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Introduction: Proof-of-principle human studies suggest that transcranial direct current stimulation (tDCS) over the dorsolateral prefrontal cortex (DLPFC) may improve depression severity. This open-label multicenter study tested remotely supervised multichannel tDCS delivered at home in patients (N=35) with major depressive disorder (MDD). The primary aim was to assess the feasibility and safety of our protocol. As an exploratory aim, we evaluated therapeutic efficacy: the primary efficacy measure was the median percent change from baseline to the end of the 4-week post-treatment follow-up period in the observer-rated Montgomery-Asberg Depression Mood Rating Scale (MADRS). Methods: Participants received 37 at-home stimulation sessions (30 minutes each) of specifically designed multichannel tDCS targeting the left DLPFC administered over eight weeks (4 weeks of daily treatments plus 4 weeks of taper), with a follow-up period of 4 weeks following the final stimulation session. The stimulation montage (electrode positions and currents) was optimized by employing computational models of the electric field generated by multichannel tDCS using available structural data from a similar population (group optimization). Conducted entirely remotely, the study employed the MADRS for assessment at baseline, at weeks 4 and 8 during treatment, and at 4-week follow-up visits. Results: 34 patients (85.3% women) with a mean age of 59 years, a diagnosis of MDD according to DSM-5 criteria, and a MADRS score ≥20 at the time of study enrolment completed all study visits. At baseline, the mean time since MDD diagnosis was 24.0 (SD 19.1) months. Concerning compliance, 85% of the participants (n=29) completed the complete course of 37 stimulation sessions at home, while 97% completed at least 36 sessions. No detrimental effects were observed, including suicidal ideation and/or behavior. The study observed a median MADRS score reduction of 64.5% (48.6, 72.4) 4 weeks post-treatment (Hedge's g = -3.1). We observed a response rate (≥ 50% improvement in MADRS scores) of 72.7% (n=24) from baseline to the last visit 4 weeks post-treatment. Secondary measures reflected similar improvements. Conclusions: These results suggest that remotely supervised and supported multichannel home-based tDCS is safe and feasible, and antidepressant efficacy motivates further appropriately controlled clinical studies.
RESUMO
OBJECTIVE: A 5-h phase advance model of insomnia was used to evaluate the efficacy of lorediplon, a new non-benzodiazepine hypnotic. METHODS: Thirty-five male, healthy subjects were included in a five-way randomized cross-over study. During each of the periods, sleep was recorded, and residual effects were measured. All subjects received lorediplon 1, 5, and 10 mg, placebo, and zolpidem 10 mg (i.e., active control). RESULTS: Polysomnographic evaluation revealed that lorediplon (5 and 10 mg) significantly decreased wake after sleep onset (WASO) and increased total sleep time. Analysis by quarters of the night showed a progressive increasing effectiveness of lorediplon 10 mg across the first three quarters. Lorediplon increased non-rapid eye movement slow wave sleep and stage N2 sleep in the second and third quarters. The magnitude of these effects was dose related, with minimal effects seen with 1 mg. No residual effects were observed 13 h post dose. CONCLUSIONS: Lorediplon demonstrated a dose-dependent improvement in sleep, whereas zolpidem showed a more sustained WASO effect. No next-day hangover effects were observed. These sleep effects are also consistent with the pharmacokinetic profile of lorediplon. These results warrant clinical trials in patients with insomnia.
