A genetic risk score to predict treatment nonresponse in psychotic depression.

Psychotic depression is a severe and difficult-to-treat subtype of major depressive disorder for which higher rates of treatment-resistant depression were found. Studies have been performed aiming to predict treatment-resistant depression or treatment nonresponse. However, most of these studies excluded patients with psychotic depression. We created a genetic risk score (GRS) based on a large treatment-resistant depression genome-wide association study. We tested whether this GRS was associated with nonresponse, nonremission and the number of prior adequate antidepressant trials in patients with a psychotic depression. Using data from a randomized clinical trial with patients with a psychotic depression (n = 122), we created GRS deciles and calculated positive prediction values (PPV), negative predictive values (NPV) and odds ratios (OR). Nonresponse and nonremission were assessed after 7 weeks of treatment with venlafaxine, imipramine or venlafaxine plus quetiapine. The GRS was negatively correlated with treatment response (r = -0.32, p = 0.0023, n = 88) and remission (r = -0.31, p = 0.0037, n = 88), but was not correlated with the number of prior adequate antidepressant trials. For patients with a GRS in the top 10%, we observed a PPV of 100%, a NPV of 73.7% and an OR of 52.4 (p = 0.00072, n = 88) for nonresponse. For nonremission, a PPV of 100%, a NPV of 51.9% and an OR of 21.3 (p = 0.036, n = 88) was observed for patients with a GRS in the top 10%. Overall, an increased risk for nonresponse and nonremission was seen in patients with GRSs in the top 40%. Our results suggest that a treatment-resistant depression GRS is predictive of treatment nonresponse and nonremission in psychotic depression.

The Relationship of Early Sleep Improvement With Response to Pharmacotherapy in Unipolar Psychotic Depression.

BACKGROUND: Since insomnia and depression are interrelated, improved sleep early in antidepressant pharmacotherapy may predict a positive treatment outcome. We investigated whether early insomnia improvement (EII) predicted treatment outcome in psychotic depression (PD) and examined if there was an interaction effect between EII and treatment type to assess if findings were treatment-specific. METHODS: This study is a secondary analysis of a randomized trial comparing 7 weeks treatment with the antidepressants venlafaxine, imipramine and venlafaxine plus the antipsychotic quetiapine in PD ( n = 114). Early insomnia improvement, defined as ≥20% reduced insomnia after 2 weeks, was assessed by the Hamilton Rating Scale for Depression (HAM-D-17). Associations between EII and treatment outcome were examined using logistic regressions. Subsequently, we added interaction terms between EII and treatment type to assess interaction effects. The predictive value of EII was compared with early response on overall depression (≥20% reduced HAM-D-17 score after 2 weeks). RESULTS: EII was associated with response (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.7-23.4; P = <0.001), remission of depression (OR, 6.1; 95% CI, 1.6-22.3; P = 0.009), and remission of psychosis (OR, 4.1; 95% CI, 1.6-10.9; P = 0.004). We found no interaction effects between EII and treatment type on depression outcome. Early insomnia improvement and early response on overall depression had a comparable predictive ability for treatment outcome. CONCLUSIONS: Early insomnia improvement was associated with a positive outcome in pharmacotherapy of PD, regardless of the medication type. Future studies are needed to confirm our findings and to examine the generalizability of EII as predictor in treatment of depression.

On the Origins of MAOI Misconceptions: Reaffirming their Role in Melancholic Depression.

The first monoamine oxidase inhibitors (MAOIs) used for the treatment of depression in the 1950-60s were credited with treating severe melancholic depression (MeD) successfully and greatly reducing the need for electroconvulsive therapy (ECT). Following the hiatus caused by the then ill-understood cheese reaction, MAOI use was relegated to atypical and treatment-resistant depressions only, based on data from insufficiently probing research studies suggesting their comparatively lesser effectiveness in MeD. The siren attraction of new 'better' drugs with different mechanisms amplified this trend. Following a re-evaluation of the data, we suggest that MAOIs are effective in MeD. Additionally, the broad unitary conceptualisation of major depressive disorder (MDD) in the DSM model diminished the chance of demonstrating distinctive responses to different antidepressant drugs (ADs) such as SSRIs, TCAs, and MAOIs, thereby further reducing the interest in MAOIs. More reliable categorical distinction of MeD, disentangling it from MDD, may be possible if more sensitive measuring instruments (CORE, SMPI) are used. We suggest these issues will benefit from re-appraisement via an inductive reasoning process within a binary (rather than a unitary) model for defining the different depressive disorders, allowing for the use of more reliable diagnostic criteria for MeD in particular. We conclude that MAOIs remain essential for, inter alia, TCA-resistant MeD, and should typically be used prior to ECT; additionally, they have a role in maintaining remission in cases treated with ECT (and ketamine/esketamine). We suggest that MAOIs should be utilized earlier in treatment algorithms and with greater regularity than is presently the case.

