To Örebro University

Despite electroconvulsive therapy (ECT) being recognized as an effective treatment for major depressive episodes (MDE), its application is subject to controversy due to concerns over cognitive side effects. The pathophysiology of these side effects is not well understood. Here, we examined the effects of ECT on blood-based biomarkers of neuronal injury and astrocytic reactivity. Participants with a major depressive episode (N = 99) underwent acute ECT. Blood was sampled just before (T0) and 30 min after (T1) the first ECT session, as well as just before the sixth session (T2; 48-72 h after the fifth session). Age- and sex-matched controls (N = 99) were recruited from the general population. Serum concentrations of neurofilament light chain (NfL), total tau protein, and glial fibrillary acidic protein (GFAP) were measured with ultrasensitive single-molecule array assays. Utilizing generalized least squares regression, we compared baseline (T0) biomarker concentrations against those of our control group, and calculated the shifts in serum biomarker concentrations from baseline to immediately post-first ECT session (T1), and prior to the sixth session (T2). Baseline analysis revealed that serum levels of NfL (p < 0.001) and tau (p = 0.036) were significantly elevated in ECT recipients compared with controls, whereas GFAP levels showed no significant difference. Relative to T0, serum NfL concentration neither changed at T1 (mean change 3.1%, 95%CI -0.5% to 6.7%, p = 0.088) nor at T2 (mean change -3.2%, 95%CI -7.6% to 1.5%, p = 0.18). Similarly, no change in total tau was observed (mean change 3.7%, 95%CI -11.6% to 21.7%, p = 0.65). GFAP increased from T0 to T1 (mean change 20.3%, 95%CI 14.6 to 26.3%, p < 0.001), but not from T0 to T2 (mean change -0.7%, 95%CI -5.8% to 4.8%, p = 0.82). In conclusion, our findings suggest that ECT induces a temporary increase in serum GFAP, possibly reflecting transient astrocytic activation. Importantly, we observed no indicators of neuronal damage or long-term elevation in any assessed biomarker.

OBJECTIVES: Depression is common in the oldest-old population (aged ≥85 years), a population in which research is lacking and the effects of psychopharmacological treatment may be adverse. Electroconvulsive therapy (ECT) appears to be well tolerated by older patients with depression; however, it is used rarely in clinical practice and research concerning the oldest-old is lacking. The objective of this study was to assess response and remission rates, as well as adverse effects, in oldest-old depressed patients treated with ECT.

METHODS: This was a nationwide Swedish register study including 522 oldest-old patients treated with ECT for depression. Two propensity score matched control groups were also included: young patients treated with ECT, and oldest-old depressed patients not treated with ECT. Response and remission rates, clinician-reported adverse events, prognostic factors (including comorbid diseases and treatment parameters), adverse events requiring hospitalization, as well as deaths within 1 week from discharge, were assessed.

RESULTS: The oldest-old receiving ECT reported higher response (81.2%) and remission (53.3%) rates than younger counterparts (67.4% versus 27.4%, respectively). Severe psychotic depression was the only prognostic factor for response and remission. The oldest-old experienced fewer adverse events, most commonly confusion and cardiovascular complications, compared to controls. Compared with oldest-old patients not receiving ECT, the ECT group had fewer hospitalizations following discharge.

CONCLUSION: ECT is a viable treatment option for oldest-old patients with depression, who show higher response and remission rates than younger patients, as well as fewer hospitalizations than oldest-old patients not treated with ECT.

Eating disorders (ED) have a high comorbidity with major depressive disorder (MDD). Antidepressants often lack effect in these patients. While electroconvulsive therapy (ECT) is the most effective treatment for severe MDD, there are no large studies in the ED patient group yet. We aimed to compare the outcome of ECT for MDD in patients with and without eating disorders. We conducted a register-based study for patients with MDD and comorbid ED treated with ECT in Sweden between 2012-2023. The outcomes were compared to a matched control group without comorbid ED. The primary outcome was a response to treatment according to the Clinical Global Impression Improvement Scale (CGI-I). Secondary outcomes were remission according to CGI-I and subjective memory complaint. There were 861 patients in the ED group and 1,722 in the control group; of these 93.2% were female. The response rate was 58.4% in the ED group and 62.4% in the control group (OR 0.8, 95% CI 0.7-0.9, p <0.05). The frequency of subjective memory complaints in the ED versus the control group was 25.9% and 24.8%, respectively (OR 1.1, 95% 0.8-1.3 CI, p = 0.6). High response rates after ECT for MDD were found in the ED group but were significantly lower than in the matched control group. Subjective memory complaints did not differ significantly. Further studies are required comparing the outcome of ECT versus alternative treatments among patients with ED complicated by severe MDD.

