Severe Major Depressive Disorder Research Articles

A resting state fMRI study of major depressive disorder with and without anxiety

BackgroundThe neurobiology of the Major depressive disorder (MDD) with anxiety is still unclear. The present study aimed to explore the brain correlates of MDD with and without anxiety in men and women during resting-state fMRI. MethodsTwo hundred and fifty-four patients with MDD (MDD with anxiety, N = 152) and MDD without anxiety, N = 102) and 228 healthy controls (HCs) participated in this study. We compared the fALFF(fractional amplitude of low-frequency fluctuations) and ReHo(regional homogeneity) of ACC(anterior cingulate cortex) and insula among these three groups. We also compared gender difference between MDD with anxiety and MDD without anxiety. ResultsWe found that the fALFF values within the ACC and insula were significantly lower in MDD with anxiety compared to without anxiety and HCs. However, we did not find differences in ReHo values among the three groups. In women, we found significant differences in fALFF values between MDD with and without anxiety. These differences were not observed in men. ConclusionsIt is possible that MDD with anxiety show less spontaneous BOLD-fMRI signal intensity within the ACC and insula compared to MDD without anxiety, especially in women. The fALFF within the ACC and insula can be a potential biomarker for severe MDD phenotype.

The sociodemographic and clinical phenotype of European patients with major depressive disorder undergoing first-line antidepressant treatment with NaSSAs

Since selective serotonin reuptake inhibitors, that are recommended as first-line antidepressant psychopharmacotherapy for major depressive disorder (MDD), may not be the optimal choice for every patient, antidepressants with different modes of action exerting a distinct set of expectant effects, represent a valuable alternative. Despite the previously observed increased prescription rates of noradrenergic and specific serotonergic antidepressants (NaSSAs) - particularly mirtazapine - in Europe, the individual profiles of patients primarily prescribed NaSSAs in real-world settings have not been systematically investigated yet. In this secondary analysis based on a European, cross-sectional, naturalistic, multicenter study involving 1410 adult males and females with primary MDD, sociodemographic and clinical variables were compared between patients dispensed NaSSAs and those with alternative first-line antidepressants. Hereby, NaSSAs were administered in 8.6 % of the sample (mirtazapine: n = 114, mianserin: n = 7). We detected associations with older mean age, male sex, unemployment, as well as additional melancholic and catatonic features, inpatient treatment, lower mean daily-dosages of the administered antidepressants but higher rates of augmentation with low-potency antipsychotics, and greater mean reductions of depressive symptoms during their current major depressive episodes. Although the study design is unsuitable to draw any causal conclusions, our findings provide a realistic picture of patients eligible for first-line antidepressant treatment with NaSSAs, especially mirtazapine, and underscore the role of this AD substance class in severe MDD. Further, they may represent a promising basis for future systematic research focusing on precision diagnostics and treatment in MDD, that would ideally result in faster responses and better outcomes, especially in the so-called difficult-to-treat conditions including treatment resistant depression.

Electroconvulsive therapy plays an irreplaceable role in treatment of major depressive disorder.

Major depressive disorder is a serious and common neuropsychiatric disorder that affects more than 350 million people worldwide. Electroconvulsive therapy is the oldest and most effective treatment available for the treatment of severe major depressive disorder. Electroconvulsive therapy modifies structural network changes in patients with major depressive disorder and schizophrenia. And it can also affect neuroinflammatory responses and may have neuroprotective effects. Electroconvulsive therapy plays an irreplaceable role in the treatment of major depressive disorder.

