Asberg Depression Rating Scale Scores Research Articles

Home-based transcranial direct current stimulation in bipolar depression: an open-label treatment study of clinical outcomes, acceptability and adverse events

BackgroundCurrent treatments for bipolar depression have limited effectiveness, tolerability and acceptability. Transcranial direct current stimulation (tDCS) is a novel non-invasive brain stimulation method that has demonstrated treatment efficacy for major depressive episodes. tDCS is portable, safe, and individuals like having sessions at home. We developed a home-based protocol with real-time remote supervision. In the present study, we have examined the clinical outcomes, acceptability and feasibility of home-based tDCS treatment in bipolar depression.ResultsParticipants were 44 individuals with bipolar disorder (31 women), mean age 47.27 ± 12.89 years, in current depressive episode of at least moderate severity (mean Montgomery Asberg Depression Rating Scale (MADRS) score 24.59 ± 2.64). tDCS was provided in bilateral frontal montage, F3 anode, F4 cathode, 2 mA, for 30 min, in a 6-week trial, for total 21 sessions, a follow up visit was conducted 5 months from baseline. Participants maintained their current treatment (psychotherapy, antidepressant or mood stabilising medication) or maintained being medication-free. A research team member was present by video conference at each session. 93.2% participants (n = 41) completed the 6-week treatment and 72.7% of participants (n = 32) completed the 5 month follow up. There was a significant improvement in depressive symptoms following treatment (mean MADRS 8.77 ± 5.37) which was maintained at the 5 month follow up (mean MADRS 10.86 ± 6.90), rate of clinical response was 77.3% (MADRS improvement of 50% or greater from baseline), and rate of clinical remission was 47.7% (MADRS rating of 9 or less). Acceptability was endorsed as “very acceptable” or “quite acceptable” by all participants. No participants developed mania or hypomania.ConclusionsIn summary, home-based tDCS with real-time supervision was associated with significant clinical improvements and high acceptability in bipolar depression. Due to the open-label design, efficacy findings are preliminary.Trial registrationClinicalTrials.gov number NCT05436613 registered on 23 June 2022 https//www.clinicaltrials.gov/study/NCT05436613.

Extended-release ketamine tablets for treatment-resistant depression: a randomized placebo-controlled phase 2 trial

Ketamine has rapid-onset antidepressant activity in patients with treatment-resistant major depression (TRD). The safety and tolerability of racemic ketamine may be improved if given orally, as an extended-release tablet (R-107), compared with other routes of administration. In this phase 2 multicenter clinical trial, male and female adult patients with TRD and Montgomery–Asberg Depression Rating Scale (MADRS) scores ≥20 received open-label R-107 tablets 120 mg per day for 5 days and were assessed on day 8 (enrichment phase). On day 8, responders (MADRS scores ≤12 and reduction ≥50%) were randomized on a 1:1:1:1:1 basis to receive double-blind R-107 doses of 30, 60, 120 or 180 mg, or placebo, twice weekly for a further 12 weeks. Nonresponders on day 8 exited the study. The primary endpoint was least square mean change in MADRS for each active treatment compared with placebo at 13 weeks, starting with the 180 mg dose, using a fixed sequence step-down closed test procedure. Between May 2019 and August 2021, 329 individuals were screened for eligibility, 231 entered the open-label enrichment phase (days 1–8) and 168 responders were randomized to double-blind treatment. The primary objective was met; the least square mean difference of MADRS score for the 180 mg tablet group and placebo was −6.1 (95% confidence interval 1.0 to 11.16, P = 0.019) at 13 weeks. Relapse rates during double-blind treatment showed a dose response from 70.6% for placebo to 42.9% for 180 mg. Tolerability was excellent, with no changes in blood pressure, minimal reports of sedation and minimal dissociation. The most common adverse events were headache, dizziness and anxiety. During the randomized phase of the study, most patient dosing occurred at home. R-107 tablets were effective, safe and well tolerated in a patient population with TRD, enriched for initial response to R-107 tablets. ClinicalTrials.gov registration: ACTRN12618001042235.

