Primary Major Depressive Disorder Research Articles

Comparison between Single-Dose and Two-Dose Psilocybin Administration in the Treatment of Major Depression: A Systematic Review and Meta-Analysis of Current Clinical Trials.

Current pharmacological treatments for major depressive disorder (MDD) are often only partially effective, with many patients experiencing no significant benefit, leading to treatment-resistant depression (TRD). Psilocybin, a classical serotonergic psychedelic, has emerged as a notable emerging treatment for such disorders. The aim of this systematic review and meta-analysis is to summarize and discuss the most recent evidence about the therapeutic effects of single-dose and two-dose psilocybin administration on the severity of depressive symptoms, as well as compare the efficacy of these interventions among patients with a primary diagnosis of MDD or TRD. Articles were collected from EBSCOhost and PubMed following the PRISMA guidelines, yielding 425 articles with 138 duplicates. After screening 287 records, 12 studies met the eligibility criteria and were included in the review. A quantitative analysis of the studies indicates that psilocybin is highly effective in reducing depressive symptoms severity among patients with primary MDD or TRD. Both single-dose and two-dose psilocybin treatments significantly reduced depressive symptoms severity, with two-dose administration sometimes yielding more pronounced and lasting effects. However, it is unclear if this was solely due to dosage or other factors. Future research should include standardized trials comparing these dosing strategies to better inform clinical practice.

Treatment adherence rates across different psychiatric disorders and settings: findings from a large patient cohort.

Approximately 50% of patients with psychiatric disorders do not fully adhere to the prescribed psychopharmacological therapy, significantly impacting the progression of the disorder and the patient's quality of life. The present study aimed to assess potential differences in terms of rates and clinical features of treatment adherence in a large cohort of psychiatric patients with different diagnoses attending various psychiatric services. The study included 307 psychiatric patients diagnosed with a primary major depressive disorder, bipolar disorder, anxiety disorder, schizophrenic spectrum disorder, or personality disorder. Patient's adherence to treatment was evaluated using the Clinician Rating Scale, with a cutoff of at least five defining adherence subgroups. One-third of the sample reported poor medication adherence. A lower rate of adherence emerged among patients with schizophrenic spectrum disorder and bipolar disorder. Subjects with poor adherence were more frequently inpatients and showed higher current substance use, a greater number of previous hospitalizations, and more severe scores at psychopathological assessment compared with patients with positive adherence. Poor adherence was associated with symptom severity and increased rates of relapses and rehospitalizations. In addition, substance use appears to be an unfavorable transdiagnostic factor for treatment adherence.

Pre-treatment frontal beta events are associated with executive dysfunction improvement after repetitive transcranial magnetic stimulation for depression: A preliminary report

Repetitive transcranial magnetic stimulation (rTMS) is an established clinical treatment for major depressive disorder (MDD) that has also been found to improve aspects of executive functioning. The objective of this study was to examine whether oscillatory burst-like events within the beta band (15–29 Hz) prior to treatment could predict subsequent change in self-reported executive dysfunction (EDF) across a clinical course of rTMS for MDD. Twenty-eight adults (64% female) with MDD completed the self-report Frontal Systems Behavior Scale (FrSBe) and provided eyes-closed resting-state electroencephalography (EEG) before and after a clinical course of rTMS therapy for primary MDD. The rate, power, duration, and frequency span of transient EEG measured oscillatory beta events were calculated. Events within delta/theta and alpha bands were examined to assess for beta specificity. After controlling for improvement in primary depressive symptoms, a lower rate of beta events at F3, Fz, F4, and Cz prior to rTMS treatment was associated with a larger improvement in EDF after rTMS treatment. In addition, a decrease in beta event rate at Fz pre-to-post treatment was associated with a larger improvement in EDF after treatment. Results were largely specific to the beta band. In this study, the rate of frontrocentral beta events prior to treatment significantly predicted the likelihood of subsequent improvement in EDF symptoms following a clinical course of rTMS for MDD. These preliminary findings suggest the potential utility of EEG measured beta events and rTMS for targeting EDF across an array of neuropsychiatric disorders.

Precision functional MRI mapping reveals distinct connectivity patterns for depression associated with traumatic brain injury.

