Getting the balance right: Established and emerging therapies for major depressive disorders

Major depressive disorder (MDD) is a common and serious illness of our times, associated with monoamine deficiency in the brain. Moreover, increased levels of cortisol, possibly caused by stress, may be related to depression. In the treatment of MDD, the use of older antidepressants such as monoamine oxidase inhibitors and tricyclic antidepressants is decreasing rapidly, mainly due to their adverse effect profiles. In contrast, the use of serotonin reuptake inhibitors and newer antidepressants, which have dual modes of action such as inhibition of the serotonin and noradrenaline or dopamine reuptake, is increasing. Novel antidepressants have additive modes of action such as agomelatine, a potent agonist of melatonin receptors. Drugs in development for treatment of MDD include triple reuptake inhibitors, dual-acting serotonin reuptake inhibitors and histamine antagonists, and many more. Newer antidepressants have similar efficacy and in general good tolerability profiles. Nevertheless, compliance with treatment for MDD is poor and may contribute to treatment failure. Despite the broad spectrum of available antidepressants, there are still at least 30% of depressive patients who do not benefit from treatment. Therefore, new approaches in drug development are necessary and, according to current research developments, the future of antidepressant treatment may be promising.

• Publication year

  2010

• Venue

  Neuropsychiatric Disease and Treatment

• Publication date

  2010-09-07

• Fields of study

  Medicine

• Identifiers
  DOI 10.2147/NDT.S10485PMID 20856599PMCID 2938284
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Bupropion

  2012influential reference
• Population Pharmacokinetics of Orally Administered Duloxetine in Patients

  2012cited by this paper
• Dual- and triple-acting agents for treating core and co-morbid symptoms of major depression: novel concepts, new drugs

  2011cited by this paper
• Double-blind, placebo-controlled comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR

  2010cited by this paper
• Steady-State Concentrations of Mirtazapine, N-Desmethylmirtazapine, 8-Hydroxymirtazapine and their Enantiomers in Relation to Cytochrome P450 2D6 Genotype, Age and Smoking Behaviour

  2009cited by this paper
• Beyond the monoaminergic hypothesis: Agomelatine, a new antidepressant with an innovative mechanism of action

  2009cited by this paper
• Superiority of escitalopram to paroxetine in the treatment of depression.

  2009cited by this paper
• Desvenlafaxine: a new antidepressant or just another one?

  2009cited by this paper
• Comparative efficacy and acceptability of 12 new-generation antidepressants: a multiple-treatments meta-analysis.

  2009cited by this paper
• The effect of venlafaxine compared with other antidepressants and placebo in the treatment of major depression

  2009cited by this paper
• Eight-week, placebo-controlled, double-blind comparison of the antidepressant efficacy and tolerability of bupropion XR and venlafaxine XR

  2009cited by this paper
• Is the significant superiority of escitalopram compared with other antidepressants clinically relevant?

  2009cited by this paper
• Neurobiological mechanisms in major depressive disorder

  2009cited by this paper
• Emotional intelligence and personality in major depression: trait versus state effects.

  2009cited by this paper
• Vilazodone: A 5‐HT1A Receptor Agonist/Serotonin Transporter Inhibitor for the Treatment of Affective Disorders

  2009cited by this paper
• Major depressive disorder and hypothalamic-pituitary-adrenal axis activity: results from a large cohort study.

  2009cited by this paper
• Cost Effectiveness of Venlafaxine Compared with Generic Fluoxetine or Generic Amitriptyline in Major Depressive Disorder in the UK

  2009cited by this paper
• Accumulation of major depressive episodes over time in a prospective study indicates that retrospectively assessed lifetime prevalence estimates are too low

  2009cited by this paper
• An Integrated Analysis of the Safety and Tolerability of Desvenlafaxine Compared with Placebo in the Treatment of Major Depressive Disorder

  2009cited by this paper
• Escitalopram versus other antidepressive agents for depression.

  2009cited by this paper
• Comparison of the Pharmacokinetics of Venlafaxine Extended Release and Desvenlafaxine in Extensive and Poor Cytochrome P450 2D6 Metabolizers

  2009cited by this paper
• Escitalopram in the treatment of adolescent depression: a randomized placebo-controlled multisite trial.

