Anger attacks are associated with persistently elevated irritability in MDD: findings from the EMBARC study

2020 ◽  
pp. 1-9 ◽  
Author(s):  
Manish K. Jha ◽  
Maurizio Fava ◽  
Abu Minhajuddin ◽  
Cherise Chin Fatt ◽  
David Mischoulon ◽  
...  
Keyword(s):  
Mixed Model ◽  
Rating Scale ◽  
Massachusetts General Hospital ◽  
Clinical Care ◽  
Aggressive Behaviors ◽  
Major Depressive ◽  
Overt Behavior ◽  
Anger Attacks ◽  
Autonomic Activation ◽  
Care Study

Abstract Background This report tests the association of self-reported symptoms of irritability with overt behavior of anger attacks (uncharacteristic sudden bouts of anger that are disproportionate to situation and associated with autonomic activation). Methods Participants of the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care study who completed Massachusetts General Hospital Anger Attacks questionnaire were included (n = 293). At each visit, the 17-item Hamilton Depression Rating Scale and the 16-item Concise Associated Symptom Tracking scale were used to measure depression, anxiety, and irritability. In those with anger attacks present v. those without anger attacks, separate t tests and mixed model analyses compared afore-mentioned symptoms at baseline and changes with treatment respectively. As anger attacks may occur without aggressive behaviors, analyses were repeated based only on the presence of aggressive behaviors. Results At baseline, those with anger attacks (n = 109) v. those without anger attacks (n = 184) had similar levels of depression but higher levels of irritability [effect size (d) = 0.80] and anxiety (d = 0.32). With acute-phase treatment, participants with anger attacks experienced a greater reduction in irritability (p < 0.001) but not in depression (p = 0.813) or anxiety (p = 0.771) as compared to those without anger attacks. Yet, irritability levels at week-8 were higher in those with anger attacks (d = 0.32) than those without anger attacks. Similar results were found in participants with aggressive behaviors. Conclusions The presence of anger attacks in outpatients with major depressive disorder may identify a sub-group of patients with persistently elevated irritability.

scholarly journals 180 Improvement of Sexual Function Observed During Treatment of Major Depressive Disorder with Adjunctive Pimavanserin

CNS Spectrums ◽  
2020 ◽  
Vol 25 (2) ◽  
pp. 313-314
Author(s):  
Marlene P. Freeman ◽  
Maurizio Fava ◽  
Bryan Dirks ◽  
Manish K. Jha ◽  
Richard C. Shelton ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Sexual Function ◽  
Rating Scale ◽  
Sexual Interest ◽  
Massachusetts General Hospital ◽  
Antidepressant Treatment ◽  
Analysis Of Covariance ◽  
Inadequate Response ◽  
Major Depressive

Abstract:Study Objectives:Sexual dysfunction occurs in 40%-60% of patients with major depressive disorder (MDD), due to either the illness itself and/or the effects of antidepressant treatment. The phase-2 CLARITY trial recently demonstrated the efficacy of adjunctive pimavanserin (PIM) for MDD when added to ongoing selective serotonin or serotonin–norepinephrine reuptake inhibitor (SSRI/SNRI) treatment. No new safety observations were reported in this study. This post-hoc analysis examines the potential impact of PIM treatment on sexual function.Method:Study methodology has been presented previously (APA 2019). Adult male and female patients with moderate-to-severe MDD were randomized to PIM 34 mg/day (n=51) or placebo (PBO, n=152) added to ongoing SSRI/SNRI treatment. Massachusetts General Hospital–Sexual Functioning Inventory (MGH-SFI) and Hamilton Depression Rating Scale, 17-item version (HAMD-17) item 14 (sexual interest) scores were examined by analysis of covariance.Results:Adjunctive PIM resulted in significantly greater 5-week reduction (improvement) relative to SSRI/SNRI treatment plus placebo on mean MGH-SFI scores (difference –0.634, SE 0.167; P<0.001; effect size [ES], Cohen’s d 0.614). Similarly, PIM resulted in greater improvement compared with placebo on individual MGH-SFI items that applied to both males and females: Interest in Sex (P=0.006; ES=0.483), Ability to Get Sexually Aroused/Excited (P=0.001; ES=0.560), Ability to Achieve Orgasm (P<0.001; ES=0.609), Overall Sexual Satisfaction (P=0.003; ES=0.524). HAMD-17 item 14 scores were also significantly more reduced (improved) with PIM (P<0.001; ES=0.574).Conclusions:These results underscore the potential of adjunctive PIM for improving sexual function in patients with MDD and inadequate response to SSRIs/SNRIs. Potential benefits should be confirmed in further studies.Funding Acknowledgements:ACADIA Pharmaceuticals Inc.

