Resistant Major Depressive Disorder Research Articles

Persistent pro-inflammatory trait in elderly patients following treatment-resistant major depressive disorder: a longitudinal exploratory study

Objectives Considering that the remission rate for major depressive disorder (MDD) in elderly patients is below 50%, there is a compelling requirement for an enhanced comprehension of the underlying mechanisms. Chronic low-grade inflammation has been posited as one potential contributor to treatment-resistant MDD in the elderly. Accordingly, the objective of our study was to explore the longitudinal trends of systemic immune markers in elderly inpatients referred to electroconvulsive therapy due to an episode of treatment resistant unipolar MDD. Methods The study encompassed 64 elderly inpatients with unipolar MDD that had failed to respond to therapy in primary health care, and 18 non-depressed controls. Blood samples were collected at pre-treatment, mid-treatment, post-treatment and 12 weeks follow-up. We assessed 27 immune markers via multiplex assays. Depressive symptoms were evaluated using the Hamilton Rating Scale of Depression at these timepoints. For controls, the immune markers and depressive symptoms, were measured at baseline and eight weeks follow-up using identical methods. Results At follow-up, patients showed higher concentrations of 23 immune markers compared to controls, although the concentration of 19 immune markers decreased significantly from pre-treatment to follow-up. No differences in immune marker concentrations between treatment responders and non-responders were observed pre- and post-treatment in the patient group. Conclusion Our findings suggest that a pro-inflammatory trait persists in elderly after an episode of treatment resistant unipolar MDD. Thus, our study supports that chronic low-grade inflammation may characterise elderly with treatment-resistant unipolar MDD.

Describing the burden of disease amongst inpatients with treatment resistant major depressive disorder in Australia.

To describe the quality of life and clinical characteristics of treatment-resistant depression (TRD) patients in an Australian patient cohort recruited cross-sectionally during admission. Inpatients admitted for TRD treatment completed a quality of life questionnaire (AQoL-8D) and a depression severity assessment (HAM-D). A chart review and patient interview occurred for demographic and patient characteristics. Comparisons between the mean AQoL-8D scores of the study population and Australian population norms occurred. 79 TRD inpatients (70.9% female), mean age of 44.8 ± 14.9 years, were recruited, with 78.5% having an anxiety disorder, 48.1% post-traumatic stress disorder, and 30.4% a personality disorder. Adjunctive to antidepressants, 92.4% were taking antipsychotics and 55.7% were taking mood stabilisers. Approximately 42% of patients received transcranial magnetic stimulation, and 35.4% received electroconvulsive therapy. Mean HAM-D score was 20.3 ± 5.2, and AQoL-8D score (120.1 ± 16.5) was significantly higher than Australian population norms (p < .001) indicating reduced quality of life. Personal and clinical characteristics of patients hospitalised for TRD were similar to TRD globally with impaired quality of life relative to the general Australian population. TRD patients on average presented with moderate/severe depression, highlighting the need for greater support for these individuals.

Sleep as a predictor of improved response to transcranial magnetic stimulation for depression (SPIRiTeD)

BackgroundTranscranial magnetic stimulation (TMS) is an evidence-based approach to treatment- resistant Major Depressive Disorder (TRD). Sleep dysfunction is associated with poor outcomes in TRD, however, the impacts of sleep dysfunction on TMS treatment has yet to be defined. This study examined the association between sleep dysfunction and improvement in depression symptoms with TMS treatment for TRD. MethodsA retrospective observational cohort study was conducted examining all Veterans receiving TMS treatments through the “VA TMS Clinical Pilot Program” over a three-year period. The Patient Health Questionnaire (PHQ-9) sleep item was utilized to assess sleep dysfunction. The association between sleep dysfunction improvements during TMS treatment with depression outcomes was analyzed. Results94.3 % (N = 778) of Veterans reported baseline sleep dysfunction. Chi-square analysis demonstrated higher rates of depression remission at the completion of TMS treatment for those with sleep improvement at weeks 1, 3 and 6 (all p < .001). ANOVA comparing sleep improvements and end of treatment PHQ-8 score (modified to remove sleep item) found a statistically significant difference in mean improvements of depression scores at all 3 time points. LimitationsLimitations include those that are inherent to retrospective studies, as well as limitations in using the PHQ-9 sleep item as the primary means to assess sleep dysfunction. ConclusionThis study reports on the largest sample size to date examining the relationship between sleep dysfunction and TMS treatment outcomes for MDD, and found that improvement in sleep dysfunction was associated with greater reductions in end of treatment depression symptoms including higher depression remission rates.

