Efficacy of Gemfibrozil as an Adjunct to Sertraline in Major Depressive Disorder, A Double-Blind, Randomized, and Placebo-Controlled Clinical Trial

Objective: Major depressive disorder (MDD) is predicted to be the first cause of burden of disease. The antidepressant activity of gemfibrozil has been recently considered. This study was designed to evaluate the effectiveness of gemfibrozil as a sertraline adjunct in treating patients with MDD. Method: A total of 46 patients with MDD based on the DSM-V criteria with a minimum score of 22 on the 17-item Hamilton Rating Scale for Depression (HAM-D) were randomized to receive either 300 mg daily gemfibrozil or placebo in addition to 100 mg sertraline for 8 weeks in a randomized, double-blind placebo-controlled trial. Patients were evaluated for response to treatment using the HAM-D score at baseline and weeks 2, 4, and 8. Results: Forty-five patients completed the study and took part in all follow-up visits. Repeated measure ANOVA with a Greenhouse-Geisser correction showed a significant difference for time×treatment interaction on within-subjects HAM-D scores [p–value= 0.026]. A significant difference was seen in time [p–value < 0.001]. The test of between-subject effects also showed a significant effect of treatment on HAM-D scores at weeks 2, 4, and 8 [p–value = 0.07]. Using KaplanMeier estimate curves, time to remission periods were significantly different between the 2 trial arms [Log-Rank p–value = 0.003]. Conclusion: Gemfibrozil is an effective adjunctive treatment in MDD and can be used to reduce depression symptoms.

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Crocus sativus L. versus Citalopram in the Treatment of Major Depressive Disorder with Anxious Distress: A Double-Blind, Controlled Clinical Trial

Pharmacopsychiatry ◽

10.1055/s-0042-116159 ◽

2016 ◽

Vol 50 (04) ◽

pp. 152-160 ◽

Cited By ~ 22

Author(s):

A. Ghajar ◽

S. Neishabouri ◽

N. Velayati ◽

L. Jahangard ◽

N. Matinnia ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Rating Scale ◽

Crocus Sativus ◽

Controlled Clinical Trial ◽

P Value ◽

Major Depressive ◽

Significant Difference ◽

Hamilton Rating Scale ◽

Crocus Sativus L

Abstract Introduction: Saffron (Crocus sativus L.) has demonstrated antidepressant effects in clinical studies and extensive anxiolytic effects in experimental animal models. Methods: 66 patients with major depressive disorder accompanied by anxious distress were randomly assigned to receive either saffron (30 mg/day) or citalopram (40 mg/day) for 6 weeks. Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A) were used to assess treatment effect during the trial. Results: 60 participants finished the study. Patients who received either saffron or citalopram showed significant improvement in scores of the Hamilton Rating Scale for Depression (P-value<0.001 in both groups) and Hamilton Rating Scale for Anxiety (P-value<0.001 in both groups). Comparison of score changes between the 2 trial arms showed no significant difference (P-value=0.984). Frequency of side effects was not significantly different between the 2 groups. Discussion: The present study indicates saffron as a potential efficacious and tolerable treatment for major depressive disorder with anxious distress.

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A randomized, double-blind, placebo-controlled 6-wk trial of the efficacy and tolerability of 5 mg vortioxetine in adults with major depressive disorder*

The International Journal of Neuropsychopharmacology ◽

10.1017/s1461145712000727 ◽

2012 ◽

Vol 16 (2) ◽

pp. 313-321 ◽

Cited By ~ 71

Author(s):