Efficacy and safety of selegiline across different psychiatric disorders: A systematic review and meta-analysis of oral and transdermal formulations.

Selegiline is an irreversible, selective type-B monoamine oxidase inhibitor (MAOI) approved for Parkison's disease-oral and major depressive disorder-transdermal formulation) resulting in non-selective MAOI activity at oral doses≥20 mg/day. The present systematic review and meta-analysis appraises the evidence of different formulations/dosages of selegiline across different psychiatric conditions. We inquired PubMed/MEDLINE/Cochrane-Central/WHO-ICTRP/Clarivate-WebOfScience and the Chinese-Electronic-Journal Database from inception to 10/26/2022 for selegiline trials involving psychiatric patients. Random-effects meta-analyses assessed heterogeneity, publication/risk biases, and confidence in the evidence, followed by sensitivity, subgroup, and meta-regression analyses. Co-primary outcomes were: changes in symptom score (standardized mean difference=SMD) and author-defined response (risk ratios=RRs). RRs of adverse events and all-cause discontinuation were secondary and acceptability outcomes, respectively. Systematic-review included 42 studies; meta-analysis, 23. Selegiline outperformed placebo in depressive symptom reduction (SMD=-0.96, 95%C.I.=-1.78, -0.14, k = 10, n = 1,308), depression (RR=1.61, 95%C.I.=1.20, 2.15, k = 9, n = 1,238) and atypical-depression response (RR=2.23, 95%C.I.=1.35, 3.68, k = 3, n = 136). Selegiline failed to outperform the placebo in negative (k = 4) or positive symptoms of schizophrenia (k = 4), attention-deficit-hyperactivity disorder (ADHD) symptoms reduction (k = 2), and smoking abstinence rate (k = 4). Selegiline did not differ from methylphenidate and ADHD scores (k = 2). No significant difference emerged in acceptability, incident diarrhea, headache, dizziness, and nausea RRs, in contrast to xerostomia (RR=1.58, 95%C.I. =1.03, 2.43, k = 6, n = 1,134), insomnia (RR=1.61, 95%C.I.=1.19, 2.17, k = 10, n = 1,768), and application-site reaction for transdermal formulation (RR=1.81, 95%C.I.=1.40, 2.33, k = 6, n = 1,662). Confidence in findings was low/very-low for most outcomes; moderate for depressive symptoms reduction (transdermal). Selegiline proved effective, safe, and well-tolerated for depressive disorders, yet further evidence is warranted about specific psychiatric disorders.

Clinical characteristics associated with relapse 2 years after electroconvulsive therapy for major depression.

OBJECTIVE: High relapse rates are observed after electroconvulsive therapy (ECT) for major depression. Identifying patients who are at increased risk for relapse to intensify their treatment regimen post-ECT might reduce relapse rates. We aimed to determine clinical characteristics that are associated with relapse within 2 years after successful ECT. METHODS: Patients who remitted to ECT in a randomised controlled trial comparing adjuvant nortriptyline and placebo during a course of bilateral ECT were followed-up prospectively for 1 year with open-label nortriptyline (Dutch Trial Register NTR5579). Second-year follow-up data were collected retrospectively. Thirty-four patients were included in this follow-up cohort. To examine the association between clinical characteristics and the risk of relapse, unadjusted hazard ratios (HRs) were calculated. RESULTS: At 2 years post-ECT, the overall relapse rate was 50%, and the HRs for relapse in patients with psychotic features, a higher severity of depression, and medication resistance prior to ECT were 0.33 (CI 0.12-0.89; p = 0.029), 0.88 (CI 0.80-0.98; p = 0.014), and 4.48 (CI 1.28-15.73, p = 0.019), respectively. No effect was found for age, sex or episode duration on the relapse rate. CONCLUSIONS: Depressed patients with psychotic features, with higher symptom severity and without medication resistance prior to ECT have a significantly decreased risk of relapse after successful ECT. A sustained remission rate of 50% over 2 years in patients with severe major depression who were treated with nortriptyline monotherapy after successful ECT is encouraging.

