Treatment-resistant Depression Patients Research Articles

The Influence of Research Follow-Up during COVID-19 Pandemic on Mental Distress and Resilience: A Multicenter Cohort Study of Treatment-Resistant Depression.

Background: During the COVID-19 outbreak, patients with mental disorders have faced more negative psychological consequences than the public. For people with treatment-resistant depression (TRD), it is unclear whether research engagement would protect them from the deterioration of their symptoms. The study aimed to examine if chronic depressive patients would have improved resilience and mental distress levels after follow-up interviews during an observation period under COVID-19. Methods: The study was nested within a three-year prospective cohort study. A two-group comparison design was conducted, i.e., the follow-up group with regular research interviews every three months after baseline assessment and the control group with one assessment-only interview. The two groups were compared with demographics, psychosocial, and suicide information. Results: Baseline assessments were not significantly different in sociodemographic variables, suicide risks, mental distress, and resilience between groups. Significant differences were detected in resilient coping and mental distress levels (p < 0.05). The follow-up group (n = 46) experienced a higher level of resilient coping (37% vs. 25%) and lower level of mental distress (47.8% vs. 64.7%) than the control group (n = 68). Conclusions: Findings highlight under universal government strategy against COVID-19, TRD patients receiving regular research follow-ups exhibited better resilience and less mental distress than those without regular support from healthcare providers.

Suicidality and Quality of Life in Treatment-Resistant Depression Patients in Latin America: Secondary Interim Analysis of the TRAL Study

BackgroundA large proportion of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD). The TRAL study examines the impact of TRD on suicidality and health-related quality of life (HRQoL) among MDD patients in 4 Latin American countries.MethodsIn this multicenter, prospective, observational study, MDD patients were recruited from 33 sites in Mexico, Colombia, Brazil, and Argentina. Patients were assessed for TRD, defined as failure to respond to ≥2 antidepressant medications of adequate dose and duration. Other assessments included current disease status, Mini International Neuropsychiatric Interview (MINI), Columbia-Suicide Severity Rating Scale (C-SSRS), 5 Level EQ-5D (EQ-5D-5L), Patient Health Questionnaire-9 (PHQ-9), and Sheehan Disability Scale (SDS).Results1,475 MDD patients were included in the analysis (mean age, 45.6 years; 78% women), and 429 met criteria for TRD. Thoughts of suicide and suicide attempts were more common among TRD patients (38.7%) compared with non-TRD patients (24.9%; P < 0.0001), according to the current disease status questionnaire. The C-SSRS showed that lifetime suicidal behavior was significantly more common among TRD patients than non-TRD patients (13.8 vs. 10.0%; P = 0.0384). Compared with non-TRD patients, TRD patients showed significantly greater adverse impacts on QoL (EQ-5D-5L), more severe depression (PHQ-9), and greater functional impairment (SDS).ConclusionTRD patients in clinical sites from Mexico, Colombia, Brazil, and Argentina were more likely to experience suicidality and negative effects on HRQoL than non-TRD patients.

Associations of Suicide Risk and Community Integration Among Patients With Treatment-Resistant Depression.

IntroductionTreatment-resistant depression (TRD) is one of the primary causes of disability and a major risk for suicide among patients living in the community. However, the suicide risks and care needs for safety among patients with TRD during the community reintegration process appear to be underestimated. This study aimed to investigate the association between community integration and suicide risks among patients with treatment-resistant depression (TRD) with sub-analysis by gender.MethodsPatients diagnosed with major depressive disorder were recruited upon psychiatrists' referral in two general hospitals in northern Taiwan during 2018–2019. The participants who experienced more than two failed treatments of antidepressants with partial remission were defined as TRD. A structured questionnaire was used to collect socio-demographic, suicidality, and psychosocial information.ResultsIn a total of 125 participants, gender difference was identified in certain community integration aspects such as home integration, productivity, and electronic social networking. The male participants appeared to have better involvement in social contact with internet but slightly less video link than women, while women had higher level of home integration in the past month. The participants who performed worse in the social integration and better home-based activity or productivity levels had higher suicide risks including suicide ideation and overall suicide risks.ConclusionsCommunity integration levels of home, social, and productivity were associated with suicidality in terms of overall suicide risk and recent suicide ideation. Facilitation of community integration at home and life arrangements might reduce suicide risks in TRD patients.

