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Ketamine vs Electroconvulsive Therapy for Treatment-Resistant Depression: A Secondary Analysis of a Randomized Clinical Trial

Author/s: 
Manish Kumar Jha, Samuel T Wilkinson, Kamini Krishnan, Katherine A Collins, Gerard Sanacora, James Murrough

Importance: The ELEKT-D: Electroconvulsive Therapy (ECT) vs Ketamine in Patients With Treatment Resistant Depression (TRD) (ELEKT-D) trial demonstrated noninferiority of intravenous ketamine vs ECT for nonpsychotic TRD. Clinical features that can guide selection of ketamine vs ECT may inform shared decision-making for patients with TRD.

Objective: To evaluate whether selected clinical features were associated with differential improvement with ketamine vs ECT.

Design, setting, and participants: This secondary analysis of an open-label noninferiority randomized clinical trial was a multicenter study conducted at 5 US academic medical centers from April 7, 2017, to November 11, 2022. Analyses for this study, which were not prespecified in the trial protocol, were conducted from May 10 to Oct 31, 2023. The study cohort included patients with TRD, aged 21 to 75 years, who were in a current nonpsychotic depressive episode of at least moderate severity and were referred for ECT by their clinicians.

Exposures: Eligible participants were randomized 1:1 to receive either 6 infusions of ketamine or 9 treatments with ECT over 3 weeks.

Main outcomes and measures: Association between baseline factors (including 16-item Quick Inventory of Depressive Symptomatology Self-Report [QIDS-SR16], Montgomery-Asberg Depression Rating Scale [MADRS], premorbid intelligence, cognitive function, history of attempted suicide, and inpatient vs outpatient status) and treatment response were assessed with repeated measures mixed-effects model analyses.

Results: Among the 365 participants included in this study (mean [SD] age, 46.0 [14.5] years; 191 [52.3%] female), 195 were randomized to the ketamine group and 170 to the ECT group. In repeated measures mixed-effects models using depression levels over 3 weeks and after false discovery rate adjustment, participants with a baseline QIDS-SR16 score of 20 or less (-7.7 vs -5.6 points) and those starting treatment as outpatients (-8.4 vs -6.2 points) reported greater reduction in the QIDS-SR16 with ketamine vs ECT. Conversely, those with a baseline QIDS-SR16 score of more than 20 (ie, very severe depression) and starting treatment as inpatients reported greater reduction in the QIDS-SR16 earlier in course of treatment (-8.4 vs -6.7 points) with ECT, but scores were similar in both groups at the end-of-treatment visit (-9.0 vs -9.9 points). In the ECT group only, participants with higher scores on measures of premorbid intelligence (-14.0 vs -11.2 points) and with a comorbid posttraumatic stress disorder diagnosis (-16.6 vs -12.0 points) reported greater reduction in the MADRS score. Those with impaired memory recall had greater reduction in MADRS during the second week of treatment (-13.4 vs -9.6 points), but the levels of MADRS were similar to those with unimpaired recall at the end-of-treatment visit (-14.3 vs -12.2 points). Other results were not significant after false discovery rate adjustment.

Conclusions and relevance: In this secondary analysis of the ELEKT-D randomized clinical trial of ECT vs ketamine, greater improvement in depression was observed with intravenous ketamine among outpatients with nonpsychotic TRD who had moderately severe or severe depression, suggesting that these patients may consider ketamine over ECT for TRD.

Keywords 
depression ketamine electroconvulsive therapy

Management of Depression in Adults: A Review

Author/s: 
Gregory E Simon, Nathalie Moise, David C Mohr

Importance: Approximately 9% of US adults experience major depression each year, with a lifetime prevalence of approximately 17% for men and 30% for women.