The prescriber's guide to classic MAO inhibitors (phenelzine, tranylcypromine, isocarboxazid) for treatment-resistant depression.

This article is a clinical guide which discusses the "state-of-the-art" usage of the classic monoamine oxidase inhibitor (MAOI) antidepressants (phenelzine, tranylcypromine, and isocarboxazid) in modern psychiatric practice. The guide is for all clinicians, including those who may not be experienced MAOI prescribers. It discusses indications, drug-drug interactions, side-effect management, and the safety of various augmentation strategies. There is a clear and broad consensus (more than 70 international expert endorsers), based on 6 decades of experience, for the recommendations herein exposited. They are based on empirical evidence and expert opinion-this guide is presented as a new specialist-consensus standard. The guide provides practical clinical advice, and is the basis for the rational use of these drugs, particularly because it improves and updates knowledge, and corrects the various misconceptions that have hitherto been prominent in the literature, partly due to insufficient knowledge of pharmacology. The guide suggests that MAOIs should always be considered in cases of treatment-resistant depression (including those melancholic in nature), and prior to electroconvulsive therapy-while taking into account of patient preference. In selected cases, they may be considered earlier in the treatment algorithm than has previously been customary, and should not be regarded as drugs of last resort; they may prove decisively effective when many other treatments have failed. The guide clarifies key points on the concomitant use of incorrectly proscribed drugs such as methylphenidate and some tricyclic antidepressants. It also illustrates the straightforward "bridging" methods that may be used to transition simply and safely from other antidepressants to MAOIs.

Cortical Inhibition and Plasticity in Major Depressive Disorder.

BACKGROUND: Major depressive disorder (MDD) is a severe psychiatric disorder that is associated with various cognitive impairments, including learning and memory deficits. As synaptic plasticity is considered an important mechanism underlying learning and memory, deficits in cortical plasticity might play a role in the pathophysiology of patients with MDD. We used Transcranial Magnetic Stimulation (TMS) to assess inhibitory neurotransmission and cortical plasticity in the motor cortex of MDD patients and controls. METHODS: We measured the cortical silent period (CSP) and short interval cortical inhibition (SICI), as well as intermittent theta-burst stimulation (iTBS), in 9 drug-free MDD inpatients and 18 controls. RESULTS: The overall response to the CSP, SICI, and iTBS paradigms was not significantly different between the patient and control groups. iTBS induction resulted in significant potentiation after 20 mins in the control group (t (17) = -2.8, p = 0.01), whereas no potentiation was observed in patients. CONCLUSIONS: Potentiation of MEP amplitudes was not observed within the MDD group. No evidence was found for medium-to-large effect size differences in CSP and SICI measures in severely depressed drug-free patients, suggesting that reduced cortical inhibition is unlikely to be a robust correlate of the pathophysiological mechanism in MDD. However, these findings should be interpreted with caution due to the high inter-subject variability and the small sample size. SIGNIFICANCE: These findings advance our understanding of neurophysiological functioning in drug-free severely depressed inpatients.

Influence of adjuvant nortriptyline on the efficacy of electroconvulsive therapy: A randomized controlled trial and 1-year follow-up.