Treatment of anxiety symptoms in patients receiving rTMS for treatment resistant depression

This retrospective analysis examined the effects of left-sided dorsolateral prefrontal cortex (DLPFC) repetitive transcranial magnetic stimulation (rTMS) on comorbid anxiety symptoms patients with treatment resistant depression (TRD). Response rates, remission rates, reliable change index (RCI), and clinically significant change (CSC) were assessed using the 7-item Generalized Anxiety Disorder Scale (GAD-7) and the 17-item Hamilton Rating Scale for Depression (HAMD-17) Anxiety subscale at over an average of 32.9 treatments ( SD ​= ​9.2). Fifty-seven TRD patients showed statistically and clinically significant improvement in all anxiety measurements with left DLPFC rTMS. This retrospective study had no sham control and allowed for medication changes during the rTMS treatment course. Left DLPFC rTMS may be an important tool in reducing anxiety in TRD patients, improving overall treatment resistant symptoms and suicide risk. • Anxious depression is associated with more suicide risk and treatment resistance. • Transcranial Magnetic Stimulation (TMS) may be a treatment option. • TMS improved anxiety in patients with treatment resistant depression and anxiety.

The Relationship Between Depression and Pain During Acute Electroconvulsive Therapy and Follow-Up Period for Patients With Treatment-Resistant Depression.

We explored the relationships between depression and pain during acute electroconvulsive therapy (ECT) and the follow-up period for patients with treatment-resistant depression and concomitant pain. During the acute ECT phase, treatment-resistant depression patients (N = 97) were randomized to receive ECT plus agomelatine 50 mg/d, or ECT plus placebo. Depression and pain severities were measured using the 17-item Hamilton Depression Rating Scale (HAMD-17), and the pain subscale of the Depression and Somatic Symptoms Scale at baseline, after every 3 ECT treatments, and after acute ECT. If patients achieved response (ie, a ≥ 50 % reduction in HAMD-17) or received at least 6 ECT treatments, they were prescribed agomelatine 50 mg/d and participated in a 12-week follow-up trial. The HAMD-17 and pain subscale were assessed at 4-week intervals. Both HAMD-17 and pain subscale scores were converted to T score units to compare the degrees of changes between depression and pain during acute ECT and the follow-up period. Eighty-two patients completing at least the first 3 ECT treatments entered the analysis. Both HAMD-17 and pain subscale decreased significantly after acute ECT. Changes of HAMD-17 T scores were significantly greater than changes of pain subscale T scores during acute ECT and follow-up period. Pain changed more slowly than did depression while measuring both during acute ECT and the follow-up period. Pain can, therefore, be considered a separate entity from depression.

334 Phase Synchrony within the Right Prefrontal Cortex Predicts Severity of Major Depression

INTRODUCTION: Widespread alteration of brain networks has been observed in people with major depression. Although many conventional treatments are available, nearly one-third of patients could become treatment-resistant. Therefore, a clearer understanding of brain networks in depression is needed in order to develop more effective treatments. As part of an ongoing trial utilizing stereo-EEG (sEEG) intracranial recordings to inform deep brain stimulation (DBS) for treatment-resistant depression (TRD), we measured neural activity in the dorsolateral prefrontal cortex (dlPFC) and orbitofrontal cortex (OFC). METHODS: Treatment-resistant depression patients (n = 2) were implanted with frontotemporal sEEG electrodes and DBS leads in the ventral capsule/ventral striatum and sub-callosal cingulate. We acquired several measurements of depression severity throughout a 9-day inpatient monitoring period using the computerized adaptive test for depression inventory (CAT-DI). We measured connectivity using the phase locking value (PLV) between oscillations in the right dlPFC and OFC during resting state. Then we examined the relationship between depression severity and peak PLV within alpha band (8-12 Hz). RESULTS: We examined the connectivity between the deepest grey matter contact in the right dlPFC and in the right OFC. Peak PLV in alpha band was correlated with CAT-DI score under eyes-open condition in patient 1 and patient 2. CONCLUSION: Phase synchrony between right dlPFC and right OFC is involved in the severity of major depression. Increased dlPFC-OFC phase synchrony may relate to increased mood control or management.

