Tom K. Birkenhäger

Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta‐analysis

Dierckx B, Heijnen WT, van den Broek WW, Birkenhäger TK. Efficacy of electroconvulsive therapy in bipolar versus unipolar major depression: a meta‐analysis. Bipolar Disord 2012: 14: 146–150.

Antidepressant pharmacotherapy failure and response to subsequent electroconvulsive therapy: a meta-analysis.

Failure to respond to antidepressants probably is the most common indication for electroconvulsive therapy (ECT). The literature seems to be divided as to whether medication resistance has a negative influence on the efficacy of subsequent ECT. Therefore, we performed a systematic review to investigate the effect of previous pharmacotherapy failure on the efficacy of ECT. Relevant cohort studies were identified from systematic search of the PubMed electronic database. Seven studies were included in this meta-analysis: the overall remission rate amounts to 48.0% (281/585) for patients with and 64.9% (242/373) for patients without previous pharmacotherapy failure. An exact analysis with the Mantel-Haenszel method (fixed effect model) shows a reduced efficacy of ECT in patients that received previous pharmacotherapy (OR, 0.52; 95% confidence interval [CI], 0.39-0.69). In conclusion, the efficacy of ECT is significantly superior in patients without previous pharmacotherapy failure as compared with medication-resistant patients. Because this finding is based on observational studies, it might be caused by a confounding factor, for example, the presence of psychotic features or the duration of the index episode. Electroconvulsive therapy seems to be an effective treatment for severely depressed patients as well as for patients with previous pharmacotherapy failure.

ECT response in delusional versus non-delusional depressed inpatients

BACKGROUND ECT is often considered more effective in delusional than in non-delusional depressives, although the literature does not support this view. METHODS We reviewed the records of 55 consecutive inpatients with major depression according to the DSM-III-R criteria and distinguished two subtypes: patients with delusions and those without. We examined whether the deluded patients showed a higher response rate. RESULTS using 50% reduction on the Hamilton Rating Scale for Depression (HRSD) as response criterion, the efficacy of ECT was higher in patients with delusional depression (92% response) than in the non-deluded patients (55% response). Considering a post-ECT HRSD score of < or =7 as response criterion, patients with delusions again showed a higher response rate (57% versus 24%). LIMITATIONS this study has a retrospective nature and a rather homogeneous sample. CONCLUSION ECT appears to be an effective treatment for severely depressed inpatients, both with and without delusions. The efficacy of ECT was superior in patients with delusional depression, considering the number of patients achieving partial remission as well as full remission.

Treatment of unipolar psychotic depression: a randomized, double-blind study comparing imipramine, venlafaxine, and venlafaxine plus quetiapine.

Wijkstra J, Burger H, van den Broek WW, Birkenhäger TK, Janzing JGE, Boks MPM, Bruijn JA, van der Loos MLM, Breteler LMT, Ramaekers GMGI, Verkes RJ, Nolen WA. Treatment of unipolar psychotic depression: a randomized, double‐blind study comparing imipramine, venlafaxine, and venlafaxine plus quetiapine.

Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder

In this study, we used new technology to investigate whether a coherent pattern of enhanced expression of inflammatory and other immune activation genes in circulating monocytes is found in patients with major depression. Since a high inflammatory state of monocytes might be related to glucocorticoid resistance, we also included the genes for the two isoforms of the glucocorticoid receptor. For this study, we aimed at finding a similar coherent pattern of inflammatory and immune activation genes in monocytes of patients with MDD and recruited 47 medication-free melancholic MDD inpatients and 42 healthy controls. A quantitative-polymerase chain reaction (Q-PCR) monocyte gene expression analysis was performed using a panel of inflammatory-related genes previously identified as abnormally regulated in mood disorder patients. Selected serum cytokines/chemokines were assessed using a cytometric bead array. Depressive symptoms were analysed using Hamilton depression scores (HAMD). Thirty-four of the 47 monocyte inflammatory-related genes were significantly upregulated and 2 were significantly downregulated as compared to controls, the latter including the gene for the active GRα in particular in those with a high HAMD score. The reduced GRα expression correlated strongly to the upregulation of the inflammatory genes in monocytes. Serum levels of IL6, IL8, CCL2 and VEGF were significantly increased in patients compared to controls. Our data show the deregulation of two interrelated homoeostatic systems, that is, the immune system and the glucocorticoid system, co-occurring in major depression.

Fatal interaction between tranylcypromine and imipramine

This case report describes a patient on tranylcypromine who erroneously received a single dose of imipramine and subsequently developed a fatal serotonin syndrome. Both the clinical features and the pathophysiology of the serotonin syndrome are discussed.