scholarly journals Lurasidone for major depressive disorder with mixed features and irritability: a post-hoc analysis

CNS Spectrums ◽  
2017 ◽  
Vol 22 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Alan C. Swann ◽  
Maurizio Fava ◽  
Joyce Tsai ◽  
Yongcai Mao ◽  
Andrei Pikalov ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Repeated Measures ◽  
Mixed Model ◽  
Rating Scale ◽  
Major Depressive ◽  
Double Blind ◽  
Post Hoc Analysis ◽  
Mixed Features ◽  
Post Hoc

ObjectiveThe aim of this post-hoc analysis was to evaluate the efficacy of lurasidone in treating major depressive disorder (MDD) with mixed features including irritability.MethodsThe data in this analysis were derived from a study of patients meeting DSM–IV–TR criteria for unipolar MDD, with a Montgomery–Åsberg Depression Rating Scale (MADRS) total score ≥26, presenting with two or three protocol-defined manic symptoms, and who were randomized to 6 weeks of double-blind treatment with either lurasidone 20–60 mg/d (n=109) or placebo (n=100). We defined “irritability” as a score ≥2 on both the Young Mania Rating Scale (YMRS) irritability item (#5) and the disruptive-aggressive item (#9). Endpoint change in the MADRS and YMRS items 5 and 9 were analyzed using a mixed model for repeated measures for patients with and without irritability.ResultsSome 20.7% of patients met the criteria for irritability. Treatment with lurasidone was associated with a significant week 6 change vs. placebo in MADRS score in both patients with (–22.6 vs. –9.5,p<0.0001, effect size [ES]=1.4) and without (–19.9 vs. –13.8,p<0.0001,ES=0.7) irritability. In patients with irritable features, treatment with lurasidone was associated with significant week 6 changes vs. placebo in both the YMRS irritability item (–1.4 vs. –0.3,p=0.0012,ES=1.0) and the YMRS disruptive-aggressive item (–1.0 vs. –0.3,p=0.0002,ES=1.2).ConclusionsIn our post-hoc analysis of a randomized, placebo-controlled, 6-week trial, treatment with lurasidone significantly improved depressive symptoms in MDD patients with mixed features including irritability. In addition, irritability symptoms significantly improved in patients treated with lurasidone.

scholarly journals Predictors of Suicidal Ideation and Attempt among Patients with Major Depressive Disorder at a Tertiary Care Hospital, Puducherry

2021 ◽  
Vol 12 (01) ◽  
pp. 122-128
Author(s):  
Ralte Lalthankimi ◽  
Padmavathi Nagarajan ◽  
Vikas Menon ◽  
Jeby Jose Olickal
Keyword(s):  
Major Depressive Disorder ◽  
Suicidal Ideation ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Tertiary Care ◽  
Severe Depression ◽  
Care Hospital ◽  
Suicidal Behaviors ◽  
Major Depressive ◽  
Severity Of Depression

Abstract Objectives Mental disorders have a large impact on death by suicide. Hence, this study aims to determine the prevalence of suicidal behaviors among major depressive disorder (MDD) patients and the associated factors. Materials and Methods This cross-sectional analytical study was conducted among individuals aged 18 to 65 years, diagnosed with MDD in the Psychiatry Outpatient Department of a Tertiary Care Center, Puducherry during March to October 2019. Severity of depression was assessed using Hamilton Depression Rating Scale and Columbia-Suicide Severity Rating Scale was used to find the suicidal behaviors. Results For 166 participants in the study, mean (standard deviation) age was 40 (11) years and majority were females (76%). More than one-third (37%) had severe or very severe depression, and the prevalence of suicidal ideation, plan, and attempts were 83, 24, and 35%, respectively. After adjusting the covariates, the severity of depression and unemployment were significantly associated with suicidal attempts (adjusted prevalence ratios [aPR] = 11.4 and 1.9), and very severe depression was associated with suicidal ideation (aPR = 1.6). Among 140 individuals with suicidal ideation, 45 (32%) had an ideation frequency of 2 to 3 times/week, 69 (50%) had ideation for 1 hour, 36 (26%) could control ideation with little difficulty, and 12% had suicidal ideation mostly to end or stop their pain. Conclusion Suicidal ideation and attempts were significantly high in MDD patients, and the severity of depression was significantly associated with it. Early identification of high-risk suicidal behavior and implementation of effective preventive interventions are necessary to reduce death by suicide in these groups.