Neurotrophic Factor Levels and Cognitive Functions before and after the Repetitive Transcranial Magnetic Stimulation in Treatment Resistant Depression.

To determine relationship between the therapeutic effect of repetitive transcranial magnetic stimulation (rTMS) on cognitive impairment and brain derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF) levels in treatment resistant depression (TRD). Descriptive study. Psychiatry Clinic of Konya Beyhekim Training and Research Hospital in Turkey, between June and November 2019. The study included 33 TRD patients and 33 healthy subjects. Patients received a total of 20 sessions of rTMS treatment. Serum BDNF and GDNF levels were measured before and after rTMS treatment. Additionally, the severity of depression as well as cognitive functions were assessed at the baseline and after the treatment. The rTMS treatment significantly improved depressive and cognitive symptoms in patients with TRD. Although the level of serum BDNF and GDNF increased after rTMS treatment, it was associated with the improvement in symptoms, but not significantly. rTMS treatment contributes to the antidepressant effect by normalising serum BDNF and GDNF levels in patients with TRD. Adding rTMS to antidepressants is, therefore, an appropriate treatment option for depressive patients with cognitive impairment. Key Words: rTMS, BDNF, GDNF, Cognitive function.

One-year incidence rate of Treatment Resistant Depression (TRD) and treatment characteristics in China

BackgroundLittle is known about the characteristics of Treatment-Resistant Depression (TRD) in China. In previous studies various identification approaches have led to a wide range of results, and it is unclear how Chinese patients compare to those in other studies. MethodsThis is a retrospective cohort study using electronic health records (EHR) from two major psychiatric hospitals in China. Adult major depressive disorder (MDD) patients who initiated pharmaceutical treatment during 2010–2018 were enrolled and follow-up was 1 year. TRD was primarily identified by consensus definition of two failures of adequate (≥4 weeks) regimens. Alternative regimens of 2-weeks and 6-weeks duration, and a data-driven definition were also applied. ResultsIn the two hospitals, 12,257 (mean age: 40.8y, 63.6% female) and 8314 (mean age: 42.4y, 68.4% female) eligible patients were included. The 1-year incidence rate of TRD was estimated to be 5.2%–7.7% using the primary definition. TRD patients had mean treatment duration of 302.5 days and 285.7 days; had 3.6 and 3.7 treatment steps on average; 94.0% and 72.6% were prescribed polypharmacy regimens, which were all marginally greater than that of non-TRD patients. Alternative definitions resulted in a wide range of incidence estimates (0.5%–20.0%). LimitationsMedications were assumed to be consumed as prescribed and lack of rating scales from EHRs may limit our TRD identification. ConclusionsThe incidence of TRD among Chinese MDD patients was comparable to other countries under similar settings and more complex treatment characteristics were observed among TRD patients. Alternative TRD definitions revealed the need for better treatment management in practices.

