Neural, Anti-Inflammatory, and Clinical Effects of Transauricular Vagus Nerve Stimulation in Major Depressive Disorder: A Systematic Review.

BACKGROUND: The discovery of effective treatments for major depressive disorder (MDD) may help target different brain pathways. Invasive vagus nerve stimulation (VNS) is an effective neuromodulation technique for the treatment of MDD; however, the effectiveness of the noninvasive technique, transauricular VNS (taVNS), remains unknown. Moreover, a mechanistic understanding of the neural effects behind its biological and therapeutic effects is lacking. This review aimed to evaluate the clinical evidence and the neural and anti-inflammatory effects of taVNS in MDD. METHODS: Two searches were conducted using a systematic search strategy reviewed the clinical efficacy and neural connectivity of taVNS in MDD in humans and evaluated the changes in inflammatory markers after taVNS in humans or animal models of depression. A risk of bias assessment was performed in all human studies. RESULTS: Only 5 studies evaluated the effects of taVNS in patients with depression. Although the studies demonstrated the efficacy of taVNS in treating depression, they used heterogeneous methodologies and limited data, thus preventing the conduct of pooled quantitative analyses. Pooled analysis could not be performed for studies that investigated the modulation of connectivity between brain areas; of the 6 publications, 5 were based on the same experiment. The animal studies that analyzed the presence of inflammatory markers showed a reduction in the level of pro-inflammatory cytokines or receptor expression. CONCLUSIONS: Data on the clinical efficacy of taVNS in the treatment of MDD are limited. Although these studies showed positive results, no conclusions can be drawn regarding this topic considering the heterogeneity of these studies, as in the case of functional connectivity studies. Based on animal studies, the application of taVNS causes a decrease in the level of inflammatory factors in different parts of the brain, which also regulate the immune system. Therefore, further studies are needed to understand the effects of taVNS in patients with MDD.

Altered Serotonin 1B Receptor Binding After Escitalopram for Depression Is Correlated With Treatment Effect.

BACKGROUND: Major depressive disorder (MDD) is commonly treated with selective serotonin reuptake inhibitors (SSRIs). SSRIs inhibit the serotonin transporter (5-HTT), but the downstream antidepressant mechanism of action of these drugs is poorly understood. The serotonin 1B (5-HT1B) receptor is functionally linked to 5-HTT and 5-HT1B receptor binding and 5-HT1B receptor mRNA is reduced in the raphe nuclei after SSRI administration in primates and rodents, respectively. The effect of SSRI treatment on 5-HT1B receptor binding in patients with MDD has not been examined previously. This positron emission tomography (PET) study aimed to quantify brain 5-HT1B receptor binding changes in vivo after SSRI treatment for MDD in relation to treatment effect. METHODS: Eight unmedicated patients with moderate to severe MDD underwent PET with the 5-HT1B receptor radioligand [11C]AZ10419369 before and after 3 to 4 weeks of treatment with the SSRI escitalopram 10 mg daily. Depression severity was assessed at time of PET and after 6 to 7 weeks of treatment with the Montgomery-Åsberg Depression Rating Scale. RESULTS: We observed a significant reduction in [11C]AZ10419369 binding in a dorsal brainstem (DBS) region containing the median and dorsal raphe nuclei after escitalopram treatment (P = .036). Change in DBS [11C]AZ10419369 binding correlated with Montgomery-Åsberg Depression Rating Scale reduction after 3-4 (r = 0.78, P = .021) and 6-7 (r = 0.94, P < .001) weeks' treatment. CONCLUSIONS: Our findings align with the previously reported reduction of 5-HT1B receptor binding in the raphe nuclei after SSRI administration and support future studies testing change in DBS 5-HT1B receptor binding as an SSRI treatment response marker.

Effectiveness of Prefrontal Transcranial Magnetic Stimulation for Depression in Older US Military Veterans.