Structured physical exercise for bipolar depression: an open-label, proof-of concept study

BackgroundPhysical exercise (PE) is a recommended lifestyle intervention for different mental disorders and has shown specific positive therapeutic effects in unipolar depressive disorder. Considering the similar symptomatology of the depressive phase in patients with bipolar disorder (BD) and unipolar depressive disorder, it is reasonable to suggest that PE may also be beneficial for bipolar depression. However, there is an absence of studies evaluating the antidepressant effect of a structured PE intervention in BD.MethodsThis is an open-label, single-arm study trial. Fifteen patients with a diagnosis of BD Type I or Type II, presenting a depressive episode were included in the study. After physical and functional evaluation, patients participated in supervised training sessions with aerobics followed by strength exercises, three times per week, for 12 weeks (36 training sessions). Depressive and manic symptoms were assessed at baseline and 2, 4, 8, and 12 weeks. Additionally, quality of Life and functioning were assessed at baseline and 4, 8, and 12 weeks). Finally, we tested cardiorespiratory fitness, muscle strength and body composition at baseline and week-12.ResultsThe mean (± SD) Montgomery Asberg Depression Rating Scale (MADRS) score at baseline was 23.6 ± 8.3 points and after 12 weeks of PE the mean score was 10.2 ± 4.8 points. Nine patients (82%) presented an antidepressant response defined as a reduction of more than 50% of depressive symptoms at week 12 with five of those patients (45%) presenting criteria for full remission. A large and significant Cohen’s D Effect Size (pre-post) was verified for MADRS reduction [1.98 (95% Confidence interval = 0.88 to 3.08)]. We did not detect a significant change in manic symptoms, functioning, and quality of life during the 12-week follow-up. At week-12, all patients increased their muscular strength (one repetition maximal test − 1RM) and reduced the percentage of body fat (spectral bioelectrical impedance analysis).ConclusionsThis study, using rigorous criteria and a structured intervention, provides valid pilot data, showing the feasibility of a structured PE intervention for the treatment of depressive symptoms in BD, and suggesting a potential adjunctive antidepressant effect. Moreover, PE showed a positive impact on muscle strength and body composition. This should be further verified by randomized controlled studies.

Effects of 4G-beta-D-Galactosylsucrose in patients with depression: A randomized, double-blinded, placebo-controlled, parallel-group comparative study

Advances in genetic research on microbiome have led to several trials on the effectiveness of synbiotics or probiotics in patients with depression; however, none have evaluated the efficacy of prebiotics. 4G-beta-D-Galactosylsucrose (Lactosucrose, LS) is selectively assimilated by Bifidobacterium as a prebiotic and improves microbiome diversity. However, as it is not clear if LS consumption can improve symptoms of depression, we investigated whether LS intake can improve depressive symptoms, quality of life (QOL), and self-efficacy by conducting a single cite, double-blinded, randomized controlled trial in 20 outpatients with depressive episodes (F32, ICD-10) for 24 weeks. Participants (age range, 36–72 years) were randomized to the LS (n = 9) or placebo groups (n = 11). Primary outcome was improvement in total Montgomery Asberg Depression Rating Scale (MADRS) score, and the secondary outcomes were MADRS subscores, global self-efficacy scale (GSES) score, World Health Organization QOL (WHO/QOL-26) score, and 16S rRNA analysis of the fecal microbiome. LS consumption did not significantly improve total MADRS scores (−2 (−16 to 16) vs 0 (−6 to 10), p = 0.552), but GSES tended to improve in the LS group (2.00 ± 4.24 vs −1.36 ± 4.15, p = 0.091) with a large effect size (Cohen's d = 0.802). Sequencing of 16S rRNA revealed individual-level differences in microbiome diversity changes due to the intervention. Thus, we show that LS intake can improve self-efficacy, but not depressive symptoms, even in a small sample. Additional studies that also regulate diet and ensure adherence may help determine a correlation between depression and the gut microbiome.

Comparative change in P300 indices following antidepressant treatment in patients with major depressive disorder.