  2009cited by this paper
• Is there a place for tricyclic antidepressants and subsequent augmentation strategies in obtaining remission for patients with treatment resistant depression?

  2009cited by this paper
• Evidence for efficacy and tolerability of vilazodone in the treatment of major depressive disorder: a randomized, double-blind, placebo-controlled trial.

  2009cited by this paper
• Escitalopram Versus SNRI Antidepressants in the Acute Treatment of Major Depressive Disorder: Integrative Analysis of Four Double-Blind, Randomized Clinical Trials

  2009cited by this paper
• Escitalopram in the treatment of major depressive disorder: a meta-analysis.

  2009cited by this paper
• Aripiprazole in refractory depression?

  2009cited by this paper
• Pharmacokinetics of duloxetine hydrochloride enteric-coated tablets in healthy Chinese volunteers: a randomized, open-label, single- and multiple-dose study.

  2009cited by this paper
• The implications of pain and physical symptoms in depression.

  2009cited by this paper
• First-line pharmacotherapies for depression - what is the best choice?

  2009cited by this paper
• Evaluation of risk factors for elevated tricyclic antidepressant plasma concentrations

  2009cited by this paper
• Mirtazapine

  2009cited by this paper
• How long should a trial of escitalopram treatment be in patients with major depressive disorder, generalised anxiety disorder or social anxiety disorder? An exploration of the randomised controlled trial database

  2009cited by this paper
• Unclear clinical significance of findings in adjunctive aripiprazole for major depressive disorder: comments on article by Marcus et al.

  2009cited by this paper
• Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders

  2008cited by this paper
• The Efficacy and Safety of Aripiprazole as Adjunctive Therapy in Major Depressive Disorder: A Second Multicenter, Randomized, Double-Blind, Placebo-Controlled Study

  2008cited by this paper
• Major depressive disorder.

  2008cited by this paper
• Efficacy, safety, and tolerability of desvenlafaxine 50 mg/day and 100 mg/day in outpatients with major depressive disorder.

  2008cited by this paper
• Effect of Desvenlafaxine on the Cytochrome P450 2D6 Enzyme System

  2008influential reference
• A meta-analysis of psychotherapy and medication in unipolar depression and dysthymia.

  2008cited by this paper
• Tolerability of Selective Serotonin Reuptake Inhibitors

  2008cited by this paper
• Major depression: emerging therapeutics.

  2008cited by this paper
• Depression in the United States household population, 2005-2006.

  2008cited by this paper
• Bupropion: a review of its use in the management of major depressive disorder.

  2008cited by this paper
• Mirtazapine versus other antidepressants in the acute-phase treatment of adults with major depression: systematic review and meta-analysis.

  2008cited by this paper
• A randomized, double-blind comparison of duloxetine and venlafaxine in the treatment of patients with major depressive disorder.

  2008cited by this paper
• Efficacy and Tolerability of Milnacipran in the Treatment of Major Depression in Comparison with Other Antidepressants

  2008cited by this paper
• The selegiline transdermal system (emsam): a therapeutic option for the treatment of major depressive disorder.

  2008cited by this paper
• Aripiprazole: in major depressive disorder.

  2008cited by this paper
• In Vitro and In Vivo Evaluations of Cytochrome P450 1A2 Interactions with Duloxetine

  2008cited by this paper
• A meta-analysis of clinical trials comparing mirtazapine with selective serotonin reuptake inhibitors for the treatment of major depressive disorder

  2008cited by this paper
• Efficacy of Duloxetine and Selective Serotonin Reuptake Inhibitors: Comparisons as Assessed by Remission Rates in Patients With Major Depressive Disorder

  2007cited by this paper
• The Clinical Pharmacokinetics of Escitalopram

  2007influential reference
• The efficacy and safety of aripiprazole as adjunctive therapy in major depressive disorder: a multicenter, randomized, double-blind, placebo-controlled study.

