Personal recovery associated with deep brain stimulation for treatment-resistant depression: A constructivist grounded theory study.

WHAT IS KNOWN ON THE SUBJECT?: Major depressive disorder is the most prevalent of all mental illnesses. 10%-20% of patients with depression and 1% of the population overall have treatment-resistant depression (TRD). DBS is an emerging investigational treatment for TRD with documented clinical efficacy and safety. The framework of the recovery model includes both clinical and personal recovery. Personal recovery is a self-process in which hope, empowerment and optimism are embraced to overcome the impact of mental illness on one's sense of self. Although clinical and functional outcomes of DBS for TRD have been well documented in the previous studies, personal recovery as an outcome has been explored only in a handful of studies. WHAT THIS PAPER ADDS TO EXISTING KNOWLEDGE?: This is the first qualitative study exploring personal recovery from DBS treatment specific to the target of subcallosal cingulate cortex in patients with TRD. Since the existing literature on personal recovery in DBS studies is limited, the contribution of this paper is crucial to this field. For individuals who responded to deep brain stimulation clinically, neither participants nor family believed it cured their depression, but rather there was a significant decrease in the severity of symptoms of depression. A holistic-oriented framework (that includes personal recovery) is significant for those individuals with TRD undergoing DBS. Personal and clinical recovery are two different constructs, and individuals may experience one or the other or both. The experience of participants who responded to deep brain stimulation recognized that the recovery from depression is a process of reconstructing self. This process involved a period of adjustment that evoked a deeper self-awareness, re-engagement with daily living and newfound gratitude in living. Individuals transitioned from an emotionally driven life to one where future goals were considered. Supportive relationships were instrumental in this process. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: A deep brain stimulation intervention for treatment-resistant depression offered individuals an opportunity for personal recovery where a reconstruction of self occurred. Personal recovery can be considered as an outcome in conjunction with clinical and functional outcomes in future DBS trials for TRD. The relevance of personal recovery in the prevention of relapses needs further investigation. To advocate for care and services that facilitate the process of recovery from depression, it is important to understand the personal dimensions and experience of recovery that may influence the process. To develop recovery-oriented interventions to help patients and families in recovery post-deep brain stimulation, further understanding of support and negotiating relationships during this life-altering experience is needed. ABSTRACT: Introduction Multiple trials of antidepressant treatments in patients with depression pose a major challenge to the mental health system. Deep brain stimulation (DBS) is an emerging and promising investigational treatment to reduce depressive symptoms in individuals with treatment-resistant depression (TRD). The clinical and functional outcomes of DBS for TRD have been well documented in previous studies; however, studies of personal recovery as an outcome of DBS specific to the target of subcallosal cingulate cortex in patients with TRD are limited. Aim To explore the processes of personal recovery in patients with treatment-resistant depression following subcallosal cingulate-deep brain stimulation. Method Participants were 18 patients with TRD who participated in the subcallosal cingulate (SCC)-DBS trial and 11 family members. They also participated in add-on individual cognitive behavioural therapy during the trial. A qualitative constructivist grounded theory approach was used to conceptualize the personal recovery process of patients and families. Results While every participant and their families' journey were unique following the deep brain stimulation intervention, a theoretical model of Balancing to Establish a Reconstructed Self emerged from the data. The themes underlying the model were (1) Balancing to Establish a Reconstructed Self: A Whole-Body Experience, (2) The Liminal Space in-between: Balancing with Cautious Optimism, (3) Hope: Transitioning from Emotion-Focussed Living to Goal-Oriented Planning and (4) Support: Negotiating Relationships. Discussion This is the first study examining recovery from patients' perspectives as an outcome of SCC-DBS intervention for TRD. The study shows that personal recovery is a gradual and continual process of reconstruction of the self, developing through supportive relationships. Clinical and personal recovery are two distinct constructs, and individuals may experience one or the other or both. Most patients who do respond clinically experience improvement in terms of having optimism and hope. Some patients, however, respond with significant symptom reduction but are not able to achieve personal recovery to experience joy or hope for improved quality of living. Implications for Practice Strategies for personal recovery for both patients and family need to be considered during and post deep brain stimulation intervention. Nurses working with these patients and families may benefit from education, training and support to assess and engage in conversations about their recovery process.

Functional outcomes with bright light in monotherapy and combined with fluoxetine in patients with major depressive disorder: Results from the LIFE-D trial.

