To Örebro University

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is an established treatment of depression. The more recently introduced intermittent Theta-burst stimulation (iTBS) has shown significant superiority over sham-stimulation and equal effect sizes to a 10 Hz protocol in one clinical trial. The aim of the current study was to investigate the effectiveness and tolerability of iTBS in a naturalistic, clinical setting. Further, we explored demographical and clinical predictors of response.

METHODS: Data was collected from seventeen rTMS-sites in Sweden between January 2018 and May 2021, through the Swedish National Quality register for repetitive Transcranial Magnetic Stimulation (Q-rTMS). We included 542 iTBS-treated patients with unipolar or bipolar depression. Outcome was assessed with Clinical Global Impression Severity and Improvement scores in an intention to treat analysis.

RESULTS: The response rate was 42.1 % and 16.1 % reached remission. The response rate was significantly larger in the oldest age group compared to the youngest (odds ratio 3.46, 95 % confidence interval 1.65-7.22). Less severe level of depression (Montgomery-Åsberg depression rating scale self-assessment < 36) at baseline predicted response and remission. Only <1 % were much or very much worse after treatment. Drop-out rate was 10.9 %. No serious adverse events were reported.

LIMITATIONS: Retrospective analysis of register data. No comparison group.

CONCLUSIONS: In a clinical setting, iTBS was shown to be safe and tolerable and the response rate was similar to that reported from clinical trials. Older age-group and less severe illness predicted response.

Aims This thesis aimed to investigate 1. the effectiveness of electroconvulsivetherapy (ECT) in bipolar depression and mania in real-life settings; 2. the prognostic factors of response to ECT; 3. readmission ratesand risk factors after the acute phase of bipolar disorder; and 4. the association between ECT and readmission rate in mania.

Methods This thesis includes four nationwide register studies. Data came from several national registers linked by personal identity numbers.

Results Response was achieved in 80.2% of ECT-treated patients with bipolardepression and 84.4% of ECT-treated patients with mania. Younger age was associated with a lower response rate to ECT in depressive episodes. Patients aged 16–30 years had a lower chance of responding than patients aged 31–40 years, 61–70, and 71–80 years. Response to ECT in mania was associated with the severity of symptoms. Patients who were markedly ill, severely ill, and among the most extremely ill had a higher chance of responding than patients with mild to moderate illness. Relapse within 3, 6, and 12 months after bipolar depression was reached by 29%, 41%, and 52% of patients, respectively. After manic episodes, 30%, 41%, and 55% of patients were readmitted within 3, 6, and 12 months, respectively. Treatment with ECT was not associated with a longer time to readmission after a manic episode than other treatments.

Conclusions Over 80% of patients with bipolar depression and mania responded to ECT. In depressive episodes, patients at lower ages had a lower chance of achieving response after ECT, and in mania, patients with more severe symptoms had a higher chance of responding to ECT. The readmission rate after both manic and depressive episodes was high. There was no significant difference between time to readmission in patients treated with and without ECT during index admission for mania.

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.

OBJECTIVE: Electroconvulsive therapy (ECT) is used in patients with severe forms of bipolar depression. ECT is effective but not all patients respond. The aim of this study was to determine prognostic factors for response to ECT in patients hospitalized for bipolar depression.

METHODS: Data were obtained from several national Swedish registers. All patients with bipolar depression treated with ECT in any hospital in Sweden between 2011 and 2016 for whom information about ECT response was available were included (n = 1251). Response was defined as a score on the Clinical Global Impression - Improvement scale of one or two. Univariate and multivariate logistic regression were conducted to investigate associations between socio-demographic and clinical factors and response.

RESULTS: Response was achieved in 80.2% patients. Older age was associated with higher response rate to ECT. Patients with comorbid obsessive-compulsive disorder or personality disorder, and patients previously treated with lamotrigine had lower response rate.

CONCLUSION: ECT for bipolar depression was associated with very high response rates. The strongest prognostic factors were higher age, absence of comorbid obsessive-compulsive disorder or personality disorder, and less prior pharmacologic treatment.

Importance: Knowledge of the effectiveness of electroconvulsive therapy (ECT) in the treatment of manic episodes is based on clinical experience, but empirical evidence is scarce. Moreover, prognostic factors associated with response to ECT in patients with mania are poorly understood.

Objective: To investigate the response to ECT in patients with manic episodes.

Design, Setting, and Participants: This nationwide, register-based observational cohort study was conducted using data from patients admitted to psychiatric departments in Sweden that reported data to the Swedish National Quality Registry for ECT (Q-ECT). Patients admitted to any hospital in Sweden and receiving ECT for a manic episode between 2012 and 2019 were considered for inclusion (605 individuals). The outcome, Clinical Global Impression Improvement scale (CGI-I) score, was available in 571 patients. Data from several national registers were combined to determine clinical and sociodemographic factors. Analysis of data occurred from April through September 2021.

Exposures: Patients treated with ECT for a mania were identified from the Q-ECT.