COVID-19 Psychiatric Inpatient Unit- experience and challenges

IntroductionOn January 2021 the Department of Psychiatry became the only unit exclusively dedicated to COVID patients with severe mental illness in acute decompensation. Only patients in risk of rapid medical deterioration were excluded and forwarded to intensive care.ObjectivesDiscussion of this unprecedented experience.MethodsAnalysis of 28 patients hospitalized during 3 months with both an acute psychiatric disorder and an SARS-CoV-2 infection; description of the multidisciplinary intervention made.ResultsOur sample was characterized by a majority of patients with an acute psychotic episode derived from a schizophrenia spectrum disorder (42%) or a bipolar affective disorder (21%). Only 3% of the patients had a diagnosis of severe major depressive disorder. And 10% of patients developed severe respiratory symptoms requiring oxygen or urgent transfer to COVID medical wards. Most patients presented periods of psychomotor agitation, lack of impulse control and self-aggression. Psychopharmacological and psychotherapeutic interventions had to be adapted to these unusual conditions. Most of them had already gone through a period of isolation in the buffer ward created to exclude false negatives, which promoted atypical deliriums and symptoms of post-traumatic stress. The psychiatric team was faced with the emergent need to adapt an intervention model based on trust to a model that had to prioritize physical safety.ConclusionsThe pandemic experience was transformative for all who lived through it. From the challenge perspective, it may have been enriching. But the maintained confrontation with the antithesis of therapy, defined by “caring, supporting, communicating, approaching”, was devastating in ways that we consider essential to be debated.DisclosureNo significant relationships.

Palliative Psychiatry for Patients With Severe and Persistent Mental Illness: A Survey on the Attitudes of Psychiatrists in India Compared to Psychiatrists in Switzerland.

ObjectivesPalliative psychiatry is a new approach for the care of patients with severe and persistent mental illness (SPMI) which systematically considers biological, psychological, social, and existential factors of care. To assess the attitudes of psychiatrists in India toward palliative psychiatry for patients with SPMI and to compare these to the attitudes of psychiatrists in Switzerland.MethodsIn an online survey, data from 206 psychiatrists in India were collected and compared with data from a previous survey among 457 psychiatrists in Switzerland.ResultsPsychiatrists in India generally considered it very important to prevent suicide in SPMI patients (97.6%). At the same time, they considered it very important to reduce suffering (98.1%) and to ensure functionality in everyday life (95.6%). They agreed that palliative psychiatry is important for providing optimal care to SPMI patients without life-limiting illness (79.6%) and considered palliative psychiatry as indicated for patients with SPMI (78.2%). By contrast, curing the illness was considered very important by only 39.8 % of respondents. Relative to psychiatrists in Switzerland, psychiatrists in India were significantly more concerned about preventing suicide and less willing to accept a reduction in life expectancy, even at the expense of quality of life in patients with severe and persistent schizophrenia and recurrent major depressive disorder. At the same time, they were significantly more likely to advocate palliative psychiatry.ConclusionMost of the participating psychiatrists in India agreed that palliative psychiatry can be indicated for patients with SPMI. The comparison with psychiatrists in Switzerland highlights the need to take account of cultural differences in future studies of this kind. In summary, this study shows the potential of palliative psychiatry as a genuine biopsychosocio-existential approach which systematically integrates biological, psychological, social, and existential factors of care.

Pharmacological treatment of major depressive disorder according to severity in psychiatric inpatients: results from the AMSP pharmacovigilance program from 2001–2017

The International Classification of Diseases (10th Version) categorizes major depressive disorder (MDD) according to severity. Guidelines provide recommendations for the treatment of MDD according to severity. Aim of this study was to assess real-life utilization of psychotropic drugs based on severity of MDD in psychiatric inpatients. Drug utilization data from the program “Drug Safety in Psychiatry” (German: Arzneimittelsicherheit in der Psychiatrie, AMSP) were analyzed according to the severity of MDD. From 2001 to 2017, 43,868 psychiatric inpatients with MDD were treated in participating hospitals. Most patients were treated with ≥ 1 antidepressant drug (ADD; 85.8% of patients with moderate MDD, 89.8% of patients with severe MDD, and 87.9% of patients with psychotic MDD). More severely depressed patients were more often treated with selective serotonin–norepinephrine reuptake inhibitors and mirtazapine and less often with selective serotonin reuptake inhibitors (p < 0.001 each). Use of antipsychotic drugs (APDs), especially second-generation APDs, increased significantly with severity (37.0%, 47.9%, 84.1%; p < 0.001 each). APD + ADD was the most used combination (32.8%, 43.6%, 74.4%), followed by two ADDs (26.3%, 29.3%, 24.9%). Use of lithium was minimal (3.3%, 6.1% ,7.1%). The number of psychotropic drugs increased with severity of MDD—patients with psychotic MDD had the highest utilization of psychotropic drugs (93.4%, 96.5%, 98.7%; p < 0.001). ADD monotherapy was observed to a lesser extent, even in patients with non-severe MDD (23.2%, 17.1%, 4.4%). Findings reveal substantial discrepancies between guideline recommendations and real-life drug utilization, indicating that guidelines may insufficiently consider clinical needs within the psychiatric inpatient setting.

