Reduction In Hamilton Depression Rating Scale Research Articles

A Randomized Controlled Trial Comparing Efficacy and Safety of Antidepressant Monotherapy.

The majority of mainstream antidepressants lack the promise of complete amelioration of symptoms. Other pitfalls include the latency period and side effects. These issues prompted investigations concerning thevarious roles of serotonin (5-HT) neurotransmissions in the etiology of depression. In this study, each study participant received vilazodone, vortioxetine, and escitalopram monotherapy for major depressive disorder (MDD)for 16 weeks. After that, the subject's scores on the Hamilton Depression Rating Scale (HDRS)-17 item version and the Montgomery Åsberg Depression Rating Scale (MADRS) were evaluated. In the study population, we kept track of the incidence of adverse events. Ninety-six patients with MDD participated in this open-label, randomized, three-arm study. Participants were allotted into three groups according to a 1:1:1 ratio and given vilazodone (20-40 mg/day), vortioxetine (5-20 mg/day), or escitalopram (10-20 mg/day) for 16 weeks. Vortioxetine and vilazodone are test medications, with escitalopram serving as the control. After the baseline visit, follow-up appointments were scheduled every four weeks. Per-protocol (PP) and intent-to-treat (ITT) populations served as means for efficacy and safety evaluations, respectively. We prospectively registered this research in the Clinical Trial Registry, India (CTRI) (2022/07/043808). Out of the 134 patients we screened, 109 (81.34%) were eligible. Ninety-six (88.07%) of them completed the 16-week trial. In the PP population (n = 96), we analyzed efficacy. They had a mean age of 46.3 ± 6.2 years. At baseline, each group's median HDRS score was 30.0 (p = 0.964). Following 16 weeks of antidepressant therapy, these scores dropped to 15.0, 14.0, and 13.0 (p = 0.002). Baseline MADRS scores for all groups were 36.0 (p = 0.741). They had corresponding values of 20.0, 18.0, and 17.0 at 16 weeks (p < 0.001). Regarding both efficacy endpoints, the post-hoc analysis with the Bonferroni correction demonstrated statistically significant differences (p < 0.001). We performed the safety assessments within our ITT population (n = 109). Ninety-six adverse events were recorded. Nonetheless, none of them seemed serious. Still, five participants opted out because of their side effects. Vomiting and nausea were the most frequent side effects. Compared to escitalopram and vilazodone, vortioxetine demonstrated a statistically significant reduction in HDRS and MADRS scores. It also had fewer and milder side effects. We recommend conducting studies involving a broader population to investigate the antidepressant effects of these medications further.

Treatment of Refractory Bipolar Depression With Stereotactic Radiosurgery Targeting the Subgenual Cingulate Cortex.

Background The subgenual cingulate cortex (SGC) has been identified as a key structure within multiple neural circuits whose dysfunction is implicated in the neurobiology of depression. Deep brain stimulation in the SGC is thought to reduce and normalize local metabolism, causing normalization of circuit behavior and an improvement in depressive symptoms. We hypothesized that nonablative stereotactic radiosurgery (SRS) to the SGC would reduce local metabolism and reduce the severity of depression in patients with treatment-resistant bipolar depression. Methods Under the FDA's Humanitarian Device Exemption program, patients were screened for inclusion and exclusion criteria. Three volunteers meeting the criteria provided informed consent. Bilateral SGC targets were irradiated to a maximum dose of 75 Gy in one fraction. Subjects were followed for one year following the procedure with mood assessments (Hamilton Depression Rating Scale (HDRS), Clinical Global Impression-Improvement, Clinical Global Impression-Severity, and Young Mania Rating Scale), neurocognitive testing (Delis-Kaplan Executive Function System, Wechsler Adult Intelligence Scale III digit span, and California Verbal Learning Test II), and imaging. Further imaging was completed approximately two years after the procedure. Clinical improvement was defined as a ≥50% reduction in HDRS. Results Two of the three subjects showed clinical improvement in depressive symptoms during the follow-up period, while one subject showed no change in symptom severity. One of three subjects was hospitalized for the emergence of an episode of psychotic mania after discontinuing antipsychotic medications against medical advice but promptly recovered with the reinstitution of an antipsychotic. Sequential assessments did not reveal impairment in any cognitive domain assessed. For one of the three subjects, MRI imaging showed evidence of edema at 12 months post-SRS, which resolved at 22 months post-procedure. In a second of three patients, there was evidence of local edema at the target site at long-term follow-up. All imaging changes were asymptomatic. Conclusion Radiosurgical targeting of the SGC may be a noninvasive strategy for the reduction of severe depression in treatment-resistant bipolar disorder. Two out of three patients showed clinical improvement. While these results are promising, further study, including improvements in target selection and dosing considerations, is needed.

