Ute Kessler

The study protocol of the Norwegian randomized controlled trial of electroconvulsive therapy in treatment resistant depression in bipolar disorder

BackgroundThe treatment of depressive phases of bipolar disorder is challenging. The effects of the commonly used antidepressants in bipolar depression are questionable. Electroconvulsive therapy is generally considered to be the most effective treatment even if there are no randomized controlled trials of electroconvulsive therapy in bipolar depression. The safety of electroconvulsive therapy is well documented, but there are some controversies as to the cognitive side effects. The aim of this study is to compare the effects and side effects of electroconvulsive therapy to pharmacological treatment in treatment resistant bipolar depression. Cognitive changes and quality of life during the treatment will be assessed.Methods/DesignA prospective, randomised controlled, multi-centre six- week acute treatment trial with seven clinical assessments. Follow up visit at 26 weeks or until remission (max 52 weeks). A neuropsychological test battery designed to be sensitive to changes in cognitive function will be used. Setting: Nine study centres across Norway, all acute psychiatric departments. Sample: n = 132 patients, aged 18 and over, who fulfil criteria for treatment resistant depression in bipolar disorder, Montgomery Åsberg Depression Rating Scale Score of at least 25 at baseline. Intervention: Intervention group: 3 sessions per week for up to 6 weeks, total up to 18 sessions. Control group: algorithm-based pharmacological treatment as usual.DiscussionThis study is the first randomized controlled trial that aims to investigate whether electroconvulsive therapy is better than pharmacological treatment as usual in treatment resistant bipolar depression. Possible long lasting cognitive side effects will be evaluated. The study is investigator initiated, without support from industry.Trial registrationNCT00664976

The Effect of Electroconvulsive Therapy on Neurocognitive Function in Treatment-Resistant Bipolar Disorder Depression

OBJECTIVE To compare the effects of right unilateral (RUL) electroconvulsive therapy (ECT) and algorithm-based pharmacologic treatment (APT) on neurocognitive function in treatment-resistant bipolar disorder depression. METHOD Inpatients with DSM-IV-TR-diagnosed, treatment-resistant bipolar depression, who were acutely admitted to 1 of the 7 clinical study centers in Norway, were recruited from May 2008 to April 2011 into a prospective, randomized controlled, 6-week acute treatment trial. General neurocognitive function was assessed with the MATRICS Consensus Cognitive Battery (MCCB), and retrograde memory for autobiographical events was assessed with the Autobiographical Memory Interview-Short Form (AMI-SF) before and shortly after (mean = 23.5 days) a trial with either RUL brief-pulse ECT (mean dose = 233.3 mC) or APT. RESULTS Seventy-three patients entered, and 39 (nECT = 19, nAPT = 20) completed. Both groups showed improvements in all MCCB domain scores, with no significant differences between the study groups (no interaction effect: F₁,₃₇ = 1.52, P = NS). Improvements in neurocognitive performance were significantly correlated with reductions in depression ratings posttreatment. The AMI-SF score was significantly lower (based on consistent answers from pre- to posttreatment) in the ECT group (72.9%) than in the APT group (80.8%, P = .025), indicating reduced consistency in autobiographical memory after ECT. CONCLUSIONS General neurocognitive function was unaffected by RUL brief-pulse ECT treatment and positively related to improved mood in bipolar depression. Autobiographical memory consistency was reduced in patients treated with ECT. The results suggest that ECT can be used in treatment-resistant bipolar depression without compromising general neurocognitive function. The clinical relevance of reduced autobiographical memory consistency in the ECT group requires further investigation. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT00664976.

Neurocognitive profiles in treatment-resistant bipolar I and bipolar II disorder depression

BackgroundThe literature on the neuropsychological profiles in Bipolar disorder (BD) depression is sparse. The aims of the study were to assess the neurocognitive profiles in treatment-resistant, acutely admitted BD depression inpatients, to compare the neurocognitive functioning in patients with BD I and II, and to identify the demographic and clinical illness characteristics associated with cognitive functioning.MethodsAcutely admitted BD I (n = 19) and BD II (n = 32) inpatients who fulfilled the DSM-IV-TR criteria for a major depressive episode were tested with the MATRICS Consensus Cognitive Battery (MCCB), the Wechsler Abbreviated Scale of Intelligence, the National Adult Reading Test, and a battery of clinical measures.ResultsNeurocognitive impairments were evident in the BD I and BD II depression inpatients within all MCCB domains. The numerical scores on all MCCB-measures were lower in the BD I group than in the BD II group, with a significant difference on one of the measures, category fluency. 68.4% of the BD I patients had clinically significant impairment (>1.5 SD below normal mean) in two or more domains compared to 37.5% of the BD II patients (p = 0.045). A significant reduction in IQ from the premorbid to the current level was seen in BD I but not BD II patients. Higher age was associated with greater neurocognitive deficits compared to age-adjusted published norms.ConclusionsA high proportion of patients with therapy-resistant BD I or II depression exhibited global neurocognitive impairments with clinically significant severity. The cognitive impairments were more common in BD I compared to BD II patients, particularly processing speed. These findings suggest that clinicians should be aware of the severe neurocognitive dysfunction in treatment-resistant bipolar depression, particularly in BD I.Trial registrationTrial registration number: NCT00664976

