Psychomotor retardation: What about the partial responders to magnetic transcranial stimulation in treatment resistant depression ?

OBJECTIVE: Psychomotor retardation is a core clinical component of Major Depressive Disorder responsible for disability and is known as a treatment response marker of biological treatments for depression. Our objective was to describe cognitive and motoric measures changes during a treatment by repetitive Transcranial Magnetic Stimulation (rTMS) within the THETAD-DEP trial for treatment-resistant depression (TRD), and compare those performances at the end of treatment and one month after between responders (>50% improvement on MADRS score), partial responders (25-50%) and non-reponders (no clinically relevant improvement). Our secondary aim was to investigate baseline psychomotor performances associated with non-response and response even partial. METHODS: Fifty-four patients with treatment-resistant unipolar depression and treated by either high frequency 10 Hz rTMS or iTBS for 4 weeks (20 sessions) underwent assessment including French Retardation Rating Scale for Depression (ERD), Verbal Fluency test, and Trail Making Test A. before, just after treatment and one month later. RESULTS: 20 patients were responders (R, 21 partial responders (PR) and 13 non-responders (NR). rTMS treatment improved psychomotor performances in the R and PR groups unlike NR patients whose psychomotor performance was not enhanced by treatment. At baseline, participants, later identified as partial responders, showed significantly higher performances than non-responders. CONCLUSION: Higher cognitivo-motor performances at baseline may be associated with clinical improvement after rTMS treatment. This work highlights the value of objective psychomotor testing for the identification of rTMS responders and partial responders, and thus may be useful for patient selection and protocol individualization such as treatment continuation for early partial responders.

Dynamics of Depressive and Psychomotor Symptoms During Electroconvulsive Therapy in Older Depressive Patients: A Case Series.

OBJECTIVE: Electroconvulsive therapy (ECT) is an effective treatment for patients experiencing a major depressive episode, especially older ones. Identification of specific responses within early ECT sessions remains an issue of debate, however. Hence, this pilot study prospectively examined the outcome in terms of depressive signs, symptom by symptom, throughout a course of ECT, concentrating particularly on psychomotor retardation symptoms. METHODS: Nine patients were clinically evaluated several times during the ECT course, before the first session and then weekly (over 3-6 weeks, according to their evolution), by completing the Montgomery-Åsberg Depression Rating Scale (MADRS), the Mini-Mental State Examination test, and the French Retardation Rating Scale for Depression for assessing the severity of psychomotor retardation. RESULTS: Nonparametric Friedman tests showed significant positive changes in mood disorders during ECT in older depressive patients (mean, -27.3% of initial MADRS total score). Fast improvement in French Retardation Rating Scale for Depression score was observed at t1 (ie, after 3-4 ECT sessions), whereas a slightly delayed improvement in the MADRS scores was found at t2 (ie, after 5-6 ECT sessions). Moreover, the scores for items linked to the motor component of psychomotor retardation (eg, gait, postural control, fatigability) were the first to significantly decrease during the first 2 weeks of the ECT course compared with the cognitive component. CONCLUSIONS: Interestingly, participants' concentration on daily functional activities, their interest and fatigability, and their reported state of sadness were the first to progress, representing possible precursor signs of positive patient outcomes after ECT.

Intermittent theta burst stimulation (iTBS) versus 10 Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) to alleviate treatment-resistant unipolar depression: A randomized controlled trial (THETA-DEP).