Findings from a pilot open-label trial of N-acetylcysteine for the treatment of pediatric mania and hypomania

BackgroundPediatric bipolar disorder is a highly prevalent and morbid disorder and is considered a prevalent public health concern. Currently approved treatments often pose the risk of serious side effects. Therefore, this study assessed the efficacy and tolerability of N-acetylcysteine (NAC), in children and adolescents with bipolar spectrum disorder.MethodsWe conducted a 12-week open-label trial of NAC for treatment of mania and hypomania in children and adolescents ages 5–17 with bipolar spectrum disorder including participants with full and subthreshold manic symptoms, accepting those with and without mixed states with co-occurring depression, and Young Mania Rating Scale scores ≥ 20 and < 40. Symptoms of mania and depression were assessed using the Young Mania Rating Scale (YMRS), Hamilton Depression Rating Scale (HDRS), Children’s Depression Rating Scale (CDRS), and Clinical Global Impression (CGI) Severity (CGI-S) and Improvement (CGI-I) scales for mania and depression.ResultsThis study had a high drop-out rate with only 53% completing all 12 weeks. There was a significant reduction in YMRS, HDRS, and CDRS mean scores from baseline to endpoint. Of the 24 exposed participants, 54% had an anti-manic response measured by a reduction in YMRS ≥ 30% and 46% had a CGI-I mania score ≤ 2 at endpoint. Additionally, 62% of participants had an anti-depressive response measured by a reduction in HDRS ≥ 30%, 31% had an anti-depressive response measured by a reduction in CDRS ≥ 30%, and 38% had a CGI-I depression score ≤ 2 at endpoint.ConclusionsThese pilot open-label findings in a small sample provide preliminary data supporting the tolerability and safety of NAC in a pediatric population. The findings of this pilot scale study indicating improvement in mania and depression are promising, but require replication with a monotherapy randomized placebo controlled clinical trial and larger sample.Trial RegistrationClinicalTrials.gov Identifier: NCT02357290. First Registration 06/02/2015.

Rapid response to selective serotonin reuptake inhibitors in post-COVID depression

The spreading of the Severe Acute Respiratory Syndrome Coronavirus (COVID-19) pandemic could be associated with psychiatric implications. After COVID-19, depression was reported in 40% of patients at one-, three-, and six-months follow-up. Emerging literature suggests anti-inflammatory and antiviral properties of antidepressants in the treatment of SARS-CoV-2. We aim to investigate the efficacy of Selective Serotonin Reuptake Inhibitor (SSRI) in treating post-COVID depression.We included 60 patients affected by a major depressive episode and treated with SSRI in the six months following recovery from COVID. The severity of depression was rated at baseline and after four weeks on the Hamilton Depression Rating Scale (HDRS). Response to treatment was considered when the patients achieved a 50% HDRS reduction. To investigate changes of depressive symptomatology over time, repeated measures ANOVAs according to clinical variables were performed.We found that 55 (92%) patients showed a clinical response to antidepressant. Patients showed a significant decrease over time of HDRS score (baseline HDRS = 23.37 ± 3.94, post-treatment HDRS = 6.71±4.41, F = 618.90, p < 0.001), irrespectively of sex, previous psychiatric history, previous history of mood disorder, and SSRI type.This is the first study to explore the SSRI efficacy in post-COVID depression, suggesting rapid antidepressant effects in most patients. SSRIs treatment could contribute to the rapid antidepressant response by directly targeting the neuroinflammation triggered by SARS-CoV-2. We suggest screening psychopathology of COVID-19 survivors to diagnose emergent depression and pharmacologically treat it to reduce the disease burden and related years of life lived with disability.

Antidepressant effects of ketamine and ECT: A pilot comparison

BackgroundTo compare the antidepressant effects and cognitive adverse effects of intravenous ketamine infusion and Electro-convulsive therapy (ECT) in persons with severe depressive episodes. MethodsThis assessor-blinded randomized control trial included 25 patients (either sex; 18–65 years) meeting ICD-10 criteria for severe depression (bipolar or unipolar). Patients received either ECT (n = 13) or intravenous infusions of ketamine hydrochloride (0.5 mg/kg over 45 min; n = 12) for six alternate day sessions over a period of two weeks. Severity of depression was assessed at baseline and on every alternate day of intervention using the Hamilton Depression Rating Scale (HDRS) and self-reported Beck Depression Inventory (BDI). ResultsBaseline socio-demographic and clinical variables including HDRS (ECT: 25.15±6.58; Ketamine: 23.33±4.05, p = 0.418) and BDI (ECT: 37.07±6.58; Ketamine: 33.33±9.29; p = 0.254) were comparable. Repeated-measures analysis of variance revealed that ECT patients showed significantly greater reduction in HDRS (group*time interaction effect; F = 4.79; p<0.001) and BDI scores (group*time interaction effect; F = 3.83; p<0.01). ECT patients had higher response rate than ketamine patients [HDRS: ECT- 13/13(100%) vs ketamine- 8/12 (66.70%); p = 0.04]. This was true for remission as well [ECT- 12/13(92.30%) vs ketamine- 6/12(50%), p = 0.030; both HDRS and BDI]. Performance on Digit Symbol Substitution Test (as part of the Battery for ECT-Related Cognitive Deficits scale) significantly improved in ketamine patients (p = 0.02) while that in ECT patients worsened non significantly (p = 0.30). LimitationsRelatively small sample size; higher proportion of dropouts in the Ketamine arm. ConclusionThis study favoured ECT over ketamine for a better efficacy over six treatment sessions in severe depression. The results need to be replicated in larger studies. Trial registrationCTRI/2019/09/021184