Depression associated with traumatic brain injury (TBI) is believed to be clinically distinct from primary major depressive disorder (MDD) and may be less responsive to conventional treatments. Brain connectivity differences between the dorsal attention network (DAN), default mode network (DMN), and subgenual cingulate have been implicated in TBI and MDD. To characterize these distinctions, we applied precision functional mapping of brain network connectivity to resting-state functional magnetic resonance imaging data from five published patient cohorts, four discovery cohorts (n = 93), and one replication cohort (n = 180). We identified a distinct brain connectivity profile in TBI-associated depression that was independent of TBI, MDD, posttraumatic stress disorder (PTSD), depression severity, and cohort. TBI-associated depression was independently associated with decreased DAN-subgenual cingulate connectivity, increased DAN-DMN connectivity, and the combined effect of both. This effect was stronger when using precision functional mapping relative to group-level network maps. Our results support the possibility of a physiologically distinct "TBI affective syndrome," which may benefit from individualized neuromodulation approaches to target its distinct neural circuitry.

Prospective study on Maresin-1 and cytokine levels in medication-naïve adolescents with first-episode major depressive disorder.

Inflammation and immune activation may play a role in the pathological mechanism of Major Depressive Disorder (MDD). Evidence from cross-sectional and longitudinal studies of adolescents and adults has shown that MDD is associated with increased plasma pro-inflammatory cytokines (e.g., IL-1β, IL-6). It has been reported that Specialized Pro-resolving Mediators (SPMs) mediate inflammation resolution, and Maresin-1 can activate the process of inflammation and promote inflammation resolution by promoting macrophage phagocytosis. However, no clinical studies have been conducted to evaluate the relationship between the levels of Maresin-1 and cytokine and the severity of MDD symptomatology in adolescents. 40 untreated adolescent patients with primary and moderate to severe MDD and 30 healthy participants as the healthy control (HC) group aged between 13 and 18 years old were enrolled. They received clinical and Hamilton Depression Rating Scale (HDRS-17) evaluation and then, blood samples were collected. Patients in the MDD group were re-evaluated for HDRS-17, and blood samples were taken after a six to eight-week fluoxetine treatment. The adolescent patients with MDD had lower serum levels of Maresin-1 and higher serum levels of interleukin 6 (IL-6) compared with the HC group. Fluoxetine treatment alleviated depressive symptoms in MDD adolescent patients, which was reflected by higher serum levels of Maresin-1 and IL-4 and lower HDRS-17 scores, serum levels of IL-6, and IL-1β. Moreover, the serum level of Maresin-1 was negatively correlated with the depression severity scores on the HDRS-17. Adolescent patients with primary MDD had lower levels of Maresin-1 and higher levels of IL-6 compared with the HC group, implying that the peripheral level of pro-inflammatory cytokines may be elevated in MDD, resulting in the insufficiency of inflammation resolution. The Maresin-1 and IL-4 levels increased after anti-depressant treatment, whereas IL-6 and IL-1β levels decreased significantly. Moreover, Maresin-1 level negatively correlated with depression severity, suggesting that reduced levels of Maresin-1 promoted the progression of MDD.

Clinical effectiveness of active Alpha-Stim AID versus sham Alpha-Stim AID in major depression in primary care in England (Alpha-Stim-D): a multicentre, parallel group, double-blind, randomised controlled trial