OBJECTIVE: There is limited evidence that adding an antidepressant to electroconvulsive therapy (ECT), compared with ECT monotherapy, improves outcomes. We aimed to determine whether the addition of nortriptyline to ECT enhances its efficacy and prevents post-ECT relapse. METHODS: We conducted a randomized, double-blind, placebo-controlled trial (RCT). Patients with major depressive disorder and an indication for ECT received either nortriptyline or placebo during a bilateral ECT course. Outcome measures were mean decrease in Hamilton Rating Scale for Depression (HRSD) score, response, remission, and time to response and remission. Patients who attained remission participated in a 1-year follow-up study with open-label nortriptyline. Outcome measures were relapse and time to relapse. RESULTS: We included 47 patients in the RCT. In the nortriptyline group, 83% showed response, 74% attained remission, and the mean decrease in HRSD score was 21.6 points. In the placebo group these figures were, respectively, 81% (p = 0.945), 73% (p = 0.928) and 20.7 points (p = 0.748). Thirty-one patients participated in the follow-up study. In patients who had received nortriptyline during the RCT, 47% relapsed at a mean of 34.2 weeks. Patients who had received placebo showed similar treatment results. In both study phases, no statistically significant differences between the nortriptyline and the placebo group were found. CONCLUSION: In our sample of severely depressed patients who were often medication resistant and suffering from psychotic depression, the addition of nortriptyline to ECT did not enhance its efficacy or prevent post-ECT relapse. Encouragingly, even in these patients ECT was highly effective and relapse rates were relatively low.

Interrogating Associations Between Polygenic Liabilities and Electroconvulsive Therapy Effectiveness.

BACKGROUND: Electroconvulsive therapy (ECT) is the most effective treatment for severe major depressive episodes (MDEs). Nonetheless, firmly established associations between ECT outcomes and biological variables are currently lacking. Polygenic risk scores (PRSs) carry clinical potential, but associations with treatment response in psychiatry are seldom reported. Here, we examined whether PRSs for major depressive disorder, schizophrenia (SCZ), cross-disorder, and pharmacological antidepressant response are associated with ECT effectiveness. METHODS: A total of 288 patients with MDE from 3 countries were included. The main outcome was a change in the 17-item Hamilton Depression Rating Scale scores from before to after ECT treatment. Secondary outcomes were response and remission. Regression analyses with PRSs as independent variables and several covariates were performed. Explained variance (R2) at the optimal p-value threshold is reported. RESULTS: In the 266 subjects passing quality control, the PRS-SCZ was positively associated with a larger Hamilton Depression Rating Scale decrease in linear regression (optimal p-value threshold = .05, R2 = 6.94%, p < .0001), which was consistent across countries: Ireland (R2 = 8.18%, p = .0013), Belgium (R2 = 6.83%, p = .016), and the Netherlands (R2 = 7.92%, p = .0077). The PRS-SCZ was also positively associated with remission (R2 = 4.63%, p = .0018). Sensitivity and subgroup analyses, including in MDE without psychotic features (R2 = 4.42%, p = .0024) and unipolar MDE only (R2 = 9.08%, p < .0001), confirmed the results. The other PRSs were not associated with a change in the Hamilton Depression Rating Scale score at the predefined Bonferroni-corrected significance threshold. CONCLUSIONS: A linear association between PRS-SCZ and ECT outcome was uncovered. Although it is too early to adopt PRSs in ECT clinical decision making, these findings strengthen the positioning of PRS-SCZ as relevant to treatment response in psychiatry.

Association of the neutrophil to lymphocyte ratio and white blood cell count with response to pharmacotherapy in unipolar psychotic depression: An exploratory analysis.

Background: Low-grade inflammation occurs in a subgroup of patients with Major Depressive Disorder (MDD) and may be associated with response to antidepressant medications. The Neutrophil to Lymphocyte Ratio (NLR) and total White Blood cell Count (WBC) are markers of systemic inflammation which have not been investigated as predictors for outcome to pharmacotherapy in unipolar depression yet. Moreover, the association between inflammation and treatment response has not been studied in unipolar Psychotic Depression (PD). We conducted an exploratory analysis to examine the prognostic significance of NLR and WBC in pharmacotherapy of PD. Methods: Baseline NLR and WBC were examined in their association with response to seven weeks of treatment with antidepressants (venlafaxine or imipramine) and the combination of an antidepressant with an antipsychotic (venlafaxine plus quetiapine) in 87 patients with PD. Logistic regression models were adjusted for age, gender, Body Mass Index (BMI), depression severity, duration of the current episode and number of previous depressive episodes. Secondary outcomes were remission of depression and disappearance of psychotic symptoms. Results: Higher NLR was associated with increased response to pharmacotherapy (Exp(B) 1.66, 95 % CI 1.03-2.66, p = 0.036), but not with remission of depression or disappearance of psychotic symptoms. WBC was not associated with any of the outcome measures. Conclusion: NLR may be a novel, inexpensive and widely available biomarker associated with response to pharmacotherapy in PD. The association between white blood cell measures and treatment outcome should be further investigated for different types of antidepressants in PD and in non-psychotic MDD.