Long versus short pulse width subcallosal cingulate stimulation for treatment-resistant depression: a randomised, double-blind, crossover trial

Stimulation adjustment is required to optimise outcomes of deep brain stimulation (DBS) for treatment-resistant depression, but controlled data for ideal stimulation parameters are poor or insufficient. We aimed to establish the efficacy and safety of short pulse width (SPW) and long pulse width (LPW) subcallosal cingulate DBS in depression. We did a double-blind, randomised, crossover trial in an academic hospital in Calgary, AB, Canada. Patients had DSM IV-defined major depressive disorder and bipolar depression (20-70 years old, both sexes) and did not respond to treatment for more than 1 year, with a score of 20 or more on the 17-item Hamilton Depression Rating Scale (HDRS) at recruitment. Patients underwent bilateral DBS implantation into the subcallosal cingulate white matter using diffusion tensor imaging tractography. Patients were randomly assigned 1:1 without stratification using a computerised list generator to receive either SPW (90 μs) or LPW (210-450 μs) stimulation for 6 months. Patients and the clinician assessing outcomes were masked to the stimulation group. Keeping frequency constant (130 Hz), either pulse width or voltage was increased monthly, based on response using the HDRS. Patients who did not respond to treatment (<50% reduction in HDRS from baseline) at 6 months crossed over to the opposite stimulation for another 6 months. All patients received individualised cognitive behavioural therapy (CBT) for 12 weeks. The primary outcome was change in HDRS at 6 months and 12 months using intention-to-treat analysis. This study is registered with ClinicalTrials.gov, NCT01983904. Between Dec 5, 2013, and Sept 30, 2016, of 225 patients screened for eligibility, 23 patients were selected for DBS surgery. After one patient withdrew, 22 (mean age 46·4 years, SEM 3·1; 10 [45%] female, 12 [55%] male) were randomly assigned, ten (45%) to LPW stimulation and 12 (55%) to SPW stimulation. Patients were followed up at 6 months and 12 months. There was a significant reduction in HDRS scores (p<0·0001) with no difference between SPW and LPW groups (p=0·54) in the randomisation phase at 6 months. Crossover groups did not show a significant decrease in HDRS within groups (p=0·15) and between groups (p=0·21) from 6-12 months. Adverse events were equal between groups. Worsening anxiety and depression were the most common psychological adverse events. One patient in the SPW group died by suicide. Both LPW and SPW stimulation of subcallosal cingulate white matter tracts carried similar risks and were equally effective in reducing depressive symptoms, suggesting a role for both pulse width and amplitude titration in optimising clinical outcomes in patients with treatment-resistant depression. Alberta Innovates Health Solutions.

Circadian Preference as a Moderator of Depression Outcome Following Cognitive Behavioral Therapy for Insomnia Plus Antidepressant Medications: A Report From the TRIAD Study.

We previously presented results from a randomized controlled trial that examined the effects of antidepressant medication plus cognitive behavioral therapy for insomnia (CBT-I) among patients with major depressive disorder (MDD) and insomnia. The current secondary analysis aims to examine whether circadian preference moderated the reduction in depression and insomnia symptom severity during this trial. A total of 139 adult participants with MDD and insomnia disorder were treated with antidepressant medication and randomized to receive 7 sessions of CBT-I or a control therapy (CTRL). Circadian preference (eveningness) was measured using the Composite Scale of Morningness (CSM). Depression symptom severity was assessed using the Hamilton Depression Rating Scale (HDRS); insomnia symptom severity was assessed using the Insomnia Severity Inventory (ISI). The moderating role of circadian preference on changes in HRSD and ISI was assessed via latent growth models within the framework of structural equation modeling. Greater evening preference was associated with smaller reduction in HDRS (P = .03) from baseline to week 6 across treatment groups. The interaction between CSM and treatment group was also significant (P = .02), indicating that participants with greater evening preference in the CTRL group had significantly smaller HDRS reduction than those with greater evening preference in the CBT-I group. Circadian preference did not share significant associations with ISI (all P > .30). Individuals with MDD and insomnia who have an evening preference are at increased risk for poor response to pharmacological depression treatment augmented with either CBT-I or CTRL behavioral insomnia treatment. However, evening types have better depression outcomes when treated with CBT-I than with CTRL for insomnia.