Cognitive disturbance is seen in patients with major depressive disorder (MDD). Event-related potential can assist in measuring the neurocognition, and P300 is the most commonly used noninvasive electrophysiological parameter for measuring cognition. The aim of this study is to assess the baseline P300 parameters, Hamilton Rating Scale for Depression (HAM-D), and Montgomery-Asberg Depression Rating Scale (MADRS) scores and compare them with their levels after 3 months of antidepressant therapy. a longitudinal study was done on total 24 diagnosed cases of major depression who underwent P300, HAM-D, and MADRS assessment in the gap of 3 months before and after starting antidepressant therapy. Newly diagnosed cases of MDD patients were assessed using HAM-D and MADRS for severity rating. P300 assessment was also carried out with auditory oddball paradigm using Nihon Kohden NCV-SMG-EP system. The assessments were repeated after 3 months of antidepressant treatment. The Wilcoxon test was used to compare mean values of P300 parameters, HAM-D, and MADRS score. Spearman correlation analysis was done to study the association between various parameters of P300 and HAM-D and MADRS score before and after treatment of 3 months of antidepressant therapy. Significant difference is shown in various parameters P300 except for A11-P300 amplitude and A31-P300 amplitude. A significant difference was shown in HAM-D and MADRS scores. No significant correlation was seen between other P300 parameters and HAM-D and MADRS scale before as well as after antidepressant therapy. P300 may be used as an index to evaluate the response to antidepressant treatment in patients with MDD.

Intranasal Ketamine for Depression in Adults: A Systematic Review and Meta-Analysis of Randomized, Double-Blind, Placebo-Controlled Trials.

BackgroundThere is growing interest in glutamatergic agents as a treatment for depression, especially intranasal ketamine, which has become a hot topic in recent years. We aim to assess the efficacy and safety of intranasal ketamine in the treatment of major depressive disorder (MDD), especially treatment-resistant depression (TRD).MethodsWe searched Medline, EMBASE, and the Cochrane Library until April 1, 2020 to identify double-blind, randomized controlled trials with allocation concealment evaluating intranasal ketamine in major depressive episodes. Clinical remission, response, and depressive symptoms were extracted by two independent raters. The outcome measures were Montgomery–Asberg Depression Rating Scale (MADRS) score improved from baseline, clinical response and remission, dissociative symptoms, and common adverse events. The analyses employed a random-effects model.ResultsData were synthesized from five randomized controlled trials (RCTs) employing an intranasal esketamine and one RCT employing intranasal ketamine, representing 840 subjects in parallel arms, and 18 subjects in cross-over designs (n = 858 with MDD, n = 792 with TRD). The weighted mean difference of MADRS score was observed to decrease by 6.16 (95% CI 4.44–7.88) in 2–4 h, 9.96 (95% CI 8.97–10.95) in 24 h, and 4.09 (95% CI 2.18–6.00) in 28 day. The pooled relative risk (RR) was 3.55 (95% CI 1.5–8.38, z = 2.89, and p < 0.001) for clinical remission and 3.22 (95% CI 1.85–5.61, z = 4.14, and p < 0.001) for clinical response at 24 h, while the pooled RR was 1.7 (95% CI 1.28–2.24, z = 3.72, and p < 0.001) for clinical remission and 1.48 (95% CI 1.17–1.86, z = 3.28, and p < 0.001) for clinical response at 28 day. Intranasal ketamine was associated with the occurrence of transient dissociative symptoms and common adverse events, but no persistent psychoses or affective switches.ConclusionOur meta-analysis suggests that repeated intranasal ketamine conducted a fast-onset antidepression effect in unipolar depression, while the mild and transient adverse effects were acceptable.Systematic Review RegistrationPROSPERO, CRD42020196856.

Relationship between childhood physical abuse and clinical severity of treatment-resistant depression in a geriatric population.

IntroductionWe assessed the correlation between childhood maltreatment (CM) and severity of depression in an elderly unipolar Treatment-Resistant Depression (TRD) sample.MethodsPatients were enrolled from a longitudinal cohort (FACE-DR) of the French Network of Expert TRD Centres.ResultsOur sample included 96 patients (33% of the overall cohort) aged 60 years or above, with a mean age of 67.2 (SD = 5.7). The majority of the patients were female (62.5%). The Montgomery and Asberg Depression Rating Scale (MADRS) and Quick Inventory Depression Scale-Self Report (QIDS-SR) mean scores were high, 28.2 (SD = 7.49) [MADRS score range: 0–60; moderate severity≥20, high severity≥35] and 16.5 (SD = 4.94) [IDS-SR score range: 0–27; moderate severity≥11, high severity≥16], respectively. Mean self-esteem scores were 22.47 (SD = 6.26) [range 0–30]. In an age- and sex-adjusted model, we found a positive correlation between childhood trauma (CTQ scores) and depressive symptom severity [MADRS (β = 0.274; p = 0.07) and QIDS-SR (β = 0.302; p = 0.005) scores]. We detected a statistically significant correlation between physical abuse and depressive symptom severity [MADRS (β = 0.304; p = 0.03) and QIDS-SR (β = 0.362; p = 0.005) scores]. We did not observe any significant correlation between other types of trauma and depressive symptom severity. We showed that self-esteem (Rosenberg scale) mediated the effect of physical abuse (PA) on the intensity of depressive symptoms [MADRS: b = 0.318, 95% BCa C.I. [0.07, 0.62]; QIDS-SR: b = 0.177, 95% BCa C.I. [0.04, 0.37]]. Preacher & Kelly’s Kappa Squared values of 19.1% (k2 = 0.191) and 16% (k2 = 0.16), respectively for the two scales, indicate a moderate effect.ConclusionTo our knowledge, this is the first study conducted in a geriatric TRD population documenting an association between childhood trauma (mainly relating to PA) and the intensity of depressive symptoms.