Electroconvulsive therapy and adiposity-related parameters in treatment-resistant depressed patients

Obesity is often accompanied by major depressive disorder (MDD), and vice versa. Latest research findings suggest the body mass index (BMI) to play a role in antidepressant treatment response in general. Our study aims to examine whether adiposity-related parameters such as BMI, glucose homeostasis, or serum lipids are associated with remission to electroconvulsive therapy (ECT). A pilot study (PS, n = 9) and a glucose study (GS, n = 29) were conducted. Blood was withdrawn directly before and 15 min (GS) as well as 1 h (PS) after the first ECT and directly before the last one (usually an ECT series comprised up to twelve sessions). BMI was associated with remission in the PS (remitters: M = 28, SD = 2.5; non-remitters: M = 22, SD = 2.08; t(7) = 3.325, p < 0.001, d = 0.24) but not in the GS or when pooled together. Glucose and insulin levels increased significantly after a single ECT session (GS: glucose: F (2,25.66) = 39.04, p < 0.001; insulin: PS: F (2,83) = 25.8, p < 0.001; GS: F (2,25.87) = 3.97, p < 0.05) but no chronic effect was detectable. Serum lipids were neither significantly altered after a single ECT session nor during a whole course of ECT. There was no difference between remitters and non-remitters in insulin, glucose, or serum lipid levels. Our study is lacking the differentiation between abdominal and peripheral fat distribution, and the sample size is small. Unexpectedly, BMI, glucose homeostasis, and lipid serum levels did not differ in patients remitting during ECT. In contrast to recently published studies, we cannot confirm the hypothesis that BMI may have an impact on ECT response.

Power signatures of habenular neuronal signals in patients with bipolar or unipolar depressive disorders correlate with their disease severity

The habenula is an epithalamic structure implicated in negative reward mechanisms and plays a downstream modulatory role in regulation of dopaminergic and serotonergic functions. Human and animal studies show its hyperactivity in depression which is curtailed by the antidepressant response of ketamine. Deep brain stimulation of habenula (DBS) for major depression have also shown promising results. However, direct neuronal activity of habenula in human studies have rarely been reported. Here, in a cross-sectional design, we acquired both spontaneous resting state and emotional task-induced neuronal recordings from habenula from treatment resistant depressed patients undergoing DBS surgery. We first characterise the aperiodic component (1/f slope) of the power spectrum, interpreted to signify excitation-inhibition balance, in resting and task state. This aperiodicity for left habenula correlated between rest and task and which was significantly positively correlated with depression severity. Time-frequency responses to the emotional picture viewing task show condition differences in beta and gamma frequencies for left habenula and alpha for right habenula. Notably, alpha activity for right habenula was negatively correlated with depression severity. Overall, from direct habenular recordings, we thus show findings convergent with depression models of aberrant excitatory glutamatergic output of the habenula driving inhibition of monoaminergic systems.

Esketamine nasal spray in patients with treatment-resistant depression: the real-world experience in the French cohort early-access programme

Objective To present the first real-world data of patients with treatment-resistant depression (TRD) treated with esketamine through a French cohort Temporary Authorisation for Use (ATUc) programme. Methods In 2019, the French Health Authorities exceptionally granted the first ATUc in psychiatry for TRD patients. Clinical characteristics, safety and efficacy data were reported by physicians. The ATUc ended ∼6 months after initiation. Results The cohort (n = 66; median age 53.0 years; 62.1% female; 78.8% with severe major depressive episodes; resistance to a mean of 4.2 previous antidepressants) received esketamine treatment for a median of 30 days. Among 46 analysed patients, 22 (47.8%) achieved response (Montgomery–Åsberg Depression Rating Scale [MADRS] total score reduction ≥50.0%) and 17 (37.0%) achieved remission (MADRS total score of ≤12) at least once at a median of 18.5 (2.0–77.0) and 21.0 (2.0–46.0) days after initiation, respectively. By Week 4, patients had a 31.6% probability of achieving remission (Kaplan–Meier method). Sedation, somnolence, dizziness, hypertension, anxiety and dissociation were the most frequently reported (>10.0%) adverse events. No new safety signals were identified. Conclusions Patient characteristics of this cohort demonstrate high-level treatment resistance. The safety and efficacy of esketamine in patients with TRD in real‐world clinical practice were consistent with Phase 3 trials. Key points Patients with treatment-resistant depression (TRD) exceptionally received esketamine nasal spray ahead of its launch through a French cohort Temporary Authorisation for Use (ATUc) programme. The clinical characteristics of 66 adult patients with TRD included in this cohort demonstrated a high-level of resistance to conventional treatments at the time of treatment request prior to esketamine initiation. No new safety signals were observed with esketamine initiation during the ATUc period compared with the Phase 3 clinical trials. The safety and efficacy of esketamine in the real world remain consistent with that established in Phase 3 clinical trials. The data collected during this ATUc also provide the first real-world data on the management and practical use of esketamine in a hospital setting in France.