OBJECTIVE: While typical aging is associated with decreased cortical volume, major depressive disorder (MDD) and posttraumatic stress disorder (PTSD) likely exacerbates this process. Cerebral atrophy leads to increased coil-to-cortex distance and when using transcranial magnetic stimulation (TMS), potentially reducing effectiveness in older adults. METHODS: Data from a large-scale quality improvement project was used. Included veterans eligible for TMS and completed TMS treatment. Age was assessed as a predictive factor of depression outcomes after TMS treatment among veterans. Secondary analyses examined the impact of age on 1) MDD response and remission and 2) MDD change within MDD-only verses comorbid MDD and PTSD groups. RESULTS: The entire sample included 471 veterans. Primary analysis revealed age as a negative predictor of depression outcomes (p = 0.019). Secondary analyses found age to be a significant predictor of remission (p = 0.004), but not clinical response. Age was not a predictive factor in depression outcomes between those with MDD-only compared to MDD+PTSD. CONCLUSIONS: Increased age predicts greater MDD symptom reduction after TMS. Although age did not predict response rates, it did predict increased rates of remission in veterans. Age did not differentially predict depression outcomes between those with or without PTSD. The sample size was sufficient to discern a difference in efficaciousness, and limitations were those inherent to registry studies in veterans. This data indicates that TMS can be an important treatment option for older individuals.

Effectiveness of a supportive care program via a smartphone application on the quality of life and care burden among family caregivers of patients with major depressive disorder: a randomized controlled trial.

BACKGROUND: The majority of patients with major depressive disorder require care that has generally affected caregivers' lives. Providing care could cause negative experiences as a care burden and deteriorate quality of life. However, there is a lack of evidence about caregiver training-based informatics and its impact on the caregiver's life. METHODS: This experimental study was carried out in Mashhad, Iran. A total of 60 primary family caregivers of patients with major depressive disorder were included in the study between February and July 2021. The quadruple block randomization method was used to allocate the participants into control and intervention groups. In the intervention group, family caregivers used the application with weekly phone calls for one month. The app contains the most important points of patient care and has the possibility of communicating with the nurse. The Novak and Guest Care Burden Inventory and the short form of the World Health Organization Quality of Life Questionnaire were completed before and after the intervention. Data analysis was performed using chi-squared tests, independent sample t tests, and analysis of covariance. RESULTS: At baseline, the mean scores of care burden and quality of life were homogeneous between the two groups. After the intervention, the mean scores of care burden and quality of life were significantly reduced and improved in the intervention group compared with the control group (p < 0.001). CONCLUSIONS: Using the application with the ability to communicate with the caregiver, along with educational support, helps to strengthen the relationship between the family caregiver and the nurse. Despite the effectiveness of the present intervention, before including this form of implementation of support in care programs, it is necessary to evaluate its other positive aspects in future studies. TRIAL REGISTRATION: Iranian Registry of Clinical Trials (IRCT), IRCT20210202050222N1. Registered on 05/02/2022.

Goal-Directed Treatment of Patients With Anxiety and Mood Disorders in a Regular Curative Mental Health Care Setting.

This study examined whether goal-directed treatment leads to improved treatment outcomes for patients with a primary mood or anxiety disorder and whether beneficial outcomes are achieved sooner compared to treatment as usual. In a quasi-experimental controlled study with a nested design, 17 therapists received training in goal-directed treatment and treated 105 patients with anxiety or mood disorders using principles of goal-directed treatment. Treatment results on a generic self-report instrument were compared with two control groups: a historical control group consisting of 16 of the 17 participating therapists, who provided treatment as usual to 97 patients before having received training in goal-directed treatment, and a parallel control group consisting of various therapists, who provided treatment as usual to 105 patients. Symptom reduction on a self-report measure was compared using multilevel analysis. A survival analysis was performed to assess whether a satisfactory end state had been reached sooner after goal-directed treatment. The results of this study show that goal-directed treatment only led to a significantly better overall treatment outcome compared to the parallel treatment as usual group. Furthermore, goal-directed treatment was significantly shorter than both treatment as usual groups. In conclusion, this research suggest that goal-directed treatment led to a similar or better treatment outcome in a shorter amount of time.

Predictors of Electroconvulsive Therapy Outcome in Major Depressive Disorder.

