ABSTRACT
BACKGROUND: While the clinical results from transcranial direct current stimulation (tDCS) for the treatment of depression have been promising, antidepressant effects in patients with medication resistance have been suboptimal. There is therefore a need to further optimise tDCS for medication resistant patients. In this clinical pilot study we examined the feasibility, safety, and clinical efficacy of combining tDCS with a psychological intervention which targets dysfunctional circuitry related to emotion regulation in depression, Cognitive Emotional Training (CET). METHODS: tDCS was administered during CET three times a week for a total of 18 sessions over 6 weeks. Mood, cognition and emotion processing outcomes were examined at baseline and after 3 and 6 weeks of treatment. RESULTS: Twenty patients with medication resistant depression participated, of whom 17 were study completers. tDCS combined with CET was found to be feasible, safe, and associated with significant antidepressant efficacy at 6 weeks, with 41% of study completers showing treatment response (≥â¯50% improvement in depression score). There were no significant cognitive enhancing effects with the exception of improved emotion recognition. Responders demonstrated superior recognition for the emotions fear and surprise at pre-treatment compared to non-responders, suggesting that better pre-treatment emotion recognition may be associated with antidepressant efficacy. LIMITATIONS: This was an open label study. CONCLUSIONS: tDCS combined with CET has potential as a novel method for optimising the antidepressant efficacy of tDCS in medication resistant patients. Future controlled studies are required to determine whether tDCS combined with CET has greater antidepressant efficacy compared to either intervention alone.
Subject(s)
Cognitive Behavioral Therapy/methods , Depressive Disorder, Major/therapy , Depressive Disorder, Treatment-Resistant/therapy , Transcranial Direct Current Stimulation/methods , Adult , Antidepressive Agents/therapeutic use , Cognition/physiology , Depression/psychology , Drug Resistance , Emotions/physiology , Female , Humans , Male , Middle Aged , Pilot Projects , Research Design , Treatment OutcomeABSTRACT
BACKGROUND: Suicide is a devastating public health problem and very few biological treatments have been found to be effective for quickly reducing the intensity of suicidal ideation (SI). We have previously shown that a single dose of ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, is associated with a rapid reduction in depressive symptom severity and SI in patients with treatment-resistant depression. METHOD: We conducted a randomized, controlled trial of ketamine in patients with mood and anxiety spectrum disorders who presented with clinically significant SI (n = 24). Patients received a single infusion of ketamine or midazolam (as an active placebo) in addition to standard of care. SI measured using the Beck Scale for Suicidal Ideation (BSI) 24 h post-treatment represented the primary outcome. Secondary outcomes included the Montgomery-Asberg Depression Rating Scale--Suicidal Ideation (MADRS-SI) score at 24 h and additional measures beyond the 24-h time-point. RESULTS: The intervention was well tolerated and no dropouts occurred during the primary 7-day assessment period. BSI score was not different between the treatment groups at 24 h (p = 0.32); however, a significant difference emerged at 48 h (p = 0.047). MADRS-SI score was lower in the ketamine group compared to midazolam group at 24 h (p = 0.05). The treatment effect was no longer significant at the end of the 7-day assessment period. CONCLUSIONS: The current findings provide initial support for the safety and tolerability of ketamine as an intervention for SI in patients who are at elevated risk for suicidal behavior. Larger, well-powered studies are warranted.
Subject(s)
Depression/drug therapy , Excitatory Amino Acid Antagonists/administration & dosage , Ketamine/administration & dosage , Suicidal Ideation , Adult , Bipolar Disorder/epidemiology , Depressive Disorder, Major/epidemiology , Double-Blind Method , Excitatory Amino Acid Antagonists/therapeutic use , Female , Humans , Ketamine/therapeutic use , Male , Middle Aged , Psychiatric Status Rating Scales , Stress Disorders, Post-Traumatic/epidemiology , Treatment OutcomeABSTRACT
There is an urgent need for more effective treatments for mood and anxiety disorders. As our understanding of the cognitive and affective neuroscience underlying psychiatric disorders expands, so do opportunities to develop novel interventions that capitalize on the capacity for brain plasticity. Cognitive training is one such strategy. This paper provides the background and rationale for developing cognitive-emotional training exercises as an intervention strategy, and proposes guidelines for the development and evaluation of cognitive training interventions with a specific focus on major depressive disorder as an example.