Vagally Mediated Heart Rate Variability Is Associated With Executive Function Changes in Patients With Treatment-Resistant Depression Following Magnetic Seizure Therapy

ObjectivesMagnetic seizure therapy (MST) is a novel investigational brain stimulation modality for patients with treatment-resistant depression (TRD). MST is a potential alternative seizure-based treatment to electroconvulsive therapy (ECT), given that it may offer equivalent antidepressant efficacy, yet with a relative sparing of cognitive functioning. Heart rate variability (HRV) is a marker of central autonomic functioning. We aimed to explore the relationships among baseline HRV, age, clinical outcome, and executive function following MST, in patients with TRD. Materials and MethodsEighty-eight TRD patients (55 females; 18–70 years) were enrolled and 48 patients completed a course of MST in an open-label study. Patients received MST treatments two to three times per week, using one of three stimulation frequencies (ie, 100 Hz, 50 Hz, or 25 Hz) at 100% stimulator output. Root mean square of the successive R-R differences (RMSSD), an index of HRV, was computed from a baseline electrocardiogram (ECG) recording. Clinical symptoms were assessed using the Hamilton Depression Rating Scale (HAM-D24) and the Quick Inventory of Depressive Symptomatology (QIDS16). Executive function was assessed using the Trail Making Test and the Mazes Test from the MATRICS battery. ResultsBaseline RMSSD was correlated with baseline HAM-D24 (r = −0.340, p = 0.001) and baseline Mazes Test (r = 0.417, p = 0.0007) but not with baseline Trail Making Test. Furthermore, baseline RMSSD was not correlated with changes on the HAM-D24, QIDS16, or total scores on the Trail Making Test. However, there was a significant correlation between baseline RMSSD and improvement on the Mazes Test following MST (r = 0.502, p = 0.0004). ConclusionsSince this is an open-label trial, the influence of the placebo effect cannot be excluded. However, our results suggest that baseline RMSSD may be a state-biomarker of depression and executive function impairment. Additionally, while baseline vagally mediated resting cardiac activity did not predict the outcome of depression, it may mediate executive function improvements following MST.

Treatment-resistant depression and labor market affiliation in the Danish welfare society: a register-based study.

We explored if patients with treatment-resistant depression (TRD) go through different states of labor market affiliation during their course of illness before they return to work or obtain early retirement as compared to patients without TRD. All adults between 18 and 58years with a first-time hospital contact due to depression in Danish patients' registers from 2000 to 2014 were followed in a nationwide labor market database. At time of TRD (index week), TRD patients were matched with patients without TRD in a 1:2 ratio. Sequence analysis and logistic regression were applied to explore the association of TRD and labor market affiliation and measures of transitions between labor market states 52weeks before and after the index week. At the index week, 14.1% of patients with TRD were in employment, whereas the proportion was 26.4% among non-TRD patients. Over time, the proportion of patients in employment increased slightly to 25.5% for TRD and 33.7% for non-TRD patients. The proportion of TRD patients with sickness absence at index was 47.0%, while the proportion was 26.2% for non-TRD patients. The adjusted odds of a below mean volatility of labor market transitions, characterized by more episodes in passive social transfer payments and disability pension, were higher among patients with TRD compared with non-TRD patients (OR 1.63, 95% CI [1.56-1.69]). Similarly, the adjusted odds of a below mean integration into employment were 1.63 higher among TRD patients compared with non-TRD patients (95% CI [1.56-1.70]). Patients with TRD have higher levels of sickness absence and lower levels of reintegration into the labor market after meeting the criteria for TRD compared with patients without TRD.