  2007cited by this paper
• Tricyclic antidepressant pharmacology and therapeutic drug interactions updated

  2007cited by this paper
• Lopinavir/ritonavir Reduces Bupropion Plasma Concentrations in Healthy Subjects

  2007cited by this paper
• Duloxetine

  2007cited by this paper
• Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-adrenoceptor antagonism.

  2007cited by this paper
• Severe depression and antidepressants: focus on a pooled analysis of placebo-controlled studies on agomelatine

  2007cited by this paper
• A meta-analysis of clinical trials comparing milnacipran, a serotonin--norepinephrine reuptake inhibitor, with a selective serotonin reuptake inhibitor for the treatment of major depressive disorder.

  2007cited by this paper
• Duloxetine versus escitalopram and placebo in the treatment of patients with major depressive disorder: onset of antidepressant action, a non-inferiority study*

  2007cited by this paper
• Pharmacokinetics of Mirtazapine: Enantioselective Effects of the CYP2D6 Ultra Rapid Metabolizer Genotype and Correlation with Adverse Effects

  2007cited by this paper
• Reduced prefrontal glutamate/glutamine and gamma-aminobutyric acid levels in major depression determined using proton magnetic resonance spectroscopy.

  2007cited by this paper
• A comparative study of the efficacy of acute and continuation treatment with escitalopram versus duloxetine in patients with major depressive disorder

  2007cited by this paper
• Cholinergic-Muscarinic Dysfunction in Mood Disorders

  2007cited by this paper
• Duloxetine: review of its pharmacology, and therapeutic use in depression and other psychiatric disorders.

  2007cited by this paper
• Duloxetine Does Not Relieve Painful Physical Symptoms in Depression: A Meta-Analysis

  2007cited by this paper
• Revisiting monoamine oxidase inhibitors.

  2007cited by this paper
• Effect of renal impairment on the pharmacokinetics of bupropion and its metabolites.

  2007cited by this paper
• Alterations in 5-HT1B Receptor Function by p11 in Depression-Like States

  2006cited by this paper
• Recent developments and current controversies in depression.

  2006influential reference
• Treatment with Venlafaxine Extended Release After SSRI Nonresponse or Intolerance: A Randomized Comparison of Standard- and Higher-dosing Strategies

  2006cited by this paper
• Lack of pharmacokinetic interaction when switching from fluoxetine to milnacipran

  2006cited by this paper
• Medication augmentation after the failure of SSRIs for depression.

  2006cited by this paper
• The safety and tolerability of duloxetine compared with paroxetine and placebo: a pooled analysis of 4 clinical trials.

  2006cited by this paper
• Effective dose of escitalopram in moderate versus severe DSM-IV major depression.

  2006cited by this paper
• A review of the pharmacological and clinical profile of mirtazapine.

  2006cited by this paper
• The role of CREB in depression and antidepressant treatment.

  2006cited by this paper
• Extended-release bupropion for patients with major depressive disorder presenting with symptoms of reduced energy, pleasure, and interest: findings from a randomized, double-blind, placebo-controlled study.

  2006cited by this paper
• Dysregulation of endogenous opioid emotion regulation circuitry in major depression in women.

  2006cited by this paper
• Bupropion extended release compared with escitalopram: effects on sexual functioning and antidepressant efficacy in 2 randomized, double-blind, placebo-controlled studies.

  2006cited by this paper
• A Double-blind Comparison Between Bupropion XL and Venlafaxine XR: Sexual Functioning, Antidepressant Efficacy, and Tolerability

  2006cited by this paper
• Low cerebrospinal fluid transthyretin levels in depression: correlations with suicidal ideation and low serotonin function.

  2006cited by this paper
• Bupropion-SR, sertraline, or venlafaxine-XR after failure of SSRIs for depression.

  2006influential reference
• Effects of the antidepressant duloxetine on body weight: analyses of 10 clinical studies.

  2006cited by this paper
• Duloxetine for the treatment of major depressive disorder: a closer look at efficacy and safety data across the approved dose range.

  2006cited by this paper
• Drug treatment of depression in the 2000s: an overview of achievements in the last 10 years and future possibilities

  2006influential reference
• The circadian basis of winter depression.