Do-not-resuscitate (DNR) status and major depressive disorder (MDD): Clinical association and hospitalization outcomes.

To understand (1) the association of Major Depressive Disorder (MDD) and do-not-resuscitate (DNR) status among hospitalized patients and (2) the association of MDD and hospitalization outcomes among DNR patients. This was a cross-sectional analysis of United States Healthcare Cost and Utilization Project, Nationwide Inpatient Sample data from 2009 to 2013 for patients >18 years. To address the first objective, we used multivariable logistic regression among all hospitalized patients to compute the adjusted odds ratio (aOR) of having DNR status if patients have active MDD of varying severities after controlling for age, sex, race, suicidal ideation, and Elixhauser Comorbidity Index. To address the second objective, we used multivariable regression among patients with DNR status to compute aOR of having hospitalization outcomes such as increased length of stay, higher total charges, leaving against medical advice, and mortality if patients have MDD. Among all hospitalizations, 2.3% had DNR status. There was an inverse association between severity of MDD and having DNR status. Relative to those without MDD, patients with moderate recurrent MDD episode (aOR 0.74 (95% confidence interval (CI): 0.65-0.85) and severe recurrent MDD episode (aOR of 0.42 (95% CI: 0.37-0.48)) were significantly less likely to have DNR status. Among DNR patients, those with all severities of MDD except mild single episode MDD were >40% less likely to die during hospitalization. Among DNR patients, patients with MDD had 0.7 day longer length of stay, and >$4,500 higher total charges. Patients are less likely to have DNR status if they have active MDD. Among patients with DNR status, those with MDD are less likely to die during hospitalization than those without MDD. With current practice, depression is not associated with increased likelihood of death due to foregoing resuscitation prematurely, though the exact mechanisms of these findings need further investigation.

Mood-congruent negative thinking styles and cognitive vulnerability in depressed COVID-19 survivors: A comparison with major depressive disorder

BackgroundCOVID-19 is associated with depressive psychopathology in survivors. Negative thinking styles are a core feature of major depression, fostering the experience of negative emotions and affects and hampering recovery. This cognitive vulnerability has been observed in medical conditions associated with depression, but never explored in post-COVID depression. MethodsWe studied 729 participants: 362 COVID-19 survivors, 73 inpatients with Major Depressive Disorder (MDD), and 294 healthy participants (HC). Severity of depression was self-rated on the Zung Self-Rating Depression Scale (ZSDS). Neuropsychological bias toward negative emotional stimuli and the negative outlook on the self were tested in a self-description task, yielding latencies and frequencies of attribution of morally tuned elements. Dimensions of negative thinking and depressive cognitive style in evaluation of hypothetical events were measured on the Cognition Questionnaire (CQ). Results22.4% COVID survivors self-rated depression above the clinical threshold. Frequencies and latencies of attribution of morally negative elements, and CQ scores, correlated between themselves and predicted ZSDS scores, with post-COVID depressed patients showing intermediate scores between the more severe MDD patients, and non-depressed post-COVID participants and HC. LimitationsRecruitment was in a single center, thus raising the possibility of population stratification. ConclusionsThe breadth of self-reproach and depressive cognitive style in evaluating events showed the same association with severity of depression in MDD and in post-COVID depressed patients, distributing along a gradient of severity, thus suggesting that individual features of negative thinking styles are shared in these conditions, and should be addressed as treatment targets in depressed COVID-19 survivors.

High efficiency of left superior frontal gyrus and the symptom features of major depressive disorder.