Randomised sham-controlled trials of cranial electrostimulation with the Alpha-Stim Anxiety Insomnia and Depression (AID) device have reported improved anxiety and depression symptoms; however, no adequately powered sham-controlled trials in major depression are available. We investigated whether active Alpha-Stim AID is superior to sham Alpha-Stim AID in terms of clinical effectiveness for depression symptoms in major depression. The Alpha-Stim-D trial was a multicentre, parallel group, double-blind, randomised controlled trial, recruiting participants from 25 primary care centres in two regions in England, UK. Eligible participants were aged 16 years or older with a current diagnosis of primary major depression, a score of 10-19 on the nine-item Patient Health Questionnaire, and had been offered or prescribed and reported taking antidepressant medication for at least 6 weeks in the previous 3 months. Main exclusion criteria were contraindications to Alpha-Stim AID device use, having persistent suicidal ideation or self-harm, neurological conditions, a substance use disorder or dependence, an eating disorder, bipolar disorder, or non-affective psychosis, or receiving psychological treatment in the past 3 months. Eligible participants were randomly assigned (1:1, minimised by region, anxiety disorder, and antidepressant use) to 1 h daily use of active (100 μA) or sham Alpha-Stim AID treatment for 8 weeks. Randomisation was via an independent web-based system, with participants, outcome assessors, and data analyst masked to treatment assignment. The primary outcome was change from baseline in score on the 17-item Hamilton Depression Rating Scale (HDRS-17, GRID version) at 16 weeks after randomisation, with participants analysed by intention to treat (ITT; all randomly assigned participants). Safety was assessed in all randomly assigned participants. The trial is registered with the ISRCTN registry (ISRCTN11853110); status completed. Between Sept 8, 2020, and Jan 14, 2022, 236 eligible participants were randomly assigned to active or sham Alpha-Stim AID (n=118 each). 156 (66%) participants were women, 77 (33%) were men, and three (1%) self-reported as other gender; 200 (85%) were White British or Irish; and the mean age was 38·0 years (SD 15·3; range 16-83). 102 (86%) participants in the active Alpha-Stim AID group and 98 (83%) in the sham group were followed up 16 weeks after randomisation. In the ITT population, mean change in GRID-HDRS-17 at 16 weeks was -5·9 (95% CI -7·1 to -4·8) in the active Alpha-Stim AID group and -6·5 (-7·7 to -5·4) in the sham group (mean change difference -0·6 [95% CI -1·0 to 2·2], p=0·46). Among the 236 participants, 17 adverse events were reported in 17 (7%) participants (nine [8%] participants in the active Alpha-Stim AID group; and eight [7%] participants in the sham group). One serious adverse event of suicidal ideation leading to hospitalisation was reported in the sham group, which was judged to be unrelated to the device. Active Alpha-Stim AID was safe and acceptable, but no more clinically effective than sham Alpha-Stim AID in major depression. National Institute for Health Research Applied Research Collaboration East Midlands and Electromedical Products International.

Effectiveness of family psychoeducation for major depressive disorder: systematic review and meta-analysis.

Although its effect has not been verified, family therapy - such as family psychoeducation (FPE) - is a widely used intervention for treating major depressive disorder (MDD). To our knowledge, no systematic review and meta-analysis exists that examines the effect of FPE on MDD. To assess evidence on the effectiveness of FPE on depressive symptoms in people with MDD. We searched several databases - including PubMed, MEDLINE and Web of Science, among others - to identify eligible studies on the topic published up to March 2022. Our criteria included studies on participants with a primary MDD diagnosis and their family members and excluded studies on people with bipolar disorders and other mental illnesses. In the included studies, family members in the control groups did not receive FPE. Participants in both the intervention and control groups received standard treatment. Two researchers independently selected relevant publications, extracted data and evaluated methodological quality using the Cochrane risk of bias assessment tool and GRADE evaluation. The protocol was registered with PROSPERO (no. CRD42020185884). The meta-analysis included five studies with 301 patients with MDD and their family members. The effect of FPE on patients' symptom severity, compared with the control condition, at 16 weeks was available for five comparisons of four randomised control trials (RCTs); a final follow-up was available for six comparisons of five RCTs. The meta-analysis showed a statistically significant improvement in patients' symptoms, compared with control, at 16 weeks (s.m.d. = -0.52, 95% CI -1.03 to -0.01) and at a final follow-up (s.m.d. = -0.53, 95% CI -0.98 to -0.08). The meta-analysis on the effect of FPE on family functioning showed a non-significant improvement both at 16 weeks and at final follow-up. FPE had a small but statistically significant effect on depressive symptoms in people with MDD, in both the short and long term. However, according to the GRADE framework, all outcomes are graded very low on certainty; therefore, more high-quality research is needed.

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.