Assessment of cognitive function following a course of electroconvulsive therapy

IntroductionECT is a potentially life-saving treatment for patients with severe or treatment resistant depression. Cognitive function disturbances following ECT are generally transient, but could be of longer duration in some casesObjectivesTo assess the cognitive side effects in patients with affective disorders treated with a course of electroconvulsive therapy (ECT).MethodsCognitive functions of patients who undergo ECT was assessed prior to start of treatment, midway of the course of treatment and after end of the course of treatment using Montreal Cognitive Assessment (MoCA). We did a retrospective analysis of MoCA scores of 15 patients who received bilateral ECT in 2017-2018. In order to assess the efficacy of ECT in the treatment of their illness, we did a retrospective analysis of Montgomery Asberg Depression Rating Scale (MADRS) scores of 18 patients who received bilateral ECT in 2017-2018ResultsOnly 7% of the patients who underwent ECT in our sample did have significant cognitive decline as per their MoCA scores. 28% of patients achieved complete remission in their depressive symptomes. 22% of patients continued on maintenance treatment. 95% of patients showed significant improvement in their symptoms following treatment with ECT where there symptoms reduced to either mild or minimal depressive symptoms.ConclusionsCognitive side effect was not a significant side effect in our sample of patients. We did see an improvement in cognitive function in a significant number of the sample of patients as they progressed with treatment, which coincided with improvement in their affective symptoms.

Depressive Symptom Trajectories Associated With Standard and Accelerated rTMS

Abstract Background To determine if an accelerated rTMS protocol results in distinct depressive symptom response trajectories, compared to a standard rTMS protocol. We also sought to validate previous analyses that identified distinct depressive symptom response trajectories with rTMS treatment using an external dataset. Method Data from two recent clinical trials comparing accelerated rTMS protocol delivered to the left dorsolateral prefrontal cortex (DLPFC) with standard once-daily rTMS protocol were used to identify depressive symptom response trajectories. The accelerated protocol in Trial 1 was conventional 10-Hz rTMS, while Trial 2 employed intermittent theta burst stimulation (iTBS). Participants were adult outpatients (18–70 years old) with bipolar or unipolar depression and moderate-severe depression (Montgomery Asberg Depression Rating Scale score >19) who had failed to respond to adequate courses of two different antidepressants. We used group-based trajectory modeling to identify MADRS response trajectories, and regression techniques adjusting for baseline depressive symptom severity to determine the association between treatment protocol and depressive symptom response trajectory. Results Treatment outcomes of 189 participants were analysed. We identified four distinct response trajectories: “nonresponse” (N = 59; 30.7%), “minimal response” (N = 65; 34.1%), “higher symptoms, response” (N = 26; 14.6%), “lower symptoms, response” (N = 39; 20.6%). We failed to find an association between rTMS protocol (accelerated vs standard) with depressive symptom response trajectory even after adjusting for baseline depressive symptom severity. Conclusion The accelerated rTMS protocol in this study did not impact depressive symptom response trajectories. This work provides further confirmatory evidence that there are distinct depressive symptom response trajectories with rTMS delivered to the left DLPFC. Australian new zealand clinical trials registry ACTRN12616000443493 and ACTRN12613000044729.

