Djamila Bennabi

Psychomotor Retardation in Depression: A Systematic Review of Diagnostic, Pathophysiologic, and Therapeutic Implications

Psychomotor retardation is a central feature of depression which includes motor and cognitive impairments. Effective management may be useful to improve the classification of depressive subtypes and treatment selection, as well as prediction of outcome in patients with depression. The aim of this paper was to review the current status of knowledge regarding psychomotor retardation in depression, in order to clarify its role in the diagnostic management of mood disorders. Retardation modifies all the actions of the individual, including motility, mental activity, and speech. Objective assessments can highlight the diagnostic importance of psychomotor retardation, especially in melancholic and bipolar depression. Psychomotor retardation is also related to depression severity and therapeutic change and could be considered a good criterion for the prediction of therapeutic effect. The neurobiological process underlying the inhibition of activity includes functional deficits in the prefrontal cortex and abnormalities in dopamine neurotransmission. Future investigations of psychomotor retardation should help improve the understanding of the pathophysiological mechanisms underlying mood disorders and contribute to improving their therapeutic management.

Risk factors for treatment resistance in unipolar depression: A systematic review

BACKGROUND Treatment resistant depression is a complex disorder and an important source of morbidity and mortality. Identification of risk factors of resistance may be useful to improve early recognition as well as treatment selection and prediction of outcome in patients with depression. METHODS The aim of this paper was to review the current status of knowledge regarding risk factors of treatment resistance in unipolar depression, in patients who failed to respond to at least two successive and adequate antidepressant treatments. RESULTS Systematic literature search yielded 8 publications exploring clinical and biological factors. Specific psychiatric comorbidities, psychosocial factors, clinical characteristics of the depressive episode and biological markers emerge as possible risk factor for treatment resistant depression. LIMITATIONS Due to the lack of objective definition and diagnostic criteria for treatment resistant depression, and the paucity of reports on risk factors, our review only summarized a small number of studies. CONCLUSION Future investigations of risk factors should help to improve the understanding of the mechanisms underlying resistance in mood disorders and contribute to improve their therapeutic management.

A Bayesian framework systematic review and meta-analysis of anesthetic agents effectiveness/tolerability profile in electroconvulsive therapy for major depression

The aim of this study was to assess the efficacy and tolerability/acceptability of 6 anesthetic agents in ECT for depressive disorders. We systematically reviewed 14 double-blind randomized controlled trials (610 participants). Efficacy was measured by the mean scores on validated depression scales at 6 ECT (or the nearest score if not available), number of responders at the end of treatment and seizure duration. The acceptability was measured by the proportion of patients who dropped out of the allocated treatment, and the tolerability by the number of serious adverse events and post-treatment cognition assessment. After excluding the trials responsible for heterogeneity, depression scores of patients who were administered methohexital were found to be significantly more improved than those who received propofol (p = 0.001). On the contrary, those who were administered propofol had lower depression scores than those with thiopental at the end of treatment (p = 0.002). Compared to propofol, methohexital was found to be significantly associated with higher seizure duration (p = 0.018). No difference was found for the acceptability profile (all p > 0.05). In summary, ketamine and methohexital may be preferred to propofol or thiopental in regard of effectiveness in depression scores and increased seizure duration. Further studies are warranted to compare ketamine and methohexital.

Motor imagery in unipolar major depression

Background: Motor imagery is a potential tool to investigate action representation, as it can provide insights into the processes of action planning and preparation. Recent studies suggest that depressed patients present specific impairment in mental rotation. The present study was designed to investigate the influence of unipolar depression on motor imagery ability. Methods: Fourteen right-handed patients meeting DSM-IV criteria for unipolar depression were compared to 14 matched healthy controls. Imagery ability was accessed by the timing correspondence between executed and imagined movements during a pointing task, involving strong spatiotemporal constraints (speed/accuracy trade-off paradigm). Results: Compared to controls, depressed patients showed marked motor slowing on both actual and imagined movements. Furthermore, we observed greater temporal discrepancies between actual and mental movements in depressed patients than in healthy controls. Lastly, depressed patients modulated, to some extent, mental movement durations according to the difficulty of the task, but this modulation was not as strong as that of healthy subjects. Conclusion: These results suggest that unipolar depression significantly affects the higher stages of action planning and point out a selective decline of motor prediction.

Cognitive effects of transcranial direct current stimulation treatment in patients with major depressive disorder: An individual patient data meta-analysis of randomised, sham-controlled trials

HighlightsIt remains unclear whether tDCS treatment has cognitive benefits in depression.This individual patient data meta‐analysis examined effects from seven RCTs.Active tDCS treatment did not cause cognitive benefits compared to sham. &NA; Transcranial direct current stimulation (tDCS) has emerged as a promising new treatment for major depression. While recent randomised, sham‐controlled studies found tDCS to have antidepressant effects, it remains to be determined whether a tDCS treatment course may also enhance cognitive function independent of mood effects in depressed patients. This systematic review and individual patient data (IPD) meta‐analysis examined cognitive outcomes from randomised, sham‐controlled trials of tDCS treatment for major depression. Seven randomised, sham‐controlled trials (n = 478 participants, 260 in active and 218 in sham) of tDCS for major depression were included. Results showed no cognitive enhancement after active tDCS compared to sham for the 12 cognitive outcomes investigated. Active relative to sham tDCS treatment was associated with reduced performance gains on a measure of processing speed (&bgr; = −0.33, 95% CI −0.58; −0.08, p = 0.011). Active tDCS treatment for depression did not show cognitive benefits independent of mood effects. Rather, tDCS treatment relative to sham stimulation for major depression may instead be associated with a reduced practice effect for processing speed.