BACKGROUND: Recently intermittent theta burst stimulation (iTBS) proved to be non-inferior to conventional repetitive transcranial magnetic stimulation (10 Hz rTMS) in unipolar depression after failure of one antidepressant trial, but to date no randomized control trial assessed the ability of iTBS to improve depression level and quality of life in more resistant features of depression with a long-term (6 month) follow-up in comparison to 10 Hz rTMS. OBJECTIVES/HYPOTHESIS: The aim of our study was to compare the efficacy of 10 Hz rTMS and iTBS in treatment-resistant unipolar depression on response rates (50% decrease of MADRS scores at one month from baseline) and change in quality of life during a 6-month follow-up. In addition, we investigated whether some clinical features at baseline were associated with the response in the different groups. METHOD: Sixty patients were randomized in a double-blind, controlled study at the University Hospital Center of Nantes, and received 20 sessions of either rTMS or iTBS applied to the left dorsolateral prefrontal cortex targeted by neuronavigation. Statistical analysis used Fischer's exact test and Chi-square test as appropriate, linear mixed model, and logistic regression (occurrence of depressive relapse and factors associated with the therapeutic response). RESULTS: Included patients showed in mean more than 3 antidepressants trials. Response rates were 36.7% and 33.3%, and remission rates were 18.5% and 14.8%, in the iTBS and 10 Hz rTMS groups respectively. Both groups showed a similar significant reduction in depression scores and quality of life improvement at 6 months. We did not find any clinical predictive factor of therapeutic response in this sample. CONCLUSION: Our study suggests the clinical interest of iTBS stimulation (which is more time saving and cost-effective as conventional rTMS) to provide long-lasting improvement of depression and quality of life in highly resistant unipolar depression.

Does the transcranial direct current stimulation improve dual-task postural control in young healthy adults?

Some studies have suggested that postural balance improved after a single session of transcranial direct current stimulation (tDCS), whereas others have found minimal, if any, effects on postural performance. To address the issue of replication in tDCS studies, we re-tested the anodal tDCS effects of left dorsolateral prefrontal cortex while performing a dual-task by increasing the attentional demands associated with more challenging proprioceptive conditions. Twenty-four young adults (mean age: 21.3 ± 1.2 years) were randomly divided into two groups (a "real tDCS" vs. a "sham tDCS" group) were asked to maintain a quiet stance on a force platform. Eight trials were conducted, with eyes open and eyes closed, standing on a firm and foam surface and performing a simple and dual-task (backward counting). The postural performance was assessed by various centre-of-pressure parameters before and immediately after a 20-min tDCS session. No main effect of group and no interaction considering this factor were observed, regardless of the centre-of-pressure variables (all p values > 0.1). No evidence of a more efficient postural control emerged after a tDCS session. Beyond promising research on tDCS to maximize cognitive and behavioural enhancement, the current results indicate that caution needs to be taken when drawing firm conclusions, at least in young healthy adults.

Translation and Cultural Adaptation of PROactive Instruments for COPD in French and Influence of Weather and Pollution on Its Difficulty Score.

Introduction: The recently developed daily and clinical visit PROactive physical activity in COPD (PPAC) instruments are hybrid tools to objectively quantify the level of physical activity and the difficulties experienced in everyday life. Our aim was to translate these instruments for the French-speaking chronic obstructive pulmonary disease (COPD) community worldwide and evaluate the influence of weather and pollution on difficulty score. Methods: The translation procedure was conducted following the guidelines for cross-cultural adaptation process. The translated clinical visit (C-PPAC) was tested among COPD patients in France. A retest was conducted after an interval of at least 2 weeks. The C-PPAC difficulty score was then tested to see how sensitive it was to the influence of weather and outdoor pollution. Results: One hundred and seventeen COPD patients (age 65±9 years; FEV1: 51±20%) from 9 regions in France were included. The French version of C-PPAC was found comprehensible by the patients with an average score of 4.8/5 on a Likert-scale. It showed good internal consistency with Cronbach's α>0.90 and a good test retest reliability with an intraclass correlation coefficient of ≥0.80. The difficulty score was negatively correlated with duration of daylight (ρ=-0.266; p<0.01) and influenced by the intensity of rainfall (light vs. heavy rainfall: 68±16 vs. 76±14 respectively, p=0.045). The score was lower in patients receiving long term oxygen therapy (60±15 vs. 71±15, p<0.01), but not correlated with the pollution indices. Conclusion: The French versions of the questionnaires of the PPAC instruments are accepted and comprehensible to COPD patients. The difficulty score of C-PPAC is sensitive to duration of daylight and rainfall. Such weather factors must be taken into consideration when evaluating the physical activity behavior using these tools in COPD.