BACKGROUND: Having young relative age in school is an identified risk factor for depression among schoolchildren, but it is unclear if this risk remains in adulthood. This study aimed to investigate the association between young relative age in school and antidepressant use across different age groups.

METHOD: This population-based study used data from the Swedish Medical Birth Register and the Prescribed Drug Register combined with data from Statistics Sweden. The population of 3,575,510 subjects, (48.6 % female), was split into different age groups, with groups spanning from 0 to 7 years of age to 40-45 years of age. The odds ratios (OR) of antidepressant use in the first as compared to the fourth birth-quarters, was determined by logistic regression. RESULTS: Young relative age was positively associated with use of antidepressants with an OR of 1.05 (95 % confidence interval, 1.05-1.06) in the study population. This association was significant in all age groups that had started school and remained among adults.

LIMITATIONS: Data on indication for antidepressant medication prescription was unavailable, some subjects might have had antidepressants for other disorders then anxiety and depression. Another limitation is that it is unclear when during schooling children were accelerated/deferred. Moreover, antidepressant medication is uncommon among small children.

CONCLUSION: This study shows that young relative age within the school year increases the prevalence of antidepressant use in all investigated age-groups that had started school, long after the end of schooling.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective treatment for depression with potential transient cognitive side effects. However, subjective memory impairment can extend over a long period after ECT.

OBJECTIVES: This study aimed to assess potential risk factors for long-term subjective memory impairment 6 months after ECT and to explore if the associations are mediated by depressive symptoms.

METHODS: This registry-based study used the Swedish National Quality Register for ECT and other national registers. Long-term subjective memory worsening was defined as a minimum 2-step worsening on the memory item from the comprehensive psychopathological rating scale (CPRS-M) from before ECT to 6 months after ECT. Changes on the scale were also analyzed in continuous models. Statistical methods used were logistic regression and linear regression analyses in univariable and multivariable models.

RESULTS: The study population consisted of 1498 patients. Subjective memory worsening occurred in 25.2 % of the population. Long-term subjective memory worsening was associated with more depressive symptoms and lower education levels. No association could be found related to ECT technical factors. The associations between age and psychiatric comorbidities with subjective memory worsening were mediated by depressive symptoms.

CONCLUSION: Patients can be informed that depressive symptoms are one of the biggest contributing factors to long-term subjective memory impairment after ECT. A successful treatment is therefore important to minimize the long-term experience of memory deficits. The number of sessions or ECT technical factors do not seem to be associated with long-term subjective memory impairment.

OBJECTIVE: This study aimed to associate antidepressants with versus without antipsychotics with readmission and suicide in patients with psychotic unipolar depression.

METHODS: Swedish national registers were used to identify inpatients with psychotic unipolar depression, treated 2007-2016. The participants collected antidepressants with or without antipsychotics from a pharmacy within 14 days after discharge and were followed up for 2 years. The primary outcome was hospital readmission due to any psychiatric disorder, suicide attempt, or completed suicide. Cox regression was used to analyze the data, which were adjusted for sex, age, prior admissions, comorbidity, electroconvulsive therapy, and other pharmacological treatments.

RESULTS: We identified 4391 patients, of which 2972 were in the antidepressant + antipsychotic combination therapy group, and 1419 were in the antidepressant monotherapy group. After 2 years, 42.3% and 36.6% of patients were readmitted or committed suicide in the combination therapy and monotherapy group, respectively. Monotherapy was significantly associated with a lower risk of reaching the outcome in the main analysis (hazard ratio = 0.86; 95% confidence interval: 0.77-0.95). The results went in the same direction in all sensitivity analyses.

CONCLUSION: Our findings do not indicate any advantage of adding antipsychotics as adjunctive to antidepressants as maintenance treatment. Considering the wide use, known side effects, and the current lack of evidence supporting the benefit, further studies on the effect of antipsychotics in the maintenance phase of psychotic unipolar depression are urgently warranted.

OBJECTIVE: The majority of patients hospitalized for treatment of a manic episode are readmitted within 2 years despite maintenance treatment. Electroconvulsive therapy (ECT) has been associated with lower rehospitalization rates in some psychiatric conditions, but its association with readmission after a manic episode has not been investigated. Therefore, the aim of this study was to determine whether the time to readmission in patients with mania treated with ECT was longer than in patients not treated with ECT and whether there were subgroups of patients that benefited more.