Is infertility really associated with higher levels of mental distress in the female population? Results from the North-Trøndelag Health Study and the Medical Birth Registry of Norway

Abstract Objective: To explore the effect of ever having tried to conceive for more than 12 months on levels of anxiety and depressive symptoms and to investigate if symptom levels of anxiety and depression in infertile women who remain childless, or go on to have children, respectively, differ from symptom levels in mothers without reports of infertility. Methods: Analyses were based on information from 12 584 Norwegian women aged 19–45 years who participated in the North-Trøndelag Health Study from 1995 to 1997 and data from the Medical Birth Registry of Norway. Anxiety and depressive symptoms were measured by the Hospital Anxiety and Depression Scale. Results: Having tried to conceive for more than 12 months (ever) was weakly associated with higher levels of depressive symptoms. In the categorical analyses, women with resolved infertility had higher levels of anxiety symptoms (B = 0.25 (95% confidence interval (CI) = 0.04–0.47)) and voluntarily childfree had lower levels of depressive symptoms (B = –0.05 (95% CI = –0.50 to –0.21)) than mothers without infertility. However, women with current primary or current secondary infertility had levels of anxiety and depression not significantly different from mothers without infertility. Conclusion: At the population level, and from a longitudinal perspective, unresolved infertility is less burdensome than findings from studies on women seeking help for infertility would suggest.

The Global ECT-MRI Research Collaboration (GEMRIC): Establishing a multi-site investigation of the neural mechanisms underlying response to electroconvulsive therapy

Major depression, currently the worlds primary cause of disability, leads to profound personal suffering and increased risk of suicide. Unfortunately, the success of antidepressant treatment varies amongst individuals and can take weeks to months in those who respond. Electroconvulsive therapy (ECT), generally prescribed for the most severely depressed and when standard treatments fail, produces a more rapid response and remains the most effective intervention for severe depression. Exploring the neurobiological effects of ECT is thus an ideal approach to better understand the mechanisms of successful therapeutic response. Though several recent neuroimaging studies show structural and functional changes associated with ECT, not all brain changes associate with clinical outcome. Larger studies that can address individual differences in clinical and treatment parameters may better target biological factors relating to or predictive of ECT-related therapeutic response. We have thus formed the Global ECT-MRI Research Collaboration (GEMRIC) that aims to combine longitudinal neuroimaging as well as clinical, behavioral and other physiological data across multiple independent sites. Here, we summarize the ECT sample characteristics from currently participating sites, and the common data-repository and standardized image analysis pipeline developed for this initiative. This includes data harmonization across sites and MRI platforms, and a method for obtaining unbiased estimates of structural change based on longitudinal measurements with serial MRI scans. The optimized analysis pipeline, together with the large and heterogeneous combined GEMRIC dataset, will provide new opportunities to elucidate the mechanisms of ECT response and the factors mediating and predictive of clinical outcomes, which may ultimately lead to more effective personalized treatment approaches.

Effects of ECT in treatment of depression: study protocol for a prospective neuroradiological study of acute and longitudinal effects on brain structure and function

BackgroundMajor depression can be a serious and debilitating condition. For some patients in a treatment resistant depressive episode, electroconvulsive treatment (ECT) is the only treatment that is effective. Although ECT has shown efficacy in randomized controlled trials, the treatment is still controversial and stigmatized. This can in part be attributed to our lack of knowledge of the mechanisms of action. Some reports also suggest potential harmful effects of ECT treatment and memory related side effects have been documented.Methods/designThe present study will apply state of the art radiology through advanced magnetic resonance imaging (MRI) techniques to investigate structural and functional brain effects of ECT. As a multi-disciplinary collaboration, imaging findings will be correlated to psychiatric response parameters, neuropsychological functioning as well as neurochemical and genetic biomarkers that can elucidate the underlying mechanisms. The aim is to document both treatment effects and potential harmful effects of ECT.Sample: n = 40 patients in a major depressive episode (bipolar and major depressive disorder). Two control groups with n = 15 in each group: age and gender matched healthy volunteers not receiving ECT and patients undergoing electrical cardioversion (ECV) for atrial fibrillation (AF). Observation time: six months.DiscussionThe study will contribute to our understanding of the pathophysiology of major depression as well as mechanisms of action for the most effective treatment for the disorder; ECT.