Randomized Double-Blind Study of Long vs. Short Pulse Width Subcallosal Cingulate Stimulation for Treatment-Resistant Depression

Background: Stimulation adjustment is required to optimize outcomes of deep brain stimulation (DBS) for treatment-resistant depression (TRD), but controlled data on ideal stimulation parameters are limited. Using a double-blind randomized cross-over design, we measured the efficacy and safety of short (SPW) and long (LPW) pulse width subcallosal cingulate (SCC) DBS. Methods: Twenty-two patients with TRD underwent bilateral DBS implantation into SCC white matter using diffusion tensor imaging tractography in an academic hospital. Patients were randomized using computer-generated numbers to receive either SPW or LPW stimulation for 6 months. Clinician assessing outcomes was blinded to stimulation group. Keeping frequency constant (130 Hz), either pulse width or voltage was increased monthly, based on response using 17-item Hamilton Depression Rating Scale (HDRS). Non-responders (< 48% reduction in HDRS from the baseline) at 6 months were crossed-over to opposite stimulation for another 6 months. Primary outcome was change in HDRS at 6 and 12 months. Findings: One responder from SPW group suicided at 3 months, therefore data from 21 patients were analyzed, as per protocol. Response rates were 48% at both 6 and 12 months for the entire sample. Both stimulation groups showed significant reduction in HDRS (p <0.001), with no difference between groups at 6 months (p=0.61), plus within (p=0.21) and between (p=0.52) cross-over groups at 12 months. Area under the curve analysis revealed a trend for stronger clinical response in the LPW group over 6-12 months (p=0.051). LPW patients had better remission rates (30-36%) than SPW (10-20%) over 6-12 months. Adverse effects and battery drainage were comparable between groups. Add-on individualized cognitive behavioral therapy did not change HDRS scores. Interpretation: While both LPW and SPW stimulation were equally safe and effective, clinical response was stronger with LPW over time, indicating a role for LPW in stimulus optimization of SCC-DBS for TRD. Trial Registration: ClinicalTrails.gov: NCT01983904 Funding Statement: Alberta Innovates and Health Solutions Declaration of Interests: Dr. Ramasubbu has received honorarium for serving in the advisory committee of Astra Zeneca, Lundbeck, Janssen, and Otsuka. He also received investigatorinitiated grant from Astra Zeneca and Pfizer. Other authors declare no potential conflict of interest. Dr. Kiss reports that Alberta health services receives value adds for research and education from Medtronic Canada, the manufacturer of the devices used in the study. These funds are only partially available for research to the authors for research and education through the Neuromodulation program. Medtronic had no involvement in any of this study. Ethics Approval Statement: This was a double-blind randomized controlled parallel and cross-over trial approved by the Conjoint Health Research Ethics board at the University of Calgary. Written informed consent was obtained.

Comparison of efficacy and tolerability of escitalopram and venlafaxine in treatment-naïve patients with unipolar nonpsychotic depression: Is there a need to revisit the prescription patterns?

Background: Depression is a common mental illness for which guidelines recommend selective serotonin reuptake inhibitors as the first-line treatment. As per the Sequenced Treatment Alternatives to Relieve Depression trial, the first antidepressant needs to be chosen carefully so that the number of treatment changes and therefore treatment resistance can be reduced. This study compared the efficacy and tolerability of escitalopram and venlafaxine, in treatment-naive patients with first-episode, nonpsychotic unipolar depression. Methodology: In this prospective, randomized, open-label study, 77 patients with the International Classification of Disease-10 Diagnostic Criteria for Research diagnosis of depression were inducted and randomly assigned using a computer-generated random table to receive either escitalopram (10–20 mg/day) or venlafaxine (75–225 mg/day) in therapeutic range for a period of 12 weeks. The assessments included the Hamilton Depression Rating Scale (HDRS) and physical investigations at baseline and weeks 2, 6, and 12. A total of 60 patients completed the study and were included in the final analysis. Results: Thirty patients in each group (n = 60) enrolled with comparable baseline assessment except significantly higher HDRS in the venlafaxine group (29.87 ± 10.58) compared to escitalopram group (21.80 ± 4.41). At 12 weeks, the reduction in HDRS was significantly early and higher in the venlafaxine group (26.3 ± 9.7) than the escitalopram group (21.3 ± 4.2). Common adverse effects in the venlafaxine group included Gastrointestinal (GI) activation and vivid dreams which were seen till 2 weeks; the escitalopram group included sexual dysfunction which lasted till the end of the study. Conclusions: Both the molecules lead to significant reduction in HDRS scores across assessment. However, venlafaxine demonstrated superior efficacy and transient adverse effects compared to escitalopram, despite having higher HDRS scores at baseline. The results of the current study indicate that serotonin–norepinephrine reuptake inhibitors such as venlafaxine should be prescribed more often in routine clinical practice.

