Predictors of inpatient suicide in an Irish psychiatric service, a longitudinal case-control study.

OBJECTIVE: Inpatient suicide remains difficult to predict. This study aimed to identify individual patient predictors to help identify those at greater risk. METHODS: This case-control study was undertaken in an independent mental health service in Ireland. Cases were drawn from all admissions to the service between March 2004 and February 2019. Controls were matched for date of admission. Univariate and multivariate analyses were conducted. RESULTS: Thirty-three cases of inpatient suicide were compared to 132 controls. The inpatient suicide rate was 76.2 per 100,000 admissions. The rate of inpatient suicide fell in line with national rates despite less restrictive practices being implemented in the service. Males accounted for 66% of cases. Hanging was the most common method of suicide overall and among male patients, and drowning was the most common among females. Male gender, tertiary referral, an adverse psychosocial event during admission, a period of absence without leave and expressing hopelessness were identified as independent risk factors for inpatient suicide. Substance use, involuntary detention, family history of suicide, and number of previous admissions were not significant. CONCLUSIONS: While not highly sensitive, a period of absence without leave, tertiary referral and hopelessness are important predictors of inpatient suicide risk that treating teams should consider in care planning.

Study protocol for Ketamine as an adjunctive therapy for major depression (2): a randomised controlled trial (KARMA-Dep [2]).

BACKGROUND: Depression is a common psychiatric disorder and a leading cause of disability worldwide. Conventional monoaminergic antidepressants have limited efficacy and take weeks to exert a therapeutic effect. Single infusions of subanaesthetic doses of ketamine exhibit rapid antidepressant action but effects are transient and relapse is common. One potential strategy for increasing ketamine's antidepressant efficacy and/or prolonging its therapeutic benefit may be serial infusions. There is limited evidence on the efficacy and safety of repeated ketamine infusions against an active comparator. METHODS: This protocol describes an ongoing pragmatic, randomised, controlled, parallel-group, patient- and rater-blind, superiority trial. Eligible adult inpatients with a confirmed DSM-5 diagnosis of a major depressive episode (unipolar or bipolar) are randomly allocated in a 1:1 ratio to a course of up to eight infusions of ketamine or midazolam twice-weekly over four weeks. The primary objective is to assess the efficacy of serial adjunctive ketamine infusions versus active comparator midazolam by measuring Montgomery-Åsberg Depression Rating Scale score difference between arms from before the first infusion to 24 h after the final infusion, supplemented by a 95% confidence interval. To facilitate generalisability of results, the trial takes place under "real world" conditions with both groups continuing to receive regular inpatient care including treatment-as-usual pharmacotherapy, nursing care, and psychological and other therapies during the randomised treatment phase and regular outpatient care thereafter. Participants are monitored for relapse during a 24-week follow-up after the end of the randomised phase. Secondary objectives of the trial are to assess: response and remission rates at the end of randomised phase; relapse status during the 24-week follow-up after the end of the randomised phase; the safety and tolerability of repeated ketamine infusions regarding psychotomimetic and other psychiatric side effects, cognitive side effects, as well as withdrawal symptoms, haemodynamic stability, neurological, urological, and other physical side effects; and quality of life and cost-effectiveness. DISCUSSION: There is an unmet clinical need for rapidly-acting novel antidepressants. This trial will provide efficacy, safety and health economic data on serial ketamine infusions and thus help inform clinical practice on the potential role of this treatment in the management of depression. TRIAL REGISTRATION: EudraCT 2019-003109-92. Registered 2 October 2019. CLINICALTRIALS: gov NCT04939649. Registered 25 June 2021.

Worsening of mental health outcomes in nursing home staff during the COVID-19 pandemic in Ireland.