BACKGROUND: Electroconvulsive therapy (ECT) is an effective therapy for major depressive disorder (MDD) patients. However, few clinical predictors are available to predict the treatment outcome. This study aimed to characterize the response trajectories of MDD patients undergoing ECT treatment and to identify potential clinical and demographic predictors for clinical improvement. METHODS: We performed a secondary analysis on data from a multicenter, randomized, blinded, controlled trial with 3 ECT modalities (bifrontal, bitemporal, unilateral). The sample consisted of 239 patients whose demographic and clinical characteristics were investigated as predictors of ECT outcomes. RESULTS: The results of growth mixture modeling suggested there were 3 groups of MDD patients: a non-remit group (n = 17, 7.11%), a slow-response group (n = 182, 76.15%), and a rapid-response group (n = 40, 16.74%). Significant differences in age, education years, treatment protocol, types of medication used, Hamilton Depression Scale, Hamilton Anxiety Scale score, Mini-Mental State Examination score, and Clinical Global Impression score at baseline were observed across the groups. CONCLUSIONS: MDD patients exhibited distinct and clinically relevant response trajectories to ECT. The MDD patients with more severe depression at baseline are associated with a rapid response trajectory. In contrast, MDD patients with severe symptoms and older age are related to a less response trajectory. These clinical predictors may help guide treatment selection.

Volume of hippocampus-amygdala transition area predicts outcomes of electroconvulsive therapy in major depressive disorder: high accuracy validated in two independent cohorts.

BACKGROUND: Although many previous studies reported structural plasticity of the hippocampus and amygdala induced by electroconvulsive therapy (ECT) in major depressive disorder (MDD), yet the exact roles of both areas for antidepressant effects are still controversial. METHODS: In the current study, segmentation of amygdala and hippocampal sub-regions was used to investigate the longitudinal changes of volume, the relationship between volume and antidepressant effects, and prediction performances for ECT in MDD patients before and after ECT using two independent datasets. RESULTS: As a result, MDD patients showed selectively and consistently increased volume in the left lateral nucleus, right accessory basal nucleus, bilateral basal nucleus, bilateral corticoamygdaloid transition (CAT), bilateral paralaminar nucleus of the amygdala, and bilateral hippocampus-amygdala transition area (HATA) after ECT in both datasets, whereas marginally significant increase of volume in bilateral granule cell molecular layer of the head of dentate gyrus, the bilateral head of cornu ammonis (CA) 4, and left head of CA 3. Correlation analyses revealed that increased volume of left HATA was significantly associated with antidepressant effects after ECT. Moreover, volumes of HATA in the MDD patients before ECT could be served as potential biomarkers to predict ECT remission with the highest accuracy of 86.95% and 82.92% in two datasets (The predictive models were trained on Dataset 2 and the sensitivity, specificity and accuracy of Dataset 2 were obtained from leave-one-out-cross-validation. Thus, they were not independent and very likely to be inflated). CONCLUSIONS: These results not only suggested that ECT could selectively induce structural plasticity of the amygdala and hippocampal sub-regions associated with antidepressant effects of ECT in MDD patients, but also provided potential biomarkers (especially HATA) for effectively and timely interventions for ECT in clinical applications.

Efficacy of dynamic interpersonal therapy for major depressive disorder in China: results of a multicentered, three-arm, randomized, controlled trial.

BACKGROUND: Dynamic interpersonal therapy (DIT) is a brief, structured psychodynamic psychotherapy with demonstrated efficacy in treating major depressive disorder (MDD). The aim of the study was to determine whether DIT is an acceptable and efficacious treatment for MDD patients in China. METHOD: Patients were randomized to 16-week treatments with either DIT plus antidepressant medication (DIT + ADM; n = 66), general supportive therapy plus antidepressant medication (GST + ADM; n = 75) or antidepressant medication alone (ADM; n = 70). The Hamilton Depression Rating Scale (HAMD) administered by blind raters was the primary efficacy measure. Assessments were completed during the acute 16-week treatment and up to 12-month posttreatment. RESULTS: The group × time interaction was significant for the primary outcome HAMD (F = 2.900, df1 = 10, df2 = 774.72, p = 0.001) in the acute treatment phase. Pairwise comparisons showed a benefit of DIT + ADM over ADM at weeks 12 [least-squares (LS) mean difference = -3.161, p = 0.007] and 16 (LS mean difference = -3.237, p = 0.004). Because of the unexpected high attrition during the posttreatment follow-up phase, analyses of follow-up data were considered exploratory. Differences between DIT + ADM and ADM remained significant at the 1-, 6-, and 12-month follow-up (ps range from 0.001 to 0.027). DIT + ADM had no advantage over GST + ADM during the acute treatment phase. However, at the 12-month follow-up, patients who received DIT remained less depressed. CONCLUSIONS: Acute treatment with DIT or GST in combination with ADM was similarly efficacious in reducing depressive symptoms and yielded a better outcome than ADM alone. DIT may provide MDD patients with long-term benefits in symptom improvement but results must be viewed with caution.