A systematic review and meta-analysis of deep brain stimulation in treatment-resistant depression

BackgroundDeep brain stimulation (DBS) has been applied in treatment-resistant depression (TRD) as a putative intervention targeting different brain regions. However, the antidepressant effects of DBS for TRD in recent clinical trials remain controversial. MethodsWe searched Scopus, EMBASE, the Cochrane Library, PubMed, and PsycINFO for all published studies investigating the efficacy of DBS in TRD up to Feb 2017. Hamilton depression rating scale (HDRS) scores and Montgomery–Asberg depression rating scale (MARDS) scores were compared between baseline levels and those after DBS using the standardized mean difference (SMD) with 95% confidence intervals (CIs). The pooled response and remission rates were described using Risk Difference with 95% CIs. ResultsWe identified 14 studies of DBS in TRD targeting the subcallosal cingulate gyrus (SCG), ventral capsule/ventral striatum (VC/VS), medial forebrain bundle (MFB), and nucleus accumbens (NAcc). The overall effect sizes showed a significant reduction in HDRS after DBS stimulation in these four regions, with a standardized mean difference of −3.02 (95% CI=−4.28 to −1.77, p<0.00001) for SCG, −1.64 (95% CI=−2.80 to −0.49, p=0.005) for VC/VS, −2.43 (95% CI=−3.66 to −1.19, p=0.0001) for MFB, and −1.30 (95% CI=−2.16 to −0.44, p=0.003) for NAcc. DBS was effective, with high response rates at 1, 3, 6, and 12months. Some adverse events (AEs), especially some specific AEs related to targeting regions, occurred during the DBS treatment. ConclusionsDBS significantly alleviates depressive symptoms in TRD patients by targeting the SCG, VC/VS, MFB, and NAcc. Several adverse events might occur during DBS therapy, although it is uncertain whether some AEs can be linked to DBS treatment. Further confirmatory trials are required involving larger sample sizes.

A combined marker of early non-improvement and the occurrence of melancholic features improve the treatment prediction in patients with Major Depressive Disorders

BackgroundEarly Improvement of depressive symptoms within two weeks of antidepressant treatment is a highly sensitive but less specific predictor of later treatment outcome. The aim of this study was to identify clinical features at treatment initiation which are associated with early improvement and non-improvement as well as to identify variables predicting non-remission in patients showing an early improvement. Methods889 patients with a major depressive episode according to DSM-IV who had participated in an antidepressant treatment trial served as study sample. Clinical predictors (demographic variables, psychopathology, comorbid disorders) were analysed in 698 (79%) early improver (Hamilton Depression Rating Scale reduction > 20% after 14 days of treatment) compared to 191 (21%) non-improver. Furthermore, clinical predictors for later remission and non-remission were analysed in the 698 patients showing an early improvement. ResultsPatients with more severe depression and suicidality were more likely to become non-improver, and also non-remitter after 8 weeks of treatment in case of early improvement. Early improver with melancholic, anxious or atypical depression as well as with comorbid social phobia or avoidant personality disorder had an increased risk for non-remission at study end. The combined marker of early non-improvement and the occurrence of melancholic features increased the specificity of treatment prediction from 30% to 90%. LimitationsComorbid disorders were only assessed at baseline. ConclusionsPatients with early non-improvement and melancholic features at treatment initiation have a particularly high risk of later non-remission. This group of patients should be considered more attention in treatment decisions.

Role of Adjunctive L-Methylfolate with Selective Serotonin Reuptake Inhibitor in Depressed Patients at a Tertiary Care Centre

Background: Present study was aimed to determine clinical outcome and tolerability in patients receiving combination of LMTF plus Escitalopram at the initiation of treatment compared with Escitalopram monotherapy. Methods: Patients aged 21- 60 years, newly diagnosed as Depression, having moderate to severe severity as per ICD-10 criteria were taken for the study after informed consent. 31 Patients taking supplemental folic acid, having current or a history of psychotic episodes, history of bipolar disorder, patient with suicidal tendencies or the patients having significiant physical and neurological illness were excluded from the study. Semi structured proforma and HDRS (Hamilton depression rating scale) was administered. Patients were divided in two groups based on the observation, one group was of L-MTF plus Escitalopram and other was of Escitalopram alone. The score was calculated for both the groups. The assessment on HDRS was done again in the follow up at 2,4,6,8 weeks. 50% or more reduction in HDRS was considered as response. Results: The sample consisted of 70 patients, 35 in each group. No significant sex differentiation was observed as well as average duration of illness was comparable in both groups. The present study demonstrated that by adding L-MTF to Escitalopram at the initiation of treatment led to greater number of responders comparison to Escitalopram monotherapy. LMTF plus Escitalopram did not demonstrate any significant decrease in HDRS on 2 weeks. Further, L-MTF plus Escitalopram group demonstrated significant decrease in HDRS (p<0.001) at 4,6,8 weeks compared with Escitalopram monotherapy group. As per table 3 nausea, constipation & somnolence were reported more in combination group while dizziness, agitation in Escitalopram group. Conclusions: Greater efficacy was observed with lmethylfolate when used as an adjunct to Escitalopram from initiation. Our present analyses establishes the relative superiority of l-methylfolate plus Escitalopram versus Escitalopram alone in MDD patients during initiation of treatment. More studies with other SSRI’s and other classes are required to validate the findings.