BACKGROUND: Mental health issues in nursing home staff during the COVID-19 pandemic have been significant; however, it is not known if these issues persist following widespread vaccination and easing of restrictions. OBJECTIVE: To quantify the mental health of nursing home staff at different timepoints during the COVID-19 pandemic in the Republic of Ireland. DESIGN/METHODS: Two identical, online, cross-sectional, nationwide, anonymous surveys of Republic of Ireland nursing home staff at two timepoints (survey 1 (S1, n = 390): November 2020 to January 2021; survey 2 (S2, N = 229: November 2021 to February 2022) during the COVID-19 pandemic. Convenience sampling was used with staff self-selecting for participation. Methods included the World Health Organisation's Well-Being Index (WHO-5), the Impact of Events Scale-Revised (IES-R), the Moral Injury Events Scale (MIES), two Likert-scale items regarding suicidal ideation and planning, the Work Ability Score (WAS), the Brief Coping Orientation to Problems Experienced (Brief-COPE) Scale, and a 15-item questionnaire assessing perceptions of the outbreak with one additional Likert-scale item on altruism. Descriptive analysis examined differences between staff based on their classification in one of three groups: nurses, healthcare assistants (HCA) and nonclinical staff. Pseudonymous identifiers were used to link responses across surveys. RESULTS: An insufficient number of participants completed both surveys for linked analyses to be performed; therefore, we performed an ecological comparison between these two independent surveys. More staff reported moderate-severe post-traumatic stress symptoms (S1 45%; S2 65%), depression (S1: 39%; S2 57%), suicidal ideation (S1: 14%; S2 18%) and suicidal planning (S1: 9%; S2 15%) later in the pandemic. There was a higher degree of moral injury at S2 (S1: 20.8 standard deviation (SD) 9.1; S2: 25.7 SD (11.3)) and use of avoidant (maladaptive) coping styles at S2 (S1: 20.8 (6.3); S2 23.0 (6.3)) with no notable differences found in the use of approach (adaptive) coping styles. Staff reported more concerns at S2 regarding contracting COVID-19, social stigma, job stress, doubts about personal protective equipment and systems and processes. CONCLUSION: In comparison to our previous survey, mental health outcomes appear to have worsened, coping did not improve, and staff concerns, and worries appear to have increased as the pandemic progressed. Follow-up studies could help to clarify is there are any lingering problems and to assess if these issues are related to the pandemic and working conditions in nursing homes.

Electroconvulsive Stimulation in Rats Induces Alterations in the Hippocampal miRNome: Translational Implications for Depression.

MicroRNAs (miRNAs) may contribute to the development of depression and its treatment. Here, we used the hypothesis-neutral approach of next-generation sequencing (NGS) to gain comprehensive understanding of the effects of a course of electroconvulsive stimulation (ECS), the animal model equivalent of electroconvulsive therapy (ECT), on rat hippocampal miRNAs. Significant differential expression (p < 0.001) of six hippocampal miRNAs was noted following NGS, after correcting for multiple comparisons. Three of these miRNAs were upregulated (miR-132, miR-212, miR-331) and three downregulated (miR-204, miR-483, miR-301a). qRT-PCR confirmed significant changes in four of the six miRNAs (miR-132, miR-212, miR-204, miR-483). miR-483 was also significantly reduced in frontal cortex, though no other significant alterations were noted in frontal cortex, cerebellum, or whole blood. Assessing the translatability of the results, miR-132 and miR-483 were significantly reduced in whole blood samples from medicated patients with depression (n = 50) compared to healthy controls (n = 45), though ECT had no impact on miRNA levels. Notably, pre-ECT miR-204 levels moderately positively correlated with depression severity at baseline and moderately negatively correlated with mood score reduction post-ECT. miRNAs were also examined in cerebrospinal fluid and serum from a separate cohort of patients (n = 8) treated with ECT; no significant changes were noted post-treatment. However, there was a large positive correlation between changes in miR-212 and mood score post-ECT in serum. Though replication studies using larger sample sizes are required, alterations in miRNA expression may be informative about the mechanism of action of ECS/ECT and in turn might give insight into the neurobiology of depression.

Whole blood mitochondrial DNA copy number in depression and response to electroconvulsive therapy.