Rakesh Jain ◽

Atul R. Mahableshwarkar ◽

Paula L. Jacobsen ◽

Yinzhong Chen ◽

Michael E. Thase

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Rating Scale ◽

P Value ◽

Depression Symptoms ◽

Major Depressive ◽

Double Blind ◽

Efficacy Measure ◽

Efficacy Measures ◽

Hamilton Anxiety Scale

Abstract Vortioxetine (Lu AA21004) is a multi-modal antidepressant in clinical development for the treatment of major depressive disorder (MDD). The current study evaluated the efficacy and tolerability of 5 mg vortioxetine compared to placebo after 6 wk of treatment in adults with MDD in an out-patient setting. Adults aged 18–75 yr, with a diagnosis of MDD and a baseline Montgomery–Asberg Depression Rating Scale (MADRS) total score ⩾30, were randomized to receive either 5 mg vortioxetine or placebo over 6 wk, followed by a 2-wk medication-free discontinuation period. The primary efficacy measure was change from baseline in Hamilton Rating Scale for Depression (HAMD)-24 total score at week 6 compared to placebo. Additional measures included response and remission rates, Clinical Global Impression Scale – Improvement scores, HAMD-24 total score in subjects with baseline Hamilton Anxiety Scale (HAMA) >19 and MADRS-S total score. Adverse events (AEs) were assessed throughout the study. A total of 600 adults were randomized. There were no significant differences in efficacy measures between subjects in the 5 mg vortioxetine and placebo groups at week 6. HAMD-24 total score in subjects with baseline HAMA >19 in the 5 mg vortioxetine group was improved at weeks 3–6 compared to the placebo group (nominal p value <0.05). The most common AEs for the vortioxetine and placebo groups were nausea (19.1 and 9.4%), headache (17.1 and 15.1%) and diarrhoea (11.4 and 7.0%), respectively. In this study of adults with MDD, 5 mg vortioxetine did not differ significantly from placebo in reducing depression symptoms after 6 wk of treatment.

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Sexual Function during Bupropion or Paroxetine Treatment of Major Depressive Disorder

The Canadian Journal of Psychiatry ◽

10.1177/070674370605100405 ◽

2006 ◽

Vol 51 (4) ◽

pp. 234-242 ◽

Cited By ~ 57

Author(s):

Sidney H Kennedy ◽

Kari A Fulton ◽

R Michael Bagby ◽

Andrea L Greene ◽

Nicole L Cohen ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Sexual Function ◽

Rating Scale ◽

Primary Objective ◽

Major Depressive ◽

Double Blind ◽

Significant Difference ◽

To Receive ◽

Over Time

Objective: The primary objective was to evaluate sexual function (SF) separately in men and women with major depressive disorder (MDD) before and during treatment with bupropion sustained release (SR) or paroxetine. The secondary objectives involved a comparative evaluation of the Sex Effects Scale (Sex FX) and the Investigator-Rated Sexual Desire and Functioning Scale (IRSD-F), as well as a comparison of antidepressant outcomes and an examination of the relation between level of depression and SF over time. Method: There were 141 patients (68 women and 73 men) who met DSM-IV criteria for a current major depressive episode. They were randomly assigned to receive bupropion SR (150 to 300 mg daily) or paroxetine (20 to 40 mg daily) under double-blind trial conditions. Patients were assessed at baseline and at 2, 4, 6, and 8 weeks with the 17-item Hamilton Depression Rating Scale (HDRS17), Sex FX, and IRSD-F. Results: Prior to treatment, women reported significantly lower SF on both the Sex FX and IRSD-F scales, compared with men. During treatment, there were no significant drug differences on measures of SF over time for women; however, men who were treated with paroxetine reported a worsening of SF, whereas bupropion SR did not significantly alter SF. Both bupropion SR and paroxetine produced clinically and statistically significant reductions in HDRS17 scores as well as comparable rates of response and remission. There was a statistically significant correlation between the 2 measures of SF at all visits. There was also a significant inverse relation between depression and SF in women, but not in men, irrespective of drug. Conclusion: According to the Sex FX scale, a significant difference in antidepressant-related sexual dysfunction was detected in men, but not women, during treatment with bupropion SR or paroxetine.