Corticomotor plasticity as a predictor of response to high frequency transcranial magnetic stimulation treatment for major depressive disorder

BackgroundMany patients with treatment-resistant depression (TRD) respond to repetitive transcranial magnetic stimulation (rTMS) treatment. This study aimed to investigate whether modulation of corticomotor excitability by rTMS predicts response to rTMS treatment for TRD in 10 Hz and intermittent theta-burst stimulation (iTBS) protocols. MethodsThirteen TRD patients underwent two evaluations of corticomotor plasticity—assessed as the post-rTMS (10 Hz, iTBS) percent change (%∆) in motor evoked potential (MEP) amplitude elicited by single-pulse TMS. Following corticomotor plasticity evaluations, patients subsequently underwent a standard 6-week course of 10 Hz rTMS (4 s train, 26 s inter-train interval, 3000 total pulses, 120% of motor threshold) to the left dorsolateral prefrontal cortex. Treatment efficacy was assessed by the Beck Depression Inventory II (BDI-II) and Hamilton Depression Rating Scale (HAM-D). The change in MEPs was compared between 10 Hz and iTBS conditions and related to the change in BDI-II and HAM-D scores. ResultsAnalyses of variance revealed that across all time-points, higher post-10 Hz MEP change was a significant predictor of greater improvement on the BDI-II (p < 0.001) and HAM-D (p = 0.022). This relationship was not observed with iTBS (p-values≥0.100). Post-hoc tests revealed the MEP change 20 min post-10 Hz was the strongest predictor of BDI-II improvement. LimitationsCortical excitability was measured from the motor cortex, rather than the dorsolateral prefrontal cortex, where treatment is applied. The 10 Hz and iTBS protocols were performed at different intensities consistent with common practice. ConclusionsModulation of corticomotor excitability by 10 Hz can predict response to rTMS treatment with 10 Hz rTMS.

Clinical and Biological Factors Are Associated with Treatment-Resistant Depression.

Background: Treatment-resistant depression (TRD) is a debilitating condition associated with unmet clinical needs. Few studies have explored clinical characteristics and serum biomarkers associated with TRD. Aims: We investigated whether there were differences in clinical and biochemical variables between patients affected by TRD than those without. Methods: We recruited 343 patients (165 males and 178 females) consecutively hospitalized for MDD to the inpatient clinics affiliated to the Fondazione IRCCS Policlinico, Milan, Italy (n = 234), and ASST Monza, Italy (n = 109). Data were obtained through a screening of the clinical charts and blood analyses conducted during the hospitalization. Results: TRD versus non-TRD patients resulted to be older (p = 0.001), to have a longer duration of illness (p < 0.001), to be more currently treated with a psychiatric poly-therapy (p < 0.001), to have currently more severe depressive symptoms as showed by the Hamilton Depression Rating Scale (HAM-D) scores (p = 0.016), to have lower bilirubin plasma levels (p < 0.001). In addition, more lifetime suicide attempts (p = 0.035), more antidepressant treatments before the current episode (p < 0.001), and a lower neutrophil to lymphocyte ratio at borderline statistically significant level (p = 0.060) were all associated with the TRD group. Conclusion: We identified candidate biomarkers associated with TRD such as bilirubin plasma levels and NLR, to be confirmed by further studies. Moreover, TRD seems to be associated with unfavorable clinical factors such as a predisposition to suicidal behaviors. Future research should replicate these results to provide robust data in support of the identification of new targets of treatment and implementation of prevention strategies for TRD.