Mitochondrial dysfunction may play a role in various psychiatric conditions. Mitochondrial DNA copy number (mtDNAcn), the ratio of mitochondrial DNA to nuclear DNA, represents an attractive marker of mitochondrial health that is easily measured from stored DNA samples, and has been shown to be altered in depression. In this study, we measured mtDNAcn in whole blood samples from medicated patients with depression (n = 100) compared to healthy controls (n = 89) and determined the relationship between mtDNAcn and depression severity and the therapeutic response to electroconvulsive therapy (ECT). We also explored the relationship between mtDNAcn and telomere length and inflammatory markers. Our results show that mtDNAcn was significantly elevated in blood from patients with depression when compared to control samples, and this result survived statistical adjustment for potential confounders (p = 0.002). mtDNAcn was significantly elevated in blood from subgroups of patients with non-psychotic or unipolar depression. There was no difference in mtDNAcn noted in subgroups of ECT remitters/non-remitters or responders/non-responders. Moreover, mtDNAcn was not associated with depression severity, telomere length, or circulating inflammatory marker concentrations. Overall, our results show that mtDNAcn is elevated in blood from patients with depression, though whether this translates to mitochondrial function is unknown. Further work is required to clarify the contribution of mitochondria and mtDNA to the pathophysiology of depression and the therapeutic response to antidepressant treatments.

Dublin hospital workers' mental health during the peak of Ireland's COVID-19 pandemic.

BACKGROUND: Hospital-based healthcare workers have experienced significant psychological stressors during the COVID-19 pandemic. AIM: To evaluate the mental health of hospital workers during the third wave of the COVID-19 pandemic in Dublin, Ireland. METHODS: Cross-sectional anonymous online survey of hospital workers (n = 377; 181 doctors (48.0%), 166 nurses (44.0%), 30 radiographers (8.0%)), collecting demographic information, COVID-19 exposure history and mental health measures. RESULTS: There were significant differences between profession groups in gender, experience, COVID-19 infection history, exposure to COVID-19 positive acquaintances, and work areas. Moderate-severe post-traumatic stress disorder (PTSD) symptoms were found in 45.1% (95% CI 40.1-50.1%) of all participants; significantly fewer doctors reported moderate-severe PTSD symptoms (26%; 95% CI 22-36%). A World Health Organisation-5 Wellbeing Index (WHO-5) score ≤ 32, indicating low mood, was reported by 52% (95% CI 47-57%) of participants; significantly fewer doctors reported low mood (46%; 95% CI 39-53%). One-week suicidal ideation and planning were reported respectively by 13% (95% CI 10-16%) and 5% (95% CI 3-7%) of participants with no between-group differences. Doctors reported significantly less moral injury than other groups. There were no significant between-group differences regarding coping styles. Work ability was insufficient in 39% (95% CI 34-44%) of staff; no between-group differences. CONCLUSIONS: Dublin hospital workers reported high levels of PTSD symptoms, mood disturbance, and moral injury during the COVID-19 pandemic. Concerning levels of suicidal ideation and planning existed in this cohort. Differences in degrees of post-traumatic stress, moral injury, and wellbeing were found between profession groups, which should be considered when planning any supports.

PARP1 and OGG1 in Medicated Patients With Depression and the Response to ECT.

BACKGROUND: Oxidative stress and oxidation-induced DNA damage may contribute to the pathophysiology of depression. Two key mediators of base excision repair (BER) in response to oxidative damage of DNA are OGG1 and PARP1. Few studies have examined changes in OGG1 or PARP1 mRNA in patients with depression or following antidepressant treatment. We examined PARP1 and OGG1 mRNA levels in patients with depression at baseline/pre-electroconvulsive therapy (baseline/pre-ECT) vs in healthy controls and in patients following a course of ECT. METHODS: PARP1 and OGG1 were examined in whole blood samples from medicated patients with depression and controls using quantitative real-time polymerase chain reaction. Exploratory subgroup correlational analyses were performed to determine associations between PARP1 and OGG1 and mood (Hamilton Depression Rating Scale 24-item version) scores as well as with vitamin B3, SIRT1, PGC1α, and tumor necrosis factor alpha levels, as previously reported on in this cohort. RESULTS: PARP1 levels were reduced in samples from patients with depression vs controls (P = .03), though no difference was noted in OGG1. ECT had no effect on PARP1 or OGG1. Higher baseline PARP1 weakly correlated with greater mood improvement post ECT (P = .008). Moreover, PARP1 positively correlated with SIRT1 at baseline and post ECT, and positive correlations were noted between change in PARP1 and change in OGG1 with change in tumor necrosis factor alpha post ECT. CONCLUSIONS: To our knowledge, this is the first study to examine the effect of ECT on BER enzymes. A better understanding of BER enzymes and DNA repair in depression could unearth new mechanisms relevant to the pathophysiology of this condition and novel antidepressant treatments.