Major depressive disorder (MDD) patients with anhedonia tend to have a poor prognosis. The underlying imaging basis for anhedonia in MDD remains largely unknown. The relationship between nodal properties and anhedonia in MDD patients need to be further investigated. Herein, this study aims to explore differences of cerebral functional node characteristics in MDD patients with severe anhedonia (MDD-SA) and MDD patients with mild anhedonia (MDD-MA) before and after the antidepressant treatment. Ninety participants with current MDD were recruited in this study. 24-Item Hamilton Depression Scale (HAMD-24) and Snaith-Hamilton Pleasure Scale (SHAPS) were used to assess the severity of depression and anhedonia at baseline and the end of 6-months treatment. The MDD patients who scored above the 25th percentile on the SHAPS were assigned to an MDD-SA group (n=19), while those who scored below the 25th percentile were assigned to an MDD-MA group (n=18). All patients in the 2 groups received antidepressant treatment. Functional magnetic resonance imaging (fMRI) images of all the patients were collected at baseline and the end of 6-months treatment. Graph theory was applied to analyze the patients' cerebral functional nodal characteristics, which were measured by efficiency (ei) and degree (ki). Repeated measures 2-factor ANCOVA showed significant main effects on group on the ei and ki values of left superior frontal gyrus (LSFG) (P=0.003 and P=0.008, respectively), and on the ei and ki values of left medial orbital-frontal gyrus (LMOFG) (P=0.004 and P=0.008, respectively). Compared with the MDD-MA group, the significantly higher ei and ki values of the LSFG (P=0.015 and P=0.021, respectively), and the significantly higher ei and ki values of the LMOFG (P=0.015 and P=0.037, respectively) were observed in the MDD-SA group at baseline. Meanwhile, higher SHAPS scores could result in higher ei and ki values of LSFG (P=0.019 and P=0.026, respectively), and higher ei value of LMOFG (P=0.040) at baseline; higher SHAPS scores could result in higher ei values of LSFG (P=0.049) at the end of 6-months treatment. The multiple linear regression analysis revealed that sex were negatively correlated with the ei and ki values of LSFG (r= -0.014, P=0.004; r=-1.153, P=0.001, respectively). The onset age of MDD was negatively correlated with the ki value of LSFG (r=-0.420, P=0.034) at the end of 6-months treatment. We also found that SHAPS scores at baseline were positively correlated with the HAMD-24 scores (r=0.387, P=0.022) at the end of 6-months treatment. There are obvious differences in nodal properties between the MDD-SA and the MDD-MA patients, such as the high ei of LSFG in the MDD-SA patients, which may be associated with the severity of anhedonia. These nodal properties could be potential biomarkers for the prognosis of MDD. The increased ei and ki values in the LSFG of MDD-SA patients may underlie a compensatory mechanism or protective mechanism. The mechanism may be an important component of the pathological mechanism of MDD-SA. The poor prognosis in the MDD-SA patients suggests that anhedonia may predict a worse prognosis in MDD patients. Sex and onset age of MDD may affect the nodal properties of LSFG at baseline and the end of 6-months treatment.

Accelerated Resting-State fMRI-Guided Theta Burst Stimulation to the Right DLPFC for Late-Life Depression: A Pilot Study