Combination of CBT and rTMS: what are the advantages?

IntroductionObsessive-Compulsive Disorder (OCD) and Major Depressive Disorder (MDD) are among the ten most disabling disorders, yet only 30-40% of people with the condition seek specialist care (WHO). Considered a relatively new tool in the treatment of OCD and MDD, repetitive transcranial magnetic stimulation (rTMS) was first used by our team 1 year ago. Based on current literature cognitive behavioural therapy (CBT) is effective in 60% of OCD cases, with MDD also having a good response rate of 50-60%. The efficacy of SSRI’s has been demonstrated, but side effects can have a negative impact on adherence in the long term. Prolonged use of certain drugs has adverse reactions that lead specifically to memory impairment, which compromises suitability for psychotherapy. The same problem applies to the use of electroconvulsive therapy (ECT) in a major depressive episode.ObjectivesOur aim was to study the efficacy of combining rTMS with CBT, to gather clinical experience on how these two different methods work in practice when combined.MethodsPatients diagnosed with therapy resistant MDD received rTMS treatment using 50Hz theta burst over 10 sessions. Therapy resistant OCD patients were treated by a 15 sessions rTMS using 1Hz single pulse. These rTMS sessions were combined with CBT, of which we would like to highlight two cases: one of them is a 34 years old woman, who has wide range of sexual, checking and contamination-related OCD symptoms and only received SSRI treatment so far. The other one is a 29 years old man, who suffers from religious obsessions, cleaning compulsions and other repetitive behaviours.Results The positive effects of rTMS treatment on working memory functions, attentional capacity and cooperative skills without significant additive effects suggest exciting possibilities for combining the two treatments, thus the combined treatment has been tested in clinical practice. In our own patient care, an important experience was that patients were committed to the therapy, felt safe and, unlike with medications, did not have to worry about side effects. While medication and ECT can make psychotherapy more difficult in the long term - mainly because of memory problems - rTMS facilitates it. Patients appreciate that we approach their problems in a complex way, and they perceive that the combination of the two very different methods reflects professionalism. Our poster attempts to present the experience of combining rTMS and CBT from the therapist’s perspective through two case studies.ConclusionsBased on our experiences it is an effective approach to combine rTMS with CBT in therapy resistant MDD and OCD patients. In the light of these results the revision of the existing guidelines are considerable.AcknowledgementsThis study has been supported by the Human Resource Development Operating Programme 5.2.6 grant.Disclosure of InterestNone Declared

Cognitive outcomes from the randomised, active-controlled Ketamine for Adult Depression Study (KADS)

BackgroundDue to its rapid antidepressant effect, ketamine has recently been clinically translated for people with treatment-resistant depression. However, its cognitive profile remains unclear, particularly with repeated and higher doses. In the present study, we report the cognitive results from a recent large multicentre randomised controlled trial, the Ketamine for Adult Depression Study (KADS). MethodsIn this randomised, double-blind, active-controlled, parallel group, multicentre phase 3 trial study we investigated potential cognitive changes following repeated treatment of subcutaneous racemic ketamine compared to an active comparator, midazolam, over 4 weeks, which involved two cohorts; Cohort 1 involved a fixed dose treatment protocol (0.5 mg/kg ketamine), Cohort 2 involved a dose escalation protocol (0.5–0.9 mg/kg) based on mood outcomes. Participants with treatment-resistant Major Depressive Disorder (MDD) were recruited from 7 mood disorder centres and were randomly assigned to receive ketamine (Cohort 1 n = 33; Cohort 2 n = 53) or midazolam (Cohort 1 n = 35; Cohort 2 n = 53) in a 1:1 ratio. Cognitive measurements were assessed at baseline and at the end of randomised treatment. ResultsResults showed that in Cohort 1, there were no differences between ketamine and midazolam in cognitive outcomes. For Cohort 2, there was similarly no difference between conditions for cognitive outcomes. LimitationsThe study included two Cohorts with different dosing regimes. ConclusionsThe findings support the cognitive safety of repeated fixed and escalating doses at least in the short-term in people with treatment resistant MDD.