Psychotherapy employed additionally to Psychopharmacotherapy is not related to Better Treatment Outcome in Major Depressive Disorder

IntroductionAlthough numerous effective antidepressant (AD) strategies are available for the treatment of major depressive disorder (MDD), many patients do not achieve satisfactory treatment response.ObjectivesThe aims of the present European, cross-sectional, multicenter, naturalistic study were (1) to determine the proportion of patients suffering from primary MDD who received additional psychotherapy to their ongoing psychopharmacotherapy and (2) to identify the associated socio-demographic and clinical patterns.MethodsPatients receiving both treatments were compared to those lacking concomitant additional psychotherapy that was manual-driven psychotherapy (MDP) in all cases.ResultsWhile 68.8% of a total of 1279 MDD patients received exclusively psychopharmacotherapy, 31.2% underwent a psychopharmacotherapy-MDP combination. The latter patient population was rather younger, higher educated, employed, exhibited an earlier mean age of MDD onset, lower severity of current depressive symptoms with lower odds of suicidality and higher rates of melancholic features, and comorbid asthma and migraine, and was generally treated with lower daily doses of their first-line ADs. Whereas agomelatine was more commonly dispensed in these patients, selective serotonin reuptake inhibitors were more often prescribed in MDD patients lacking additional MDP. No significant between-group differences were detected in terms of treatment outcome.ConclusionsThe fact that the employment of additional MDP was not related to better treatment outcome in MDD represents our major and clinically most relevant finding. Generally, MDP was employed in a minority of our patients who experienced rather beneficial socio-demographic and clinical characteristics. This might reflect an inferior accessibility of these psychotherapeutic techniques for patients who are more severely ill and less socio-economically privileged.DisclosureReferences Bartova L, Fugger G, Dold M, Swoboda MMM, Zohar J, Mendlewicz J, Souery D, Montgomery S, Fabbri C, Serretti A, Kasper S. Combining psychopharmacotherapy and psychotherapy is not associated with better treatment outcome in major depressive disor

The sociodemographic and clinical profile of patients with major depressive disorder receiving SSRIs as first-line antidepressant treatment in European countries

IntroductionDue to favorable antidepressant (AD) efficacy and tolerability, selective-serotonin reuptake inhibitors (SSRIs) are consistently recommended as substances of first choice for the treatment of major depressive disorder (MDD) in international guidelines. However, little is known about the real-world clinical correlates of patients primarily prescribed SSRIs in contrast to those receiving alternative first-line ADs.MethodsThese secondary analyses are based on a naturalistic, multinational cross-sectional study conducted by the European Group for the Study of Resistant Depression at ten research sites. We compared the socio-demographic and clinical characteristics of 1410 patients with primary MDD, who were either prescribed SSRIs or alternative substances as first-line AD treatment, using chi-squared tests, analyses of covariance, and logistic regression analyses.ResultsSSRIs were prescribed in 52.1% of MDD patients who showed lower odds for unemployment, current severity of depressive symptoms, melancholic features, suicidality, as well as current inpatient treatment compared to patients receiving alternative first-line ADs. Furthermore, patients prescribed SSRIs less likely received add-on therapies including AD combination and augmentation with antipsychotics, and exhibited a trend towards higher response rates.ConclusionA more favorable socio-demographic and clinical profile associated with SSRIs in contrast to alternative first-line ADs may have guided European psychiatrists’ treatment choice for SSRIs, rather than any relevant pharmacological differences in mechanisms of action of the investigated ADs. Our results must be cautiously interpreted in light of predictable biases resulting from the open treatment selection, the possible allocation of less severely ill patients to SSRIs as well as the cross-sectional study design that does not allow to ascertain any causal conclusions.

Overview of a large transcranial magnetic stimulation patient outcomes database

Abstract While there is a clear evidence base from randomized clinical trials that demonstrate the efficacy of Transcranial Magnetic Stimulation (TMS) in the treatment of major depressive disorder (MDD), greater understanding of best practices in routine clinical practice is critically needed. This symposium will provide an in depth look at the first ten years of data collection of patient demographics, treatment parameters and outcomes from the NeuroStar® Advanced Therapy System Clinical Outcomes Registry. Methods: Registry data were collected at 103 practice sites. Of 7759 participants, 5010 patients were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the Patient Health Questionaire-9 (PHQ-9) before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3,814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. CGI-S ratings were obtained in smaller samples. Results: In the total ITT and Completer samples, response (58–83%) and remission (28–62%) rates were notably high across self-report and clinician-administered assessments. Female patients and those treated with a larger number of pulses per session had superior clinical outcomes. Conclusions: The extent of clinical benefit reported by patients and clinicians following TMS in routine practice compares favorably with alternative interventions for treatment-resistant depression. Strong efficacy and the low side effect and medical risk profile suggest that TMS be evaluated as a first-line treatment for MDD. The findings demonstrate the power of creating a large registry of clinical outcomes in MDD. Keywords: TMS, treatment outcomes, registry

Symptom dimensions of major depression in a large community-based cohort.

