Pharmacotherapy of Major Depressive Disorder: Focus on Duloxetine

2009 ◽  
Vol 1 ◽  
pp. CMT.S1988
Author(s):  
Katsumasa Muneoka
Keyword(s):  
Major Depressive Disorder ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Plasma Levels ◽  
Cytochromes P450 ◽  
Placebo Control ◽  
Major Depressive ◽  
Double Blind ◽  
Therapeutic Doses

The serotonin-noradrenaline reuptake inhibitor duloxetine is a second-generation antidepressant for the treatment of major depressive disorder (MDD). Its inhibitory potency for serotonin (5-HT) and noradrenaline (NA) reuptake has been demonstrated in animal and in vitro studies. Human studies of peripheral markers of neurotransmission show inhibition of 5-HT reuptake by duloxetine and also support its potency in NA reuptake inhibition. Moreover, a positron emission tomography study in human brains shows that therapeutic doses of duloxetine result in >80% occupancy of 5-HT transporters. Duloxetine is metabolized by hepatic enzymes and cytochromes P450 CYP2D6 and CYP1A2, and plasma duloxetine concentrations increase linearly according to oral dose. In double-blind, randomized, placebo-control studies of MDD, duloxetine-treated patients show significantly increased response and remission rates and significantly longer time to relapse compared to placebo-treated patients. Moreover, duloxetine is efficacious for the treatment of generalized anxiety disorder (GAD) and pain-related diseases such as diabetic peripheral neuropathic pain (DPNP). A daily dose of 60 mg daily seems most effective for treating MDD, GAD and DPNP. Duloxetine is similar in efficacy to fluoxetine, paroxetine and escitalopram for MDD, although escitalopram is better for improving sleep. The most common treatment-emergent side effects of duloxetine are nausea, dry mouth, fatigue and decreased appetite. Studies suggest an association with the incidence of increased sweating or somnolence at higher doses and an association with irritability or anxiety at high plasma levels of duloxetine. Discontinuation rates due to adverse events are higher in patients who receive duloxetine versus placebo in short-term but not long-term studies. Interestingly, there is not a strong correlation between clinical efficacy and plasma levels of duloxetine. Therefore, although duloxetine is safe and tolerated at therapeutic doses of 60-120 mg/day, the dose should be adjusted while the patient is carefully monitored for efficacy and adverse events.

scholarly journals The effects of intramuscular administration of scopolamine augmentation in moderate to severe major depressive disorder: a randomized, double-blind, placebo-controlled trial

2020 ◽  
Vol 10 ◽  
pp. 204512532093855
Author(s):  
Jingjing Zhou ◽  
Jian Yang ◽  
Xuequan Zhu ◽  
Tarek Zghoul ◽  
Lei Feng ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Dose Group ◽  
Response Rate ◽  
Secondary Outcome ◽  
Control Group ◽  
Placebo Control ◽  
High Dose ◽  
Major Depressive ◽  
Double Blind

Introduction: Major depressive disorder (MDD) is a common affective disorder. Currently established pharmacotherapies lack rapid clinical response, thereby limiting their ability to bring instant relief to patients. A series of clinical trials has demonstrated the antidepressant effects of scopolamine, yet few have studied the effects of add-on scopolamine to currently available antidepressants. It is not known whether conventional antidepressant treatment with a 3-day scopolamine injection could speed up oral antidepressant efficacy. The main focus of this study is to detect the capacity of the rapid-onset efficacy of such a treatment option. Methods and analysis: This study consisted of a single-centre, double-blind, three-arm randomized trial with a 4-week follow-up period. Sixty-six participants meeting entry criteria were randomly allocated to three treatment groups: a high-dose group, a low-dose group and a placebo control group. Psychiatric rating scales were administered at baseline and seven viewing points following the administration of intramuscular injections. The primary outcome measure was length of time from randomization (baseline) to early improvement. Results: Both primary and secondary outcome measures consistently showed no differences among the three groups. The cumulative response rate and the remission rate were 72.7% (48/66) and 47.0% (31/66). Intramuscular scopolamine treatment was relatively well tolerated. Two subjects with high-dose injections dropped out because of a drug-related side effect. Conclusion: Contrary to our prediction, we found that, compared to placebo (0.9% saline i.m.), scopolamine was not associated with a significantly faster antidepressant response rate. Trial registration: ClinicalTrials.gov, NCT03131050. Registered on 18 April 2017.

Aripiprazole Augmentation in Major Depressive Disorder: A Double-Blind, Placebo-Controlled Study in Patients with Inadequate Response to Antidepressants

CNS Spectrums ◽  
2009 ◽  
Vol 14 (4) ◽  
pp. 197-206 ◽  
Author(s):  
Robert M. Berman ◽  
Maurizio Fava ◽  
Michael E. Thase ◽  
Madhukar H. Trivedi ◽  
René Swanink ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Controlled Study ◽  
Inadequate Response ◽  
Completion Rates ◽  
Madrs Total Score ◽  
Major Depressive ◽  
Double Blind

ABSTRACTIntroduction: Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.Methods: Patients (N=1, 147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2–20 mg/day). Primary outcome was the mean change in Montgomery-Åsberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).Results: Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (−10.1) than placebo (−6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).Conclusion: For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196).

scholarly journals Beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder: a protocol for a systematic review of published and unpublished data with meta-analyses and trial sequential analyses