Serum brain-derived neurotrophic factor level in relation to illness severity and episode duration in patients with major depression

BACKGROUND Since there are few data on the possible association between BDNF levels and characteristics of major depression, the present study assesses brain-derived neurotrophic factor (BDNF) levels in three drug-free patient samples, and explores whether episode duration, and severity correlate with serum BDNF levels. METHOD Serum BDNF levels were measured in 42 drug-free patients with major depression. The duration of the index episode and the presence of psychotic features were assessed with the Schedule for Affective Disorders and Schizophrenia, and the severity of depression was measured with the 17-item Hamilton Rating Scale for Depression. The sample was divided into three groups: severely depressed inpatients without psychotic features, severely depressed inpatients with psychotic features, and moderately depressed outpatients. RESULTS Mean serum BDNF level in the total sample was 18.0 ± 2.8 ng/ml, with no significant difference between the three patient samples (F = 1.80, df = 2, p = 0.18). Mean serum BDNF level was significantly lower in patients with an index episode over one year, compared with patients who had a shorter index episode (F = 4.90, df = 1, p = 0.033). CONCLUSION These data show that patients with a long index episode have significantly lower serum BDNF levels. We found no influence of the presence of psychotic features and severity of depression on serum BDNF levels.

A double-blind randomized study comparing imipramine with fluvoxamine in depressed inpatients

ObjectiveTo compare the efficacy of imipramine and fluvoxamine in inpatients from two centers suffering from a depressive disorder according to DSM IV criteria.MethodsThe study included 141 patients with a depressive disorder according to DSM IV criteria. After a drug-free and placebo run-in period of 1 week, patients were randomized to imipramine or fluvoxamine; doses of both drugs were adjusted to a predefined target blood level. Efficacy was evaluated 4 weeks after attaining predefined adequate plasma level.ResultsThe mean age of the study group (47 males, 94 females) was 51.8 (range 19–65) years. Of these 141 patients, 56 had episode duration longer than 1 year, 48 had mood congruent psychotic features, and 138 patients received medication. Seven patients did not complete the medication trial. The total number of patients using concurrent medication was 12/138 (8.6%). On the primary outcome criteria patients on imipramine improved significantly better on the change of illness severity score of the CGI (χ2 exact trend test=4.089, df=1, P=0.048). There was no significant difference in 50% or more reduction on the HRSD, the other primary outcome criterion. On the secondary outcome criteria the mean reduction of the HRSD scores was significantly larger in the imipramine group than in the fluvoxamine group (mean difference=3.1, standard error (SE)=1.4, t=2.15, df=136, P=0.033). There was no significant difference in the number of patients with an HRSD ≤7 at the final evaluation.ConclusionsIn depressed inpatients imipramine is more efficacious than fluvoxamine. Both drugs were well tolerated by all patients.

S100B Serum Levels Predict Treatment Response in Patients with Melancholic Depression.

Background: There is an ongoing search for biomarkers in psychiatry, for example, as diagnostic tools or predictors of treatment response. The neurotrophic factor S100 calcium binding protein B (S100B) has been discussed as a possible predictor of antidepressant response in patients with major depression, but also as a possible biomarker of an acute depressive state. The aim of the present study was to study the association of serum S100B levels with antidepressant treatment response and depression severity in melancholically depressed inpatients. Methods: After a wash-out period of 1 week, 40 inpatients with melancholic depression were treated with either venlafaxine or imipramine. S100B levels and Hamilton Depression Rating Scale (HAM-D) scores were assessed at baseline, after 7 weeks of treatment, and after 6 months. Results: Patients with high S100B levels at baseline showed a markedly better treatment response defined as relative reduction in HAM-D scores than those with low baseline S100B levels after 7 weeks (P=.002) and 6 months (P=.003). In linear regression models, S100B was a significant predictor for treatment response at both time points. It is of interest to note that nonresponders were detected with a predictive value of 85% and a false negative rate of 7.5%. S100B levels were not associated with depression severity and did not change with clinical improvement. Conclusions: Low S100B levels predict nonresponse to venlafaxine and imipramine with high precision. Future studies have to show which treatments are effective in patients with low levels of S100B so that this biomarker will help to reduce patients’ burden of nonresponding to frequently used antidepressants.

Effect of Antidepressant Medication Resistance on Short-term Response to Electroconvulsive Therapy

Abstract: This prospective study assessed the influence of resistance to antidepressant pharmacotherapy on the short-term response to subsequent electroconvulsive therapy (ECT). Previous research has shown that patients with medication resistance were less likely to respond to ECT. This finding may be applicable to the population of depressed inpatients in The Netherlands, where ECT is often preceded by several medication trials. Eighty-five patients (61 female and 24 male patients) with DSM-IV criteria for depressive disorder, both with and without mood congruent psychotic features, were included for analysis. Medication resistance was rated with the Antidepressant Treatment History Form. Medication resistance was predefined in accordance with the previous research in this field. When a reduction of at least 50% on the 17-item version of the Hamilton Rating Scale for Depression (HRSD) between pre- and post-ECT is used as response criterion, medication-resistant patients were equally likely to respond to subsequent ECT (30/48 = 82.5%) than patients without medication resistance (30/37 = 81.1%). Even when post-ECT HRSD score ≤7 was used (full remission), there was no significant difference between medication-resistant patients (21/48 = 43.8%) and patients without medication resistance (15/37 = 40.5%). When potential confounding variables were taken into account, these differences remain nonsignificant. In contrast to earlier research, medication resistance does not influence short-term response to subsequent ECT and it can still be of considerable efficacy.