<h3>Introduction</h3> Repetitive transcranial magnetic stimulation (rTMS) is FDA-approved for treatment of major depressive disorder; however, its efficacy in late-life depression (LLD) may be reduced due to age-related changes (see Figure 1). rTMS of the dorsolateral prefrontal cortex (DLPFC) has been shown to affect mood control via modulation of the subgenual cingulate cortex (SgCC). The area within the DLPFC having maximum anticorrelated activity to the SgCC is currently believed the most efficacious target for rTMS for depression. While trials of accelerated neuronavigated rTMS to the left DLPFC for depression have shown large effects for depression,¹ there has not yet been a validation of this technique specifically for LLD. Additionally, no studies have tested accelerated intermittent theta burst stimulation (iTBS) to the right DLPFC for depression, although it may have benefit for both depression and anxiety.² We proposed a pilot study of accelerated resting-state functional MRI (rsfMRI)-guided iTBS for LLD and hypothesized that this intervention would result in a significant improvement in depressive and generalized anxiety disorder symptoms. <h3>Methods</h3> A total of 18 elderly patients (ages 50-79 years) with a clinical diagnosis of moderate to severe major depressive disorder of at least 6 months' duration were recruited from local clinics. Each patient underwent rsfMRI and behavioral assessment prior to treatment. Change in depressive symptoms was measured by the Inventory of Depressive Symptoms (IDS-30-C). Change in anxiety symptoms was measured by the Generalized Anxiety Disorder-7 (GAD-7). Each participant's unique stimulation target was found by preprocessing resting-state data within Analysis of Functional NeuroImages (AFNI). A connectivity map of the bilateral SgCC as defined by the Brainnetome atlas was computed and smoothed to 12mm. The maximally anti-correlated voxel within the DLPFC search region (Brodmann areas 9 and 46) was located. A 3mm sphere around the target voxel was warped to subject space and exported to a neuronavigation system. Each participant received 45 sessions of iTBS to their fMRI target with a Magventure MagPro X100 stimulator with Cool-B70 coil (see Figure 2). Stimulation parameters were: 5Hz burst frequency, 50Hz intraburst frequency, 2 second train duration, 8 second intertrain interval, 60 trains/session, 5 sessions/day, 50 minute intersession interval, for 9 days totaling 81,000 pulses. After the 15th and 45th treatments, participants repeated clinical and imaging assessments (see Figure 3). Depression scores were elicited by phone interview at one and three months after treatment. Means and standard deviations of depressive and anxious symptoms were calculated for each visit. Repeated measures analysis of variances (ANOVA) was used to assess change in symptoms over time. Changes in connectivity between nodes in the default mode network (DMN), salience network (SN), and frontoparietal network (FPN) were analyzed with independent components analysis (ICA) in Statistical Parametric Mapping (SPM). <h3>Results</h3> Mean age of the 18 patients (2M, 16F) was 63 ± 7.4 years. Mean duration of depression was 166 ± 154.4 months. Nine patients had comorbid GAD and five patients had comorbid posttraumatic stress disorder. Four of the 18 patients had previously undergone ECT. Mean depression (IDS-30-C) scores decreased throughout the study protocol (Visit 1: 39.31 ± 9.24; Visit 2: 30.74 ± 10.44; Visit 3: 20.79 ± 8.13) and remained below pre-treatment values at one month (19.84 ± 15.63) and three months (20.34 ± 14.15) (F(4,28) = 7.15, p = .0004, ??_p² = 0.5) (see Figure 4). Mean GAD-7 scores (N=18) also decreased with treatment (Visit 1: 9.95 ± 5.89; Visit 2: 9.58 ± 5.28; Visit 3: 6.53 ± 5.00) (F(2,36) = 7, p < .006, ??_p² = 0.28) (see Figure 5). Preliminary analysis of changes in connectivity from Visit 1 to Visit 3 indicate significantly increased within-network connectivity in the DMN (p = .003), and decreased between-network connectivity between the DMN and FPC (p = .011). <h3>Conclusions</h3> In this single-arm, uncontrolled pilot study, accelerated rsfMRI-guided iTBS to the right DLPFC in patients with LLD was effective in reducing both symptoms of depression and generalized anxiety. Connectivity changes in DMN and FPN network components were also observed. Future work should confirm these effects in a larger sample size and controlled study design. <h3>Secondary Rationale</h3> Reason for Late-Breaking Status: Data collection was continued beyond the regular submission deadline to attain greater statistical power to inform study conclusions. <h3>This research was funded by</h3> UNM Successful Aging Pilot Grant, Mind Research Network Center of Biomedical Research Excellence (COBRE) Pilot Grant (NIH/NIGMS 5P30GM122734-03)

Relationship between depressive symptoms and adherence to direct-acting antivirals: Implications for Hepatitis C treatment among people who inject drugs on medications for opioid use disorder