scholarly journals Effect of Lacticaseibacillus paracasei Strain Shirota on Improvement in Depressive Symptoms, and Its Association with Abundance of Actinobacteria in Gut Microbiota

2021 ◽  
Vol 9 (5) ◽  
pp. 1026
Author(s):  
Machiko Otaka ◽  
Hiroko Kikuchi-Hayakawa ◽  
Jun Ogura ◽  
Hiroshi Ishikawa ◽  
Yukihito Yomogida ◽  
...  
Keyword(s):  
Depressive Symptoms ◽  
Gut Microbiota ◽  
Intestinal Permeability ◽  
Rating Scale ◽  
Psychiatric Symptoms ◽  
Daily Intake ◽  
Probiotic Strain ◽  
Major Depressive ◽  
Colony Forming Units ◽  
And Biological Markers

We previously reported lower counts of lactobacilli and Bifidobacterium in the gut microbiota of patients with major depressive disorder (MDD), compared with healthy controls. This prompted us to investigate the possible efficacy of a probiotic strain, Lacticaseibacillus paracasei strain Shirota (LcS; basonym, Lactobacillus casei strain Shirota; daily intake of 8.0 × 1010 colony-forming units), in alleviating depressive symptoms. A single-arm trial was conducted on 18 eligible patients with MDD or bipolar disorder (BD) (14 females and 4 males; 15 MDD and 3 BD), assessing changes in psychiatric symptoms, the gut microbiota, and biological markers for intestinal permeability and inflammation, over a 12-week intervention period. Depression severity, evaluated by the Hamilton Depression Rating Scale, was significantly alleviated after LcS treatment. The intervention-associated reduction of depressive symptoms was associated with the gut microbiota, and more pronounced when Bifidobacterium and the Atopobium clusters of the Actinobacteria phylum were maintained at higher counts. No significant changes were observed in the intestinal permeability or inflammation markers. Although it was difficult to estimate the extent of the effect of LcS treatment alone, the results indicated that it was beneficial to alleviate depressive symptoms, partly through its association with abundance of Actinobacteria in the gut microbiota.

scholarly journals Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeffrey D. Voigt ◽  
Andrew F. Leuchter ◽  
Linda L. Carpenter
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
High Frequency Stimulation ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Major Depressive ◽  
Significant Difference ◽  
Theta Burst

AbstractPatients with major depressive disorder (MDD) may be refractory to or have contraindications that preclude treatment with antidepressant pharmacotherapies. Alternative therapies such as repetitive transcranial magnetic stimulation (rTMS) continue to evolve, and include theta burst stimulation (TBS), which has advantages over conventional rTMS. The aim of this study was to identify and meta-analyze efficacy data from all randomized controlled trials (RCTs) investigating TBS as a treatment for MDD. Published reports of RCTs (January 1, 2010 to October 23, 2020) were identified via systematic searches in computerized databases, followed by review of individual reports for inclusion. Inclusion criteria included primary diagnosis of MDD ≥ 1 week duration of therapy with ≥10 sessions, and treatment with any form of TBS. The Cochrane GRADE methodology and PRISMA criteria were used for evaluation of individual trials. Data from ten RCTs were included, representing 667 patients. Of these, 8 RCTs compared TBS to sham treatment and one compared TBS to standard rTMS (i.e., high frequency stimulation over left dorsolateral prefrontal cortex [HFL]). Quality of evidence assessment yielded high confidence in the finding of TBS being superior to sham on response measured by the Hamilton Depression Rating Scale (HRSD) (RR = 2.4; 95% CI: 1.27 to 4.55; P = 0.007; I2 = 40%). Comparison of HRSD response rates for TBS versus rTMS produced no statistically significant difference (RR = 1.02; 95% CI: 0.85 to 1.23; P = 0.80; I2 = 0%). The incidence of adverse events between TBS and rTMS was not statistically different. The findings of a positive effect of TBS vs. sham, and noninferiority of TBS vs. standard HFL rTMS support the continued development of TBS to treat depression.