METHODS: This was a nationwide register-based, observational study. All patients diagnosed with bipolar disorder, manic episode, admitted to any hospital in Sweden between 2012 and 2021 were included. Patients contributed data to the study for every admission. All admissions were followed up until psychiatric readmission, death, or the end of the study (December 31, 2021). Association between ECT and time to readmission was analyzed. A paired samples model was performed for 377 patients with at least two admissions for mania, treated with ECT at one admission and without ECT at the other admission. Times to readmission were analyzed.

RESULTS: A total of 12,337 admissions were included; mean (SD) age 47.7 (17.2), 5443 (44.1%) men. Readmission rate within 1 year was 54.6%. ECT was administered in 902 (7.3%) admissions. Within 30 days after admission, 182 out of 894 (20.4%) patients treated with ECT versus 2105 out of 11,305 (18.6%) patients treated without ECT were readmitted. There was no association between ECT and time to readmission (aHR 1.00, 95% CI 0.86-1.16, p = 0.992) in the model with all admissions. The paired samples model included 754 admissions (377 patients), mean (SD) age during admission without ECT was 45.6 (16.5), and with ECT 46.6 (16.4), 147 (39.0%) were men. In that model, readmission rate within 30 days for treatment with ECT was 19.0%, and for treatments without ECT, 24.1% (aHR 0.75, 95% CI 0.55-1.02, p = 0.067).

CONCLUSION: Readmission rates after inpatient treatment of mania were high. ECT was not significantly associated with longer time to readmission, but there was a trend toward a protective effect of ECT when admissions with and without ECT were compared within the same patients.

AIMS: To examine the association between pulse width and HRQoL measured within one week after electroconvulsive therapy (ECT) and at six-month follow-up in patients with unipolar or bipolar depression.

METHODS: This was an observational register study using data from the Swedish National Quality Registry for ECT (2011-2019). Inclusion criteria were: age ≥18 years; index treatment for unipolar/bipolar depression; unilateral electrode placement; information on pulse width; EQ-5D measurements before and after ECT. Multiple linear regressions were performed to investigate the association between pulse width (<0.5 ms; 0.5 ms; >0.5 ms) and HRQoL (EQ-5D-3L index; EQ VAS) one week after ECT (primary outcome) and six months after ECT (secondary outcome).

RESULTS: The sample included 5,046 patients with unipolar (82%) or bipolar (18%) depression. At first ECT session, 741 patients (14.7%) had pulse width <0.5 ms, 3,639 (72.1%) had 0.5 ms, and 666 (13.2%) had >0.5 ms. There were no statistically significant associations between pulse width and HRQoL one week after ECT. In the subsample of patients with an EQ-5D index recorded six months after ECT (n = 730), patients receiving 0.5 ms had significantly lower HRQoL (-0.089) compared to <0.5 ms, after adjusting for demographic and clinical characteristics (p = .011). The corresponding analysis for EQ VAS did not show any statistically significant associations.

CONCLUSION: No robust associations were observed between pulse width and HRQoL after ECT. On average, significant improvements in HRQoL were observed one week and six months after ECT for patients with unipolar or bipolar disease, independent of the pulse width received.

OBJECTIVE: To determine whether the rates of readmissions and suicide vary in psychotic unipolar depression based on whether patients receive maintenance electroconvulsive therapy (M-ECT) following the initial series of ECT, and to examine if there is an age-dependent association.

METHODS: We used Swedish national registries to identify hospitalized patients with psychotic unipolar depression, treated 2008-2019 who received ECT during their hospital stay. The patients who received subsequent M-ECT within 14 days after discharge were compared with those who did not. The primary composite outcome was time to readmission due to a psychiatric disorder, suicide attempt, or suicide within 2 years from discharge. Data were analyzed using Cox regression adjusted for previous psychiatric admissions, age, sex, comorbidity, and pharmacological treatment. We also conducted a within-individual analysis using the sign-test, with patients having ≥1 hospital episode followed by M-ECT and ≥1 hospital episode without M-ECT.

RESULTS: A total of 1873 patients were included, of which 130 received M-ECT. There was no statistically significant group difference regarding the primary outcome in the whole sample. However, when stratified by age, there was a significant difference in favor of M-ECT for patients >65 years (adjusted hazard ratio 0.55, 95% confidence interval 0.35-0.87). The within-individual analysis, including 46 patients, significantly favored M-ECT.

CONCLUSION: M-ECT was not associated with a differential risk of the composite of readmission and suicide in psychotic depression. Among patients >65 years, M-ECT was significantly associated with a decreased risk of the outcome. The possibility of residual confounding cannot be excluded.