The Downstaging Concept in Treatment-Resistant Depression: Spotlight on Ketamine

Treatment-resistant depression is a pleomorphic phenomenon occurring in 30% of patients with depression. The chance to achieve remission decreases with every subsequent episode. It constitutes a significant part of the global disease burden, causes increased morbidity and mortality, and is associated with poor quality of life. It involves multiple difficult-to-treat episodes, with increasing resistance over time. The concept of staging captures the process of changes causing increasing treatment resistance and global worsening of functioning in all areas of life. Ketamine is a novel rapid-acting antidepressant with neuroplastic potential. Here, we argue that ketamine use as an add-on treatment of resistant major depressive disorder, based on its unique pharmacological properties, can reverse this process, give hope to patients, and prevent therapeutic nihilism.

Efficacy and Safety of Subcutaneous Esketamine in the Treatment of Suicidality in Major Depressive Disorder and Bipolar Depression.

Affective disorders account for most cases of suicide. The pharmacological arsenal to treat suicidality is limited and available agents take too long to take effect. A large body of evidence shows optimal results of ketamine for treating depression, but the evidence concerning suicidality has not been fully described. We report the first real-world study of severely depressed patients presenting with suicide ideation who were treated with repeated administration of subcutaneous esketamine. We analyzed data from 70 acutely depressed subjects diagnosed with resistant major depressive disorder or bipolar depression. Subjects were administered subcutaneous esketamine once a week for 6 weeks. The primary efficacy endpoint, the change from baseline to 24-h post-administration 6 in the item 10 Montgomery-Åsberg Depression Rating Scale score, was analyzed using a mixed-effects repeated-measures model. There were significant effects for time on item 10 Montgomery-Åsberg Depression Rating Scale scores (p < 0.0001) but not for a time × diagnosis interaction (p = 0.164) from baseline to the end of the study. Efficacy of esketamine did not differ between groups (major depressive disorder vs bipolar depression) at any timepoint. Statistical significance on suicidality scores was observed from 24 h after the first administration (p < 0.001), and a further reduction was observed with repeated administrations. Esketamine was safe and well tolerated. Mean heart rate remained stable during the administrations and the blood pressure increase was self-limited. Repeated subcutaneous esketamine administration had significant anti-suicidality effects in both major depressive disorder and bipolar groups, with a rapid onset of action and a good tolerability profile. Large randomized controlled trials are warranted to confirm these preliminary findings.

A pilot study of accelerated deep transcranial magnetic stimulation effects on cognitive functioning in patients diagnosed with treatment resistant major depressive disorder

The purpose of this study was to assess cognitive functioning in patients diagnosed with major depressive disorder (MDD) treated with two different accelerated deep transcranial magnetic stimulation (dTMS) modalities as an add-on to stable pharmacotherapy.A total of 32 adult psychiatric inpatients diagnosed with treatment resistant MDD were allocated by stratified randomization into two groups: a group treated with dTMS twice a day during 2 weeks, and a group treated with dTMS twice a day during 3 weeks. Clinical psychologists assessed participants´ cognitive functions (memory, visuospatial functioning, executive functions, psychomotor speed, verbal fluency) via a battery of instruments, after the inclusion, and by the end of treatment.Our findings showed mild to moderate improvements in the majority of administered tests measuring different cognitive functions, meaning that patients achieved significantly better results by the end of the treatment compared to baseline, regardless of the duration of the treatment (2 or 3 weeks). No adverse effects on cognition were observed. The results seem promising in the context of treating the cognitive symptoms associated with functional recovery of patients suffering from depression.

Efficacy and safety of intermittent theta burst stimulation (iTBS) in treatment resistant depression

IntroductionRepetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulatory treatment option, which is used in a variety of neurological and psychiatric diseases. It is approved for depression treatment and recommended in international guidelines. A significant reduction in treatment duration was achieved by using theta burst stimulation (TBS) protocols, which are practicable and non-inferior to conventional TMS.ObjectivesTo analyse the efficacy and safety of intermittent theta burst stimulation (iTBS) of left DLPFC in inpatients with treatment-resistant depression.MethodsWe evaluated n=44 inpatients with treatment resistant major depressive disorder (n=37) and bipolar depression (n=7), who were treated with the 5 Hz intermittent TBS once daily for 3-6 weeks according to clinical decision. A total of 600 pulses and 200 bursts were applied in each treatment session. Clinical and response data were obtained by chart review.ResultsMean age at time of first stimulation was 54 years. 61,3 % of patients were female. On average, the current episode started 21 months before the first stimulation. In total, 924 treatment sessions were performed. On average, patients received 21 sessions. The mean MADRS Score pre-treatment was 27.2. Post-treatment, there was a clear reduction in depression severity (MADRS 18.3). No severe adverse events and no seizures occurred in this clinical observational analysis.ConclusionsIntermittent TBS is efficacious and safe in patients with chronic and refractory depression.DisclosureNo significant relationships.