BACKGROUND: Bright light therapy has been shown to improve depressive symptoms in patients with nonseasonal major depressive disorder (MDD) but there are few studies examining functional outcomes. METHODS: We examined secondary functional outcomes in the 8-week randomized, placebo-sham-controlled LIFE-D trial comparing light therapy, fluoxetine, and the combination in patients with nonseasonal MDD. Functional assessments included the Sheehan Disability Scale (SDS) and, for employed participants, the Lam Employment Absence and Productivity Scale (LEAPS). Analysis of covariance (ANCOVA) was conducted with SDS and LEAPS change scores from baseline to week 8 as dependent variables, treatment modality (light, fluoxetine) as an independent variable, and baseline SDS and LEAPS scores as covariates. RESULTS: Of 122 randomized participants, SDS data were available for 105 and LEAPS data for 70. For the SDS, there were no interaction effects, but there was a significant small- to medium-sized main effect of light treatment on total SDS scores with corresponding significant effects in the Social Life and Family Life domains, but not in the Work/Study domain. There were no significant interaction or main effects with LEAPS scores. CONCLUSION: Light therapy significantly improved social and family life functioning in patients with MDD. However, work functioning was not significantly improved despite large effect sizes; these results were limited by low statistical power because of small sample sizes. Future studies should use longer treatment durations and be powered to detect clinically relevant differences in functional outcomes.

Quality of Life Impacts of Bright Light Treatment, Fluoxetine, and the Combination in Patients with Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial.

OBJECTIVE: Bright light therapy is increasingly recommended (alone or in combination with antidepressant medication) to treat symptoms of nonseasonal major depressive disorder (MDD). However, little is known about its impacts on quality of life (QoL), a holistic, patient-valued outcome. METHODS: This study utilizes secondary outcome data from an 8-week randomized, controlled, double blind trial comparing light monotherapy (n = 32), fluoxetine monotherapy (n = 30), and the combination of these (n = 27) to placebo (n = 30). QoL was assessed using the Quality of Life Enjoyment and Satisfaction Questionnaire Short Form (Q-LES-Q-SF). Treatment-related differences in QoL improvements were assessed using a repeated measures analysis of variance. The influence of potential predictors of QoL (demographic variables and change in depressive symptoms) were investigated via hierarchical linear regression. RESULTS: Q-LES-Q-SF scores significantly improved across all treatment conditions; however, no significant differences were observed between treatment arms. QoL remained poor relative to community norms by the end of the trial period: Across conditions, 70.6% of participants had significantly impaired QoL at the 8-week assessment. Reduction in depressive scores was a significant predictor of improved QoL, with the final model accounting for 54% of variance in QoL change scores. CONCLUSION: The findings of this study emphasize that improvement in QoL and reduction in depressive symptoms in MDD, while related, cannot be taken to be synonymous. Adjunctive therapies may be required to address unmet QoL needs in patients with MDD receiving antidepressant or light therapies. Further research is required to explore additional predictors of QoL in order to better refine treatments for MDD.

Appetitive Symptoms Differentially Predict Treatment Response to Fluoxetine, Light, and Placebo in Nonseasonal Major Depression.

OBJECTIVE: We previously reported that morning bright light therapy is efficacious in adults with nonseasonal major depressive disorder (MDD), both on its own and in combination with fluoxetine. Given that appetitive symptoms predict response to bright light therapy in seasonal depression, we examined, in this secondary analysis, whether the same held true in these nonseasonal MDD patients. METHODS: Data were collected from October 7, 2009, to March 11, 2014. One hundred twenty-two patients who met DSM-IV-TR criteria for MDD without a seasonal pattern were randomly assigned to light monotherapy, fluoxetine, combination light and fluoxetine, or double-placebo (inactivated negative ion generator plus placebo pill). Multiple regression assessed the percentage change in Montgomery-Asberg Depression Rating Scale (MADRS) scores based on treatment condition, appetitive symptom score at baseline (sum of 4 items on the Structured Interview Guide for the Hamilton Depression Rating Scale, Seasonal Affective Disorders version), and the condition-by-appetitive score interaction. Sex was considered as a possible moderator of these effects. RESULTS: The overall regression model predicting treatment response was highly significant (P < .001), and the treatment condition-by-appetitive score interaction was a strong predictor of MADRS change scores (t = 2.65, P = .009). For individuals in the placebo group, more appetitive symptoms at baseline predicted less decrease in MADRS scores at 8 weeks (r = -0.37; large effect size). In contrast, for individuals in the active treatment groups, more appetitive symptoms at baseline predicted more of a decrease in depression scores at 8 weeks (fluoxetine group r = +0.23, medium effect size; light therapy group r = +0.11, small effect size; combination group r = +0.32, medium to large effect size). No moderation effect of sex was found. CONCLUSIONS: More severe appetitive symptoms at baseline predicted treatment response differentially across the 4 treatment groups. Contrary to prior findings in seasonal depression, this association was not robust for MDD patients receiving light therapy alone, although it was stronger in patients receiving fluoxetine with or without light. As the group sample sizes were modest, the current findings should be considered as preliminary only. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00958204.

Thalamocortical connectivity in major depressive disorder.