Influence of an adjuvant antidepressant on the efficacy of electroconvulsive therapy: A systematic review and meta-analysis.

OBJECTIVE: The primary indication for electroconvulsive therapy is medication-resistant major depression. There is some evidence that combining electroconvulsive therapy with an antidepressant, instead of electroconvulsive therapy monotherapy, might improve remission rates. However, data on this topic have not been systematically studied. We undertook a systematic review and meta-analysis to determine the effectiveness of an adjuvant antidepressant during electroconvulsive therapy for major depression. METHODS: Embase, Medline Ovid, Web of Science, Cochrane Central, PsychINFO Ovid and Google Scholar were searched up to January 2019. Randomized controlled trials and cohort studies reporting on the influence of an adjuvant antidepressant on the efficacy of electroconvulsive therapy for major depression were included. Authors independently screened records, extracted data and assessed study quality. We reported this systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Nine studies were included in the meta-analysis. The meta-analysis revealed a significant advantage of adjuvant antidepressants versus placebo. The overall effect size per category of antidepressant was as follows: tricyclic antidepressants: Hedges' g 0.32 (95% confidence interval: [0.14, 0.51]) (k = 6) with low heterogeneity (I2: 4%, p = 0.39); selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors: Hedges' g 0.27 (95% confidence interval: [0.03, 0.52]) (k = 2) with a lack of heterogeneity (I2: 0%, p = 0.89); and monoamine oxidase inhibitors: Hedges' g 0.35 (95% confidence interval: [-0.07, 0.77]) with moderate heterogeneity (I2: 43%, p = 0.17) (k = 3). CONCLUSION: An adjuvant antidepressant enhances the efficacy of electroconvulsive therapy for major depression. Tricyclic antidepressants, selective serotonin reuptake inhibitors/serotonin noradrenaline reuptake inhibitors and monoamine oxidase inhibitors showed the same effect size. However, the effect sizes of tricyclic antidepressants and monoamine oxidase inhibitors are most likely underestimated, due to insufficient doses in most of the included studies. We recommend the routine use of an adequately dosed antidepressant during electroconvulsive therapy for major depression.

Psychomotor Retardation and the prognosis of antidepressant treatment in patients with unipolar Psychotic Depression.

BACKGROUND: Psychomotor Retardation is a key symptom of Major Depressive Disorder. According to the literature its presence may affect the prognosis of treatment. Aim of the present study is to investigate the prognostic role of Psychomotor Retardation in patients with unipolar Psychotic Depression who are under antidepressant treatment. METHODS: The Salpetriere Retardation Rating Scale was administered at baseline and after 6 weeks to 122 patients with unipolar Psychotic Depression who were randomly allocated to treatment with imipramine, venlafaxine or venlafaxine plus quetiapine. We studied the effects of Psychomotor Retardation on both depression and psychosis related outcome measures. RESULTS: 73% of the patients had Psychomotor Retardation at baseline against 35% after six weeks of treatment. The presence of Psychomotor Retardation predicted lower depression remission rates in addition to a higher persistence of delusions. After six weeks of treatment, venlafaxine was associated with higher levels of Psychomotor Retardation compared to imipramine and venlafaxine plus quetiapine. CONCLUSIONS: Our data confirm that Psychomotor Retardation is a severity marker of unipolar Psychotic Depression. It is highly prevalent and predicts lower effectivity of antidepressant psychopharmacological treatment.

Performance of the Psychotic Depression Assessment Scale as a Predictor of ECT Outcome.

