Although repetitive transcranial magnetic stimulation (rTMS) is an effective and commonly used treatment option for treatment-resistant depression, its cost-effectiveness remains much less studied. In particular, the comparative cost-effectiveness of rTMS and other treatment options, such as antidepressant medication, has not been investigated.
An economic evaluation with 12 months follow-up was conducted in the Dutch care setting as part of a pragmatic multicenter randomized controlled trial, in which patients with treatment-resistant depression were randomized to treatment with rTMS or treatment with the next pharmacological step according to the treatment algorithm. Missing data were handled with single imputations using predictive mean matching (PMM) nested in bootstraps. Incremental cost-effectiveness and cost-utility ratios (ICERs/ICURs) were calculated, as well as cost-effectiveness planes and cost-effectiveness acceptability curves (CEACs).
Higher QALYs, response, and remission rates were found for lower costs when comparing the rTMS group to the medication group. After 12 months, QALYs were 0.618 in the rTMS group and 0.545 in the medication group. The response was 27.1% and 24.4% and remission was 25.0% and 17.1%, respectively. Incremental costs for rTMS were −€2.280, resulting in a dominant ICUR for QALYs and ICER for response and remission.
rTMS appears to be a cost-effective treatment option for treatment-resistant depression when compared to the next pharmacological treatment step. The results support the implementation of rTMS as a step in the treatment algorithm for depression.
The trial is registered within the Netherlands Trial Register (code: NL7628, date: March 29, 2019)
There is growing interest in the use of psychedelic-assisted therapy (PAT) for major depressive disorder (MDD), including treatment-resistant depression. We used randomized controlled trial (RCT) data to compare summary estimates of change in depression ratings with PAT versus comparator treatments in MDD. We also compared response and remission rates, and adverse effects.
We searched MEDLINE, EMBASE, Cochrane Central Register for Controlled Trials (CENTRAL), and SCOPUS from inception till April 2024. Our primary efficacy outcome was 1-week (or nearest) between-group change in depression ratings. Secondary efficacy outcomes were changes in depression ratings at days 2, 14, and 42 (or nearest) and study-defined response and remission rates at week 1 (or nearest). Safety outcomes were reported adverse effects. We pooled outcomes in random-effects meta-analyses using standardized mean difference (SMD; Hedges g) for continuous outcomes and risk ratio (RR) for categorical outcomes.
We found 6 eligible RCTs (pooled N = 427), all on psilocybin. The pooled SMD for 1-week between-group change in depression ratings was −0.72 [95% CI, −0.95 to −0.49; I2 = 17%; 5 RCTs; n = 403], favouring PAT; results were similar at days 2, 14, and 42. The response [RR = 3.42; 95% CI, 2.35–4.97; I2 = 0%; 4 RCTs; n = 373] and remission [RR = 3.66; 95% CI, 2.26–5.92; I2 = 0%; 4 RCTs; n = 373] rates also favored PAT. The PAT group had a small but significantly increased risk of developing any adverse event [RR = 1.20; 95% CI, 1.01–1.42; I2 = 43%; 4 RCTs; n = 373] and a significantly higher risk of experiencing headache [RR = 1.78; 95% CI, 1.10–2.86; I2 = 52%; 4 RCTs; n = 373] and dizziness [RR = 6.52; 95% CI, 1.19–35.87; I2 = 0%; 3 RCTs; n = 269]. Low heterogeneity characterized most analyses and findings were similar in sensitivity analyses.
Antidepressant effects of psilocybin-assisted therapy are superior (with at least medium effect sizes) to comparator interventions for at least up to 6 weeks postintervention.
Egsgaard et al. (2024) highlight the temporal patterns of postpartum depression (PPD) risk in twin parents versus singleton parents. However, additional factors such as social support systems, delivery mode, and cultural influences require exploration.
To discuss the role of structured postpartum care, cesarean sections, and mother-infant bonding in moderating PPD risk, especially within cultural contexts.
These factors may explain the gender-specific temporal patterns observed by Egsgaard et al. Future research should integrate sociocultural and clinical variables to inform interventions for twin parents at risk of PPD.
Mood, activity, and instability in symptomatology hold significant roles in bipolar disorder (BD) and unipolar disorder (UD). The objectives were to examine disparities in these symptoms among patients with BD and UD.
Data from two studies including patients with BD and UD, respectively, were combined for exploratory analyses. Patients provided daily smartphone-based evaluations of mood and activity/energy for a 6-month period. A total of 47 patients with BD and 59 patients with UD were included in the analyses. The dataset contains more than 13,000 patient-reported evaluations of mood and activity. Daily mood and activity instability measures were calculated using the root squared successive difference method.
