Am J Psychiatry
· 2026 Mar · PMID 41807319
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OBJECTIVE: The objective of this study was to assess the efficacy of theta-burst stimulation (TBS) in treating late-life depression. METHODS: A triple-blind, sham-controlled randomized clinical trial was performed. The s...OBJECTIVE: The objective of this study was to assess the efficacy of theta-burst stimulation (TBS) in treating late-life depression. METHODS: A triple-blind, sham-controlled randomized clinical trial was performed. The study included participants age 60 and older with a diagnosis of moderate to severe major depressive disorder who were not using antidepressants. Exclusion criteria included other psychiatric disorders, neurological disorders, and contraindications to TBS. TBS was administered bilaterally, with intermittent TBS on the left dorsolateral prefrontal cortex (DLPFC) and continuous TBS on the right DLPFC, with 1,800 pulses at each side. Participants underwent 20 daily sessions of active or sham TBS over 20 consecutive weekdays and one additional session during weeks 6, 8, and 12 (totaling 23 sessions). RESULTS: A total of 108 participants (mean age, 67 years) were enrolled and underwent either active or sham TBS. In an intention-to-treat analysis, there was no significant difference between groups at week 6 in mean reduction in Hamilton Depression Rating Scale (HAM-D) score (mean difference, -1.65, 95% CI=-3.38, 0.08). By week 12, active TBS was associated with a significantly greater reduction in HAM-D score compared to sham (mean difference, -1.89, 95% CI=-3.75, -0.03), with response rates of 52% in the active group and 33% in the sham group. Linear mixed models analyzing HAM-D score did not show a statistically significant greater reduction in the active TBS group compared to the sham group at week 6 (Cohen's d=-0.36, 95% CI=-0.74, 0.01). CONCLUSIONS: The active TBS group did not have a statistically significant greater reduction in HAM-D scores compared to the sham group at week 6. By week 12, however, active TBS was superior to sham stimulation in reducing depressive symptoms in patients with late-life depression, suggesting TBS as a possible treatment option for this population.
Rovers JJE, van Eijndhoven PFP, Abbot C
… +19 more, Argyelan M, Bouckaert F, Brunoni AR, Espinoza RT, van Exel E, Gazdag G, van den Heuvel L, Kessler U, Loo C, McLoughlin D, Nordanskog P, Regenold WT, Sackeim H, Somers M, Takamiya A, Thirthalli J, van Waarde J, Tendolkar I, Dols A
Am J Psychiatry
· 2026 Jun · PMID 41807318
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OBJECTIVE: Electroconvulsive therapy (ECT) is a highly effective treatment for depression, yet relapse rates up to 50% within a year are reported. Studies have examined ECT, pharmacological, and nonpharmacological relaps...OBJECTIVE: Electroconvulsive therapy (ECT) is a highly effective treatment for depression, yet relapse rates up to 50% within a year are reported. Studies have examined ECT, pharmacological, and nonpharmacological relapse prevention strategies, and although current guidelines provide general recommendations, no consensus-based or operationalized guidance exists regarding optimal relapse prevention after successful ECT for major depressive disorder. The aims of this study were to identify relapse prevention strategies commonly implemented after ECT, to evaluate their perceived effectiveness among international ECT experts, and to establish consensus-based personalized clinical recommendations. METHODS: A multiround Delphi study was conducted with a global panel of 18 ECT experts. Consensus was defined as ≥80% agreement on Likert-scale responses. RESULTS: Consensus was reached on key clinical factors influencing relapse prevention, including treatment resistance, psychiatric comorbidities, and prior ECT response. An essential relapse prevention strategy, namely, pharmacotherapy with lithium and an antidepressant (a tricyclic antidepressant, venlafaxine, or a prior effective antidepressant), was endorsed for all patients. Continuation ECT by means of tapering, rather than abrupt cessation, was recommended for patients at high risk of relapse and with severe or psychotic depression. Psychotherapy was considered beneficial as an adjunctive rather than a standalone treatment. No consensus was reached on the role of repetitive transcranial magnetic stimulation, esketamine, or optimal treatment duration of relapse prevention beyond 6 months. CONCLUSIONS: This Delphi study provides expert-based guidance on relapse prevention following successful ECT for major depressive disorder. While pharmacotherapy and continuation ECT are core strategies, personalized adjustments based on clinical risk factors remain essential. Further empirical research is needed to refine guidelines and improve long-term outcomes.