L’efficacité de l’eskétamine dans le trouble dépressif majeur résistant : une revue systématique de la littérature

ObjectiveMajor depression is a significant public health problem since its lifetime prevalence is estimated at 15–18 %. Its standard treatment is based on the use of antidepressant medications but their effectiveness is limited. Indeed, only two thirds of patients with a major depressive episode will reach remission after two lines of conventional treatment. In major depression, there are arguments in favour of disturbances in neuronal glutamatergic transmission. Esketamine appears to have an antidepressant action through modulation of the NMDA receptors involved in this glutamatergic neurotransmission. The aim of this review to systematically investigate the efficacy of esketamine combined with an SSRI or SNRI for major depressive disorder resistant to treatment. MethodA systematic review on the efficacy of esketamine in combination with an SSRI or SNRI for resistant major depressive disorder was performed in July 2021 in the PUBMED database according to the PRISMA criteria. The key words used are: “depressed” [All Fields] OR “depression” [MeSH Terms] OR “depression” [All Fields] OR “depressions” [All Fields] OR “depression s” [All Fields] OR “depressive disorder”[MeSH Terms] OR (“depressive”[All Fields] AND“disorder”[All Fields]) OR“depressive disorder”[All Fields] OR“depressivity”[All Fields] OR“depressive”[All Fields] OR “depressively” [All Fields] OR “depressiveness” [All Fields] OR “depressives” [All Fields]) AND (“esketamine” [Supplementary Concept] OR “esketamine” [All Fields] OR “esketamine” [All Fields]. The inclusion criteria were: efficacy on depressive symptoms of intranasal esketamine combined with an SSRI or an SNRI for major depressive disorder resistant to at least two lines of treatment, RCT and meta-analysis, individual≥18 years, articles in English and French. ResultsFour randomized double-blind studies were selected on the basis of these criteria. The included studies are of grade A and B which leads to a high level of scientific evidence. ConclusionsIntranasal esketamine in combination with sertraline, escitalopram, duloxetine or venlafaxine prolonged release is more effective than the monotherapy use of these four molecules for the treatment of resistant depression. It has been shown to be effective for a population aged between 18 and 74 years at doses between 28mg and 84mg. Currently, based on these results, intranasal esketamine should be proposed as a second level of treatment after an unsuccessful trial of two antidepressants. It is nevertheless advisable to be careful in its use in a clinical psychiatric population: exclusion of suicidal ideation or antecedent of suicidal acting, absence of psychotic depression, use exclusively for unipolar major depressive disorder. The different conditions of use are also notified in the product characteristics of the European Medicines Agency. Finally, further comparative studies are needed in the future, in the absence of funding from the pharmaceutical company producing esketamine.

Relationship of Childhood Trauma with Transcranial Magnetic Stimulation Outcome for Depression