In linear mixed effect regression models adjusted for age, sex, and work status, there were statistically significant lower levels of activity in patients with BD as compared with patients with UD overall, during euthymic states and during depressive states (B: −0.61, 95% CI: −0.98; −0.24, p = 0.001). There were no statistically significant differences in mood instability and activity instability between patients with BD and patients with UD overall, during euthymic states and during depressive states, when accounting for multiple testing (p > 0.012).
Analyses were exploratory and post hoc. Findings should be interpreted with caution. The sample size was modest.
Patients with BD presented with lower level of activity as compared with patients with UD. There were no differences in mood and activity instability between these groups. Future studies including larger sample sizes should investigate differences between BD and UD.
Trial Registration: ClinicalTrials.gov identifier: NCT03033420
Antipsychotics are recommended after first-episode psychosis. Knowledge on the current use patterns in real-world settings is thus important to inform clinical practice. We aimed to describe antipsychotic initiation during 1 year after first-episode psychosis and its associated factors.
Population-based cohort study using linked nationwide health and population registers from Norway. The study population comprised 8052 persons aged 16–45 years with first-episode psychosis diagnosed in secondary care (ICD-10 F20, F22–F29) in the period 2011–2019. Initiation of antipsychotic use was defined as being dispensed antipsychotics (ATC N05A, excl. lithium) at least once from −90 to +365 days from secondary care diagnosis of first-episode psychosis. Antipsychotic polypharmacy during follow-up was defined as having at least 90 days with overlapping drug use periods modeled using the Prescriptions to Drug Use Periods method. Adjusted risk ratios (aRRs) with 95% confidence intervals (CIs) for the association between socioeconomic and clinical factors and initiation of antipsychotic use were calculated using modified Poisson regression.
In total, 4413 persons (54.8%) initiated antipsychotic use after first-episode psychosis with proportions ranging from 45.5% in 2012 to 62.1% in 2019. Oral formulations of olanzapine (34.9%), quetiapine (21.2%), and aripiprazole (11.6%) were most common at initiation, whereas long-acting injectables (LAIs) and clozapine were rarely used. Among the initiators, 13.8% started a polypharmacy period lasting more than 90 days. Factors associated with antipsychotic initiation were lower age (aRR 1.14, 95% CI 1.08–1.21; 26–35 years vs. 36–45 years), higher education (1.11, 1.05–1.18), being employed (1.04, 1.00–1.09), being hospitalized (1.13, 1.09–1.18), being diagnosed late in the study period (1.16, 1.11–1.22; 2017–2019 vs. 2011–2013), or with previously diagnosed bipolar disorder, depression, or anxiety disorders.
The antipsychotic use pattern is largely within the current clinical guideline. Primary non-compliance and disease severity may explain the socioeconomic and clinical differences related to initiation of antipsychotic use.
Repetitive transcranial magnetic stimulation (rTMS) is effective for treatment-resistant depression (TRD). Optimal rTMS parameters remain unclear, especially whether number of sessions or amount of pulses contribute more to treatment outcome. We hypothesize that treatment outcome depends on the number of sessions rather than on the amount of pulses.
We searched databases for randomized clinical trials (RCTs) on high-frequent (HF) or low-frequent (LF)-rTMS targeting the left or right DLPFC for TRD. Treatment efficacy was measured using standardized mean difference (SMD), calculated from pre- and post-treatment depression scores. Meta-regressions were used to explore linear associations between SMD and rTMS pulses, pulses/session and sessions for HF and LF-rTMS, separately for active and sham-rTMS. If these variables showed no linear association with SMD, we divided the data into quartiles and explored subgroup SMDs.
Eighty-seven RCTs were included: 67 studied HF-rTMS, eleven studied LF-rTMS, and nine studied both. No linear association was found between SMD and amount of pulses or pulses/session for HF and LF-rTMS. Subgroup analyses showed the largest SMDs for 1200–1500 HF-pulses/session and 360–450 LF-pulses/session. The number of sessions was significantly associated with SMD for active HF (β = 0.09, p < 0.05) and LF-rTMS (β = 0.06, p < 0.01). Thirty was the maximal number of sessions, in the included RCTs.
More rTMS sessions, but not more pulses, were associated with improved treatment outcome, in both HF and LF-rTMS. Our findings suggest that 1200–1500 HF-pulses/session and 360–450 LF-pulses/session are already sufficient, and that a treatment course should consist of least 30 sessions for higher chance of response.
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