A qualitative and quantitative account of patient’s experiences of ketamine and its antidepressant properties

2021 ◽  
pp. 026988112199832
Author(s):  
Rachael L Sumner ◽  
Emme Chacko ◽  
Rebecca McMillan ◽  
Meg J Spriggs ◽  
Christie Anderson ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Qualitative Interviews ◽  
Qualitative Interview ◽  
Preliminary Evidence ◽  
Altered States Of Consciousness ◽  
Altered States ◽  
Major Depressive ◽  
States Of Consciousness

Background: Ketamine is central to one of the most rapidly growing areas of neuroscientific research into novel treatments for depression. Limited research has indicated that the psychedelic properties of ketamine may play a role in its antidepressant effects. Aim: The aim of the current study was to explore the psychedelic experiences and sustained impact of ketamine in major depressive disorder. Methods: In the current study, ketamine (0.44 mg/kg) was administered to 32 volunteers with major depressive disorder in a crossover design with the active-placebo remifentanil, in a magnetic resonance imaging (MRI) environment. The 11-dimension altered states of consciousness questionnaire and individual qualitative interviews were used to capture the acute psychedelic experience. The Montgomery-Asberg Depression Rating Scale and further interviewing explored lasting effects. The second qualitative interview took place ⩾3 weeks post-ketamine. Results: Greater antidepressant response (reduction in Montgomery-Asberg Depression Rating Scale at 24 h) correlated with the 11-dimension altered states of consciousness dimensions: spirituality, experience of unity, and insight. The first qualitative interview revealed that all participants experienced perceptual changes. Additional themes emerged including loss of control and emotional and mood changes. The final interview showed evidence of a psychedelic afterglow, and changes to perspective on life, people, and problems, as well as changes to how participants felt about their depression and treatments. Conclusions: The current study provides preliminary evidence for a role of the psychedelic experience and afterglow in ketamine’s antidepressant properties. Reflexive thematic analysis provided a wealth of information on participants’ experience of the study and demonstrated the psychedelic properties of ketamine are not fully captured by commonly used questionnaires.

Major Depressive Disorder With Anger Attacks and Subcortical MRI White Matter Hyperintensities

2007 ◽  
Vol 195 (2) ◽  
pp. 175-178 ◽  
Author(s):  
Dan V. Iosifescu ◽  
Perry F. Renshaw ◽  
Darin D. Dougherty ◽  
In Kyoon Lyoo ◽  
Ho Kyu Lee ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
White Matter ◽  
Depressive Disorder ◽  
White Matter Hyperintensities ◽  
Major Depressive ◽  
Anger Attacks

Propofol Anaesthesia in Electroconvulsive Therapy

1994 ◽  
Vol 165 (4) ◽  
pp. 506-509 ◽  
Author(s):  
Christopher F. Fear ◽  
Carl S. Littlejohns ◽  
Eryl Rouse ◽  
Paul McQuail
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Electroconvulsive Therapy ◽  
Rating Scale ◽  
Induction Agent ◽  
Double Blind Study ◽  
Major Depressive ◽  
Seizure Duration ◽  
Double Blind ◽  
Induction Agents

BackgroundThe induction agent propofol is known to reduce electroconvulsive therapy (ECT) seizure duration. It is assumed that outcome from depression is adversely affected by this agent. This study compares propofol and methohexitone as induction agents for ECT.MethodIn a prospective, randomised, double-blind study 20 subjects with major depressive disorder (DSM-III-R criteria) received propofol or methohexitone anaesthesia. The Hamilton Depression Rating Scale and Beck Depression Inventory were used to assess depression before therapy, at every third treatment, and at the end of therapy. Seizure duration was measured using the cuff technique.ResultsMean seizure durations (P < 0.01) and mean total seizure duration (P < 0.01) were shorter in the propofol group. There was no difference in outcome.ConclusionsUse of propofol may not adversely affect outcome from depression and it is not necessarily contraindicated as an induction agent for ECT. Our results should be interpreted cautiously, and larger studies are needed.