Background: Childhood trauma has lasting effects on treatment outcomes for many illnesses including major depressive disorder (MDD) but the relationship with transcranial magnetic stimulation (TMS) is unknown.Methods: Childhood Trauma Questionnaire (CTQ), a questionnaire to assess severity and type of childhood trauma, was collected in a naturalistic outpatient setting from patients receiving TMS for treatment resistant MDD. Inventory of Depressive Symptomatology Self Report (IDS-SR) was used to assess depression symptom severity, clinical response and remission. Standard treatment was given at 10 Hz stimulation to the dorsolateral left prefrontal cortex at 120% maximum intensity relative to their motor threshold for 3000-4000 pulses/daily for six weeks.Results: 117 patients receiving TMS completed CTQ. More severe trauma showed less improvement after TMS as seen via a negative correlation between IDS-SR %change and CTQ total score (r=-.251, p<0.01). Specifically, less improvement correlated with degree of physical abuse (r=-.245, p<0.01) and physical neglect (r=-.251, p<0.01). Non-responders had significantly worse scores in physical abuse (p<.01), sexual abuse (p<.05), and physical neglect (p<.05) compared to responders. Significant chi-square associations between physical neglect and non-response (χ=8.623, p<0.05); and sexual abuse and non-remission (χ=9.214, p<0.05) were present.Conclusion: Our data show that certain types of trauma may have more impact on TMS outcomes than others. Based on these results, future studies examining the possible biological pathways and mechanisms contributing to the differences in severely depressed patients with and without certain types of childhood trauma could lead to a more personalized treatment algorithm leading to improved efficacy of TMS.Conflicts of Interest: None to reportFunding: This work was supported by grants from the National Institute of Mental Health (NIMH) R25MH101076 (Dr. AM Fukuda) and P20GM130452 (E Tirrell & Dr. LL Carpenter), and by Butler Internal Funding. Background: Childhood trauma has lasting effects on treatment outcomes for many illnesses including major depressive disorder (MDD) but the relationship with transcranial magnetic stimulation (TMS) is unknown. Methods: Childhood Trauma Questionnaire (CTQ), a questionnaire to assess severity and type of childhood trauma, was collected in a naturalistic outpatient setting from patients receiving TMS for treatment resistant MDD. Inventory of Depressive Symptomatology Self Report (IDS-SR) was used to assess depression symptom severity, clinical response and remission. Standard treatment was given at 10 Hz stimulation to the dorsolateral left prefrontal cortex at 120% maximum intensity relative to their motor threshold for 3000-4000 pulses/daily for six weeks. Results: 117 patients receiving TMS completed CTQ. More severe trauma showed less improvement after TMS as seen via a negative correlation between IDS-SR %change and CTQ total score (r=-.251, p<0.01). Specifically, less improvement correlated with degree of physical abuse (r=-.245, p<0.01) and physical neglect (r=-.251, p<0.01). Non-responders had significantly worse scores in physical abuse (p<.01), sexual abuse (p<.05), and physical neglect (p<.05) compared to responders. Significant chi-square associations between physical neglect and non-response (χ=8.623, p<0.05); and sexual abuse and non-remission (χ=9.214, p<0.05) were present. Conclusion: Our data show that certain types of trauma may have more impact on TMS outcomes than others. Based on these results, future studies examining the possible biological pathways and mechanisms contributing to the differences in severely depressed patients with and without certain types of childhood trauma could lead to a more personalized treatment algorithm leading to improved efficacy of TMS. Conflicts of Interest: None to report Funding: This work was supported by grants from the National Institute of Mental Health (NIMH) R25MH101076 (Dr. AM Fukuda) and P20GM130452 (E Tirrell & Dr. LL Carpenter), and by Butler Internal Funding.

Effects of transcranial magnetic stimulation on anhedonia in treatment resistant major depressive disorder.

BackgroundAnhedonia is one of the defining features of depression but it remains difficult to target and treat. Transcranial magnetic stimulation (TMS) is a proven treatment for depression, but its effects on anhedonia and whether anhedonia can be used as a predictive biomarker of response is not well known.MethodsSnaith–Hamilton Pleasure Scale was administered to patients with depression before and after a standard course of TMS in a naturalistic outpatient setting.Results144 patients were analyzed. There was an overall significant improvement in anhedonia from pre‐ to post‐treatment (7.69 ± 3.88 vs. 2.96 ± 3.45; p < .001). Significant correlations between improvements in anhedonia and other depressive symptoms were present (r = 0.55, p < .001). Logistic regression revealed that baseline anhedonia severity was not a significant predictor of clinical outcome.ConclusionThis is the first large, naturalistic study examining the effects of standard, non‐research TMS on anhedonia. Among depressed patients, TMS resulted in significant improvements in anhedonia. Patients with severe baseline anhedonia had an equal chance of achieving clinical response/remission. Patients with anhedonia should not be excluded from treatment if they are safe for outpatient care and otherwise appropriate candidates for treatment.

Plasma Levels of Brain-Derived Neurotrophic Factor and S100B in Relation to Antidepressant Response to Ketamine.

