioration appeared to have a negative impact on the individual treatment outcome in the short-term. Results encourage further research concerning adverse treatment effects in the context of short- and long-term treatment outcome investigating how relevant adverse effects are.

Reply to: Continuation Antidepressant Strategies After Electroconvulsive Therapy: Ultrabrief Pulse Versus Cognitive-Behavioral Therapy

To the Editor:In their correspondence, the colleagues Youssef and McCallraise important issues concerning our study in which wecompared efficacy and tolerability of continuation electrocon-vulsive therapy (ECT), cognitive-behavioral therapy, and antide-pressant medication after successful acute ECT (1). We arethankful for their thoughtful remarks, which give us the oppor-tunity to explain in more detail the rational for some key studydesign details.Youssef and McCall are concerned that the study results mighthave been biased in not favoring ECT due to the use of propofolinstead of methohexital. They argue that anticonvulsant effects ofpropofol might have reduced the efficacy of ECT. We are aware ofstudies indicating reduced effects due to shorter seizure duration;therefore, we ensured that all stimulation parameters indicating asuccessful seizure, such as seizure duration, were adjusted toachieve the recommended range. Of relevance in this context,several previous studies have indicated that ECT with propofol isas effective as treatments with other anesthetics [for review, see(2)]. Even more, there are first evidences that propofol is capableof enhancing effects of ECT in an animal model in both thebehavioral and molecular levels (3).They correctly note that the switch from bilateral ECT in theacute phase to unilateral ECT in the continuation phase mighthave biased the data in not favoring ECT by providing apotentially ineffective treatment to some of the patients. How-ever, in our study, the number of patients receiving bilateral ECTwas small and exploratory comparison revealed that ECT was notless effective here as compared with those patients in whichacute ECT was already effective when administered unilaterally.On another note, Youssef and McCall stress the unexpectedresults that continuation ECT plus medication is less effective thanmedication alone. Like them, we were surprised by these findings,which from our perspective might indicate that the interaction ofultrabrief ECT and pharmacologic agents (including propofol) isnot sufficiently understood and urgently need to be investigatedin more detail in future studies.Finally, they state that the findings might not be generalizableto practice in the United States, since methohexital is mostly usedand propofol is rarely used. From our perspective, we agree thatat the present stage our data should not be generalized.However, negative (or positive) impact of propofol on efficacyand tolerability of ECT has yet to be determined in studiescomparing different anesthesia regimes. In this context, we wouldeven extend this point and state that the good tolerability asindicated with the positive cognitive profile also cannot begeneralized.In sum, we think that our data provide first evidence thatcognitive-behavioral therapy can be used as a helpful interven-tion in the continuation phase of treatment of depressive illnessafter successful ECT.Eva-Lotta Brakemeier

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