Connectivity-Guided Theta Burst Transcranial Magnetic Stimulation Versus Repetitive Transcranial Magnetic Stimulation for Treatment-Resistant Moderate to Severe Depression: Magnetic Resonance Imaging Protocol and SARS-CoV-2–Induced Changes for a Randomized Double-blind Controlled Trial

BackgroundDepression is a substantial health and economic burden. In approximately one-third of patients, depression is resistant to first-line treatment; therefore, it is essential to find alternative treatments. Transcranial magnetic stimulation (TMS) is a neuromodulatory treatment involving the application of magnetic pulses to the brain that is approved in the United Kingdom and the United States in treatment-resistant depression. This trial aims to compare the clinical effectiveness, cost-effectiveness, and mechanism of action of standard treatment repetitive TMS (rTMS) targeted at the F3 electroencephalogram site with a newer treatment—a type of TMS called theta burst stimulation (TBS) targeted based on measures of functional brain connectivity. This protocol outlines brain imaging acquisition and analysis for the Brain Imaging Guided Transcranial Magnetic Stimulation in Depression (BRIGhTMIND) study trial that is used to create personalized TMS targets and answer the proposed mechanistic hypotheses.ObjectiveThe aims of the imaging arm of the BRIGhTMIND study are to identify functional and neurochemical brain signatures indexing the treatment mechanisms of rTMS and connectivity-guided intermittent theta burst TMS and to identify imaging-based markers predicting response to treatment.MethodsThe study is a randomized double-blind controlled trial with 1:1 allocation to either 20 sessions of TBS or standard rTMS. Multimodal magnetic resonance imaging (MRI) is acquired for each participant at baseline (before TMS treatment) with T1-weighted and task-free functional MRI during rest used to estimate TMS targets. For participants enrolled in the mechanistic substudy, additional diffusion-weighted sequences are acquired at baseline and at posttreatment follow-up 16 weeks after treatment randomization. Core data sets of T1-weighted and task-free functional MRI during rest are acquired for all participants and are used to estimate TMS targets. Additional sequences of arterial spin labeling, magnetic resonance spectroscopy, and diffusion-weighted images are acquired depending on the recruitment site for mechanistic evaluation. Standard rTMS treatment is targeted at the F3 electrode site over the left dorsolateral prefrontal cortex, whereas TBS treatment is guided using the coordinate of peak effective connectivity from the right anterior insula to the left dorsolateral prefrontal cortex. Both treatment targets benefit from the level of MRI guidance, but only TBS is provided with precision targeting based on functional brain connectivity.ResultsRecruitment began in January 2019 and is ongoing. Data collection is expected to continue until January 2023.ConclusionsThis trial will determine the impact of precision MRI guidance on rTMS treatment and assess the neural mechanisms underlying this treatment in treatment-resistant depressed patients.Trial RegistrationISRCTN Registry ISRCTN19674644; https://www.isrctn.com/ISRCTN19674644International Registered Report Identifier (IRRID)DERR1-10.2196/31925

Treatment-Resistant Depression in Poland-Epidemiology and Treatment.

(1) Background: Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide. Although several antidepressant drugs have been developed, up to 30% of patients fail to achieve remission, and acute remission rates decrease with the number of treatment steps required. The aim of the current project was to estimate and describe the population of treatment-resistant depression (TRD) patients in outpatient clinics in Poland. (2) Methods: The project involved a representative sample of psychiatrists working in outpatient clinics, chosen through a process of quota random sampling. The doctors completed two questionnaires on a consecutive series of patients with MDD, which captured the patients’ demographics, comorbidities, and medical histories. TRD was defined as no improvement seen after a minimum of two different antidepressant drug therapies applied in sufficient doses for a minimum of 4 weeks each. The data were weighted and extrapolated to the population of TRD outpatients in Poland. (3) Results: A total of 76 psychiatrists described 1781 MDD patients, out of which 396 fulfilled the criteria of TRD. The TRD patients constituted 25.2% of all MDD patients, which led to the number of TRD outpatients in Poland being estimated at 34,800. The demographics, comorbidities, medical histories, and histories of treatment of Polish TRD patients were described. In our sample of the TRD population (mean age: 45.6 ± 13.1 years; female: 64%), the patients had experienced 2.1 ± 1.6 depressive episodes (including the current one), and the mean duration of the current episode was 4.8 ± 4.4 months. In terms of treatment strategies, most patients (around 70%) received monotherapy during the first three therapies, while combination antidepressant drugs (ADs) were applied more often from the fourth line of treatment. The use of additional medications and augmentation was reported in only up to one third of the TRD patients. During all of the treatment steps, patients most often received a selective serotonin reuptake inhibitor (SSRI) and a serotonin norepinephrine reuptake inhibitor (SNRI). (4) Conclusions: TRD is a serious problem, affecting approximately one fourth of all depressive patients and nearly 35,000 Poles.