EEG Synchronized TMS for Individualized Therapy in Major Depressive Disorder

2011 ◽  
Vol 26 (S2) ◽  
pp. 1144-1144
Author(s):  
Y. Jin ◽  
J. Phillips ◽  
Yueqin Huang ◽  
Steven Heurta
Keyword(s):  
Major Depressive Disorder ◽  
Side Effects ◽  
Depressive Disorder ◽  
Active Treatment ◽  
Rating Scale ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Stimulus Frequency ◽  
List Type ◽  
Major Depressive ◽  
Double Blind

IntroductionEfficacy of conventional repetitive transcranial magnetic stimulation (rTMS) in major depressive disorder (MDD) is limited. The authors report here on an alternative treatment using low energy synchronized TMS (sTMS) at the intrinsic frequency of subjects’ alpha electroencephalogram (EEG).ObjectivesEstablish efficacy and safety profile of sTMS in MDD.Aim(1)Examine the clinical effectiveness of sTMS.(2)Identify adverse effects associated with sTMS.MethodsFifty-two MDD subjects with 17-item Hamilton Depression Rating Scale (HAMD17) scores >17 were enrolled into a randomized, sham controlled, double-blind trial. Current medication remained unchanged during the trial. Depressive symptoms were evaluated by HAMD17 administered weekly.EEGs were recorded at baseline to determine the stimulus frequency and at week 4 to evaluate the physiological effect. sTMS was delivered through three 6000-G cylindrical neodymium magnets synchronously rotating at a rate equal to the subject's intrinsic alpha frequency.ResultsForty-five subjects completed at least 1 week of treatment and were evaluable. Those who received active treatment had superior clinical response to sham (t = 2.54, P = 0.01), where 55.2% in the active treatment group were clinical responders versus 12.5% in sham (X2 = 7.82, P = 0.005). No significant side effects were reported. The clinical improvement was correlated with the degree of EEG improvement (r = .46, P = 0.009).ConclusionsA therapeutic effect in MDD subjects can be achieved through administration of sTMS at the subject's alpha EEG frequency. Because of minimal side effects, this appears to be a safe and effective treatment option.

scholarly journals Treatment of major depressive disorder with bilateral theta burst stimulation: study protocol for a randomized, double-blind, placebo-controlled multicenter trial (TBS-D)

2021 ◽  
Author(s):  
Christian Plewnia ◽  
Bettina Brendel ◽  
Tobias Schwippel ◽  
Vanessa Nieratschker ◽  
Thomas Ethofer ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Rating Scale ◽  
Treatment Time ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Theta Burst Stimulation ◽  
Burst Stimulation ◽  
Major Depressive ◽  
Resting Motor Threshold ◽  
Theta Burst

AbstractRepetitive transcranial magnetic stimulation (rTMS) of the dorsolateral prefrontal cortex (dlPFC) is currently evolving as an effective and safe therapeutic tool in the treatment of major depressive disorder (MDD). However, already established rTMS treatment paradigms are rather time-consuming. With theta burst stimulation (TBS), a patterned form of rTMS, treatment time can be substantially reduced. Pilot studies and a randomized controlled trial (RCT) demonstrate non-inferiority of TBS to 10 Hz rTMS and support a wider use in MDD. Still, data from placebo-controlled multicenter RCTs are lacking. In this placebo-controlled multicenter study, 236 patients with MDD will be randomized to either intermittent TBS (iTBS) to the left and continuous TBS (cTBS) to the right dlPFC or bilateral sham stimulation (1:1 ratio). The treatment will be performed with 80% resting motor threshold intensity over six consecutive weeks (30 sessions). The primary outcome is the treatment response rate (Montgomery-Asberg Depression Rating Scale reduction ≥ 50%). The aim of the study is to confirm the superiority of active bilateral TBS compared to placebo treatment. In two satellite studies, we intend to identify possible MRI-based and (epi-)genetic predictors of responsiveness to TBS therapy. Positive results will support the clinical use of bilateral TBS as an advantageous, efficient, and well-tolerated treatment and pave the way for further individualization of MDD therapy.Trial registration: ClinicalTrials.gov (NCT04392947).

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