Observations: Major depression is defined by depressed mood, loss of interest in activities, and associated psychological and somatic symptoms lasting at least 2 weeks. Evaluation should include structured assessment of severity as well as risk of self-harm, suspected bipolar disorder, psychotic symptoms, substance use, and co-occurring anxiety disorder. First-line treatments include specific psychotherapies and antidepressant medications. A network meta-analysis of randomized clinical trials reported cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy all had at least medium-sized effects in symptom improvement over usual care without psychotherapy (standardized mean difference [SMD] ranging from 0.50 [95% CI, 0.20-0.81] to 0.73 [95% CI, 0.52-0.95]). A network meta-analysis of randomized clinical trials reported 21 antidepressant medications all had small- to medium-sized effects in symptom improvement over placebo (SMD ranging from 0.23 [95% CI, 0.19-0.28] for fluoxetine to 0.48 [95% CI, 0.41-0.55] for amitriptyline). Psychotherapy combined with antidepressant medication may be preferred, especially for more severe or chronic depression. A network meta-analysis of randomized clinical trials reported greater symptom improvement with combined treatment than with psychotherapy alone (SMD, 0.30 [95% CI, 0.14-0.45]) or medication alone (SMD, 0.33 [95% CI, 0.20-0.47]). When initial antidepressant medication is not effective, second-line medication treatment includes changing antidepressant medication, adding a second antidepressant, or augmenting with a nonantidepressant medication, which have approximately equal likelihood of success based on a network meta-analysis. Collaborative care programs, including systematic follow-up and outcome assessment, improve treatment effectiveness, with 1 meta-analysis reporting significantly greater symptom improvement compared with usual care (SMD, 0.42 [95% CI, 0.23-0.61]).

Conclusions and relevance: Effective first-line depression treatments include specific forms of psychotherapy and more than 20 antidepressant medications. Close monitoring significantly improves the likelihood of treatment success.

Keywords 
depression Adults

Exercise as a treatment for depression

Author/s: 
Carl Zhou, Nicholas Fabiano

Exercise effectively treats depression and may decrease suicide attempts

A 2023 meta-analysis of randomized controlled trials (RCTs) found that supervised, group or non-group, moderate- or vigorous-intensity, aerobic or resistance exercises (excluding mind–body activities such as yoga) decreased depressive symptoms among participants with depression, with a number needed to treat of 2 and an effectiveness comparable to first-line treatments such as psychotherapy and medication. Another 2023 meta-analysis of RCTs found that exercise decreased suicide attempts among people with mental or physical illness.

Keywords 
exercise depression exercise therapy Suicide Prevention

Screening for Depression and Suicide Risk in Children and Adolescents

Author/s: 
Jin, Jill

Depression is a leading cause of disability in the US. Children and adolescents with depression typically have functional impairments in their performance at school or work as well as in their interactions with their families and peers. Depression can also negatively affect the developmental trajectories of affected youth. Major depressive disorder (MDD) in children and adolescents is strongly associated with recurrent depression in adulthood; other mental disorders; and increased risk for suicidal ideation, suicide attempts, and suicide completion. Suicide is the second-leading cause of death among youth aged 10 to 19 years. Psychiatric disorders and previous suicide attempts increase suicide risk.

Keywords 
depression screening adolescents

The Management of Major Depressive Disorder: Synopsis of the 2022 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

Author/s: 
McQuaid, J. R., Buelt, A., Capaldi, V., Fuller, M., Issa, F., Lang, A. E., Hoge, C., Sall, J., Wiechers, I. R., Williams, S.

Abstract
Description: In February 2022, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) approved a joint clinical practice guideline (CPG) for the management of major depressive disorder (MDD). This synopsis summarizes key recommendations.

Methods: Senior leaders within the VA and the DoD assembled a team to update the 2016 CPG for the management of MDD that included clinical stakeholders and conformed to the National Academy of Medicine's tenets for trustworthy CPGs. The guideline panel developed key questions, systematically searched and evaluated the literature, created two 1-page algorithms, and distilled 36 recommendations for care using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. Select recommendations that were identified by the authors to represent key changes from the prior CPG are presented in this synopsis.

Recommendations: The scope of the CPG is diverse; however, this synopsis focuses on key recommendations that the authors identified as important new evidence and changes to prior recommendations on pharmacologic management, pharmacogenomics, psychotherapy, complementary and alternative therapies, and the use of telemedicine.