Transcutaneous Vagus Nerve Stimulation Modulates Default Mode Network in Major Depressive Disorder

BackgroundDepression is the most common form of mental disorder in community and health care settings and current treatments are far from satisfactory. Vagus nerve stimulation (VNS) is a Food and Drug Administration approved somatic treatment for treatment-resistant depression. However, the involvement of surgery has limited VNS only to patients who have failed to respond to multiple treatment options. Transcutaneous VNS (tVNS) is a relatively new, noninvasive VNS method based on the rationale that there is afferent/efferent vagus nerve distribution on the surface of the ear. The safe and low-cost characteristics of tVNS have the potential to significantly expand the clinical application of VNS. MethodsIn this study, we investigated how tVNS can modulate the default mode network (DMN) functional connectivity (FC) in mild or moderate major depressive disorder (MDD) patients. Forty-nine MDD patients were recruited and received tVNS or sham tVNS (stVNS) treatments. ResultsThirty-four patients completed the study and were included in data analysis. After 1 month of tVNS treatment, the 24-item Hamilton Depression Rating Scale score reduced significantly in the tVNS group as compared with the stVNS group. The FC between the DMN and anterior insula and parahippocampus decreased; the FC between the DMN and precuneus and orbital prefrontal cortex increased compared with stVNS. All these FC increases are also associated with 24-item Hamilton Depression Rating Scale reduction. ConclusionstVNS can significantly modulate the DMN FC of MDD patients; our results provide insights to elucidate the brain mechanism of tVNS treatment for MDD patients.

Abstract W P125: Telephone versus In-person Psychosocial Behavioral Treatment in Post-Stroke Depression

Background: We previously showed that a brief psychosocial behavioral intervention delivered in-person by advanced practice nurses was effective in reducing post-stroke depression (PSD). Purpose: This randomized clinical trial compared a shortened (6 week) intervention by telephone or in-person to usual care in volunteers within 4 months of an ischemic or hemorrhagic stroke. Methods: 100 stroke survivors who screened positive for depression (Geriatric Depression Score &gt;11) were randomized to usual care (UC), telephone intervention (TI), or in-person intervention (IPI). Primary outcomes were percent reduction in the Hamilton Depression Rating Scale (HDRS) at 8 weeks, 21 weeks and 12 months following study entry. Outcome assessors were masked to randomization status. Results: All three groups had similar depression scores at baseline (HDRS mean 18 for UC and TI, 19 for IPI). The mean percent reduction in HDRS scores for telephone and in-person groups was 42% and 40% immediately following the intervention at 8 weeks compared to a 30% reduction in the usual care group. However the difference only trended toward significance, controlling for age, with older age associated with better response (p = 0.31). There was a greater early reduction in depression in the UC group than in our previous work (30% HDRS reduction vs 18% at 8 weeks). By 21 weeks and 12 months following entry there was no significant difference between groups in HDRS reduction (40% UC, 40% TI, 39% IPI and 37% UC, 42% TI and 44% IPI, respectively). Conclusions: A brief psychosocial intervention for PSD reduced depression somewhat more than usual care (p=.31) right after treatment but the difference between groups was even less at 21 weeks and one year following entry. The reduction in depression was slightly smaller than in our earlier study for the intervention groups, and the usual care group improved more. The comparability of telephone and in-person follow-up and treatment for depression is important given mandated post-hospital follow-up for comprehensive stroke centers. The improved response to brief therapy for older participants suggests tailoring of care to provide individualized follow-up.

The Effect of Recent Bereavement on Outcomes in a Primary Care Depression Intervention Study

Although bereavement and depression are both common in older primary care patients, the effect of bereavement on depression intervention outcomes is unknown. We examined whether standard interventions for depression in primary care were as effective for bereaved as for non-bereaved depressed patients. Randomized controlled trial. Twenty community-based primary care practices in New York City, greater Philadelphia, and Pittsburgh. Randomization to either intervention or usual care occurred by practice. Patients aged 60 years or older who met criteria for major depression or clinically significant minor depression (N= 599). Patients who did not complete the bereavement measure or who were missing 4-month data were excluded (final N= 417). Study-trained depression care managers offered guideline-concordant recommendations to primary care physicians at intervention sites and assisted patients with treatment adherence. Patients who did not wish to take antidepressants could receive interpersonal psychotherapy. Bereavement was captured using the Louisville Older Persons Events Schedule. Depression severity was assessed using the 24-item Hamilton Depression Rating Scale (HDRS). Outcomes at 4 months were remission (HDRS≤7) and response (HDRS reduction≥50% from baseline). Logistic regressions indicated that, for non-bereaved participants, response and remission were higher in intervention than usual care. However, recently bereaved older adults were less likely to achieve response or remission at 4 months if treated in the intervention condition. Standard depression care management appears to be ineffective among recently bereaved older primary care patients. Greater attention should be paid in primary care to emotional distress in the context of bereavement.