Neurological soft signs are increased in major depressive disorder irrespective of treatment.

The significance of neurological soft signs (NSS) in major depressive disorder (MDD) remains unclear and the stability of NSS in relation to antidepressant treatment has never been investigated. We hypothesized that NSS are relatively stable trait markers of MDD. We thus predicted that patients show more NSS than healthy controls, irrespective of illness duration and antidepressant treatment. To test this hypothesis, NSS were assessed in chronically depressed, medicated MDD patients before (n = 23) and after (n = 18) a series of electroconvulsive therapy (ECT). In addition, NSS were assessed once in acutely depressed, unmedicated MDD patients (n = 16) and healthy controls (n = 20). We found that both chronically depressed, medicated MDD patients and acutely depressed, unmedicated MDD patients showed more NSS than healthy controls. The degree of NSS in both patient groups did not differ. Importantly, we found no change in NSS after on average eleven sessions of ECT. Thus, the manifestation of NSS in MDD seems to be independent of illness duration and pharmacological and electroconvulsive antidepressant treatment. From a clinical perspective, our findings corroborate the neurological safety of ECT.

The Ghent Psychotherapy Study: A Pragmatic, Stratified, Randomized Parallel Trial into the Differential Efficacy of Psychodynamic and Cognitive-Behavioral Interventions in Dependent and Self-Critical Depressive Patients.

INTRODUCTION: Different types of psychotherapy are effective for treating major depressive disorder across groups yet show large within-group differences. Patient personality style is considered a potentially useful variable for treatment matching. OBJECTIVE: This study is the first experimental test of the interaction between therapeutic approach and patients' dependent versus self-critical personality styles. METHODS: A pragmatic stratified parallel trial was carried out with 100 adult patients diagnosed with DSM-IV-TR major depressive disorder. They were randomly assigned to short-term (16-20 sessions) cognitive behavioral therapy (CBT) or short-term psychodynamic psychotherapy (STPP). Patients were assessed at baseline, during therapy, post-therapy, and at 3- and 6-month follow-up. Primary outcome is depression severity measured by the Hamilton Rating Scale for Depression posttreatment. Primary analysis was by intention to treat. This trial is registered with the ISRCTN registry (www.isrctn.com), number ISRCTN17130982. RESULTS: The intention-to-treat sample consisted of 100 participants; 40 with self-critical and 60 with dependent personality styles were randomized to either CBT (n = 50) or STPP (n = 50). We observed no interaction effect (-0.34 [-6.14, 5.46]) between therapy and personality style and found no evidence for a difference in effectiveness between the treatments in general in terms of symptom reduction and maintained benefits at 6-month follow-up. CONCLUSION: We found no evidence that dependent versus self-critical personality styles moderate the relation between treatment and outcome in depression. Research using individual patient data could gain further insight into why specific therapeutic approaches work better for specific patients.

Agreement between survey- and register-based measures of depression in Denmark.

