ECT is particularly effective in patients with depression with psychotic features and in elderly people with depression. More research on both biological and clinical predictors is needed to further evaluate the position of ECT in treatment protocols for major depression. Declaration of interest None.

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 appears to be equally effective for both bipolar and unipolar depression and the remission rates are encouraging, especially for bipolar depression.

Low-grade inflammation plays a role not only in the pathogenesis of major depressive disorder (MDD) but probably also in the poor responsiveness to regular antidepressants. There are also indications that anti-inflammatory agents improve the outcomes of antidepressants. Aim: To study whether the presence of low-grade inflammation predicts the outcome of antidepressants, anti-inflammatory agents, or combinations thereof. Methods: We carried out a systematic review of the literature on the prediction capability of the serum levels of inflammatory compounds and/or the inflammatory state of circulating leukocytes for the outcome of antidepressant/anti-inflammatory treatment in MDD. We compared outcomes of the review with original data (collected in two limited trials carried out in the EU project MOODINFLAME) on the prediction capability of the inflammatory state of monocytes (as measured by inflammatory gene expression) for the outcome of venlafaxine, imipramine, or sertraline treatment, the latter with and without celecoxib added. Results: Collectively, the literature and original data showed that: 1) raised serum levels of pro-inflammatory compounds (in particular of CRP/IL-6) characterize an inflammatory form of MDD with poor responsiveness to predominately serotonergic agents, but a better responsiveness to antidepressant regimens with a) (add-on) noradrenergic, dopaminergic, or glutamatergic action or b) (add-on) anti-inflammatory agents such as infliximab, minocycline, or eicosapentaenoic acid, showing—next to anti-inflammatory—dopaminergic or lipid corrective action; 2) these successful anti-inflammatory (add-on) agents, when used in patients with low serum levels of CRP/IL-6, decreased response rates in comparison to placebo. Add-on aspirin, in contrast, improved responsiveness in such “non-inflammatory” patients; 3) patients with increased inflammatory gene expression in circulating leukocytes had a poor responsiveness to serotonergic/noradrenergic agents. Conclusions: The presence of inflammation in patients with MDD heralds a poor outcome of first-line antidepressant therapies. Immediate step-ups to dopaminergic or glutamatergic regimens or to (add-on) anti-inflammatory agents are most likely indicated. However, at present, insufficient data exist to design protocols with reliable inflammation parameter cutoff points to guide such therapies, the more since detrimental outcomes are possible of anti-inflammatory agents in “non-inflamed” patients.