The influence of concomitant antidepressant medication on safety, tolerability and clinical effectiveness of electroconvulsive therapy.

BACKGROUND: A major problem in the treatment of severe depression is the onset latency until clinical improvement. So far, electroconvulsive therapy (ECT) is the most effective somatic treatment of depression. This holds especially true for treatment-refractory disturbances. However, not all patients respond to conventional unilateral ECT. In certain cases, subsequent clinical response can be achieved using bilateral or high-dose unilateral ECT. Also, a concomitant pharmacotherapy can be utilized to augment therapeutic effectiveness. Surprisingly, data in this field are widely lacking and only few studies showed advantages of an ECT/tricyclic antidepressant combination. METHOD: We retrospectively evaluated 5482 treatments in 455 patients to investigate possible therapeutic advantages in combination therapies versus ECT monotherapy. Main outcome criteria were clinical effectiveness and tolerability. Moreover, treatment modalities and ictal neurophysiological parameters that might influence treatment outcome were analysed. RESULTS: A total of 18.2% of our treatments were ECT monotherapy, 8.87% were done with one antidepressant. Seizure duration was unaffected by the most antidepressants. SSRI caused a lengthened seizure activity. Postictal suppression was lower in mirtazapine and higher in SSRI and SNRI treated patients. A significant enhancement of therapeutic effectiveness could be seen in the patient group receiving tricyclics, SSRI or mirtazapine. Serious adverse events were not recorded. CONCLUSION: Our study supports the hypothesis that mirtazapine can be used to enhance the therapeutic effectiveness of ECT. Controlled studies are necessary to further investigate the possible advantages of ECT and pharmacotherapy combinations, especially the use of modern dually acting antidepressants which have proven their good effectiveness in treatment-resistant depression.

The influence of concomitant neuroleptic medication on safety, tolerability and clinical effectiveness of electroconvulsive therapy.

BACKGROUND: Electroconvulsive therapy (ECT) is still considered to be the most efficacious treatment option in major depressive disorder and treatment-resistant schizophrenia. Unfortunately, in some cases patients do not respond sufficiently to conventional unilateral ECT, or even to bilateral or high dose ECT. In these cases, concomitant pharmacotherapy can be a useful augmentation strategy to improve clinical effectiveness. Interestingly, there is not much data about ECT and concomitant neuroleptic medication. METHOD: We evaluated 5482 treatments in 455 patients in our retrospective study to see whether there might be differences between combination therapies (ECT and concomitant neuroleptic medication) and ECT monotherapy. We focused on clinical effectiveness and tolerability; furthermore we investigated treatment modalities and ictal neurophysiological parameters that might influence the treatment. RESULTS: A total of 18.2% of all treatments were done with no psychotropic medication, 2.8% with a neuroleptic monotherapy. Seizure duration according to EEG derivations turned out to be significantly longer in patients treated with neuroleptics of lower antipsychotic potency, whereas seizure duration in EMG was shorter in treatments done with atypical substances. Postictal suppression was highest in treatments done with atypical neuroleptics, whereas the same group was lowest regarding convulsion energy and convulsion concordance indices. The best therapeutic effectiveness was seen in treatments done with atypical substances. Adverse effects were not influenced significantly by concomitant neuroleptic medication. CONCLUSION: Our study suggests that there might be a clinical benefit by combining ECT treatment with neuroleptic medication; especially atypical substances seem to enhance improvement. The tolerability of ECT treatment was not influenced by concomitant neuroleptic medication.

Human bone marrow as a source to generate CMV-specific CD4+ T cells with multifunctional capacity.

The bone marrow (BM) is an important compartment for T cell memory. In cytomegalovirus (CMV)-seropositive individuals peripheral blood (PB) CMV-specific T cells constitute a large fraction of PB T cells but are mostly differentiated effector/effector memory T cells with limited survival and proliferative potential. In this study, we performed a comprehensive analysis of the CMV-specific T cell response in BM studying both CD4+ and CD8+ T cell responses against overlapping peptide pools of the CMV proteins pp65 and immediate early protein-1. CMV-specific T cell responses were characterized ex vivo and after in vitro expansion of paired PB/BM samples by multiparameter flow cytometry determining surface phenotype, cytokine profile, and cytotoxic capability. Comparable frequencies of CMV-specific T cells were found in un-manipulated PB and BM. Both total CD4+ and CD8+ T cells could be more rapidly expanded from BM. Expanded BM T cells contained significantly higher frequencies of CMV-specific CD4+ T cells than PB. Furthermore, higher frequencies of specific CD4+ T cells from BM were multifunctional, characterized by simultaneous production of interferon-gamma, tumor necrosis factor, and interleukin-2. Use of BM may thus facilitate more rapid generation of adoptive T cells with enhanced functionality.