BACKGROUND: Register-based studies of major depressive disorder (MDD) do not capture all prevalent cases, as untreated cases and diagnoses made by general practitioners are not recorded in the registers. We examined the prevalence and agreement of survey- and register-based measures of depression, and explored sociodemographic and health-related factors that may have influenced this agreement. METHODS: All 32,407 participants in the 2017 Central Denmark Region How are you? survey were linked to hospital and prescription records. A checklist for depressive symptoms within the last 14 days (Major Depression Inventory; MDI) from the survey was compared with register-based assessment of hospital-diagnosed MDD and/or prescriptions for antidepressants. We estimated agreement between survey-based and register-based measures for depression and used logistic regression models to explore selected associated factors. RESULTS: In total, 5.9% of How are you? survey participants screened positive for current depression on the MDI. Of these, 51.3% (95% confidence interval (CI): 49.0-53.6) filled a prescription for an antidepressant medication during the 10 years prior or 2 years following the administration of the survey, and 14.5% (95% CI: 12.9-16.2) were treated for MDD in a psychiatric hospital-based setting. When using a higher threshold of the MDI indicating more severe current depression, 22.8% (95% CI: 19.6-26.1) of those who screened positive also received an MDD diagnosis and 63.4% (95% CI: 59.7-67.2) were prescribed antidepressants during this 12-year period. Among those with current depression, female sex, older age, chronic diseases, hospital-treated self-harm, and being permanently outside the workforce were associated with having a register-based MDD diagnosis or antidepressant prescription. Among those with a register-based depression record, female sex, younger age, hospital-treated self-harm, stress, and severe loneliness were associated with current depression. CONCLUSION: We found that as few as 15% of individuals with current depression in the general Danish population were captured by the psychiatric hospital register, while 51% of these individuals were identifiable in the prescription register. These findings demonstrate that register-based measures significantly underestimate the true prevalence of depression by identifying only the cases that are most severe.

Transcranial alternating current stimulation for treating depression: a randomized controlled trial.

Treatment of depression with antidepressants is partly effective. Transcranial alternating current stimulation can provide a non-pharmacological alternative for adult patients with major depressive disorder. However, no study has used the stimulation to treat first-episode and drug-naïve patients with major depressive disorder. We used a randomized, double-blind, sham-controlled design to examine the clinical efficacy and safety of the stimulation in treating first-episode drug-naïve patients in a Chinese Han population. From 4 June 2018 to 30 December 2019, 100 patients were recruited and randomly assigned to receive 20 daily 40-min, 77.5 Hz, 15 mA, one forehead and two mastoid sessions of active or sham stimulation (n = 50 for each group) in four consecutive weeks (Week 4), and were followed for additional 4-week efficacy/safety assessment without stimulation (Week 8). The primary outcome was a remission rate defined as the 17-item Hamilton Depression Rating Scale (HDRS-17) score ≤ 7 at Week 8. Secondary analyses were response rates (defined as a reduction of ≥ 50% in the HDRS-17), changes in depressive symptoms and severity from baseline to Week 4 and Week 8, and rates of adverse events. Data were analysed in an intention-to-treat sample. Forty-nine in the active and 46 in the sham completed the study. Twenty-seven of 50 (54%) in the active treatment group and 9 of 50 (18%) in the sham group achieved remission at the end of Week 8. The remission rate was significantly higher in the active group compared to that in the sham group with a risk ratio of 1.78 (95% confidence interval, 1.29, 2.47). Compared with the sham, the active group had a significantly higher remission rate at Week 4, response rates at Weeks 4 and 8, and a larger reduction in depressive symptoms from baseline to Weeks 4 and 8. Adverse events were similar between the groups. In conclusion, the stimulation on the frontal cortex and two mastoids significantly improved symptoms in first-episode drug-naïve patients with major depressive disorder and may be considered as a non-pharmacological intervention for them in an outpatient setting.

Medicare Benefits Schedule item numbers for transcranial magnetic stimulation (TMS): Questions arising.

OBJECTIVE: Four Medicare Benefits Schedule item numbers for Transcranial Magnetic Stimulation (TMS) treatment of unresponsive MDD were declared in Australia in 2021. They are accompanied by rules/conditions. The aim is to consider these rules/conditions in light of recent research and real-world experience. CONCLUSIONS: While evidence supports some listed rules/conditions, others lack clinical justification and deserve to be reconsidered. These include (a) ineligibility of patients who have previously received TMS, (b) a lifetime total limit of 50 treatments, (c) a second/final course being unavailable for 4 months following the completion of the first course, and (d) the second/final course being limited to 15 treatments.

Effect of Problem Area on Outcomes Among Adolescents Treated With Interpersonal Psychotherapy for Depression.