Our understanding of major depression is complicated by substantial heterogeneity in disease presentation, which can be disentangled by data-driven analyses of depressive symptom dimensions. We aimed to determine the clinical portrait of such symptom dimensions among individuals in the community. This cross-sectional study consisted of 25 261 self-reported White UK Biobank participants with major depression. Nine questions from the UK Biobank Mental Health Questionnaire encompassing depressive symptoms were decomposed into underlying factors or 'symptom dimensions' via factor analysis, which were then tested for association with psychiatric diagnoses and polygenic risk scores for major depressive disorder (MDD), bipolar disorder and schizophrenia. Replication was performed among 655 self-reported non-White participants, across sexes, and among 7190 individuals with an ICD-10 code for MDD from linked inpatient or primary care records. Four broad symptom dimensions were identified, encompassing negative cognition, functional impairment, insomnia and atypical symptoms. These dimensions replicated across ancestries, sexes and individuals with inpatient or primary care MDD diagnoses, and were also consistent among 43 090 self-reported White participants with undiagnosed self-reported depression. Every dimension was associated with increased risk of nearly every psychiatric diagnosis and polygenic risk score. However, while certain psychiatric diagnoses were disproportionately associated with specific symptom dimensions, the three polygenic risk scores did not show the same specificity of associations. An analysis of questionnaire data from a large community-based cohort reveals four replicable symptom dimensions of depression with distinct clinical, but not genetic, correlates.

Aggressive outbursts among adults with major depressive disorder: Results from the Collaborative Psychiatric Epidemiological Surveys

IntroductionLittle is known about the epidemiology of aggressive outbursts, including physical assault, property destruction, and verbal aggression, among adults with unipolar Major Depressive Disorder (MDD). MethodsWe examined the prevalence and correlates of aggressive outbursts among adults with primary MDD (N = 2539) from the Collaborative Psychiatric Epidemiological Surveys (N = 20,013) using generalized linear models. ResultsThe prevalence estimate of any aggressive outbursts was 58.7% among adults with MDD. MDD was associated with aggressive outbursts independent of other psychiatric diagnoses. The prevalence of aggressive outbursts differed significantly by age, race/ethnicity, sex, education, marital status, and employment status, and psychiatric diagnoses. Aggressive outbursts were associated with greater severity and earlier age of onset for MDD. Positive associations were also found between the frequency of aggressive outbursts and depressive symptoms including weight/appetite change, fatigue, recurrent thoughts of death. Moreover, aggressive outbursts significantly multiplied the odds of experiencing more severe functional impairment, suicidal ideation, suicide plan, and suicide attempt. ConclusionAggressive outbursts are much more common than previously recognized among adults with MDD. The significant association of aggressive outbursts with MDD characteristics, increased functional impairment, and suicidal thoughts and behaviors make them an important target for assessment and treatment for adults with MDD.

DEPRESSION AS THE FIRST SYMPTOM OF FRONTAL LOBE GRADE 2 MALIGNANT GLIOMA

DEPRESSION AS THE FIRST SYMPTOM OF FRONTAL LOBE GRADE 2 MALIGNANT GLIOMA

Comparison of clinical outcomes with two Transcranial Magnetic Stimulation treatment protocols for major depressive disorder