Cost-utility analysis of transcranial direct current stimulation (tDCS) in non-treatment-resistant depression: the DISCO randomised controlled study protocol.

INTRODUCTION: Depression is among the most widespread psychiatric disorders in France. Psychiatric disorders are associated with considerable social costs, amounting to €22.6 billion for treatment and psychotropic medication in 2011. Treatment as usual (TAU), mainly consisting of pharmacotherapy and psychotherapy, is effective for only a third of patients and in most cases fails to prevent treatment resistance and chronicity. Transcranial direct current stimulation (tDCS) consists in a non-invasive and painless application of low-intensity electric current to the cerebral cortex through the scalp. Having proved effective in depressed patients, it could be used in combination with TAU to great advantage. The objective is to compare, for the first time ever, the cost-utility of tDCS-TAU and of TAU alone for the treatment of a depressive episode that has been refractory to one or two drug treatments. METHODS AND ANALYSIS: This paper, based on the DISCO study protocol, focuses on the design of a prospective, randomised, controlled, open-label multicentre economic study to be conducted in France. It will include 214 patients with unipolar or bipolar depression, assigning them to two parallel arms: group A (tDCS-TAU) and group B (TAU alone). The primary outcome is the incremental cost-effectiveness ratio, that is, the ratio of the difference in cost between each strategy to the difference in their effects. Their effects will be expressed as numbers of quality-adjusted life-years, determined through administration of the EuroQol Five-Dimension questionnaire over a 12-month period to patients (EQ-5D-5L). Expected benefits are the reduction of treatment resistance and suicidal ideation as well as social and professional costs of depression. Should depression-related costs fall significantly, tDCS might be considered an efficient treatment for depression. ETHICS AND DISSEMINATION: This protocol has been approved by a French ethics committee, the CPP--Est IV (Comité de Protection des Personnes-Strasbourg). Data are to be published in peer-reviewed medical journals. TRIAL REGISTRATION NUMBER: RCB 2018-A00474-51; NCT03758105.

Combined Measures of Psychomotor and Cognitive Alterations as a Potential Hallmark for Bipolar Depression.

OBJECTIVE: The current study aimed to examine whether specific features of psychomotor retardation (PMR) and cognitive functioning established different profiles in unipolar (UD) and bipolar depression (BD). METHODS: Two groups of age-matched patients with UD (n=54) and BD (n=20) completed the Montgomery-Asberg Depression Rating Scale (MADRS/60), the Montreal Cognitive Assessment (MoCA/30), and the Salpêtrière Retardation Rating Scale (SRRS/60). We analyzed the group effect and then performed intra-group analyses. RESULTS: The BD patients have higher SRRS score, and lower MoCA score than UD despite no difference on the level of depression between UD and BD. Our results show that PMR can be predicted by the level of depression in UD and by the cognitive alteration and onset of disease in BD. CONCLUSION: PMR is a relevant marker of depression. Our results highlight the importance of concomitant evaluation of psychomotor and cognitive functions in the distinction of UD and BD symptoms.

Cognitive component of psychomotor retardation in unipolar and bipolar depression: Is verbal fluency a relevant marker? Impact of repetitive transcranial stimulation.