OBJECTIVES: The presence of psychotic symptoms is an important predictor of responsiveness to electroconvulsive therapy (ECT). This study investigates whether a continuous severity measure, the Psychotic Depression Assessment Scale (PDAS), is a more accurate predictor. METHODS: Depression severity was assessed before and after the ECT course using the Montgomery-Asberg Depression Rating Scale (MADRS) in 31 patients with psychotic depression and 34 depressed patients without psychotic symptoms. Logistic regression models for MADRS response and remission were fitted, with either the PDAS total score or the dichotomous predictors "absence/presence of psychotic symptoms" as the independent variables. Age, episode duration, and treatment resistance were added as covariates. RESULTS: Both the asserted presence of psychotic symptoms and a higher PDAS total score reflected MADRS response (areas under the curve, 0.83 and 0.85, respectively), with MADRS remission also being predicted by the presence of psychotic symptoms and higher PDAS scores (areas under the curves, 0.86 and 0.84, respectively). Age was a contributor to these prediction models, with response and remission rates being highest in the older patients. Psychotic Depression Assessment Scale scores decreased significantly during ECT: at end point, 81.5% of the patients showed significant response and 63.9% had achieved remission. CONCLUSIONS: The PDAS indeed accurately predicts response to and remission after ECT in (psychotic) depression and most pronouncedly so in older patients but seems to have no clear advantage over simply verifying the presence of psychotic symptoms. This could be the consequence of a ceiling effect, as ECT was extremely effective in patients with psychotic depression.ClinicalTrials.gov: Identifier: NCT02562846.

Low-Grade Inflammation as a Predictor of Antidepressant and Anti-Inflammatory Therapy Response in MDD Patients: A Systematic Review of the Literature in Combination With an Analysis of Experimental Data Collected in the EU-MOODINFLAME Consortium.

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.

Influence of age on ECT efficacy in depression and the mediating role of psychomotor retardation and psychotic features.

OBJECTIVE: To investigate whether older age predicts a higher efficacy of electroconvulsive therapy (ECT) in severely depressed patients. Also, to analyze whether psychomotor disturbance and/or psychotic features might explain the potential higher efficacy of ECT in older age. METHOD: A total of 96 patients with major depressive disorder treated with bilateral ECT were evaluated. The 17-item HAM-D and the MADRS were used to evaluate the efficacy of ECT and time to remission, respectively. Psychomotor disturbance was defined according the HAM-D. RESULTS: Middle-aged (MA; 50-70 years) and older-aged (OA; ≥70 years) patients had a non-significant larger symptom reduction compared with young-aged (YA; <50 years) patients. Medium effect size was found in favor of MA (d = 0.44) and small effect size in favor of OA (d = 0.30), when compared to YA. Patients with psychotic features and patients with psychomotor retardation had a significantly larger symptom reduction (p < 0.001 and p = 0.005, respectively; d = 0.88 and d = 0.66, respectively). The association between age and ECT efficacy is mediated by psychomotor retardation (p = 0.049) and in lesser extent by psychotic features (p = 0.071). CONCLUSION: The results show that psychomotor retardation and psychotic features are strong predictors of ECT efficacy and explain the association between age and ECT efficacy. Instead of focusing on the age of a patient, clinicians should focus on the presence of psychomotor disturbances and psychotic features of depression, when considering ECT treatment.

The Maudsley Staging Method as predictor of electroconvulsive therapy effectiveness in depression.

OBJECTIVE: To investigate the potential role of the Maudsley Staging Method (MSM) in the prediction of electroconvulsive therapy (ECT) outcome in severely depressed adults. METHOD: Between August 2015 and August 2017, 73 consecutive patients with a major depressive episode (DSM-IV-TR) scheduled for ECT were recruited. Prior to their first ECT session, the MSM was completed to assess the level of therapy resistance. To determine the reduction in depression severity and response and remission rates, symptom severity was assessed at baseline and within one week after the last ECT session using the 17-item Hamilton Depression Rating Scale (HDRS17). RESULTS: The percentage of symptom reduction following ECT was best predicted by the MSM episode duration and depression severity factors (R2 completer sample 0.24). Episode duration alone was the best predictor of remission (area under the ROC curve for completers: 0.72). Adding age to the models increased their predictive capacity. CONCLUSION: An adapted version of the MSM gauging shorter episode duration, more severe depressive symptoms and older age is significantly associated with ECT effectiveness in adults with severe recurrent depression and is thus highly suitable for use in clinical practice, promoting the shared treatment decision-making process.