BackgroundInterferon-based regimens exacerbated depressive symptoms, which interfered with treating hepatitis C virus (HCV) among people who inject drugs (PWID). Direct-acting antivirals (DAA) are not associated with worsening depressive symptoms; however, the impact of depressive symptoms on adherence remains little known. We examined the association between depressive symptoms and adherence to DAA among HCV-infected PWID. A secondary aim was to identify the optimal cut-off for major depressive disorder for this population. MethodsParticipants were 150 HCV-infected PWID on maintenance treatment enrolled in a randomized clinical trial testing three HCV care models. Severity of depressive symptoms were assessed using the Beck Depression Inventory-II (BDI-II) at baseline and every 4 weeks during treatment. Current major depressive disorder at baseline was diagnosed by the Mini-International Neuropsychiatric Interview. Adherence was measured during treatment (weeks 1–12) using electronic blister packs ResultsBDI-II scores ≥ 18 were identified as the optimal threshold for diagnosing major depressive disorder. Participants with BDI scores ≥ 18 at baseline had significantly lower adherence rates at weeks 1–4 of treatment compared to those with BDI scores < 18 (b = −0.23, 95% CI: 0.45–0.01, p = 0.044), but not in any other time intervals (weeks 5–8, b = −0.03, 95% CI: −0.32, 0.26, p = 0.825; weeks 9–12, b = −0.33, 95% CI −0.70, 0.02, p = 0.066). ConclusionsElevated depressive symptoms were associated with lower adherence to DAA only during the first 4 weeks of HCV treatment. Neither severe depressive symptoms nor major depressive disorder appears to be a barrier to DAA adherence among PWID.

Disrupted default mode network and executive control network are associated with depression severity on structural network.

Major depressive disorder (MDD) is a psychiatric disorder with a relatively limited response to treatment. It is necessary to better understand the neuroanatomical mechanisms of structural networks. The current study recruited 181 first-onset, untreated adult MDD patients: slight MDD (SD, N = 23), moderate MDD (MD, N = 77), Heavy MDD (HD, N = 81) groups; along with a healthy control group (HC, N = 81) with matched general clinical data. FreeSurfer was used to preprocess T1 images for gray matter volume (GMV), and the default mode network (DMN) and the execution control network (ECN) were analyzed by structural covariance network (SCN). Present study found that the GMV of brain regions reduced with the severity of the disease. Specifically, the GMV of the left anterior cingulate gyrus (ACC.L) is negatively correlated with MDD severity. In addition, the SCN connectivity of the whole-brain network increases with the increase of severity in MDD. ACC.L is a key brain region with increased connectivity between the left orbitofrontal in DMN and between the right orbitofrontal in ECN, which leads to damage to the balance of neural circuits. Patients with smaller GMV of ACC.L are more likely to develop severe MDD, and as a key region in both networks which have distinct structural network models in DMN and ECN. MDD patients with different severity have different neuroimaging changes in DMN and ECN.

Naturalistic Study of Depression Associated with Parkinson's Disease in a National Public Neurological Referral Center in Mexico.

Major depressive disorder (MDD) is a major health problem in Parkinson’s disease (PD) patients. We described the clinical and sociodemographic factors of MDD among patients with PD at a national neurological referral center in Mexico. One hundred patients with PD + MDD were included in the study. All the patients were evaluated during the “ON” treatment phase of PD. Clinical scales for cognition (MMSE and MoCA) and MDD (MADRS) were applied. The mean age was 58.49 ± 11.02 years, and 57% of the sample was male. The most frequent symptom of PD was tremor (67%), and onset was more frequent on the right side (57%). Additionally, 49% of the patients with PD had moderate to severe (M/S) MDD. Selective serotonin reuptake inhibitors were the most frequent antidepressant treatment (69%). The scores of the scales were MADRS 21.33 ± 5.49, MoCA 21.06 ± 4.65, and MMSE 26.67 ± 1.20. The females had lower MMSE scores compared to the males (p = 0.043). The patients with M/S MDD had more rigidity at the beginning of PD (p = 0.005), fewer march alterations (p = 0.023), and a greater prevalence of left-side initial disease (p = 0.037). Rigidity was associated with M/S MDD (OR 3.75 p = 0.013). MDD was slightly more frequent in the males than in the females. The MDD symptoms and cognitive impairment were worse in the female population.