Butelman ER, Huang Y, Goldstein RZ
… +1 more, Alia-Klein N
Am J Psychiatry
· 2026 May · PMID 41807315
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OBJECTIVE: Substance use disorders (SUDs) are associated with risk of psychiatric comorbidities, with inconsistent sex differences across studies. The objective of this study was to determine odds of psychiatric comorbid...OBJECTIVE: Substance use disorders (SUDs) are associated with risk of psychiatric comorbidities, with inconsistent sex differences across studies. The objective of this study was to determine odds of psychiatric comorbidities based on sex in persons with a primary diagnosis of opioid, alcohol, or cannabis dependence, using a national clinical dataset. METHODS: This was a cross-sectional study of data from state-funded and state-run mental health programs in 2022 (Mental Health Client-Level Data, from the U.S. Substance Abuse and Mental Health Services Administration). Data were obtained from adults (age ≥18 years) with a primary diagnosis of either opioid (N=28,808), alcohol (N=23,281), or cannabis dependence (N=5,961). Data from individuals with each SUD were examined for psychiatric comorbidity outcomes, based on secondary diagnoses of an anxiety disorder, bipolar disorder, a depressive disorder, schizophrenia or other psychotic disorder, or a trauma- and stressor-related disorder versus no comorbidity. Data were analyzed with multinomial logistic regressions, examining sex, race, ethnicity, and age as predictors. RESULTS: Males with a primary diagnosis of opioid, alcohol, or cannabis dependence had lower adjusted odds of anxiety, bipolar, depressive, and trauma- and stressor-related disorders compared to females. However, males with opioid or cannabis dependence had higher adjusted odds of schizophrenia or other psychotic disorders compared to females. Adjusted analyses also detected associations of race and ethnicity with specific comorbidities. CONCLUSIONS: In this recent national clinical dataset, sex-based differences were observed in specific psychiatric comorbidities for each of these three SUDs. Future studies should examine biopsychosocial mechanisms that underlie these differences, with the goal of improving personalized care.
Am J Psychiatry
· 2026 Apr · PMID 41776722
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OBJECTIVE: The authors compared the risk of mental disorders between patients with cannabis use disorder (CUD) and those with other substance use disorders (SUDs). METHODS: The TriNetX Research Network was queried to ide...OBJECTIVE: The authors compared the risk of mental disorders between patients with cannabis use disorder (CUD) and those with other substance use disorders (SUDs). METHODS: The TriNetX Research Network was queried to identify patients with SUDs and no preceding mental disorders and compare 1) adult patients with CUD only versus those with other SUDs, 2) pediatric patients with CUD only versus those with other SUDs, and 3) adult patients with CUD plus another SUD versus those with comorbid noncannabis SUDs. Propensity score matching was performed on demographic characteristics and 24 risk factors or comorbidities. Subsequent diagnosis of schizophrenia and other common mental disorders was assessed. RESULTS: Compared to adults with other SUDs, those with noncomorbid CUD (N=345,903 for both cohorts) had a lower risk of schizophrenia (0.34% vs. 0.42%; relative risk [RR]=0.81, 95% CI=0.75, 0.88), depression (1.35% vs. 1.74%; RR=0.78, 95% CI=0.75, 0.81), and psychotic disorders (0.36% vs. 0.52%; RR=0.68, 95% CI=0.63, 0.73). Compared to pediatric patients with other SUDs, those with CUD (N=24,793 for both cohorts) had a higher risk of schizophrenia (0.29% vs. 0.19%; RR=1.52, 95% CI=1.06, 2.19), depression (1.65% vs. 1.27%; RR=1.30, 95% CI=1.13, 1.51), and anxiety disorders (8.13% vs. 6.71%; RR=1.21, 95% CI=1.14, 1.29). Compared to adult patients with other SUDs, those with CUD and a comorbid SUD (N=203,916 for both cohorts) had a decreased risk of schizophrenia (1.94% vs. 2.25%; RR=0.86, 95% CI=0.83, 0.90), depression (3.98% vs. 5.67%; RR=0.70, 95% CI=0.68, 0.72), bipolar disorder (4.23% vs. 5.60%; RR=0.76, 95% CI=0.74, 0.78), and anxiety disorders (16.20% vs. 21.36%; RR=0.76, 95% CI=0.75, 0.77). CONCLUSIONS: CUD-associated mental health risks varied by age and comorbid SUDs, possibly due to earlier onset of mental disorders in cannabis users or age-related differences in CUD effects.