BACKGROUND: Major Depressive Disorder (MDD) is highly prevalent and potentially devastating, with widespread aberrations in brain activity. Thalamocortical networks are a potential candidate marker for psychopathology in MDD, but have not yet been thoroughly investigated. Here we examined functional connectivity between major cortical areas and thalamus. METHOD: Resting-state fMRI from 54 MDD patients and 40 healthy controls were collected. The cortex was segmented into six regions of interest (ROIs) consisting of frontal, temporal, parietal, and occipital lobes and pre-central and post-central gyri. BOLD signal time courses were extracted from each ROI and correlated with voxels in thalamus, while removing signals from every other ROI. RESULTS: Our main findings showed that MDD patients had predominantly increased connectivity between medial thalamus and temporal areas, and between medial thalamus and somatosensory areas. Furthermore, a positive correlation was found between thalamo-temporal connectivity and severity of symptoms. LIMITATIONS: Most of the patients in this study were not medication naïve and therefore we cannot rule out possible long-term effects of antidepressant use on the findings. CONCLUSION: The abnormal connectivity between thalamus and temporal, and thalamus and somatosensory regions may represent impaired cortico-thalamo-cortical modulation underlying emotional, and sensory disturbances in MDD. In the context of similar abnormalities in thalamocortical systems across major psychiatric disorders, thalamocortical dysconnectivity could be a reliable transdiagnostic marker.

Efficacy of Bright Light Treatment, Fluoxetine, and the Combination in Patients With Nonseasonal Major Depressive Disorder: A Randomized Clinical Trial.

IMPORTANCE: Bright light therapy is an evidence-based treatment for seasonal depression, but there is limited evidence for its efficacy in nonseasonal major depressive disorder (MDD). OBJECTIVE: To determine the efficacy of light treatment, in monotherapy and in combination with fluoxetine hydrochloride, compared with a sham-placebo condition in adults with nonseasonal MDD. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, placebo- and sham-controlled, 8-week trial in adults (aged 19-60 years) with MDD of at least moderate severity in outpatient psychiatry clinics in academic medical centers. Data were collected from October 7, 2009, to March 11, 2014. Analysis was based on modified intent to treat (randomized patients with ≥1 follow-up rating). INTERVENTIONS: Patients were randomly assigned to (1) light monotherapy (active 10,000-lux fluorescent white light box for 30 min/d in the early morning plus placebo pill); (2) antidepressant monotherapy (inactive negative ion generator for 30 min/d plus fluoxetine hydrochloride, 20 mg/d); (3) combination light and antidepressant; or (4) placebo (inactive negative ion generator plus placebo pill). MAIN OUTCOMES AND MEASURES: Change score on the Montgomery-Åsberg Depression Rating Scale (MADRS) from baseline to the 8-week end point. Secondary outcomes included response (≥50% reduction in MADRS score) and remission (MADRS score ≤10 at end point). RESULTS: A total of 122 patients were randomized (light monotherapy, 32; fluoxetine monotherapy, 31; combination therapy, 29; placebo, 30). The mean (SD) changes in MADRS score for the light, fluoxetine, combination, and placebo groups were 13.4 (7.5), 8.8 (9.9), 16.9 (9.2), and 6.5 (9.6), respectively. The combination (effect size [d] = 1.11; 95% CI, 0.54 to 1.64) and light monotherapy (d = 0.80; 95% CI, 0.28 to 1.31) were significantly superior to placebo in the MADRS change score, but fluoxetine monotherapy (d = 0.24; 95% CI, -0.27 to 0.74) was not superior to placebo. For the respective placebo, fluoxetine, light, and combination groups at the end point, response was achieved by 10 (33.3%), 9 (29.0%), 16 (50.0%), and 22 (75.9%) and remission was achieved by 9 (30.0%), 6 (19.4%), 14 (43.8%), and 17 (58.6%). Combination therapy was superior to placebo in MADRS response (ß = 1.70; df = 1; P = .005) and remission (ß = 1.33; df = 1; P = .02), with numbers needed to treat of 2.4 (95% CI, 1.6 to 5.8) and 3.5 (95% CI, 2.0 to 29.9), respectively. All treatments were generally well tolerated, with few significant differences in treatment-emergent adverse events. CONCLUSIONS AND RELEVANCE: Bright light treatment, both as monotherapy and in combination with fluoxetine, was efficacious and well tolerated in the treatment of adults with nonseasonal MDD. The combination treatment had the most consistent effects. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00958204.

Lamotrigine treatment for post-stroke pathological laughing and crying.

Pathologic laughing and crying (PLC) is a common distressing and socially disabling condition in stroke patients. Antidepressants, particularly selective serotonin reuptake inhibitors (SSRIs), have been increasingly recognized as the treatment of choice for pathologic crying (PC). However, little is known about etiologies and other treatment options for various clinical manifestations of PLC. This case report illustrates the beneficial effect of lamotrigine, a novel antiepileptic drug with antidepressant and mood-stabilizing properties in post-stroke PLC. A 60-year-old woman developed PLC after an ischemic stroke affecting the left frontal and temporal lobes. She was treated with lamotrigine initially at the dose of 50 mg a day, which was gradually increased to 100 mg a day over a 4-week period. There was a significant and rapid recovery in both laughing and crying components of PCL with lamotrigine treatment. The symptoms of pathologic laughing have shown a better response to lamotrigine than PC. Controlled investigations are needed to evaluate the beneficial as well as the differential effects of lamotrigine on PLC.