OBJECTIVES: To review the definitions of treatment-resistant mania (TRM) in the literature and propose criteria for an operationalized definition. METHODS: A systematic search of five databases (MEDLINE, EMBASE, PsychInfo, Cochrane Central, and CINAHL) and data extraction of eligible articles. RESULTS: In total, 47 articles addressing the concept of TRM were included, comprising 16 case reports, 11 case series, 3 randomized clinical trials, 8 open-label clinical trials, 1 experimental study, 7 narrative reviews, and 1 systematic review. While reviews discussed several challenges in defining TRM, definitions varied substantially based on different criteria for severity of mania, duration of mania, and use of specific therapeutic agents with minimal dosages and duration of treatment. Only a handful of the reviewed articles operationalized these criteria. CONCLUSION: While the concept of TRM has been discussed in the literature for over three decades, we could not find an agreed-upon operationalized definition based on specific criteria. We propose and discuss a possible definition that could be used by clinicians to guide their practice and by researchers to assess the prevalence of TRM and develop and test interventions targeting TRM.

• Klíčová slova
• bipolar disorder, clinical trials, mania, pharmacotherapy, psychopharmacology, systematic review, treatment refractory, treatment resistance,
• MeSH
• bipolární porucha diagnóza   farmakoterapie   MeSH
• dospělí MeSH
• lidé MeSH
• mánie * farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• systematický přehled MeSH

Repetitive transcranial magnetic stimulation (rTMS) is an effective treatment for depressive disorder, with outcomes approaching 45-55% response and 30-40% remission. Eligible predictors of treatment outcome, however, are still lacking. Few studies have investigated quantitative electroencephalography (QEEG) parameters as predictors of rTMS treatment outcome and none of them have addressed the source localization techniques to predict the response to low-frequency rTMS (LF rTMS). We investigated electrophysiological differences based on scalp EEG data and inverse solution method, exact low-resolution brain electromagnetic tomography (eLORETA), between responders and non-responders to LF rTMS in resting brain activity recorded prior to the treatment. Twenty-five unmedicated depressive patients (mean age of 45.7 years, 20 females) received a 4-week treatment of LF rTMS (1 Hz; 20 sessions per 600 pulses; 100% of the motor threshold) over the right dorsolateral prefrontal cortex. Comparisons between responders (≥50% reduction in Montgomery-Åsberg Depression Rating Scale score) and non-responders were made at baseline for measures of eLORETA current density, spectral absolute power, and inter-hemispheric and intra-hemispheric EEG asymmetry. Responders were found to have lower current source densities in the alpha-2 and beta-1 frequency bands bilaterally (with predominance on the left side) in the inferior, medial, and middle frontal gyrus, precentral gyrus, cingulate gyrus, anterior cingulate, and insula. The most pronounced difference was found in the left middle frontal gyrus for alpha-2 and beta-1 bands (p < 0.05). Using a spectral absolute power analysis, we found a negative correlation between the absolute power in beta and theta frequency bands on the left frontal electrode F7 and the change in depressive symptomatology. None of the selected asymmetries significantly differentiated responders from non-responders in any frequency band. Pre-treatment reduction of alpha-2 and beta-1 sources, but not QEEG asymmetry, was found in patients with major depressive disorder who responded to LF rTMS treatment. Prospective trials with larger groups of subjects are needed to further validate these findings.

• Klíčová slova
• EEG asymmetry, LORETA, major depressive disorder, quantitative electroencephalography, repetitive transcranial magnetic stimulation,
• Publikační typ
• časopisecké články MeSH

OBJECTIVE: Transcranial direct-current stimulation (tDCS), a relatively new neuromodulation approach, provides some evidence of an antidepressant effect. This randomized, 4-week, double-blind study with 8-week, open-label, follow-up compared the efficacy and tolerability of left anodal tDCS with venlafaxine ER (VNF) in the treatment of depression and prevention of early relapse. METHODS: Subjects (n = 57) received tDCS (2 mA, 20 sessions, 30 mins) plus placebo (n = 29) or VNF plus sham tDCS (n = 28). Responders to both interventions entered the open-label follow-up. The primary outcome was score change in the Montgomery-Åsberg Depression Rating Scale (MADRS) at week 4 of the study. Secondary outcomes were response, remission, dropout rates and relapse rates within the follow-up. UNLABELLED: The mean change in the MADRS score from baseline to week for patients treated with tDCS was 7.69 (95% CI, 5.09-10.29) points and 9.64 (95% CI, 6.20-13.09) points for patients from the VNF group, a nonsignificant difference (1.95, 95% CI -2.25-6.16; t (55) = 0.93, p= 0.36, Cohen´s d = 0.24). There were no significant between-group differences in the MADRS scores from baseline to endpoint (intention-to-treat analysis). The response/remission rate for tDCS (24%/17%) and VNF (43%/32%) as well as the dropout rate (tDCS/VNF; 6/6) did not differ significantly between groups. In the follow-up, relapse (tDCS/VNF; 1/2) and dropout (tDCS/VNF; 2/3) rates were low and comparable. LIMITATIONS: A relatively small sample size and short duration of the antidepressant treatment; no placebo arm. CONCLUSION: Overall, this study found a similar efficacy of tDCS and VNF in the acute treatment of depression and prevention of early relapse. The real clinical usefulness of tDCS and its optimal parameters in the treatment of depression should be further validated.

• Klíčová slova
• depression, tDCS, transcranial direct-current stimulation, treatment, venlafaxine ER,
• Publikační typ
• časopisecké články MeSH