Comparative efficacy, cognitive effects and acceptability of electroconvulsive therapies for the treatment of depression: protocol for a systematic review and network meta-analysis.

INTRODUCTION: There have been important advances in the use of electroconvulsive therapy (ECT) to treat major depressive episodes. These include variations to the type of stimulus the brain regions stimulated, and the stimulus parameters (eg, stimulus duration/pulse width). Our aim is to investigate ECT types using a network meta-analysis (NMA) approach and report on comparative treatment efficacy, cognitive side effects and acceptability. METHOD: We will conduct a systematic review to identify randomised controlled trials that compared two or more ECT protocols to treat depression. This will be done using the following databases: Embase, MEDLINE PubMed, Web of Science, Scopus, PsycINFO, Cochrane CENTRAL and will be supplemented by personal contacts with researchers in the field. All authors will be contacted to provide missing information. Primary outcomes will be symptom severity on a validated continuous clinician-rated scale of depression, cognitive functioning measured using anterograde verbal recall, and acceptability calculated using all-cause drop-outs. Secondary outcomes will include response and remission rates, autobiographical memory following a course of ECT, and anterograde visuospatial recall.Bayesian random effects hierarchical models will compare ECT types. Additional meta-regressions may be conducted to determine the impact of effect modifiers and patient-specific prognostic factors if sufficient data are available. DISCUSSION: This NMA will facilitate clinician decision making and allow more sophisticated selection of ECT type according to the balance of efficacy, cognitive side effects and acceptability. ETHICS: This systematic review and NMA does not require research ethics approval as it will use published aggregate data and will not collect nor disclose individually identifiable participant data. PROSPERO REGISTRATION NUMBER: CRD42022357098.

Blood cell ratios in mood and cognitive outcomes following electroconvulsive therapy.

Systemic inflammation is commonly reported in depression, with dysregulation of both the innate and adaptive arms of the immune system documented. Obtaining ratios of neutrophils, platelets, and monocytes to counts of lymphocytes (NLR, PLR, MLR, respectively) represents a low-cost and easily reproducible measure of an individual's inflammatory burden that can be calculated effortlessly from routine clinical full white blood cell counts. Electroconvulsive therapy (ECT) remains the most effective acute antidepressant treatment for depression but is often limited by its cognitive side-effects. Here, we examined differences in blood cell ratios in subgroups of depressed patients (unipolar/bipolar, psychotic/non-psychotic, early-onset/late-onset) and ECT-related subgroups (responder/non-responder, remitter/non-remitter). We also explored the relationships between blood cell ratios and depression severity and immediate cognitive outcomes post-ECT. Our results show baseline NLR was raised in patients with psychotic depression. In the entire group of patients, significant negative correlations were noted between the PLR and SII and baseline HAM-D24 score, signifying that lower systemic inflammation is associated with more severe depressive symptoms. Significant positive correlations were noted between various blood cell ratios and mean time to recovery of orientation in the entire group of patients and in depression subgroups, indicating that increased peripheral inflammation is linked to worse cognitive outcomes post-ECT. Overall, our results suggest that assessment of blood cell ratios could be useful for predicting mood changes in patients at risk of developing depressive episodes or relapse following successful treatment or for identifying those at risk for cognitive side-effects following ECT.

International pooled patient-level meta-analysis of ketamine infusion for depression: In search of clinical moderators.