BackgroundTranscranial magnetic stimulation (TMS) is an effective treatment for major depressive disorder (MDD). The rest time between pulse trains is the inter-train interval (ITI). Since 2016, some TMS clinicians have adopted a stimulation protocol with shorter ITIs than were used in regulatory clinical trials. ObjectiveTo contrast treatment outcomes with the Standard TMS protocol (38.5 min per session) and the “Dash” protocol, which, at the shortest ITI, has a session duration of 18.75 min. MethodsRegistry data were collected at 103 practice sites. Of 7759 participants, 5010 were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the PHQ-9 before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. Within the ITT sample, 613 patients were treated with the Standard NeuroStar 38-min protocol and 1493 patients with the new Dash protocol. CGI-S ratings were obtained in smaller samples. Treatment outcomes were also examined in subgroups considered Completers, as well as the subgroups who met criteria for Full Adherence to the Standard or Dash protocol parameters. ResultsIn the ITT, Completer, and Fully Adherent samples, response (58–72%) and remission (28–53%) rates were notably high across PHQ-9 and CGI-S ratings. The Standard and Dash protocols did not differ in number of treatment sessions, and both manifested strong antidepressant effects. ConclusionsThe Standard and Dash protocols did not meaningfully differ in efficacy.

A Network Analysis of Major Depressive Disorder Symptoms and Age- and Gender-Related Differences in People over 65 in a Madrid Community Sample (Spain).

Major depressive disorder (MDD) is one of the most prevalent conditions among mental disorders in individuals over 65 years. People over 65 who suffer from MDD are often functionally impaired, chronically physically ill, and express cognitive problems. The concordance between a clinician-assessed MDD diagnosis in a primary care setting and MDD assessed with a structured clinical interview in older adults is only approximately 18%. Network analysis may provide an alternative statistical technique to better understand MDD in this population by a dimensional approach to symptomatology. The aim of this study was to carry out a network analysis of major depressive disorder (MDD) in people over 65 years old. A symptom network analysis was conducted according to age and gender in 555 people over 65, using a sample from the MentDis_ICF65+ Study. The results revealed different networks for men and women, and for the age groups 65–74 and 75–84. While depressive mood stood out in women, in men the network was more dispersed with fatigue or loss of energy and sleep disturbances as the main symptoms. In the 65–74 age group, the network was complex; however, in the 75–84 age group, the network was simpler with sleep disturbances as the central symptom. The gaps between the networks indicate the different characteristics of MDD in the elderly, with variations by gender and age, supporting the idea that MDD is a complex dynamic system that has unique characteristics in each person, rather than a prototypical classification with an underlying mental disorder. These unique characteristics can be taken into account in the clinical practice for detection and intervention of MDD.

Comparison of Naturalistic Treatment Outcomes with the Standard 38-Minute Protocol vs. Shortened (“Dash”) Protocol: A NeuroStar® Registry Database Study

Background: Optimized Transcranial magnetic stimulation (TMS) protocols for major depressive disorder (MDD) are needed to improve patient convenience and access. The FDA-approved NeuroStar protocol initially required 38 minutes per session (based on 4-second trains and 26-second inter-train-intervals (ITIs)). In 2017, a new (“Dash”) protocol with shorter (11- to 25-second) ITIs was approved, reducing total session times to as short as 19 minutes. We compared naturalistic treatment outcomes for Standard and Shortened “Dash” TMS protocols. Methods: NeuroStar registry data from 103 practice sites represent 7,759 patients. N=5,010 selected for this analysis (intent-to-treat (ITT) sample) had primary MDD diagnoses, age ≥18, baseline PHQ-9 ≥10, and at least one PHQ-9 assessment after treatments began. N=613 received Standard protocol TMS and n=1,493 were treated with Dash. “Completers” (N=3,814) were those who received ≥20 sessions and had a PHQ-9 at end of their acute course. Results: Overall response rate was 57.7% (65.0% for completers) and remission (PHQ-9<5) rate 27.9% (31.7% for completers). No difference was detected between Standard and Dash protocols in longitudinal, mixed-model analyses of PHQ-9 scores. Logistic regression models with/without covariates (e.g., age, motor threshold) did not reveal an effect of protocol on response or remission. PHQ-9 improvement and number of treatments administered were equivalent for both protocols. Conclusions: These large TMS registry outcomes are consistent with other naturalistic data. No efficacy differences were found between Standard and Dash protocols, providing support for use of the quicker protocol in standard clinical practice. Limitations include lack of randomized assignment to protocol group. This study was supported by Neuronetics Inc.

Alcohol Induced Depression: Clinical, Biological and Genetic Features.