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The efficacy of levomilnacipran ER across symptoms of major depressive disorder: a post hoc analysis of 5 randomized, double-blind, placebo-controlled trials

CNS Spectrums ◽

10.1017/s1092852915000899 ◽

2016 ◽

Vol 21 (5) ◽

pp. 385-392 ◽

Cited By ~ 5

Author(s):

Roger S. McIntyre ◽

Carl Gommoll ◽

Changzheng Chen ◽

Adam Ruth

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Rating Scale ◽

Phase Iii ◽

Depression Symptoms ◽

Major Depressive ◽

Double Blind ◽

Post Hoc Analysis ◽

Symptom Domains ◽

Post Hoc

ObjectiveA post hoc analysis evaluated the effects of levomilnacipran ER on individual symptoms and symptom domains in adults with major depressive disorder (MDD).MethodsData were pooled from 5 Phase III trials comprising 2598 patients. Effects on depression symptoms were analyzed based on change from baseline in individual Montgomery–Åsberg Depression Rating Scale (MADRS) item scores. A1dditional evaluations included resolution of individual symptoms (defined as a MADRS item score ≤1 at end of treatment) and concurrent resolution of all 10 MADRS items, all MADRS6 subscale items, and all items included in different symptom clusters (Dysphoria, Retardation, Vegetative Symptoms, Anhedonia).ResultsSignificantly greater mean improvements were found on all MADRS items except Reduced Appetite with levomilnacipran ER treatment compared with placebo. Resolution of individual symptoms occurred more frequently with levomilnacipran ER than placebo for each MADRS item (all P<.05), with odds ratios (ORs) ranging from 1.26 to 1.75; resolution of all 10 items was also greater with levomilnacipran ER (OR=1.57; P=.0051). Significant results were found for the MADRS6 subscale (OR=1.73; P<.0001) and each symptom cluster (OR range, 1.39 [Vegetative Symptoms] to 1.84 [Retardation]; all clusters, P<.01).ConclusionAdult MDD patients treated with levomilnacipran ER improved across a range of depression symptoms and symptom domains.

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Factor analysis of electroacupuncture and selective serotonin reuptake inhibitors for major depressive disorder: an 8-week controlled clinical trial

Acupuncture in Medicine ◽

10.1136/acupmed-2017-011412 ◽

2019 ◽

Vol 38 (1) ◽

pp. 45-52

Author(s):

Xinjing Yang ◽

Weijun Gong ◽

Xuehong Ma ◽

Sihan Wang ◽

Xueqin Wang ◽

...

Keyword(s):

Clinical Trial ◽

Factor Analysis ◽

Major Depressive Disorder ◽

Depressive Disorder ◽

Serotonin Reuptake ◽

Rating Scale ◽

Selective Serotonin ◽

Controlled Clinical Trial ◽

Major Depressive ◽

Significant Difference

Background: There is evidence supporting electroacupuncture (EA) for the treatment of major depressive disorder (MDD), but its characteristics have not been well investigated. Objective: To investigate the effectiveness and characteristics of EA in MDD. Methods: 60 subjects were enrolled—35 in the EA group and 25 in the selective serotonin reuptake inhibitor (SSRI) group based on their preferences—in an 8-week non-randomised controlled clinical trial. The 24-item Hamilton depression rating scale (HAMD-24) and clinical global impression (CGI) were adopted for clinical assessment. The Columbia suicide severity rating scale and adverse event form were used to measure safety and tolerability. The characteristics of EA and SSRIs were compared by analysing seven factors of the HAMD-24. Results: There was no significant difference between the two groups in terms of HAMD-24 response rate after intervention (P>0.05). Patients treated with EA demonstrated a significant reduction in CGI scores (P<0.05) with fewer adverse events compared with SSRIs (P<0.01). Although HAMD-24 factor analysis showed both EA and SSRIs could improve factor scores in cognitive impairment, diurnal variation, retardation, sleep disturbance, anxiety/somatisation and feelings of despair, EA showed greater improvement in anxiety/somatisation and feelings of despair than SSRIs (P<0.05). Conclusions: There was no significant difference between EA and SSRIs in the treatment of MDD with respect to our primary outcome. However, as a potential therapy for MDD, EA appeared to result in greater symptom improvement than SSRI treatment with respect to anxiety/somatisation and feelings of despair. The results of this secondary analysis should be interpreted cautiously given the inherent issues of multiple testing.

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

Translational Psychiatry ◽

10.1038/s41398-021-01441-4 ◽

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.

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Propofol Anaesthesia in Electroconvulsive Therapy

The British Journal of Psychiatry ◽

10.1192/bjp.165.4.506 ◽

1994 ◽

Vol 165 (4) ◽

pp. 506-509 ◽

Cited By ~ 45

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.