The yearly peak age of the onset of major depressive disorder over the past 5 years at a general hospital in Saudi Arabia

Objectives: Patients with major depressive disorder (MDD) do not exhibit usual mood swings and emotional reactions to difficulties in life. Patients with MDD experience specific symptoms such as decreased mood, loss of interest, and suicidal thoughts, particularly those with moderate, severe, or recurrent MDD. Depression can become a severe health condition, and MDD can lead to significant morbidity and mortality, and functional impairment. A total of 260 million people are diagnosed as having MDD worldwide, with a global prevalence of 3627 per 100,000 individuals.&#x0D; Methods and Materials: This cross-sectional study recruited 2894 patients who were interviewed at a psychiatric clinic and were diagnosed as having MDD from January 1, 2016, to December 31, 2020, at Hera General Hospital, Makkah, Saudi Arabia. From the hospital’s health information system, we extracted the following data using the patient arrival report for psychiatric clinics.&#x0D; Results: The mean age of MDD onset was 43 years in Saudi Arabia with a peak age between 35 and 40 years and an average age between 43 and 46 years.&#x0D; Conclusion: The mean and peak ages of MDD onset in Saudi Arabia differ from those in other countries. Our findings can help set a screening age for depression in the Saudi population in primary healthcare centers.

Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up.

Background:Preliminary data suggest that psilocybin-assisted treatment produces substantial and rapid antidepressant effects in patients with major depressive disorder (MDD), but little is known about long-term outcomes.Aims:This study sought to examine the efficacy and safety of psilocybin through 12 months in participants with moderate to severe MDD who received psilocybin.Methods:This randomized, waiting-list controlled study enrolled 27 patients aged 21–75 with moderate to severe unipolar depression (GRID-Hamilton Depression Rating Scale (GRID-HAMD) ⩾ 17). Participants were randomized to an immediate or delayed (8 weeks) treatment condition in which they received two doses of psilocybin with supportive psychotherapy. Twenty-four participants completed both psilocybin sessions and were followed through 12 months following their second dose.Results:All 24 participants attended all follow-up visits through the 12-month timepoint. Large decreases from baseline in GRID-HAMD scores were observed at 1-, 3-, 6-, and 12-month follow-up (Cohen d = 2.3, 2.0, 2.6, and 2.4, respectively). Treatment response (⩾50% reduction in GRID-HAMD score from baseline) and remission were 75% and 58%, respectively, at 12 months. There were no serious adverse events judged to be related to psilocybin in the long-term follow-up period, and no participants reported psilocybin use outside of the context of the study. Participant ratings of personal meaning, spiritual experience, and mystical experience after sessions predicted increased well-being at 12 months, but did not predict improvement in depression.Conclusions:These findings demonstrate that the substantial antidepressant effects of psilocybin-assisted therapy may be durable at least through 12 months following acute intervention in some patients.

Ten Sessions of 30 Min tDCS over 5 Days to Achieve Remission in Depression: A Randomized Pilot Study.

Although transcranial Direct Current stimulation (tDCS) shows promise in the treatment of major depressive episodes, the optimal parameters and population to target remain unclear. We investigated the clinical interest of a 10 session tDCS regimen in patients with mild to severe treatment-resistant depression, in a pilot double-blind, randomized sham-controlled trial. tDCS was delivered over 5 consecutive days (two 30 min sessions per day separated by at least 2 h, 2 mA). The anode and cathode were placed over the left and the right dorsolateral prefrontal cortex, respectively. One month after tDCS, we observed significantly fewer patients who achieved remission (MADRS10 < 10) in the sham group (0 out of 18 patients) than in the active group (5 out of 21 patients; p = 0.05). However, no significant difference was observed between the groups regarding the mean scores of severity changes throughout the study period. Bifrontal add-on tDCS delivered twice per day over 5 days, in combination with antidepressant medication, can be a safe and suitable approach to achieve remission in patients with mild to severe treatment-resistant major depressive disorder. However, in regards to the pilot nature and limitations of the present study, further studies are needed before any frank conclusions can be made regarding the use of tDCS with the proposed parameters in clinical settings.