Depressive symptom trajectories associated with standard and accelerated rTMS

BackgroundTo determine if an accelerated rTMS protocol results in distinct depressive symptom response trajectories, compared to a standard rTMS protocol. We also sought to validate previous analyses that identified distinct depressive symptom response trajectories with rTMS treatment using an external dataset. MethodData from two recent clinical trials comparing accelerated rTMS protocol delivered to the left dorsolateral prefrontal cortex (DLPFC) with standard once-daily rTMS protocol were used to identify depressive symptom response trajectories. The accelerated protocol in Trial 1 was conventional 10-Hz rTMS, while Trial 2 employed intermittent theta burst stimulation (iTBS). Participants were adult outpatients (18–70 years old) with bipolar or unipolar depression and moderate-severe depression (Montgomery Asberg Depression Rating Scale score >19) who had failed to respond to adequate courses of two different antidepressants. We used group-based trajectory modeling to identify MADRS response trajectories, and regression techniques adjusting for baseline depressive symptom severity to determine the association between treatment protocol and depressive symptom response trajectory. ResultsTreatment outcomes of 189 participants were analysed. We identified four distinct response trajectories: “nonresponse” (N = 59; 30.7%), “minimal response” (N = 65; 34.1%), “higher symptoms, response” (N = 26; 14.6%), “lower symptoms, response” (N = 39; 20.6%). We failed to find an association between rTMS protocol (accelerated vs standard) with depressive symptom response trajectory even after adjusting for baseline depressive symptom severity. ConclusionThe accelerated rTMS protocol in this study did not impact depressive symptom response trajectories. This work provides further confirmatory evidence that there are distinct depressive symptom response trajectories with rTMS delivered to the left DLPFC. Australian new zealand clinical trials registryACTRN12616000443493 and ACTRN12613000044729.

Regional homogeneity and functional connectivity analysis of resting-state magnetic resonance in patients with bipolar II disorder.

To explore the characteristics of local brain activity in patients with bipolar depression and its correlation with clinical features.In accord with the diagnostic and statistical manual of mental disorders-IV of bipolar disorder, 21 patients were enrolled while 21 healthy controls were matched with similar gender, age, level of educations. A 3.0T GE magnetic resonance scanner was used to collect the imaging data, and a 2-sample t test was performed. Regional homogeneity (ReHo) method was used to estimate regional activation patterns through indices of localized concordance. ReHo values were compared between groups. Seed-based correlation analysis was used to analyze functional connections.In the patients’ group, ReHo (regional homogeneity) values of resting state functional magnetic resonance imaging data on the right cerebellum 4 and 5 area, cerebellar vermis 6 area, left insula were positively correlated with Hamilton depression scale (HAMD) scores. ReHo values on the left of the triangle of inferior frontal gyrus, right inferior frontal gyrus of orbital region showed negative correlation with HAMD scores. The value of ReHo in the patients’ group was positively correlated with the patients’ Hamilton anxiety scale score in the right fusiform gyrus, and negative correlation was found in the left insula. The ReHo value of the patients’ group was negatively correlated with the patients’ Montgomery Asberg depression rating scale score in regions of the midbrain. The value of ReHo in patients’ group was significantly reduced in the right central front.The depression and anxiety severity of bipolar depression patients may be associated with the consistency activity of left insula, right cerebellum, and cerebellar vermis related area, fusiform gyrus. In addition, the ReHo of the midbrain neurons activity may be associated with depression level of patients with bipolar II disorder.

Improvement after two sessions of electroconvulsive therapy predicts final remission in in-patients with major depression.

ObjectiveTo investigate whether early improvement, measured after two electroconvulsive therapy (ECT) sessions, is a good predictor of eventual remission in severely depressed in‐patients receiving ECT.MethodA prospective cohort study was performed that included 89 major depressive disorder in‐patients treated with bilateral ECT. Sensitivity, specificity, and predictive values were computed for various definitions of early improvement (15%, 20%, 25%, and 30% reduction on the Montgomery Asberg depression rating scale (MADRS) score) after 1 week (i.e. two sessions) of ECT regarding prediction of remission (final MADRS score ≤ 9).ResultsA 15% reduction in MADRS score appeared to be the best definition of early improvement, with modest sensitivity (51%) and relatively good specificity (79%). Kaplan–Meier analysis showed a more than 2‐week shorter time to remission in patients with early improvement compared with patients lacking early improvement.ConclusionEarly improvement during an ECT course may be assessed after two ECT sessions. Such improvement, defined as a 15% reduction in the MADRS score, is a moderately sensitive predictor for eventual remission in an in‐patient population with severe major depression.