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EEG Synchronized TMS for Individualized Therapy in Major Depressive Disorder

European Psychiatry ◽

10.1016/s0924-9338(11)72849-8 ◽

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.

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Omega-3 as an adjunctive therapy of sertraline and venlafaxine substantially improves symptoms of major depressive disorder: A double-blind, placebo-controlled study

Current Psychopharmacologye ◽

10.2174/2211556010666210712185437 ◽

2021 ◽

Vol 10 ◽

Author(s):

Mohammad Ahadifard Moghaddam ◽

Malihe Farid ◽

Mahboobeh Mehrabani Natanzi ◽

Zohre Khodaii ◽

Rahim Badrfam ◽

...

Keyword(s):

Major Depressive Disorder ◽

Depressive Symptoms ◽

Depressive Disorder ◽

Controlled Study ◽

P Value ◽

Omega 3 ◽

Major Depressive ◽

Double Blind ◽

Double Blind Clinical Trial ◽

Severity Of Depression

Background: Due to the possible effect of omega-3 fatty acids on reducing depressive symptoms, in this study, we investigated these effects in combination with other antidepressants. Methods: The study was a double-blind clinical trial on 100 patients with major depressive disorder who were divided into four groups of 25 each and treated with 50 mg daily sertraline plus placebo, 50 mg daily sertraline plus two grams Omega 3 daily, 75 mg daily venlafaxine plus placebo, and 75 mg daily venlafaxine plus 2 g Omega 3 daily for 6 weeks. Results: The mean Hamilton depression rating score of sertraline and venlafaxine plus omega-3 after treatment were 4.42 and 4.23 respectively versus sertraline and venlafaxine plus placebo 14.4 and 14.2 respectively (P value=0.0001). Conclusion: Omega-3 enhanced the clinical function of sertraline and venlafaxine to reduce the severity of depression. Adding omega-3 to either sertraline or venlafaxine does not have a comparative advantage over each other in terms of the improvement of severity of depressive symptoms. Trial registration : number is IRCT20190302042885N1.

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Efficacy of levomilnacipran extended-release in major depressive disorder: pooled analysis of 5 double-blind, placebo-controlled trials

CNS Spectrums ◽

10.1017/s1092852914000273 ◽

2014 ◽

Vol 20 (2) ◽

pp. 148-156 ◽

Cited By ~ 12

Author(s):

Stuart A. Montgomery ◽

Carl P. Gommoll ◽

Changzheng Chen ◽

William M. Greenberg

Keyword(s):

Major Depressive Disorder ◽

Depressive Disorder ◽

Extended Release ◽

Rating Scale ◽

Pooled Analysis ◽

Major Depressive ◽

Double Blind ◽

Madrs Score ◽

Wide Range ◽

Remission Rates

Introduction/ObjectivePost hoc analyses were conducted to evaluate the efficacy of levomilnacipran extended-release (ER) in subgroups of patients with major depressive disorder (MDD).MethodsData were pooled from 5 completed Phase II/III studies. Patients were categorized by sex, age, MDD duration, recurrence of MDD, current episode duration, number of prior episodes, and baseline Montgomery–Åsberg Depression Rating Scale (MADRS) score. Efficacy was evaluated by MADRS least squares (LS) mean change from baseline, response (MADRS improvement ≥50%), and remission (MADRS ≤10).ResultsIn the pooled population, treatment with levomilnacipran ER versus placebo resulted in greater improvement in MADRS score (−15.8 versus −12.9; LS mean difference, −2.9; P < .001) and higher response rates (44.7% versus 34.5%; P < .001). Comparable treatment effects were found in most subgroups. Remission rates in the overall population were higher for levomilnacipran ER versus placebo (27.7% versus 21.5%; P < .05); notably high remission rates were seen in patients with baseline MADRS score < 30 (48.8% versus 28.9%; P < .001).DiscussionClinically meaningful improvements in depressive symptoms were found across subgroups, including statistically significant outcomes for both response and remission.ConclusionLevomilnacipran ER was efficacious across a wide range of MDD patients, including men and women, ages 18–78, with varying histories and symptom severity.

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