Safety and acceptability of transcranial direct current stimulation for the acute treatment of major depressive episodes: Analysis of individual patient data

BACKGROUND Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation modality that has been increasingly used for major depressive disorder (MDD) treatment. Although studies in healthy volunteers showed that the technique is well-tolerated, tDCS safety and acceptability have not been sufficiently explored in patients with MDD. METHODS We collected individual patient data from 6 randomized clinical trials that had been previously identified in a systematic review and meta-analysis. Primary outcomes were safety (rate of adverse events) and acceptability (rate of dropouts). Secondary outcomes were clinical, demographic and treatment predictors of the primary outcomes. RESULTS Dropout rates between active (8.8%) and sham (12%) groups were not significantly different (OR= 0.7, p=0.38). Adverse event rates between active (73.5%) and sham (68.3%) groups were not significantly different (OR= 1.4, p= 0.23). Higher current densities were associated with lower adverse event rates. LIMITATIONS Dropout reasons were not systematically reported and adverse events were not collected using questionnaires standardized across studies. CONCLUSIONS Active tDCS is as acceptable and safe as sham tDCS, as found in randomized clinical trials of MDD.

Dépression résistante : les stratégies de changement et d’association de médicaments antidépresseurs

Switching antidepressant medication may be helpful in depressed patients having no benefit from the initial antidepressant treatment. Before considering switching strategy, the initial antidepressant treatment should produce no therapeutic effect after at least 4 weeks of administration at adequate dosage. Choosing an antidepressant of pharmacologically distinct profile fails to consistently demonstrate a significant superiority in terms of effectiveness over the switching to another antidepressant within the same pharmacological class. Augmenting SSRI/SNRIs with mirtazapine/mianserin has become the most recommended strategy of antidepressant combinations. Augmenting SSRI with tricyclic drugs is now a less recommended strategy of antidepressant combinations given the increased risk for the occurrence of pharmacokinetic drug-drug interactions and adverse effects.

Transcranial Direct Current Stimulation (tDCS): A Promising Treatment for Major Depressive Disorder?

Background: Transcranial direct current stimulation (tDCS) opens new perspectives in the treatment of major depressive disorder (MDD), because of its ability to modulate cortical excitability and induce long-lasting effects. The aim of this review is to summarize the current status of knowledge regarding tDCS application in MDD. Methods: In this review, we searched for articles published in PubMed/MEDLINE from the earliest available date to February 2018 that explored clinical and cognitive effects of tDCS in MDD. Results: Despite differences in design and stimulation parameters, the examined studies indicated beneficial effects of tDCS for MDD. These preliminary results, the non-invasiveness of tDCS, and its good tolerability support the need for further research on this technique. Conclusions: tDCS constitutes a promising therapeutic alternative for patients with MDD, but its place in the therapeutic armamentarium remains to be determined.

Dépression résistante : les stratégies de potentialisation

Lithium is among the most classically recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with lithium requires achieving plasma levels above 0.5 mEq/L. Mood-stabilizing antiepileptic drugs such as carbamazepine, valproate derivatives or lamotrigine have not demonstrated conclusive therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Thyroid hormones are considered among the currently recommended add-on therapeutic strategy for the management of depressive patients showing unsuccessful response to standard antidepressant medications. The effectiveness of the add-on strategy with thyroid hormones requires achieving plasma concentration of TSH close to the lower limits at the normal range (0.4 μUI/L) or even below it. Second-generation antipsychotics such as aripiprazole or quetiapine have consistently demonstrated significant therapeutic effects for the management of depressive patients showing unsuccessful response to standard antidepressant medications. Second-generation antipsychotics however require the careful monitoring of both cardiovascular and metabolic adverse effects.

Facteurs prédictifs de rémission sous antidépresseurs chez le sujet âgé souffrant de dépression unipolaire : revue systématique de la littérature

Late-life depression is a heterogeneous mood disorder frequently associated with many adverse conditions, including decreased cognitive function and an elevated risk for comorbid medical disorders, as well as with an elevated mortality rate. Late-life depression encompasses both late-onset as well as early-onset depression that occurs or continues into later years of life. Conventional treatment often required several trials of antidepressants before an effective regimen can be found for an individual. This is associated with persistent depressive symptoms, a disability in activities of daily living and an increased risk of suicide and worsening of medical comorbidities. Thus, in the elderly, it is particularly important to identify predictors of treatment remission to reduce these risks. The purpose of this paper was to review the current status of knowledge regarding predictors of remission to antidepressants among older depressed patients. Patients with high number of cardiovascular risk factors, poor performance in working memory, verbal fluency tests and executive functioning, reduced volumes of cerebral structures (hippocampus, anterior cingular cortex, orbitofrontal cortex) were more likely to reach remission. Reduction of depression score during the first weeks of treatment was correlated with remission. However, more studies are needed to confirm these results.