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Sophie Juul ◽  
Faiza Siddiqui ◽  
Marija Barbateskovic ◽  
Caroline Kamp Jørgensen ◽  
Michael Pascal Hengartner ◽  
...  
Keyword(s):  
Systematic Review ◽  
Major Depressive Disorder ◽  
Depressive Symptoms ◽  
Adverse Events ◽  
Depressive Disorder ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Major Depressive ◽  
Serious Adverse Events ◽  
Harmful Effects

Abstract Background Major depressive disorder is one of the most common, burdensome, and costly psychiatric disorders worldwide. Antidepressants are frequently used to treat major depressive disorder. It has been shown repeatedly that antidepressants seem to reduce depressive symptoms with a statistically significant effect, but the clinical importance of the effect sizes seems questionable. Both beneficial and harmful effects of antidepressants have not previously been sufficiently assessed. The main objective of this review will be to evaluate the beneficial and harmful effects of antidepressants versus placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. Methods/design A systematic review with meta-analysis will be reported as recommended by Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA), bias will be assessed with the Cochrane Risk of Bias tool-version 2 (ROB2), our eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, Trial Sequential Analysis will be conducted to control for random errors, and the certainty of the evidence will be assessed with the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. To identify relevant trials, we will search both for published and unpublished trials in major medical databases from their inception to the present. Clinical study reports will be obtained from regulatory authorities and pharmaceutical companies. Two review authors will independently screen the results of the literature searches, extract data, and perform risk of bias assessment. We will include any published or unpublished randomised clinical trial comparing one or more antidepressants with placebo, ‘active placebo’, or no intervention for adults with major depressive disorder. The following active agents will be included: agomelatine, amineptine, amitriptyline, bupropion, butriptyline, cianopramine, citalopram, clomipramine, dapoxetine, demexiptiline, desipramine, desvenlafaxine, dibenzepin, dosulepin, dothiepin, doxepin, duloxetine, escitalopram, fluoxetine, fluvoxamine, imipramine, iprindole, levomilnacipran, lofepramine, maprotiline, melitracen, metapramine, milnacipran, mirtazapine, nefazodone, nortriptyline, noxiptiline, opipramol, paroxetine, protriptyline, quinupramine, reboxetine, sertraline, trazodone, tianeptine, trimipramine, venlafaxine, vilazodone, and vortioxetine. Primary outcomes will be depressive symptoms, serious adverse events, and quality of life. Secondary outcomes will be suicide or suicide attempt, suicidal ideation, and non-serious adverse events. Discussion As antidepressants are commonly used to treat major depressive disorder in adults, a systematic review evaluating their beneficial and harmful effects is urgently needed. This review will inform best practice in treatment and clinical research of this highly prevalent and burdensome disorder. Systematic review registration PROSPERO CRD42020220279

scholarly journals Impact of Repetitive Transcranial Magnetic Stimulation (rTMS) on Theory of Mind and Executive Function in Major Depressive Disorder and Its Correlation with Brain-Derived Neurotrophic Factor (BDNF): A Randomized, Double-Blind, Sham-Controlled Trial

2021 ◽  
Vol 11 (6) ◽  
pp. 765
Author(s):  
Jie Tong ◽  
Jie Zhang ◽  
Ying Jin ◽  
Weiqing Liu ◽  
Hao Wang ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Executive Function ◽  
Transcranial Magnetic Stimulation ◽  
Theory Of Mind ◽  
Depressive Disorder ◽  
Magnetic Stimulation ◽  
Repetitive Transcranial Magnetic Stimulation ◽  
Major Depressive ◽  
Double Blind ◽  
Perseverative Errors

Background: Studies have implicated hypofrontality in the pathogenesis of impaired theory of mind (ToM) and executive function (EF) in major depressive disorder (MDD). These symptoms are usually resistant to treatment. Repetitive transcranial magnetic stimulation (rTMS) has been shown to reverse hypofrontality. Moreover, BDNF is an effective biomarker of antidepressant effects, but there have been very few studies on the correlation between BDNF and rTMS. We aimed to evaluate the efficacy of 20 sessions of a 10 Hz unilateral rTMS intervention over the left dorsolateral prefrontal cortex (DLPFC) in improving ToM and EF in patients with MDD and its correlation with BDNF. Methods: A total of 120 MDD patients were enrolled in this randomized, sham-controlled, double-blind trial. Each participant received 20 sessions of rTMS at 10 Hz frequency through the active or the sham coil over 4 weeks. ToM was assessed with the facial emotion identification test (FEIT) and hinting task (HT). EF was assessed with the Wisconsin card sorting test (WCST). BDNF assessments were carried out at baseline and 2-, 4-, 12-, and 24-week follow-ups. Results: The improvement in the ToM (FEIT, HT) in the active rTMS group was significantly different from that in the sham rTMS group (F = 18.09, p < 0.001; F = 5.02, p = 0.026). There were significant differences in the WCST (categories completed, response errors, response perseverative errors, non-response perseverative errors) after logarithmic transformation at different time points in the active rTMS group (F = 14.71, p < 0.001; F = 5.99, p = 0.046; F = 8.90, p = 0.031; F = 2.31, p = 0.048). However, there was no significant difference in log transformed BDNF concentration between the two groups (t = 0.07 to t = 1.29, p > 0.05). BDNF was negatively correlated with WCST categories completed at the 24th week (r = −0.258, p = 0.046). Conclusions: The results show that rTMS may improve the ToM and EF of patients with MDD and there was no significant correlation with serum BDNF concentration. RTMS can not only be used for treatment of patients with MDD but also has a positive effect on ToM and EF.

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