Background: In clinical practice, there is the need to have clinical and biological markers to identify induced depression. The objective was to investigate clinical, biological and genetic differences between Primary Major Depression (Primary MD) and Alcohol Induced MD (AI-MD). Methods: Patients, of both genders, were recruited from psychiatric hospitalisation units. The PRISM instrument was used to establish the diagnoses. Data on socio-demographic/family history, clinical scales for depression, anxiety, personality and stressful life events were recorded. A blood test was performed analysing biochemical parameters and a Genome Wide Association Study (GWAS) to identify genetic markers associated with AI-MD. Results: A total of 80 patients were included (47 Primary MD and 33 AI-MD). The AI-MD group presented more medical comorbidities and less family history of depression. There were differences in traumatic life events, with higher scores in the AI-MD (14.21 ± 11.35 vs. 9.30 ± 7.38; p = 0.021). DSM-5 criteria were different between groups with higher prevalence of weight changes and less anhedonia, difficulties in concentration and suicidal thoughts in the AI-MD. None of the genetic variants reached significance beyond multiple testing thresholds; however, some suggestive variants were observed. Conclusions: This study has found clinical and biological features that may help physicians to identify AI-MD and improve its therapeutic approach.

Clinical outcomes in a large registry of patients with major depressive disorder treated with Transcranial Magnetic Stimulation

BackgroundRandomized clinical trials have demonstrated that Transcranial Magnetic Stimulation (TMS) is an effective treatment for episodes of major depressive disorder (MDD). However, characterization of outcomes in routine clinical practice is needed, as well as identification of patient- and treatment-related outcome predictors. This study documented patient-rated (PHQ-9) and clinician-rated (CGI-S) clinical outcomes in the NeuroStar® Advanced Therapy System Clinical Outcomes Registry. MethodsRegistry data were collected at 103 practice sites. Of 7759 participants, 5010 patients were included in an intent-to-treat (ITT) sample, defined as a primary MDD diagnosis, age ≥ 18, and completion of the PHQ-9 before TMS and with at least one PHQ-9 assessment after baseline. Completers (N = 3,814) were responders or had received ≥ 20 sessions and had an end of acute treatment PHQ-9 assessment. CGI-S ratings were obtained in smaller samples. ResultsIn the total ITT and Completer samples, response (58–83%) and remission (28–62%) rates were notably high across self-report and clinician-administered assessments. Female patients and those treated with a larger number of pulses per session had superior clinical outcomes. LimitationsSite participation in the registry was voluntary and treatment was open label. ConclusionsThe extent of clinical benefit reported by patients and clinicians following TMS in routine practice compares favorably with alternative interventions for treatment-resistant depression. Strong efficacy and the low side effect and medical risk profile suggest that TMS be evaluated as a first-line treatment for MDD. The findings derive from the largest registry of clinical outcomes in MDD for any treatment.

Trastorno por uso de cocaína y depresión: Cuando el diagnóstico clínico no es suficiente

Cocaine use is a growing global health problem and patients with cocaine use disorders (CUD) present several complications, including high rates of major depression. These subjects present two types of major depressive disorder (MDD): primary major depressive disorder (P-MDD) and cocaine-induced major depressive disorder (CI-MDD). To improve treatment, it is necessary to distinguish between both types. The aim of this study was to assess the differences in depressive symptomatology criteria (P-MDD vs CI-MDD) in CUD patients. Secondary data analysis was carried out with a cross-sectional sample of 160 patients presenting CUD and MDD. Clinical assessment was performed using the Psychiatric Research Interview for Substance and Mental Disorders (PRISM). A differential diagnosis was obtained between P-MDD and CI-MDD. Men represented 80% of the sample, the mean age was 38.61 years, and 64.5% had elementary studies. CI-MDD diagnosis (61.3%) was more frequent than P-MDD (38.7%). There was a younger age of CUD onset in CI-MDD patients. In addition, 79.4% of the patients had another substance use disorder diagnosis. The criterion "Changes in weight or appetite" was more prevalent (57.1%) in P-MDD group. We found differences in the criterion "Changes in weight or appetite". Further research is needed in this field to establish a differential diagnosis and thus provide better treatment for CUD patients.