Inflammation and Neurodegeneration in Patients with Early-Stage and Chronic Bipolar Disorder

The increase in the circulatory cytokine levels observed in patients with bipolar disorder (BD) may imply involvement of inflammation in the pathogenesis of mood disorders. However, the association between the inflammatory process and the stage and severity of illness is not well understood. In this study, our aim was to investigate the association between neuroinflammation and disease progression in the clinical course of BD. IL-6, TNF-α, IL-1 receptor antagonist (IL-1RA), neuronspecific enolase (NSE) and S100B were measured by ELISA in plasma samples of patients at early-stage BD (n=30), chronic BD (n=77) and healthy controls (n=30). Chronic BD patients showed significantly increased levels of all measured inflammatory markers as compared to early-stage BD patients and the healthy controls. IL-6 and IL-1RA levels correlated with NSE and/or S100B levels and TNF-α levels correlated with Montgomery- Asberg Depression Rating Scale scores and Clinical Global Impression Scale scores. Our results indicate that inflammation appears to be particularly associated with IL-1RA and IL-6 activity, progressing at later stages of BD and possibly associated with gliosis and neuronal loss.

The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study

ObjectiveTo investigate the efficacy of adjunctive N-acetylcysteine (NAC) for the treatment of acute bipolar depression. MethodA randomized, double-blind, multicentre, placebo-controlled trial including adult subjects diagnosed with bipolar disorder, currently experiencing a depressive episode. Participants were treated with 3 g/day NAC or placebo as an adjunctive to standard treatment for 20 weeks, followed by a 4-week washout where the blinding was maintained. The primary outcome was the mean change in the Montgomery Asberg Depression Rating Scale (MADRS) score over the 20-week treatment phase. Linear Mixed Effects Repeated Measures (LMERM) was used for analysing the primary outcome. ResultsA total of 80 subjects were included. The mean MADRS score at baseline was 30.1 and 28.8 in participants randomized to NAC and placebo, respectively. Regarding the primary outcome measure, the between-group difference (NAC vs. placebo) was 0.5, which was statistically non-significant (95% CI: -7.0-5.9;p = 0.88). All findings regarding secondary outcomes were statistically or clinically insignificant. LimitationsThe study had a placebo response rate of 55.6% - high placebo response rates are associated with failure to separate from placebo. ConclusionsBased on our primary outcome measure, we could not confirm previous studies showing a therapeutic effect of adjunctive NAC treatment on acute bipolar depression. Further studies with larger samples are needed to elucidate if specific subgroups could benefit from adjunctive NAC treatment.

Clinical factors predicting treatment resistant depression: affirmative results from the European multicenter study.

ObjectivesClinical variables were investigated in the ‘treatment resistant depression (TRD)‐ III’ sample to replicate earlier findings by the European research consortium ‘Group for the Study of Resistant Depression’ (GSRD) and enable cross‐sample prediction of treatment outcome in TRD.Experimental procedures TRD was defined by a Montgomery and Åsberg Depression Rating Scale (MADRS) score ≥22 after at least two antidepressive trials. Response was defined by a decline in MADRS score by ≥50% and below a threshold of 22. Logistic regression was applied to replicate predictors for TRD among 16 clinical variables in 916 patients. Elastic net regression was applied for prediction of treatment outcome.ResultsSymptom severity (odds ratio (OR) = 3.31), psychotic symptoms (OR = 2.52), suicidal risk (OR = 1.74), generalized anxiety disorder (OR = 1.68), inpatient status (OR = 1.65), higher number of antidepressants administered previously (OR = 1.23), and lifetime depressive episodes (OR = 1.15) as well as longer duration of the current episode (OR = 1.022) increased the risk of TRD. Prediction of TRD reached an accuracy of 0.86 in the independent validation set, TRD‐I.ConclusionSymptom severity, suicidal risk, higher number of lifetime depressive episodes, and comorbid anxiety disorder were replicated as the most prominent risk factors for TRD. Significant predictors in TRD‐III enabled robust prediction of treatment outcome in TRD‐I.