Pharmacist assessment of drug-gene interactions and drug-induced phenoconversion in major depressive\xa0disorder: a case report

BackgroundResponse to antidepressant therapy is highly variable among individuals. Pharmacogenomic (PGx) testing presents an opportunity to guide drug selection while optimizing therapy outcomes and/or decreasing the risk for toxicity.Case presentationA patient with multiple comorbidities, including severe major depressive disorder (MDD), experienced adverse drug events and undesirable response to multiple antidepressant medications (i.e., bupropion, escitalopram, and venlafaxine). A clinical pharmacist assessed significant drug-gene, drug-drug, and drug-drug-gene interactions as well as other clinical factors to provide recommendations for antidepressant therapy optimization.ConclusionThis case highlights the importance of PGx testing and the key role of pharmacists in identifying and mitigating drug-related problems and optimizing drug therapy in patients with MDD.

Differential Predictors of Suicidal Ideation and Suicide Attempts: Internalizing Disorders and Substance Use in a Clinical Sample of Adolescents

Objective: Dually diagnosed adolescents are a high-risk population for experiencing suicidal thoughts and behavior. Given that research suggests risk factors for suicidal ideation and suicide attempts may be different, this study examined whether internalizing disorder severity, frequency of substance use, and the interaction between them differentiated adolescents who attempted suicide from those who ideated. Methods: Baseline data from 287 adolescents who received formal substance use disorder (SUD) treatment were used in this analysis. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) severity as well as past-3 month use of alcohol, cannabis, and other illicit drugs were considered. The outcome of interest was a three-category measure of suicide risk: no reported suicidal ideation or attempts, suicidal ideation only, and suicide attempts. Results: Over half of the sample disclosed prior suicidal ideation (30.0%) or attempts (27.9%). Multinomial logistic regression models indicated more severe MDD and GAD symptomology differentiated ideators from non-suicidal adolescents, but internalizing disorder severity did not differ between ideators and attempters. Substance use frequency did not differ between suicide risk groups. MDD severity and frequency of alcohol use interacted to increase the risk of attempts, yet the effects were minimal. Instead, prior weapon violence victimization and sexual abuse were the largest differentiators between attempters and ideators. Conclusions: Findings suggest that internalizing disorder severity and prior traumatic experiences put adolescents with SUD histories at higher risk of suicidal thoughts and behaviors. Thus, integrating evidence-based suicide prevention and intervention efforts into SUD treatment is critical, particularly for dually diagnosed adolescents who meet these risk profiles. Psychotherapy and medication may help curtail the development of ideation by reducing symptoms of MDD and GAD, whereas adolescents with prior traumatic experiences may benefit from additional treatments shown to lower risk of suicide attempts.

Modern neurosurgical techniques for psychiatric disorders.

Psychosurgery refers to an ensemble of more or less invasive techniques designed to reduce the burden caused by psychiatric diseases in patients who have failed to respond to conventional therapy. While most surgeries are designed to correct apparent anatomical abnormalities, no discrete cerebral anatomical lesion is evident in most psychiatric diseases amenable to invasive interventions. Finding the optimal surgical targets in mental illness is troublesome. In general, contemporary psychosurgical procedures can be classified into one of two primary modalities: lesioning and stimulation procedures. The first group is divided into (a) thermocoagulation and (b) stereotactic radiosurgery or recently introduced transcranial magnetic resonance-guided focused ultrasound, whereas stimulation techniques mainly include deep brain stimulation (DBS), cortical stimulation, and the vagus nerve stimulation. The most studied psychiatric diseases amenable to psychosurgical interventions are severe treatment-resistant major depressive disorder, obsessive-compulsive disorder, Tourette syndrome, anorexia nervosa, schizophrenia, and substance use disorder. Furthermore, modern neuroimaging techniques spurred the interest of clinicians to identify cerebral regions amenable to be manipulated to control psychiatric symptoms. On this way, the concept of a multi-nodal network need to be embraced, enticing the collaboration of psychiatrists, psychologists, neurologists and neurosurgeons participating in multidisciplinary groups, conducting well-designed clinical trials.

Agomelatine in children and adolescents with moderate to severe major depressive disorder: an open-label extension study

Agomelatine in children and adolescents with moderate to severe major depressive disorder: an open-label extension study