Depression is disabling and highly prevalent. Intravenous (IV) ketamine displays rapid-onset antidepressant properties, but little is known regarding which patients are most likely to benefit, limiting personalized prescriptions. We identified randomized controlled trials of IV ketamine that recruited individuals with a relevant psychiatric diagnosis (e.g., unipolar or bipolar depression; post-traumatic stress disorder), included one or more control arms, did not provide any other study-administered treatment in conjunction with ketamine (although clinically prescribed concurrent treatments were allowable), and assessed outcome using either the Montgomery-Åsberg Depression Rating Scale or the Hamilton Rating Scale for Depression (HRSD-17). Individual patient-level data for at least one outcome was obtained from 17 of 25 eligible trials [pooled n = 809]. Rates of participant-level data availability across 33 moderators that were solicited from these 17 studies ranged from 10.8% to 100% (median = 55.6%). After data harmonization, moderators available in at least 40% of the dataset were tested sequentially, as well as with a data-driven, combined moderator approach. Robust main effects of ketamine on acute [~24-hours; ß*(95% CI) = 0.58 (0.44, 0.72); p < 0.0001] and post-acute [~7 days; ß*(95% CI) = 0.38 (0.23, 0.54); p < 0.0001] depression severity were observed. Two study-level moderators emerged as significant: ketamine effects (relative to placebo) were larger in studies that required a higher degree of previous treatment resistance to federal regulatory agency-approved antidepressant medications (≥2 failed trials) for study entry; and in studies that used a crossover design. A comprehensive data-driven search for combined moderators identified statistically significant, but modest and clinically uninformative, effects (effect size r ≤ 0.29, a small-medium effect). Ketamine robustly reduces depressive symptoms in a heterogeneous range of patients, with benefit relative to placebo even greater in patients more resistant to prior medications. In this largest effort to date to apply precision medicine approaches to ketamine treatment, no clinical or demographic patient-level features were detected that could be used to guide ketamine treatment decisions.Review Registration: PROSPERO Identifier: CRD42021235630.

Peripheral blood inflammatory markers in depression: Response to electroconvulsive therapy and relationship with cognitive performance.

The inflammatory response may play a role in depression and the response to antidepressants. Electroconvulsive therapy (ECT), the most acutely powerful antidepressant treatment, can also affect the innate immune system. Here, we determined circulating blood concentrations of the inflammatory mediators C-reactive protein (CRP), IL-1ß, IL-6, IL-10, and TNF-α in depressed patients compared to healthy controls and assessed the effect of ECT on their concentrations. Relationships between inflammatory mediator concentrations and mood/cognition scores were also explored. Plasma CRP, IL-1ß, IL-6, IL-10, and TNF-α concentrations were examined in 86 depressed patients and 57 controls. Relationships between inflammatory mediators and clinical or cognitive outcomes following ECT were assessed using correlation and linear regression analyzes, respectively. CRP, IL-6, IL-10, and TNF-α were elevated in patients at baseline/pre-ECT compared to controls. However, only IL-6 and TNF-α survived adjustment for potential confounders. IL-1ß was undetectable in most samples. ECT did not significantly alter plasma concentrations of any of the inflammatory mediators. No relationship was identified between CRP, IL-6, IL-10, and TNF-α and mood or neurocognitive scores. Overall, our data do not support a major role for these four inflammatory markers in clinical outcomes following ECT or in cognition.

The Ketamine Side Effect Tool (KSET): A comprehensive measurement-based safety tool for ketamine treatment in psychiatry.

OBJECTIVES: On a background of the rapidly expanding clinical use of ketamine and esketamine for treatment of depression and other conditions, we examined safety monitoring, seeking to identify knowledge gaps relevant to clinical practice. METHODS: An international group of psychiatrists discussed the issue of safety of ketamine and esketamine and came to a consensus on key safety gaps. RESULTS: There is no standard safety monitoring for off-label generic ketamine. For intranasal esketamine, each jurisdiction providing regulatory approval may specify monitoring. Treatment is often provided beyond the period for which safety has been demonstrated, with no agreed framework for monitoring of longer term side effects for either generic ketamine or intranasal esketamine. LIMITATIONS: The KSET has established face and content validity, however it has not been validated against other measures of safety. CONCLUSIONS: We recommend the Ketamine Side Effect Tool (KSET) as a comprehensive safety monitoring tool for acute and longer term side effects.

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.

Decision-making Capacity for Treatment After Electroconvulsive Therapy for Depression.