OBJECTIVE: Interpersonal psychotherapy for adolescents (IPT-A) aims to treat depression by addressing one of four problem areas: grief, role disputes, role transitions, or interpersonal deficits. This study compared the characteristics of adolescents by problem area and evaluated the impact of problem area on outcomes. METHODS: Forty adolescents (ages 12-17) participated in a randomized trial of adaptive treatment strategies that included IPT-A. RESULTS: Adolescents with role disputes were younger than adolescents with interpersonal deficits or role transitions and had worse expectations for therapeutic alliance than those in the transitions group. Adolescents with interpersonal deficits had higher attachment avoidance than those in the transitions group. Posttreatment, adolescents in the transitions group had more severe depression and social adjustment problems than those in the deficits group and more social adjustment problems than those in the disputes group. CONCLUSIONS: This preliminary study's findings suggest that differing IPT-A problem areas may affect prognosis.

Change in reflective functioning in interpersonal psychotherapy and cognitive behavioral therapy for major depressive disorder.

BACKGROUND: Patients with Major Depressive Disorder (MDD) have been found to have restricted capacity for mentalization, and it is possible that this constitutes a vulnerability factor for developing depression. Due to its focus on linking depressive symptomatology to emotions and interpersonal relations, it was hypothesized that Interpersonal Psychotherapy (IPT) would improve mentalization more than Cognitive Behavioral Therapy (CBT). METHODS: In a randomized controlled trial of 90 patients undergoing IPT and CBT for MDD, Reflective Functioning (RF) was rated from Adult Attachment and from Depression-Specific Reflective Functioning (DSRF) Interviews before and after therapy. Treatment outcome was assessed using the Beck Depression Inventory-II. RESULTS: The interaction between time and treatment approach was statistically significant, with RF improving significantly more in IPT than in CBT. Change in RF was not correlated with change in depression. The difference in DSRF ratings before and after therapy was not statistically significant for any of the treatments. CONCLUSIONS: IPT may improve mentalization more than CBT. However, although RF increased significantly in IPT, the mean level was still low after therapy. A limitation of the study is the large amount of post-treatment missing data. More research is needed to understand the potential role of mentalization in symptom reduction.

Dynamic Interpersonal Therapy for U.S. Veterans in a Primary Care Setting.

OBJECTIVE: Brief dynamic interpersonal therapy (DIT) is an evidence-based psychodynamic intervention for depression offered by the U.K. National Health Service and previously studied in the context of a U.S. Department of Veterans Affairs medical center. This study assessed the clinical value of DIT in primary care for veterans with general medical conditions. METHODS: The authors examined outcome data of veterans (N=30; all but one had ≥1 comorbid general medical conditions) referred to DIT from primary care. RESULTS: Veterans who began treatment with clinically elevated depression or anxiety experienced a 42% reduction in symptom severity, as measured by the nine-item Patient Health Questionnaire or by the seven-item Generalized Anxiety Disorder questionnaire, respectively, representing large effect sizes. CONCLUSIONS: Significant decreases in depression and anxiety symptoms suggest the utility of DIT for veterans with comorbid general medical conditions. DIT's dynamically informed framework may improve patients' help seeking, which is relevant for patients experiencing comorbid medical conditions.

Pharmacotherapy for Depression and Anxiety in the Primary Care Setting.

The prevalence of mental health disorders is rising with the coronavirus of 2019 pandemic, and millions of Americans reside in areas with mental health professional shortages. Primary care providers have an opportunity to provide care for commonly occurring mental health disorders. Using a holistic conceptualization of recovery in mental illness, this report provides evidence-based guidance for initiation, titration, and discontinuation of pharmacotherapy for mild to moderate depression and anxiety in the primary care setting. The use of measurement-based care, selection of appropriate class and agent for individual candidates, and patient education are addressed. Best practices for troubleshooting, titration, and referral are discussed.

Racemic Ketamine as an Alternative to Electroconvulsive Therapy for Unipolar Depression: A Randomized, Open-Label, Non-Inferiority Trial (KetECT).

