Inflammation and Response to ECT in Treatment-Resistant Depression

• Electroconvulsive therapy (ECT) is a highly effective treatment for major depressive disorder
• A portion of patients fail to respond to ECT, and clinical variables have overall limited utility as a predictor of response

• Inclusion criteria were current major depressive episode; at least two prior major depressive episodes, and failure to respond to at least two previous antidepressant trials
• Exclusion criteria were alcohol or other substance abuse within the past 6 months (or dependence within the past 12 months); psychotic disorder, dementia, serious medical illness, onset of depression after age 50; prior ECT; and or other neuromodulatory treatment within the past 6 months
• Patients were tapered off of psychotropic medications 48 to 72 hours prior to ECT

• Patients had clinical assessment (Montgomery-Asberg Depression Rating Scale; MADRS) and blood draw for inflammatory markers (CRP, IL-1beta, IL-6, IL-8, and TNF-alpha) at three time points: within 24 hours of the first ECT (T1), between the second and third ECT (T2), and again after the end of the ECT series (T3; 4-6 weeks after the first treatment)
• Subjects received either 5 times seizure threshold for right unilateral ECT using ultrabrief pulse width (0.3 msec), or 1.5 times seizure threshold for bilateral ECT using brief pulse wide (0.5 msec) 3 times weekly for a mean of 11.5 sessions (range 6 to 22), using methohexital 1mg/kg for anesthesia and succinylcholine 1 mg/kg. Meta-regression analyses examined moderating effects of age, illness duration, geography, study design, and study quality on associations between risk factors and suicidality
• Repeated-measures analysis of variance was used to evaluate changes in inflammatory marker levels during treatment
• Univariate regression analyses were used to evaluate baseline (and change in) inflammatory marker levels as predictors of clinical outcome, defined as MADRS score at the end of treatment, controlling for age, duration of current episode, and baseline symptom severity
• Analyses were stratified by sex

• Mean subject age was 43, the mean duration of the current depressive episode was 2 years, and the mean baseline MADRS score was 40
• MADRS scores significantly decreased over the course of the trial (mean 17.5 at T3)
• CRP and IL-6 levels increased significantly from T1 to T2, and decreased significantly from T2 to T3 (though no significant change from T2 to T3)
• Higher baseline IL-6 levels predicted lower end-of-treatment MADRS scores following ECT (beta=-0.48)
• No other inflammatory markers were associated with MADRS scores
• Neither the change in CRP nor IL-6 predicted end-of-treatment MADRS scores
• Responders and remitters following ECT had significantly higher baseline IL-6 levels
• In sex-stratified analyses, both CRP and IL-6 predicted lower end-of-treatment MADRS scores in women, but not men

• The authors concluded that higher baseline CRP and IL-6 predicted better response to ECT in patients with TRD
• They note that changes in these inflammatory markers over time may represent acute stress-induced inflammation in response to the initiation of ECT
• Limitations of the present study include the small sample size, and the impact of the discontinuation of psychotropic medications prior to ECT on inflammatory marker levels
• Further studies of inflammatory markers as predictors of response to ECT are warranted