Rapid Antidepressant Effect of Ketamine in the Electroconvulsive Therapy Setting

Studies now provide strong evidence that the N-methyl-D-aspartate receptor antagonist ketamine possesses rapidly acting antidepressant properties. This study aimed to determine if a low dose of ketamine could be used to expedite and augment the antidepressant effects of electroconvulsive therapy (ECT) treatments in patients experiencing a severe depressive episode. Subjects with major depressive disorder or bipolar disorder referred for ECT treatment of a major depressive episode were randomized to receive thiopental alone or thiopental plus ketamine (0.5 mg/kg) for anesthesia before each ECT session. The Hamilton Depression Rating Scale (HDRS) was administered at baseline and at 24 to 72 hours after the first and sixth ECT sessions. Electroconvulsive therapy exerted a significant antidepressant effect in both groups (F2,24 = 14.35, P < 0.001). However, there was no significant group effect or group-by-time interaction on HDRS scores. In addition, post hoc analyses of the time effect on HDRS showed no significant HDRS reduction after the first ECT session for either group. The results of this pilot study suggest that ketamine, at a dose of 0.5 mg/kg, given just before ECT, did not enhance the antidepressant effect of ECT. Interestingly, the results further suggest that the coadministration of ketamine with a barbiturate anesthetic and ECT may attenuate the immediate antidepressant effects of the N-methyl-D-aspartate antagonist.

Pretreatment cerebral metabolic activity correlates with antidepressant efficacy of vagus nerve stimulation in treatment-resistant major depression: A potential marker for response?

Pretreatment brain activity in major depressive disorder correlates with response to antidepressant therapies, including pharmacotherapies and transcranial magnetic stimulation. The purpose of this trial was to examine whether pretreatment regional metabolic activity in selected regions of interest (ROIs) predicts antidepressant response following 12 months of vagus nerve stimulation (VNS) in 15 patients with treatment-resistant major depression (TRMD). Fluorodeoxyglucose positron emission tomography (FDG PET) was used to assess regional mean relative cerebral metabolic rate for glucose (CMRGlu) in four ROIs (anterior insular, orbitofrontal, anterior cingulate, and dorsolateral prefrontal cortices) at baseline (prior to VNS activation). Depression severity was assessed at baseline and after 12 months of VNS using the Hamilton Depression Rating Scale (HDRS), with response defined as ≥ 50% reduction in HDRS from baseline. Baseline CMRGlu in the anterior insular cortex differentiated VNS responders (n=11) from nonresponders (n=4) and correlated with HDRS change (r=.64, p=.01). In a regression analysis, lower anterior insular cortex CMRGlu (p=.004) and higher orbitofrontal cortex CMRGlu (p=.047) together predicted HDRS change (R(2)=.58, p=.005). In a whole brain, voxel-wise analysis, baseline CMRGlu in the right anterior insular cortex correlated with HDRS change (r=.78, p=.001). Sample size was small, limiting statistical power; patients remained on their psychiatric medications; study was open-label and uncontrolled. This preliminary study suggests that pretreatment regional CMRGlu may be useful in predicting response to VNS in TRMD patients.

Randomised controlled trial to determine the clinical effectiveness and cost-effectiveness of selective serotonin reuptake inhibitors plus supportive care, versus supportive care alone, for mild to moderate depression with somatic symptoms in primary care: the THREAD (THREshold for AntiDepressant response) study