AIMS: In the literature, psychomotor retardation (PMR) is increasingly highlighted as a relevant marker for depression. Currently, we chose to focus on the fluency capacities as an evaluation of the frontal lobes functioning to reach a better understanding of cognitive and neurobiological mechanisms involved in PMR in depression. The aims of this study were: (i) to explore the cognitive component of PMR through the analysis of verbal fluency (VF) performance in unipolar and bipolar depression; and (ii) to examine whether a repetitive transcranial magnetic stimulation treatment could improve concomitantly the PMR and VF capacities, as a relevant marker characteristic of the cognitive component of PMR. METHODS: Fifteen unipolar and 15 bipolar patients were compared to 15 healthy adults. Before treatment, the results showed VF deficits, particularly marked in the bipolar group. The investigation of the interplay between PMR, VF performance, Montgomery-Åsberg Depression Rating Scale scores, and Montreal Cognitive Assessment scores showed that the deficits in these various dimensions were not homogeneous. RESULTS: The absence of correlation between the psychomotor retardation scale (the French Retardation Rating Scale for Depression) and VF, and the correlation with MoCA raise the hypothesis of a more global cognitive impairment associated with PMR in the BD group. The repetitive transcranial magnetic stimulation treatment had a positive impact on depression, PMR, and fluency scores. CONCLUSION: Correlations between the Retardation Rating Scale for Depression and VF performances appeared after treatment, showing the cognitive role of psychomotor functioning in depression. Further analyses, including other cognitive measures in an objective evaluation of PMR, are required for a better understanding of these complex relationships.

Efficacy of intermittent Theta Burst Stimulation (iTBS) and 10-Hz high-frequency repetitive transcranial magnetic stimulation (rTMS) in treatment-resistant unipolar depression: study protocol for a randomised controlled trial.

BACKGROUND: The treatment of depression remains a challenge since at least 40% of patients do not respond to initial antidepressant therapy and 20% present chronic symptoms (more than 2 years despite standard treatment administered correctly). Repetitive transcranial magnetic stimulation (rTMS) is an effective adjuvant therapy but still not ideal. Intermittent Theta Burst Stimulation (iTBS), which has only been used recently in clinical practice, could have a faster and more intense effect compared to conventional protocols, including 10-Hz high-frequency rTMS (HF-rTMS). However, no controlled study has so far highlighted the superiority of iTBS in resistant unipolar depression. METHODS/DESIGN: This paper focuses on the design of a randomised, controlled, double-blind, single-centre study with two parallel arms, carried out in France, in an attempt to assess the efficacy of an iTBS protocol versus a standard HF- rTMS protocol. Sixty patients aged between 18 and 75 years of age will be enrolled. They must be diagnosed with major depressive disorder persisting despite treatment with two antidepressants at an effective dose over a period of 6 weeks during the current episode. The study will consist of two phases: a treatment phase comprising 20 sessions of rTMS to the left dorsolateral prefrontal cortex, localised via a neuronavigation system and a 6-month longitudinal follow-up. The primary endpoint will be the number of responders per group, defined by a decrease of at least 50% in the initial score on the Montgomery and Asberg Rating Scale (MADRS) at the end of rTMS sessions. The secondary endpoints will be: response rate 1 month after rTMS sessions; number of remissions defined by a MADRS score of <8 at the endpoint and 1 month after; the number of responses and remissions maintained over the next 6 months; quality of life; and the presence of predictive markers of the therapeutic response: clinical (dimensional scales), neuropsychological (evaluation of cognitive functions), motor (objective motor testing) and neurophysiological (cortical excitability measurements). DISCUSSION: The purpose of our study is to check the assumption of iTBS superiority in the management of unipolar depression and we will discuss its effect over time. In case of a significant increase in the number of therapeutic responses with a prolonged effect, the iTBS protocol could be considered a first-line protocol in resistant unipolar depression. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier NCT02376491 . Registered on 17 February 2015 at http://clinicaltrials.gov .

Posture-cognitive dual-tasking: A relevant marker of depression-related psychomotor retardation. An illustration of the positive impact of repetitive transcranial magnetic stimulation in patients with major depressive disorder.