Keywords 
Department of Veterans Affairs veterans Department of Defense Algorithms alternative therapies

Volunteering and Subsequent Health and Well-Being in Older Adults: An Outcome-Wide Longitudinal Approach

Author/s: 
Kim, E.S., Whillans, A.V., Lee, M.T., Chen, Y., VanderWeele, T.J.

ntroduction: Growing evidence documents strong associations between volunteering and favorable health and well-being outcomes. However, epidemiological studies have not evaluated whether changes in volunteering are associated with subsequent health and well-being outcomes.

Methods: Data were from 12,998 participants in the Health and Retirement Study-a large, diverse, prospective, and nationally representative cohort of U.S. adults aged >50 years. Using multiple logistic, linear, and generalized linear regression models, this study evaluated if changes in volunteering (between t0, 2006/2008 and t1, 2010/2012) were associated with 34 indicators of physical health, health behaviors, and psychosocial well-being (in t2, 2014/2016). Models adjusted for sociodemographics, physical health, health behaviors, psychosocial factors, and personality, as well as volunteering and all outcomes in the prebaseline wave (t0, 2006/2008). Results accounted for multiple testing and data were analyzed in 2019.

Results: During the 4-year follow-up period, participants who volunteered ≥100 hours/year (versus 0 hours/year) had a reduced risk of mortality and physical functioning limitations, higher physical activity, and better psychosocial outcomes (higher: positive affect, optimism, and purpose in life; lower: depressive symptoms, hopelessness, loneliness, and infrequent contact with friends). Volunteering was not associated with other physical health outcomes (diabetes, hypertension, stroke, cancer, heart disease, lung disease, arthritis, overweight/obesity, cognitive impairment, and chronic pain), health behaviors (binge drinking, smoking, and sleep problems), or psychosocial outcomes (life satisfaction, mastery, health/financial mastery, depression, negative affect, perceived constraints, and contact with other family/children).

Conclusions: With further research, volunteering is an activity that physicians might suggest to their willing and able patients as a way of simultaneously enhancing health and society.

Keywords 
volunteering volunteer health benefits

Treatment of Depression in Children and Adolescents: A Systematic Review. Comparative Effectiveness Review No. 224

Author/s: 
Viswanathan, M, Kennedy, SM, McKeeman, J, Christian, R, Coker-Schwimmer, Cook Middleton, Bann, C, Lux, L, Randolph, Forman-Hoffman, V

Background. Depressive disorders can affect long-term mental and physical health functioning among children and adolescents, including increased risk of suicide. Despite access to several nonpharmacological, pharmacological, and combined treatment options for childhood depression, clinicians contend with sparse evidence and are concerned about harms associated with treatment.

Methods. We conducted a systematic review to evaluate the efficacy, comparative effectiveness, and moderators of benefits and harms of available nonpharmacological and pharmacological treatments for children and adolescents with a confirmed diagnosis of a depressive disorder (DD)—major depressive disorder (MDD), persistent depressive disorder (previously termed dysthymia) or DD not otherwise specified. We searched five databases and other sources for evidence available from inception to May 29, 2019, dually screened the results, and analyzed eligible studies.

Results. We included in our analyses data from 60 studies (94 articles) that met our review eligibility criteria. For adolescents (study participants’ ages range from 12 to 18 years) with MDD, cognitive behavioral therapy (CBT), fluoxetine, escitalopram, and combined fluoxetine and CBT may improve depressive symptoms (1 randomized controlled trial [RCT] each, n ranges from 212 to 311); whether the magnitude of improvement is clinically significant is unclear. Among adolescents or children with MDD, CBT plus medications (8–17 years) may be associated with lower rates of relapse (1 RCT [n = 121]). In the same population (6–17 years), selective serotonin reuptake inhibitors (SSRIs) may be associated with improved response (7 RCTs [n = 1,525]; risk difference [RD], 72/1,000 [95% confidence interval (CI), 2 to 24], I2 = 9%) and functional status (5 RCTs [n = 941]; standardized mean difference, 0.16 [95% CI, 0.03 to 0.29]; I2 = 0%). For adolescents or children with any DD (7–18 years), CBT or family therapy may be associated with improvements in symptoms, response, or functional status (1 RCT each, n ranges from 64 to 99). Among children with any DD (7–12 years), family-based interpersonal therapy may be associated with improved symptoms (1 RCT, n = 38). Psychotherapy trials did not report harms. SSRIs may be associated with a higher risk of serious adverse events among adolescents or children with MDD (7–18 years; 9 RCTs [n = 2,206]; RD, 20/1,000 [95% CI, 1 to 440]; I2, 4%) and with a higher risk of withdrawal due to adverse events among adolescents with MDD (12–18 years; 4 RCTs [n = 1,296], RD, 26/1,000 [95% CI, 6 to 45]; I2, 0%). Paroxetine (1 RCT [n = 180]) may be associated with a higher risk of suicidal ideation or behaviors among adolescents with MDD (12–18 years). Evidence was insufficient to judge the risk of suicidal ideation or behavior for other SSRIs for adolescents and children with MDD or other DD (7–18 years) (10 RCTs [n = 2,368]; relative risk, 1.14 [95% CI, 0.89 to 1.45]; I2, 8%). However, this report excluded data on inpatients and those without depressive disorders, whom the Food and Drug Administration included in finding an increased risk of suicidality for all antidepressants across all indications.