To determine (1) the effectiveness and cost-effectiveness of selective serotonin reuptake inhibitor (SSRI) treatment plus supportive care, versus supportive care alone, for mild to moderate depression in patients with somatic symptoms in primary care; and (2) the impact of the initial severity of depression on effectiveness and relative costs. To investigate the impact of demographic and social variables. The study was a parallel group, open-label, pragmatic randomised controlled trial. The study took place in a UK primary care setting. Patients were referred by 177 GPs from 115 practices around three academic centres. Patients diagnosed with new episodes of depression and potentially in need of treatment. In total, 602 patients were referred to the study team, of whom 220 were randomised. GPs were asked to provide supportive care to all participants in follow-up consultations 2, 4, 8 and 12 weeks after the baseline assessment, to prescribe an SSRI of their choice to patients in the SSRI plus supportive care arm and to continue treatment for at least 4 months after recovery. They could switch antidepressants during treatment if necessary. They were asked to refrain from prescribing an antidepressant to those in the supportive care alone arm during the first 12 weeks but could prescribe to these patients if treatment became necessary. The primary outcome measure was Hamilton Depression Rating Scale (HDRS) score at 12-week follow-up. Secondary outcome measures were scores on HDRS at 26-week follow-up, Beck Depression Inventory, Medical Outcomes Study Short Form-36 (SF-36), Medical Interview Satisfaction Scale (MISS), modified Client Service Receipt Inventory and medical record data. SSRIs were received by 87% of patients in the SSRI plus supportive care arm and 20% in the supportive care alone arm. Longitudinal analyses demonstrated statistically significant differences in favour of the SSRI plus supportive care arm in terms of lower HDRS scores and higher scores on the SF-36 and MISS. Significant mean differences in HDRS score adjusted for baseline were found at both follow-up points when analysed separately but were relatively small. The numbers needed to treat for remission (to HDRS > 8) were 6 [95% confidence interval (CI) 4 to 26)] at 12 weeks and 6 (95% CI 3 to 31) at 26 weeks, and for significant improvement (HDRS reduction > or = 50%) were 7 (95% CI 4 to 83) and 5 (95% CI 3 to 13) respectively. Incremental cost-effectiveness ratios and cost-effectiveness planes suggested that adding an SSRI to supportive care was probably cost-effective. The cost-effectiveness acceptability curve for utility suggested that adding an SSRI to supportive care was cost-effective at the values of 20,000 pounds-30,000 pounds per quality-adjusted life-year. A poorer outcome on the HDRS was significantly related to greater severity at baseline, a higher physical symptom score and being unemployed. Treatment with an SSRI plus supportive care is more effective than supportive care alone for patients with mild to moderate depression, at least for those with symptoms persisting for 8 weeks and an HRDS score of > or = 12. The additional benefit is relatively small, and may be at least in part a placebo effect, but is probably cost-effective at the level used by the National Institute for Health and Clinical Excellence to make judgements about recommending treatments within the National Health Service. However, further research is required.

Effects of adjunctive reboxetine in patients with duloxetine-resistant depression: a 12-week prospective study

The efficacy of the combination therapy with two antidepressants from different pharmacological families in patients with treatment-resistant depression has been reported in multiple studies. In this prospective 12-weeks open-label study, we assessed the effectiveness of the addition of reboxetine to 79 depressive outpatients diagnosed with major depressive disorder (MDD) according to the DSM-IV criteria who had previously not responded, or had done so only in a partial way, over 8 weeks of conventional treatment, in monotherapy, with duloxetine. Efficacy was assessed using the 21-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Improvement (CGI-I). Safety was evaluated by recording spontaneously reported adverse events. Data were analysed on an intent-to-treat basis, using the last-observation-carried-forward method. Mean HDRS reduction was 65.5% (P < 0.0001). The percentages of responders (>or=50% reduction in HDRS) and patients considered benefiting from complete remission (HDRS <or= 10 points) at week 12 were 76% and 69.3%, respectively. By the end of the treatment, the score of CGI-I decreased 68.5% (P < 0.0001). Percentage of patient improving (CGI < 4 points) was 95.8%. The most common non-serious adverse events were dry mouth, increased sweating, constipation and difficulty passing urine. The results of this study suggest that the combination strategy with reboxetine may be an effective and well-tolerated tool in duloxetine-resistant patients.

Repetitive Transcranial Magnetic Stimulation for Treatment of Medication-Resistant Depression in Older Adults

The antidepressant effects of repetitive transcranial magnetic stimulation (rTMS) are well documented, but studies to date have produced heterogeneous results in late-life depression. To address this matter, we evaluated the efficacy of both high- and low-frequency rTMS delivered to the prefrontal cortex of older adults with treatment-resistant major depression. Forty-nine older adults (69 +/- 6.7 years) with treatment-refractory major depressive disorders underwent a series of rTMS treatments as an adjuvant to pharmacotherapy. Patients received high-frequency rTMS delivered to the left dorsolateral prefrontal cortex, low-frequency stimulation to the right dorsolateral prefrontal cortex, or a combination thereof, at 80-110% of the motor threshold. There was a modest, but statistically significant, mean reduction (24.7%) in Hamilton Depression Rating Scale (HDRS) scores from baseline to the end of treatment. Nine patients were classified as responders (50% HDRS reduction), and 4 patients reached remission status (final HDRS score <8). Similar improvements in HDRS scores were observed for high- and low-frequency rTMS. Treatment was generally well tolerated, and no serious adverse effects were reported. The findings support the contention that in older adults with treatment-refractory depression, rTMS can be an effective treatment alternative for some patients.