Right unilateral electroconvulsive therapy does not cause more cognitive impairment than pharmacologic treatment in treatment-resistant bipolar depression: A 6-month randomized controlled trial follow-up study

Electroconvulsive therapy is an effective treatment for bipolar depression, but there are concerns about whether it causes long‐term neurocognitive impairment.

Remifentanil as an adjunct to anaesthesia for electroconvulsive therapy fails to confer long-term benefits

Background: Adding the &mgr;‐opioid receptor agonist remifentanil to agents used to induce general anaesthesia in electroconvulsive therapy (ECT) can reduce the required doses of induction agents and their unfavourable effects on seizure threshold and quality. However, whether remifentanil has favourable long‐term treatment effects in terms of response and remission rates, speed of response and remission, and side‐effects has not been studied. Methods: This retrospective, register‐based cohort study involved patients with major depression consecutively treated at two units at different hospitals in Norway with the same ECT procedure. Both units used thiopental for ECT anaesthesia, but only one unit added remifentanil (R+; n=47; 541 sessions), whereas the other did not (R–; n=119; 1166 sessions). A Cox proportional hazards model for interval‐censored data was conducted to examine the effects of remifentanil on the time to response and remission from depressive symptoms, whilst adjusting for age, sex, and baseline depression score. Results: Both R+ and R– patients showed substantial reductions of depressive symptoms, with no difference in the response (76% in both groups) or remission (63% vs 65%) rate. However, R+ patients responded (hazard ratio=0.59; 95% confidence interval: 0.4–0.8) and remitted (hazard ratio=0.72; 95% confidence interval: 0.5–1.0) more slowly, and reported more often side‐effects of nausea (30% vs 8%; P<0.001), dizziness (22% vs 8%; P=0.027), and headache (48% vs 23%; P=0.004). Conclusions: The use of adjunctive remifentanil was associated with more short‐term side‐effects and no favourable long‐term clinical outcomes. The practice of routinely adding remifentanil to barbiturate anaesthesia should therefore be reconsidered.

1600 – Establishment of a regional register for neurstimulation treatment in the western part of norway

Introduction Electroconvulsive therapy (ECT) is a highly effective treatment option mainly in severe depression. ECTs longterm effects on cognitive function are currently unknown, limiting its use. Transcranial magnet stimulation (TMS), is considered less effective than ECT in treatment of severe depression, but is without cognitive side effects. TMS is studied to a less degree than ECT. Objectives There is a need of large scale studies of effect, side effects and patients’ subjective experience of ECT and TMS. Aims Generate data to better predict which patients will benefit from ECT and TMS by establishing a regional register including all patients referred to ECT and TMS as part of an ordinary clinical treatment practice in the western part of Norway. Methods All patients referred to ECT and TMS in Bergen and Stavanger will be asked to participate in the study. There are no exclusion criteria. Demographics and course of illness factors will be recorded before start of ECT. Severity of the depressive disorder and treatment effects will be evaluated with a mix of self evaluation and clinician administrated standardized rating instruments. There will be a follow up at 6 months. Date from the described register will be merged with other relevant central Norwegian health registers. Results We expect the described regional register to offer an opportunity to determine predictors for effect, side effects and subjective satisfaction of the treatments. Conclusion This register is investigator initiated, with the aim to investigate which patient will benefit from ECT and TMS without serious side effects.

PW01-98 - No predictive value of anxiety- and depression symptoms for sub- or infertility

Objective Mental distress has been suggested as an etiological factor of fertility problems. The aim of the study was to investigate the predictive value of common mental symptoms for fertility problems in a population sample. Methods The predictive value of anxiety and depression symptoms for incident fertility problems over an 11 year span was investigated in a N=5,873 female sub-sample from the Nord-Trondelag Health Studies (HUNT 1 and HUNT 2). Only women who had not experienced fertility problems at the time of HUNT 1 were included. Fertility problems were reported retrospectively at HUNT 2. Sub-/infertility was defined as having tried to get pregnant for more than one year without success. Symptoms of anxiety and depression at HUNT 1 were measured by the one-dimensional 12-item Anxiety Depression Index (ADI). Results Mean age at HUNT 2 was 42 years (S.D. 4.96, range 28-49). N=152 reported having tried to get pregnant for more than one year. No predictive value of anxiety and/or depression symptoms for sub-/infertility was found (crude OR=0.97 (95% CI=0.82; 1.15), p=0.736; analyses adjusted for age, level of education, civil status, somatic conditions, parity, and gynaecological surgery: OR=0.97 (95% CI=0.81; 1.15), p=0.687). Results were comparable in a sub-sample who had never been pregnant. Conclusion There is no prospective effect of common mental health symptoms on incident fertility problems in women. This zero-finding emerges from a large population-based data set with a long follow-up interval, and it provides evidence against the hypothesised causal relationship between mental distress and sub-/infertility.