Conclusion. Efficacious treatments exist for adolescents with MDD. SSRIs may be associated with increased withdrawal and serious adverse events. No evidence on harms of psychotherapy were identified.

Keywords 
children adolescent child depression treatment cognitive behavioral therapy selective serotonin reuptake inhibitors

Mental Health Conditions Among Patients Seeking and Undergoing Bariatric Surgery: A Meta-analysis

Author/s: 
Dawes, AJ, Maggard-Gibbons, M, Maher, AR, Booth, MJ, Miake-Lye, I, Shekelle, PG

IMPORTANCE:

Bariatric surgery is associated with sustained weight loss and improved physical health status for severely obese individuals. Mental health conditions may be common among patients seeking bariatric surgery; however, the prevalence of these conditions and whether they are associated with postoperative outcomes remains unknown.

OBJECTIVE:

To determine the prevalence of mental health conditions among bariatric surgery candidates and recipients, to evaluate the association between preoperative mental health conditions and health outcomes following bariatric surgery, and to evaluate the association between surgery and the clinical course of mental health conditions.

DATA SOURCES:

We searched PubMed, MEDLINE on OVID, and PsycINFO for studies published between January 1988 and November 2015. Study quality was assessed using an adapted tool for risk of bias; quality of evidence was rated based on GRADE (Grading of Recommendations Assessment, Development and Evaluation) criteria.

FINDINGS:

We identified 68 publications meeting inclusion criteria: 59 reporting the prevalence of preoperative mental health conditions (65,363 patients) and 27 reporting associations between preoperative mental health conditions and postoperative outcomes (50,182 patients). Among patients seeking and undergoing bariatric surgery, the most common mental health conditions, based on random-effects estimates of prevalence, were depression (19% [95% CI, 14%-25%]) and binge eating disorder (17% [95% CI, 13%-21%]). There was conflicting evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Neither depression nor binge eating disorder was consistently associated with differences in weight outcomes. Bariatric surgery was, however, consistently associated with postoperative decreases in the prevalence of depression (7 studies; 8%-74% decrease) and the severity of depressive symptoms (6 studies; 40%-70% decrease).

CONCLUSIONS AND RELEVANCE:

Mental health conditions are common among bariatric surgery patients-in particular, depression and binge eating disorder. There is inconsistent evidence regarding the association between preoperative mental health conditions and postoperative weight loss. Moderate-quality evidence supports an association between bariatric surgery and lower rates of depression postoperatively.

Keywords 
mental health bariatric surgery weight loss depression meta-analysis

Systole and Diastole, Strength and Openness

Author/s: 
Farrell, C.M.

Seize diastole,” my medical school professor said. The words were a clever metaphor for a life well lived. During systole, the powerful myocardium contracts, generating pressure that propels open the aortic valve. Blood flows out into the circulation.

Diastole, the process of letting go and filling up, is not as exciting. It could even be taken for granted, cut shorter and shorter. But without adequate time for diastole, there’s no blood to be thrust forward. Homeostasis crumbles. Just as the myocardium needs time to release and refill, so does the soul...

 

Keywords 
depression medical students internship residency
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