OBJECTIVES: Depression can impair decision-making capacity (DMC) for health care decisions. However, it is unclear whether DMC improves after treatments for depression such as electroconvulsive therapy (ECT). There is limited evidence available on DMC for treatment in patients with depression referred for ECT, and it is unknown whether ECT has any impact on DMC. We hypothesized that ECT will improve DMC in severely depressed patients and that this change will be associated with reduced depressive symptom severity. METHODS: Using the MacArthur Competence Assessment Tool-Treatment, 4 abilities related to DMC were evaluated: Understanding, Appreciation, Reasoning, and Expressing a choice. This prospective study compared DMC abilities, depression severity, and cognition scores in 24 patients hospitalized with a major depressive episode before and 3 to 5 days after a course of ECT. RESULTS: Although Understanding scores significantly improved after ECT (P = 0.004, r = 0.41), there was no change in other abilities related to DMC or cognition scores. As expected, there was a large improvement in mood ratings after ECT, but the change in DMC abilities was not associated with change in depressive symptoms. CONCLUSIONS: To our knowledge, this is the first study to provide data on the effects of ECT on DMC in patients with depression. Abilities related to DMC that may be affected in this group before treatment include Understanding and Reasoning. Findings indicate that DMC to consent to treatment mostly does not change after a course of ECT and some aspects can improve in patients with depression.

Microglia and their LAG3 checkpoint underlie the antidepressant and neurogenesis-enhancing effects of electroconvulsive stimulation.

Despite evidence implicating microglia in the etiology and pathophysiology of major depression, there is paucity of information regarding the contribution of microglia-dependent molecular pathways to antidepressant procedures. In this study, we investigated the role of microglia in a mouse model of depression (chronic unpredictable stress-CUS) and its reversal by electroconvulsive stimulation (ECS), by examining the effects of microglia depletion with the colony stimulating factor-1 antagonist PLX5622. Microglia depletion did not change basal behavioral measures or the responsiveness to CUS, but it completely abrogated the therapeutic effects of ECS on depressive-like behavior and neurogenesis impairment. Treatment with the microglia inhibitor minocycline concurrently with ECS also diminished the antidepressant and pro-neurogenesis effects of ECS. Hippocampal RNA-Seq analysis revealed that ECS significantly increased the expression of genes related to neurogenesis and dopamine signaling, while reducing the expression of several immune checkpoint genes, particularly lymphocyte-activating gene-3 (Lag3), which was the only microglial transcript significantly altered by ECS. None of these molecular changes occurred in microglia-depleted mice. Immunohistochemical analyses showed that ECS reversed the CUS-induced changes in microglial morphology and elevation in microglial LAG3 receptor expression. Consistently, either acute or chronic systemic administration of a LAG3 monoclonal antibody, which readily penetrated into the brain parenchyma and was found to serve as a direct checkpoint blocker in BV2 microglia cultures, rapidly rescued the CUS-induced microglial alterations, depressive-like symptoms, and neurogenesis impairment. These findings suggest that brain microglial LAG3 represents a promising target for novel antidepressant therapeutics.

Usefulness of Hamilton rating scale for depression subset scales and full versions for electroconvulsive therapy.

OBJECTIVES: We investigated the predictive value of subset scales and full versions of the Hamilton Rating Scale for Depression (HAMD) for therapeutic outcomes in ECT. METHODS: This secondary analysis of patients with major depression (N = 136; 63% female; age = 56.7 [SD = 14.8]) from the EFFECT-Dep trial (NCT01907217) examined the predictive value of Evans-6, Toronto-7, Gibbons-8 and Maier-Philip 6 HAMD subset scales and three 'full' versions (HAMD-17, HAMD-21 and HAMD-24) on therapeutic outcomes. We also examined early improvement on subset scales and full versions as predictors of response and remission and explored predictive abilities of individual HAMD-24 items. RESULTS: The subset scales and full scales lacked sufficient predictive ability for response and remission. Receiver operating characteristic curves identified a lack of discriminative capacity of HAMD subset scales and full versions at baseline to predict response and remission. Only the Maier-Philip-6 was significantly associated with percentage reduction in HAMD-24 scores from baseline to end of ECT course. Early improvement on most of the subset scales and full versions was a sensitive and specific predictor of response and remission. Four of the HAMD-24 items were significantly associated with response and one with remission. CONCLUSIONS: Limited utility of the HAMD subset scales and full versions in this context highlight a need for more tailored depression rating scales for ECT.