Factors associated with psycho-cognitive functions in patients with persistent pain after surgery for femoral neck fracture

To solve problems arising from fracture of the femoral neck in elderly people, the proportion of which continues to increase in the population of Japan, we need to examine factors in patients with fractured femur necks to develop and ways to assist affected patients. In this study, we examined the relationships among sex, age, fracture site, operative procedure, physique, lifestyle, psycho-cognitive functions, and types of pain in 142 patients, performed multiple regression analysis using the Mini-Mental State Examination (MMSE) and the Montgomery–Asberg Depression Rating Scale (MADRS) scores as dependent variables, and created MMSE and MADRS models. The results of analysis of the MMSE and MADRS models identified night pain and the number of family members as factors that affected mental function in a population with persistent pain for 1 week after surgery for fractured femoral neck. In addition, the number of family members was identified in multiple regression analysis models as a factor associated with psycho-cognitive functions. Pain, night pain in particular, affects psycho-cognitive functions. We speculated that emotional ups and downs were associated with the number of family members. The results showed that the patients living with family members maintained psycho-cognitive functions better than did those living alone, even when they experienced pain in their daily lives. We speculated that emotional changes were associated with number of family members. Patients living with family members maintained psycho-cognitive functions better than did those living alone, even when they experienced pain in their daily lives.

Exploring alternative rTMS strategies in non-responders to standard high frequency left-sided treatment: A switching study

BackgroundHigh-frequency left-sided repetitive transcranial magnetic stimulation (rTMS) is now commonly used treatment for patients with depression. However, there are several other forms of rTMS (low-frequency right-sided and sequential bilateral rTMS) which have also been shown to be effective. No information has been systematically gathered on the likelihood of response to alternative forms of rTMS in patients who do not improve after an initial course of left-sided treatment. ObjectiveTo evaluate whether there are differences in antidepressant response between switching to either low-frequency right sided or sequential bilateral stimulation or continuing high-frequency left-sided TMS following non-response to an initial course of high-frequency left-sided rTMS. Methods113 rTMS naïve patients were provided with an initial three-week course of high-frequency left-sided rTMS. Non-responders were then randomised to receive another three weeks of left-sided treatment (n = 21), right-sided low frequency stimulation (n = 18) or sequential bilateral rTMS (n = 20). ResultsAlthough there was an overall improvement in depressive symptoms in the randomised phase of the study, no significant differences in response was seen between the three treatment groups on Montgomery Asberg Depression Rating Scale or Hamilton Depression Rating Scale scores. LimitationsThe main limitation of the study was the duration of treatment provided in both the lead in and random treatment phases. ConclusionThis study does not provide evidence for differences in response to different forms of rTMS in initial non-responders to left-sided stimulation. However, further studies with longer periods of treatment and a larger sample size are required to definitively establish or exclude between group differences in rTMS response in initial non-responders to treatment.

Quantifying iron deposition within the substantia nigra of Parkinson's disease by quantitative susceptibility mapping

BackgroundIron deposition within the substantia nigra (SN) has been postulated to play a vital role in Parkinson's disease (PD). The aim of this study was to explore the inherent link of PD patients between their substantia nigra iron accumulation and clinical status using quantitative susceptibility mapping (QSM) which is now considered to be the only quantitative imaging technique of brain iron deposition. Methods44 PD patients and 31 age- and gender-matched healthy controls underwent quantitative susceptibility mapping (QSM) were recruited in this study. We firstly divided the patients into mild symptom severity (MSP) and advanced symptom severity (ASP) groups concerning their disease stage, aiming to illuminate the relationship between iron deposition in SN of PD and disease progression. Then, we classified the patients with Parkinson's disease into three subgroups: tremor-dominant PD (TD), akinetic/rigidity-dominant PD (AR), mixed-PD (M) according to their dominant motor symptoms in order to investigate whether there are any effects of SN iron accumulation to different subtypes of PD patients. ResultsCompared to healthy controls, patients with PD have increased QSM magnetic values in the substantia nigra (138.039±37.320 vs 179.553±65.715; P=0.001). More prominent statistically significance of the difference of SN iron deposition between healthy controls (HC) and advanced symptom severity (ASP) subgroup was displayed (138.039±37.320 vs 232.827±92.040; P<0.001). Besides, among the three clinical phenotypes both TD and AR subgroup showed significant difference compared with healthy controls concerning the QSM values (138.039±37.320 vs 185.864±99.851; P=0.013; 188.148±52.958 vs 138.039±37.320; P=0.001). Furthermore, the iron content in the SN of PD patients was significantly correlated with the Hoehn-Yahr stage, the Unified Parkinson's Disease Rating Scale (UPDRS), Montgomery Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Scale (HAMA) scores (r=0.417, P=0.005; r=0.300, P=0.048; r=0.540, P<0.001; r=0.553, P<0.001). In MSP the significantly correlation was displayed only in MADRS, HAMA scores (r=0.429, P=0.013; r=0.492, P=0.004), when disease progressed into advanced severity stage all these clinical measures (Hoehn-Yahr stage, UPDRS-3, UPDRS, HAMA, and MADRS scores) we had recruited into this study shown prominent correlation to SN iron content (r=0.650, P=0.030; r=0.709, P=0.015; r=0.708, P=0.015; r=0.758, P=0.007; r=0.683, P=0.020). In the three phenotypes the correlation between iron content and MADRS, HAMA scores (r=0.686, P=0.002; r=0.633, P=0.006) was found in AR subgroups exclusively. ConclusionsPatients with PD exhibited significantly higher magnetic susceptibility values, especially in those who are in advanced disease severity stage, which confirmed that iron accumulation in the SN is in line with Parkinson's disease progression. Furthermore, we testified that there are actually some inherent effects of substantia nigra iron deposition to the clinical symptoms of Parkinson's disease. Moreover, it seems that akinetic/rigidity-dominant PD subgroup was affected most by SN iron accumulation.