BackgroundEvidence demonstrates that brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B) have a pivotal role in the pathogenesis of major depressive disorder (MDD) and they are proposed as predictors of antidepressant response. Ketamine produces rapid antidepressant effects in MDD and pre-clinical studies suggest the necessity of increased BDNF levels for the antidepressant action of ketamine. However, studies observing the change of blood BDNF levels after ketamine intervention are inconsistent and studies about the role of plasma S100B in ketamine administration in MDD patients are lacking.MethodWe evaluated mature BDNF (mBDNF), S100B levels in plasma and their associations with depression severity in 30 Selective Serotonin Reuptake Inhibitor (SSRI)-resistant MDD patients enrolled in a randomized controlled trial of ketamine compared (n = 20) to a placebo (n = 10) control (saline). Severity of depression was assessed using the Montgomery–Åsberg Depression Rating Scale (MADRS).ResultsPlasma mBDNF and S100B were not significantly changed after 1–2 days of single ketamine compared to placebo. Plasma mBDNF and S100B levels did not significantly differ in responders compared to non-responders of ketamine treatment. The change of plasma mBDNF levels was positively correlated with the improvement of MADRS score after 1–2 weeks of open-label ketamine treatment (rho = 0.495, p = 0.031), though this change did not survive correction for multiple comparisons.ConclusionThese findings do not support the hypothesis that ketamine treatment increases BDNF plasma levels in MDD patients. No effect of ketamine treatment on S100B plasma levels was seen.

P11 (S100A10) as a potential predictor of ketamine response in patients with SSRI-resistant depression

BackgroundKetamine can act as antidepressant in patients with major depressive disorder (MDD) who are treatment-resistant. P11 has been implicated in ketamine's mechanism of action and proposed as biomarker for treatment response to other antidepressants. This study explores the effect of ketamine on peripheral p11 and the potential role for p11 as response marker for ketamine treatment. MethodsThirty Selective Serotonin Reuptake Inhibitor resistant MDD patients were randomized to either 0.5 mg/kg ketamine or placebo intravenous treatment. Using multicolor Flow Cytometry, peripheral p11 levels were measured before and 1-2 days after treatment. ResultsP11 levels were decreased within the ketamine group in both cytotoxic T cell and T helper cells populations, although this did not significantly differ from changes seen in the placebo group. Baseline p11 levels in cytotoxic T cells were significantly correlated with antidepressant response to ketamine treatment. LimitationsThis study was part of a larger study examining the effect of ketamine on the serotonin system in MDD patients, therefore the number of study subjects was limited to that of the primary study. ConclusionsHigh baseline p11 levels in cytotoxic T cells were associated with a stronger reduction of depressive symptoms in MDD patients after ketamine treatment. Future studies should confirm if peripheral p11 levels could be used as a predictor of ketamine treatment response.

Pilot Study of High Frequency Transcranial Magnetic Stimulation for Bipolar Depression

Transcranial Magnetic Stimulation (TMS) is now a standard treatment approach for treatment resistant major depressive disorder. There is growing clinical experience to support the use of TMS in bipolar depression. This study sought to collect open label safety and effectiveness data in a sample of patients with bipolar depression.

Characteristics of Patients Who Received Deep Brain Stimulation in Obsessive-Compulsive Disorder Versus Major Depressive Disorder

Deep brain stimulation (DBS) is cleared for treatment of obsessive-compulsive disorder (OCD) but is an investigational treatment for major depressive disorder (MDD). Also, ECT can be used in treatment resistant MDD but not OCD. The aim of this study is to compare the characteristics of patients who received DBS as part of standard care for OCD versus those who received it a part of a research protocol for MDD.

Telomere attrition and inflammatory load in major depressive disorder

Patients with major depressive disorder (MDD) present features that suggest the involvement of accelerated aging, such as increased circulating inflammatory markers and shorter telomere length (TL). Here we measured T-lymphocytes TL with quantitative fluorescent in situ hybridization (Q-FISH) and plasma levels of inflammatory markers in a cohort of 37 patients with MDD and 36 non-psychiatric controls (C). TL was shorter in MDD compared to C (F=8.52, p=0.005). Patients with treatment resistant (TR) MDD showed higher levels of TNFα compared to non-TR (adjusted p= 0.034) and C (adjusted p=0.025), suggesting that treatment resistance might be associated with increased inflammation compared to non-TR.DisclosureNo significant relationships.

What is the durability of deep TMS for major depressive disorder?