A head-to-head randomised controlled trial of aripiprazole versus quetiapine as augmenting agents in treatment-resistant depression

Introduction: Almost 30%–50% of the patients with major depressive disorder can be categorised as treatment-resistant depression (TRD). The use of augmenting agents such as aripiprazole (ARI) and quetiapine (QP) to the existing antidepressant (AD) therapy could be a suitable alternative for treating TRD. The superiority of anyone over others is not established in short-term studies. Hence, the present study was performed to compare the safety and efficacy of ARI and QP for the treatment of TRD. Materials and Methods: In the present study, a total of 50 patients with TRD who showed insufficient response to at least two ADs for 12 weeks were enrolled. The participants were assigned randomly in a double-blind trial to receive ARI (10 mg/day; n = 25) or QP (300 mg/day; n = 25) in addition to their standard AD therapy for 12 weeks. Montgomery–Åsberg Depression Rating Scale (MADRS) and the Clinical Global Impressions (CGI) scale were used to measure treatment efficacy. The safety was evaluated by recording treatment-caused adverse effects (AEF). Results: A significant decrease in MADRS score was observed with ARI groups than in the QP group (‒7.5; ‒4.6, P < 0.001). The CGI scores in the ARI group also exhibit significant improvement compared with the QP group. There was a non-significant change in CGI score recorded in both groups. The AEF was observed in 11% of patients with more incidences in the QP groups. The incidences of AEFs resulting in discontinuation of therapy were found low in both groups (ARI: 1.6%; QP: 3.2%). Conclusion: The findings of this study conclude that TRD patients can be more benefitted by ARI augmentation therapy than QP.

Abnormal habenula functional connectivity characterizes treatment-resistant depression

BackgroundA significant proportion of patients with major depressive disorder are resistant to antidepressant medication and psychological treatments. A core symptom of treatment-resistant depression (TRD) is anhedonia, or the inability to feel pleasure, which has been attributed to disrupted habenula function – a component of the reward network. This study aimed to map detailed neural circuitry architecture related to the habenula to identify neural mechanisms of TRD. Methods35 TRD patients, 35 patients with treatment-sensitive depression (TSD), and 38 healthy controls (HC) underwent resting-state functional magnetic resonance imaging. Functional connectivity analyses were performed using the left and right habenula as seed regions of interest, and the three groups were compared using whole-brain voxel-wise comparisons. ResultsThe TRD group demonstrated hyperconnectivity of the left habenula to the left precuneus cortex and the right precentral gyrus, compared to the TSD group, and to the right precuneus cortex, compared to the TSD and HC groups. In contrast, TSD demonstrated hypoconnectivity than HC for both connectivity measures. These connectivity values were significantly higher in patients with a history of suicidal ideation. ConclusionsThis study provides evidence that, unlike TSD, TRD is characterized by hyperconnectivity of the left habenula particularly with regions of the default mode network. An increased interplay between reward and default mode networks is linked to suicidality and could be a possible mechanism for anhedonia in hard to treat depression.

P.0224 Dosing regimen overview of treatment-resistant depression patients treated with esketamine: eskale study interim analysis

P.0224 Dosing regimen overview of treatment-resistant depression patients treated with esketamine: eskale study interim analysis