This study examined whether postural control variables, particularly the center-of-pressure (COP) velocity-based parameters, could be a relevant hallmark of depression-related psychomotor retardation (PMR). We first aimed at investigating the interplay between the PMR scores and the COP performance in patients with major depressive disorder (MDD), as compared to age-matched healthy controls; secondly, we focused on the impact of a repetitive transcranial magnetic stimulation (rTMS) treatment on depression, PMR scores and postural performance. 16 MDD patients, and a control group of 16 healthy adults, were asked to maintain quiet standing balance during two trials with or without vision, and while backward counting (dual task). All the position and velocity-based COP variables were computed. Before and after the rTMS session (n eligible MDD = 10), we assessed the depression level with the Montgomery-Asberg Depression Rating Scale (MADRS), the PMR scores with the French Retardation Rating Scale for Depression (ERD), and postural performance. Before the treatment, significant positive partial correlations were found between the pre-ERD scores and the velocity-based COP variables, especially in the dual-task conditions (p < 0.05). In contrast, there was no significant correlation between the post-ERD scores and any postural parameter after the treatment. The MADRS and ERD scores showed a significant decrease between before and after the rTMS intervention. For the first time, the findings clearly validated the view that the assessment of postural performance - easy to envisage in clinical settings-constitutes a reliable and objective marker of PMR in MDD patients.

Repeated self-evaluations may involve familiarization: An exploratory study related to Ecological Momentary Assessment designs in patients with major depressive disorder.

A growing body of research in clinical psychology is now relying on Ecological Momentary Assessment (EMA). EMA is fitted to investigate fluctuating processes and as such, it is of particular interest in a clinical context in which patients are often characterized by fluctuating behaviors and affective states or symptoms. EMA typically involves frequent self-evaluations over long periods, which may influence patient response. The present study aimed to determine whether EMA follow-ups could influence the participants' self-evaluations over time. The sample comprised 24 outpatients suffering from a Major Depressive Disorder (15 women, age = 51.4 ± 9.6). This study relied on an EMA protocol involving self-evaluations of seven depressive symptoms twice a day over 5 months. Patients did not show any clinical improvement following the clinical screening and the level of depressive symptoms during the follow-up. As a novel finding, significant moderate to large effects were observed for decreased variability and instability of psychological states over time. The main difference in temporal properties of psychological states was found after the first two weeks of the follow-up. This study characterized early changes in patients' self-evaluations, suggesting the idea of a valuable familiarization period during the first two weeks of an EMA follow-up.

Effect of Repetitive Transcranial Magnetic Stimulation on Psychomotor Retardation in Major Depression: A Pilot Feasibility Study.

This pilot study investigated the feasibility of a comprehensive battery of tests assessing psychomotor retardation after a 3-week protocol of repetitive transcranial magnetic stimulation for depression. In addition to the beneficial effect of this treatment on depression, the results showed positive changes in psychomotor retardation.

Balance characteristics in patients with major depression after a two-month walking exercise program: A pilot study.

UNLABELLED: Recent studies have demonstrated impaired balance performance in patients with major depressive disorder (MDD) in comparison to healthy controls (HC), which is likely to be related to deficits in integration of visual and proprioceptive inputs necessary for efficient postural control. In parallel, considerable literature supports the positive effects of a walking program on depressive symptoms. Thus this study aimed to determine the effects of a two-month walking program on implicit postural control strategies in MDD. Compared with twelve age- and body mass index-matched non-psychiatric HC (mean age 50.41 ± 6.93 years; five women), nine MDD (mean age 51.88 ± 10.01 years; five women) performed two sessions of standing postural control assessment, separated by eight weeks of the walking program, while the HC were only assessed at t0. The walking program included one-hour supervised walking sessions, three times a week over a two-month period. Postural performance was assessed by various center of pressure (COP) parameters, in particular those that bound the COP velocity of postural sway. The primary findings were that MDD patients exhibited positive physical activity-related changes in postural performance, with a decrease in body sway in the most difficult condition (with a foam surface). The real impact of the walking program on COP velocity-based variables suggests that MDD patients improved their ability to make more efficient postural corrections, which is useful for daily activities and autonomy. A balance assessment in the clinical screening routine might be used as a new index of the effectiveness of walking programs recommended for people with depression. TRIAL REGISTRATION: This study is registered at http://clinicaltrials.gov/: NCT01995422.