Efficacy of vestibular stimulation treatment in the depressive phase of bipolar disorder: study protocol for a randomized, double-blind, controlled trial

Background and objectives: Bipolar disorder (BD) is a neuropsychiatric disorder characterized by the oscillation of mood states between hypoactive/pessimistic (depressive phase) and hyperactive/optimistic states (manic/hypomanic phase). Previous studies evidenced that a particular technique of neuro-vestibular stimulation is an effective treatment for major depression. This study will investigate the efficacy of the said vestibular stimulation technique in the depressive phase of BD, and will compare it with sham vestibular stimulation. Design: A double-blind, randomized controlled study. Methods: One hundred and twenty patients with bipolar type I or II, currently undergoing a depressive phase, will be randomized into the experimental group (n = 60) or control group (n = 60), receiving three sessions of real/sham vestibular stimulation. Outcome measures: The primary outcome is the change in Montgomery Asberg Depression Rating Scale scores from baseline to post 4 and 12 weeks. The secondary outcome is the vestibular activity assessed at baseline, post 4 and 2 weeks. Discussion: Currently, no treatment has proved efficacy for bipolar depression. Studies have demonstrated that lateralized neuro-vestibular stimulation is an effective treatment for mayor depression but has not been studied in the depressive phase of bipolar disorder. This investigation will give the first evidence supporting or denying the use of vestibular stimulation treatment in BD depression. Ethics and dissemination: This study protocol was approved by the Ethics Committee of SSMO (Servicio de Salud Metropolitano Oriente) in Santiago, Chile (approval No. 08032016) on March 8, 2016. The results of the study will be published in scientific journals and other media. Trial registration: ClinicalTrials.gov Identifier: NCT02778256.

Acute and chronic changes in brain activity with deep brain stimulation for refractory depression.

Deep brain stimulation is a potential option for patients with treatment-refractory depression. Deep brain stimulation benefits have been reported when targeting either the subgenual cingulate or ventral anterior capsule/nucleus accumbens. However, not all patients respond and optimum stimulation-site is uncertain. We compared deep brain stimulation of the subgenual cingulate and ventral anterior capsule/nucleus accumbens separately and combined in the same seven treatment-refractory depression patients, and investigated regional cerebral blood flow changes associated with acute and chronic deep brain stimulation. Deep brain stimulation-response was defined as reduction in Montgomery-Asberg Depression Rating Scale score from baseline of ≥50%, and remission as a Montgomery-Asberg Depression Rating Scale score ≤8. Changes in regional cerebral blood flow were assessed using [15O]water positron emission tomography. Remitters had higher relative regional cerebral blood flow in the prefrontal cortex at baseline and all subsequent time-points compared to non-remitters and non-responders, with prefrontal cortex regional cerebral blood flow generally increasing with chronic deep brain stimulation. These effects were consistent regardless of stimulation-site. Overall, no significant regional cerebral blood flow changes were apparent when deep brain stimulation was acutely interrupted. Deep brain stimulation improved treatment-refractory depression severity in the majority of patients, with consistent changes in local and distant brain regions regardless of target stimulation. Remission of depression was reached in patients with higher baseline prefrontal regional cerebral blood flow. Because of the small sample size these results are preliminary and further evaluation is necessary to determine whether prefrontal cortex regional cerebral blood flow could be a predictive biomarker of treatment response.