BACKGROUND: Ketamine has emerged as a fast-acting and powerful antidepressant, but no head to head trial has been performed, Here, ketamine is compared with electroconvulsive therapy (ECT), the most effective therapy for depression. METHODS: Hospitalized patients with unipolar depression were randomized (1:1) to thrice-weekly racemic ketamine (0.5 mg/kg) infusions or ECT in a parallel, open-label, non-inferiority study. The primary outcome was remission (Montgomery Åsberg Depression Rating Scale score ≤10). Secondary outcomes included adverse events (AEs), time to remission, and relapse. Treatment sessions (maximum of 12) were administered until remission or maximal effect was achieved. Remitters were followed for 12 months after the final treatment session. RESULTS: In total 186 inpatients were included and received treatment. Among patients receiving ECT, 63% remitted compared with 46% receiving ketamine infusions (P = .026; difference 95% CI 2%, 30%). Both ketamine and ECT required a median of 6 treatment sessions to induce remission. Distinct AEs were associated with each treatment. Serious and long-lasting AEs, including cases of persisting amnesia, were more common with ECT, while treatment-emergent AEs led to more dropouts in the ketamine group. Among remitters, 70% and 63%, with 57 and 61 median days in remission, relapsed within 12 months in the ketamine and ECT groups, respectively (P = .52). CONCLUSION: Remission and cumulative symptom reduction following multiple racemic ketamine infusions in severely ill patients (age 18-85 years) in an authentic clinical setting suggest that ketamine, despite being inferior to ECT, can be a safe and valuable tool in treating unipolar depression.

Absence of early mood improvement as a robust predictor of rTMS nonresponse in major depressive disorder.

BACKGROUND: Symptoms of major depressive disorder (MDD) are reported to change early in treatment with repetitive transcranial magnetic stimulation (rTMS). We evaluated early changes in sleep, anxiety, and mood as predictors of nonresponse to rTMS treatment. METHODS: Three hundred twenty-nine subjects with nonpsychotic MDD completed a 6-week course of rTMS treatment. Subjects were stratified by the severity of their baseline depression, and had their overall depressive symptoms recorded every week of treatment. We evaluated lack of improvement in sleep, anxiety, and mood symptoms after 1 and 2 weeks as potential predictors of eventual nonresponse, defined as <50% improvement in compositive depressive symptoms after 6 weeks. This was measured as negative predictive value (NPV; the likelihood that lack of early symptom improvement accurately predicted eventual treatment nonresponse). RESULTS: Subjects with severe or very severe baseline depression achieving <20% improvement in mood at 1 week were correctly predicted as nonresponders with NPVs largely >90%. At 2 weeks, subjects with very severe baseline depression who failed to demonstrate any improvement in mood were all nonresponders. Lack of improvement in sleep at 2 weeks was also a significant predictor. CONCLUSIONS: Identifying a lack of early mood improvement is a practical and robust method to predict rTMS nonresponse. This suggests a treatment protocol change may be indicated in patients with more severe baseline depression showing minimal early mood improvement.

Moderators of Cognitive Behavioral Treatment for Insomnia on Depression and Anxiety Outcomes.

PURPOSE OF REVIEW: With a focus on reviewing adequately powered randomized controlled trials, we present recent research on the potential of cognitive behavioral therapy for insomnia (CBT-I) to improve depression and anxiety outcomes among patients with insomnia and one of the following comorbid psychiatric disorders: major depressive disorder (MDD), generalized anxiety disorder (GAD), or posttraumatic stress disorder (PTSD). We also examine potential moderators of CBT-I on depression and anxiety outcomes in this population. RECENT FINDINGS: Despite high comorbidity rates, current behavioral and pharmacological treatments for MDD, GAD, and PTSD do not substantially target or improve insomnia symptoms; residual insomnia is exceedingly common even among patients who experience remission. Insomnia plays a critical role in the onset and maintenance of depression and anxiety, and treating insomnia with CBT-I may improve global outcomes for patients with MDD, GAD, and PTSD. CBT-I is superior to traditional depression/anxiety treatment in improving insomnia symptoms among patients with comorbid psychiatric disorders. Results are mixed on whether CBT-I (either alone or augmented with depression/anxiety treatment) is effective in improving overall MDD, GAD, and PTSD outcomes. Evening circadian preference and depression/anxiety symptom severity may moderate the effect of CBT-I on depression and anxiety outcomes.