Background: Deep TMS(dTMS) is widely used for the treatment of resistant major depressive disorder(MDD). The durability of response to dTMS has not been studied. Methods: A single clinical-site's database was analyzed for patients with MDD that responded or remitted after a course of dTMS. Durability was defined as days to loss of efficacy by patient and clinician survey. Three-months-post-treatment was the minimum follow-up time for inclusion, unless durability was lost earlier. Response was defined by at least a 50% reduction in depression rating scale score and remission was defined by a score within normal range. Results: One-hundred responders had at least three months of durability data available. 71/100(71%) patients remitted. While there was no statistically significant difference in durability between remitters (954±103) and non-remitters (631±114), a post-hoc analysis reveals a tendency of remitters to have longer durability. By survival analysis, after 1 year the dTMS effect was durable in 64/100 of patients (68% of remitters and 55% of non-remitters), after 2 years in 44/100 (48% and 34%) and after 3 years in 33/100 (38% and 21%). We also observed that number of lifetime failed medications tended to negatively correlate with durability. All other assessed factors including age/gender/race/number of treatments/%change did not correlate with durability. Conclusions: dTMS for MDD has an overall average durability of 860 days and median durability of 561 days. Multisite data collection with current episode duration, and detailed lifetime history of episodes, treatments and comorbidities are warranted for more informative guidance. Conflicts of Interest: AT has a financial interest in Brainsway and Advanced Mental Health Care. MD has a financial interest in Advanced Mental Health Care. RG is employed by Brainsway. Funding: None

Music and rTMS; Novel combination approach for the treatment of depression

Abstract: Background: Standard treatments are often ineffective in Major Depressive Disorder (MDD). Repetitive Transcranial Magnetic Stimulation (rTMS) is effective in treatment resistant MDD. Music therapy is an established health profession with proven benefits in depression and anxiety. Combining treatments with rTMS often improves outcomes. We introduce proof of concept for novel combination approach, music with rTMS. Methods/Design: Nine adult patients with treatment resistant MDD were treated. TMS was delivered using H1-coil to left dorsolateral prefrontal cortex using standard high frequency parameters. Patients listened to music simultaneously with stimulation every session for 20 minutes. The type of music played was based on the patient’s preference. They were asked to choose something that induces positive emotions in them, possibly chills or Goosebumps (i.e intense pleasure). Response was measured with Hamilton Depression Rating Scale (HAM-D). Results: Response and remission rates were 89% and 56% respectively. Mean change in total HAM-D score was –15.3 (SD=3.6). There were no treatment emergent side effects. Conclusion: We demonstrate the feasibility of combining music with rTMS in this open label proof of concept series. This method is easy to set up and deliver. We encourage more research into this area for finding proof of efficacy. Disclosures – None

Anhedonia in Major Depressive Disorder: Can it be the Chicken AND the Egg for Transcranial Magnetic Stimulation?

Background: Anhedonia is a severely debilitating hallmark feature of Major Depressive Disorder (MDD) and a symptom which is often difficult to treat. Little is known regarding the relationship between anhedonia and transcranial magnetic stimulation (TMS). Improvement in anhedonia after TMS and its potential utility as a predictor of clinical outcome were studied. Methods: Snaith-Hamilton Pleasure Scale (SHAPS), a validated 14-question self-assessment for anhedonia, was collected in a naturalistic setting before and after TMS for treatment resistant MDD. Inventory of Depressive Symptomatology Self Report (IDS-SR) was used as a measure of clinical response and remission of MDD. For each session, stimulation at 120% of motor threshold was administered over the left dorsolateral prefrontal cortex at 10 Hz for 3000-4000 pulses/session. Results: Data from 116 clinic patients receiving TMS for the first time who completed SHAPS from July 2016 to October 2019 were analyzed. 72.4% (n=84) of the patients met criteria for severe anhedonia (defined as SHAPS score>5) prior to TMS. The group showed significant improvement in hedonic drive from baseline to post-treatment on SHAPS overall (7.95±3.78 vs 3.11±3.64, p<.00001). The % change in SHAPS was significantly greater in responders vs non-responders (68.8%±27.6 vs 20.8±24.4, p<.00001). However, TMS non-responders, responders, and remitters did not differ on baseline mean SHAPS, and logistic regression showed baseline anhedonia severity was not a significant predictor of clinical outcome. Conclusion: Greater anhedonia among MDD patients in this study did not predict different outcomes for TMS. However, TMS is an efficacious intervention for anhedonic symptoms.