Main Outcomes and Measures: Response to ECT was defined by a CGI-I score of 1 (very much improved) or 2 (much improved). Remission was defined as a Clinical Global Impression Severity scale (CGI-S) score of 1 (reference range or not ill) or 2 (minimally ill) within 1 week after ECT. Univariate and multivariable regression models were used to investigate associations of sociodemographic factors, psychopharmacology, and comorbidities with response.

Results: Among 571 patients with mania treated with ECT (211 [37.0%] men; median [IQR] age, 46 [31-59] years), 482 patients (84.4%) responded to ECT. Comorbid anxiety and obsessive-compulsive disorder (OCD) were associated with lower odds of response to ECT (adjusted odds ratio [aOR], 0.48; 95% CI, 0.25-0.90 and aOR, 0.17; 95% CI, 0.06-0.56, respectively). Patients who were markedly ill (aOR, 2.93; 95% CI, 1.23-7.00), severely ill (aOR, 2.60; 95% CI, 1.06-6.34), or among the most extremely ill (aOR, 7.94; 95% CI, 2.16-29.21) according to CGI-S score had higher odds of response than those with mild or moderate illness.

Conclusions and Relevance: This study found that ECT was associated with improvement for mania in clinical settings, with especially high response rates in patients with severe illness and those without comorbid anxiety or OCD.

Background: Electroconvulsive therapy (ECT) is effective in bipolar depression, but relapse is common. The aim of the study was (i) to identify prognostic factors (ii) and to determine the impact of pharmacological approaches on the risk for rehospitalization or suicide.

Methods: This register study analyzed data from individuals treated with inpatient ECT for bipolar depression. Subjects were identified using the Swedish National Patient Register between 2011 and 2014 and the Swedish National Quality Register for ECT. Other national registers provided data on psychopharmacotherapy, socio-demographic factors, and causes of death. The endpoint was the composite of rehospitalization for any psychiatric disorder, suicide attempt or completed suicide (RoS). Cox regression was used to calculate hazard ratios in univariate and multivariate models.

Results: Data from 1255 patients were analyzed. The mean period of follow-up was 346 days.

A total of 29%, 41%, and 52% of patients reached RoS at 3, 6, and 12 months post-discharge. A history of multiple psychiatric admissions, lower age, and post-discharge treatment with antipsychotics or benzodiazepines was associated with RoS.

Limitations: Indication bias may have affected the results.

Conclusions: A history of multiple hospital admissions and lower age are key predictors of the composite of rehospitalization or suicide in patients treated with ECT for bipolar depression. Lithium might be effective. By contrast, antipsychotics and benzodiazepines were associated with increased risk, but possibly this finding was influenced by indication bias.

Up to 30% of patients with schizophrenia respond insufficiently to antipsychotic drugs. Electroconvulsive therapy (ECT) has been reported to effectively augment the effects of antipsychotics in some of these patients. To date, there are few established predictors of treatment response to ECT in patients with schizophrenia. The primary aim was to determine the response rate to ECT in patients with schizophrenia. The secondary aim was to investigate predictors of treatment response. All patients admitted to any Swedish hospital for schizophrenia from 2011 to 2017, who were treated with ECT while in inpatient care, were included in the Swedish National Quality Registry for ECT (Q-ECT), and were assessed using the Clinical Global Impression – Improvement (CGI-I) scale after treatment were included. CGI-I scores of 1 or 2 were considered a response to treatment. Multiple national registries were used to obtain information on demographics and clinical variables. The study included 285 patients who were concurrently treated with antipsychotic drugs. The response rate to ECT was 73.0%. Among those patients with outcome data, treatment with long-acting injectable antipsychotics was predictive of a better response, whereas comorbid substance use disorders were predictive of a worse response. This study provides new evidence on predictors of who might respond among patients with schizophrenia treated by ECT. Additional studies of ECT in schizophrenia are needed.

OBJECTIVES: Electroconvulsive therapy (ECT) and repetitive transcranial magnetic stimulation (rTMS) are both effective in treating depression. Although rTMS induces fewer adverse effects, its effectiveness relative to ECT is not well established. The aim of this study was to investigate the treatment outcomes of ECT and rTMS in patients who have received both interventions.

METHODS: This was a register-based observational crossover study in patients with depression who had undergone ECT and rTMS in Sweden between 2012 and 2021. Primary outcome was reduction in the Montgomery-Åsberg Depression Rating Scale-Self-report (MADRS-S) score. Secondary outcome was response defined as a 50% or greater decrease in the MADRS-S score. Subgroup analyses were performed to identify factors that predicted differential responses between rTMS and ECT. Continuous and categorical variables were analyzed using paired-samples t tests and McNemar tests, respectively.

RESULTS: In total, 138 patients across 19 hospitals were included. The MADRS-S score after ECT and rTMS was reduced by 15.0 and 5.6 (P = 0.0001) points, respectively. Response rates to ECT and rTMS were 38% and 15% (P = 0.0001), respectively. Electroconvulsive therapy was superior across all subgroups classified according to age and severity of depression.

CONCLUSIONS: Our results suggest that ECT is more effective than rTMS in treating depression among patients who have received both interventions. Age and baseline depression severity did not predict who would similarly benefit from rTMS and ECT.