  2006cited by this paper
• Agomelatine

  2006cited by this paper
• Medical management of depression.

  2006cited by this paper
• Placebo-controlled trial of agomelatine in the treatment of major depressive disorder.

  2006cited by this paper
• Sexual functioning assessed in 4 double-blind placebo- and paroxetine-controlled trials of duloxetine for major depressive disorder.

  2005cited by this paper
• Depression and cortisol responses to psychological stress: a meta-analysis.

  2005cited by this paper
• Duloxetine pharmacokinetics in cirrhotics compared with healthy subjects.

  2005cited by this paper
• The medical management of depression.

  2005cited by this paper
• The effect of cimetidine or omeprazole on the pharmacokinetics of escitalopram in healthy subjects.

  2005cited by this paper
• Cardiovascular Profile of Duloxetine, a Dual Reuptake Inhibitor of Serotonin and Norepinephrine

  2005cited by this paper
• Duloxetine 60 mg once-daily in the treatment of painful physical symptoms in patients with major depressive disorder.

  2005influential reference
• Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs.

  2005cited by this paper
• Efficacy and Safety of Second-Generation Antidepressants in the Treatment of Major Depressive Disorder

  2005cited by this paper

• Psychobiotics: A Novel Approach to the Treatment ofMental Diseases

  2019cites this paper
• Peppermint (Mentha piperita) as Antidepressant on Male Wistar Rat (Rattus norvegicus) Exposed to Blue Light

  2019cites this paper
• Effect Of High Lithium Carbonate Doses On Rat Brain Content Of Some Neurotransmitters

  2017cites this paper
• Efeitos do tratamento subcrônico com fluoxetina sobre os comportamentos e parâmetros oxidativos de ratos submetidos ao exercício físico exaustivo

  2017cites this paper
• Augmentation of effect of venlafaxine by folic acid in behavioral paradigms of depression in mice: Evidence of serotonergic and pro-inflammatory cytokine pathways

  2016cites this paper
• The Effect of Data Curation on the Accuracy of Quantitative Structure-Activity Relationship Models

  2015cites this paper
• S-adenosylmethionine (SAMe) and Magnesium Orotate as adjunctives to SSRIs in sub-optimal treatment response of depression in adults: A pilot study

  2015cites this paper
• Triple reuptake inhibitors: a patent review (2006 – 2012)

  2014cites this paper
• An Adrenal Mass and Increased Catecholamines: Monoamine Oxidase or Pheochromocytoma Effect?

  2014cites this paper
• Core discrete event simulation model for the evaluation of health care technologies in major depressive disorder.

  2014cites this paper
• The gastrointestinal tract microbiome, probiotics, and mood

  2014cites this paper
• Synthesis and biological evaluation of 3-phenethylazetidine derivatives as triple reuptake inhibitors.

  2014cites this paper
• Economic Evaluation Core Discrete Event Simulation Model for the Evaluation of Health Care Technologies in Major Depressive Disorder

  2014cites this paper
• ORIGINAL RESEARCH Economic Evaluation Core Discrete Event Simulation Model for the Evaluation of Health Care Technologies in Major Depressive Disorder

  2014cites this paper
• Efficacy and tolerability of the novel triple reuptake inhibitor amitifadine in the treatment of patients with major depressive disorder: a randomized, double-blind, placebo-controlled trial.

  2012cites this paper
• Evaluation of the pharmacological descriptors related to the induction of antidepressant activity and its prediction by QSAR/QRAR methods.

  2012cites this paper
• Anxiolytic- and antidepressant-like effects of an ethanolic extract of the aerial parts of Hilleria latifolia (Lam.) H. Walt. in mice

  2011cites this paper
• Vilazodone for the Treatment of Depression

  2011cites this paper
• The importance of norepinephrine in depression

  2011cites this paper
• I bisogni non risolti della depressione maggiore

  2011cites this paper
• Unmet needs in major depression

  2011cites this paper
• Assessing the Efficacy of Methods for Treatment-Resistant Depression: A Review

  year unknowncites this paper