major depression
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Introduction
A major mood disorder characterized by one (single) or more (recurrent) episodes of major depression, with or without full recovery between episodes.
* Also see depression in the elderly
Classification
- depression with psychotic features
- delusions or hallucinations
- generally concurrent & logically consistent with the depressed mood
- depression with melancholic features
- prominent psychomotor retardation or agitation
- loss of interest
- worsening in the morning
- early morning awakening
- depression with atypical features
- overeating
- oversleeping
- weight gain
- sensitivity to personal rejection
- mood that responds to external events
Etiology
- independent risk factors
- disability is a risk factor
- associated of chronic disease with major depression is related to degree of disablity rather than the chronic disease itself[2]
- cardiovascular events
- risk factors in reproductive age women[16]
- government insurance, hypertension
Epidemiology
- most often begins in mid 20's
- less common in community-dwelling elderly
- more prevalent in specific groups of elderly
- hospitalized patients (12%)
- patients with chronic illness
- nursing home residents (16%)
- prevalence is 9-21% in adolescents[4]
- prevalence in reproductive age women is 4.8%[16]
- prevalence of antidepressant use in reproductive age women with major depression is 32%[16]
Pathology
- > 1/3 of patients with treatment-resistant depression have cerebral folate deficiency[10]
- low plasma arginine associated with diminished production of nitric oxide & perhaps increased oxidative stress[15]
Genetics
- PDLIM5 is commonly increased in the brain of patients with bipolar disorder, schizophrenia, & major depression
- associated with defects in DCNP1 gene
- cyclic pattern of major circadian clock genes BMAL, PER1, PER2, PER3 & others, are much weaker patients with major depresion[6]
- other implicated genes: CPLX2
Clinical manifestations
- see depression & depression in the elderly
- most elderly patients present with multiple somatic complaints, anxiety, poor sleep or concerns with cognitive impairment
- elderly patients may be unable/unwilling to express sadness[2]
- severe major depression indicated by PHQ-9 score of 20-17[29]
Diagnostic criteria
Minimal criteria:
- a depressed mood or anhedonia resulting in impaired function
- symptoms should be present every day or nearly every day for at least 2 weeks
- at least 4 additional symptoms must be present:
- unintentional weight loss or decreased appetite or weight gain
- insomnia or hypersomnia
- psychomotor agitation or retardation with slow speach
- fatigue
- feeling or inappropriate sense of worthlessness or guilt
- indecisiveness or inability to concentrate
- suicidal ideation or recurrent thoughts of death
- loss of interest
- symptoms should NOT be due to bereavement
Laboratory
- tetrahydrobiopterin in CSF low in 1/3 of patients with refractory depression[10]
- serum arginine low
Radiology
- functional MRI (fMRI)[12]
- subcallosal cingulate cortex connectivity to dorsal midbrain, ventrolateral prefrontal cortex-insula, & ventromedial prefrontal cortex differentiate cognitive behavorial therapy (CBT) responders from medication responders
- greater connectivity to these areas associated with CBT remission & medication failure[12]
- absence or reversal of this pattern yields opposite results
Complications
- increased morbidity & mortality[2]
- hopelessness is the best predictor of suicide in the elderly[32]
- lower medical compliance
- lower participation in rehabilitation
- osteoporosis in young women, especially in connection with borderline personality disorder[3]
Differential diagnosis
- other depressed mood disorders
- dysthymia
- adjustment disorder with depressed mood
- seasonal affective disorder
- bipolar disorder (assess for episodes of mood elevation)
- bereavement
- normal sadness
- personality disorder
- borderline personality disorder
- volatile interpersonal relationships
- episodes of intense anger[3]
- attributes problems to others
- complaints about healthcare providers
- comorbid personality disorder in 1/4 of inpatients with major depression[2]
- borderline personality disorder
- persistent depressive disorder
- presence of symptoms for >= 2 years without remission lasting > 2 months
- symptoms generally less severe than major depression
Management
- see depression, see STAR*D
- pharmacologic therapy indicated for severe depression[29]
- shared decision making improves treatment adherence[12]
- cognitive behavioral therapy & 2nd generation antidepressants equally effective as initial therapy[19]
- pharmacologic therapy indicated for severe depression (NEJM)[29]
- PHQ-9 score of >15 warrants treatment antidepressant, psychotherapy &/or a combination of treatment
- PHQ-9 score of >19 indicates severe major depression warranting treatment with antidepressant & psychotherapy[29]
- PHQ-9 score of <5 is goal of treating major depression[29]
- major depression with psychotic features (includes delusions)
- responds poorly to antidepressants alone
- cognitive behavioral therapy improves response to antidepressant in the elderly (GRS9)[2]
- addition of antipsychotic agent may improve response
- escitalopram plus ziprasidone better than escitalopram alone (response rate 35.2% vs 20.5% for placebo, NNT=4)
- patients with anhedonia, abulia, fatigue, or psychomotor retardation should receive treatment with an SNRI rather than SSRI[24]
- addition of lithium carbonate may improve response to antidepressant in the elderly (GRS9)[2]
- a single dose of psilocybin 25 mg reduces depression scores with 8 days & over a period of 3-6 weeks[31]
- gepirone (Exxua) FDA approve for treatment of major depression
- electroconvulsive therapy for treatment-resistant depression[2][18] or delusional depression[22]
- intravenous ketamine or intranasal esketamine equally effective for suicidal ideation in patients with major depression[23]
- only esketamine FDA-approved for major depression
- ketamine somewhat less effective than electroconvulsive therapy (ECT)[23]
- neurostimulation offers promise for treatment-resistant depression[9]
- repetitive transcranial magnetic stimulation effective, but less so than electroconvulsive therapy[18]
- transcranial direct current stimulation is effective, low-cost, underutilized, but insufficiently studied in treatment-resistant patients[18]
- folinic acid (1-2 mg/kg/day) may be of benefit in treatment-resistant depression[10]
- anti-inflammatory agents might be helpful as monotherapy or add-on[20]
- adjunctive treatment with probiotics may improve symptoms of depression & anxiety[30]
- prognosis
- early response of irritability symptoms to antidepressants might predict subsequent treatment outcomes[17]
- partial response at 4 weeks increases the likelihood of full remission[2]
- comorbidity of anxiety & major depression in the elderly predicts more severe & treatment-resistant disease than either alone[2]
- presence of a personality disorder is a negative indicator for return to full function[2]
- 8-year mortality for patients managed in primary care is the same as for the general population[7]
- residual symptoms associated with shortened time to relapse, longer & more-severe subsequent depressive episodes, & poorer long-term psychosocial functioning, despite equivalent antidepressant treatment relative to asymptomatic patients[11]
- lifetime therapy for patients with > 2 episodes of major depression[25][26][27]; including recurrence within 1 year of treatment & suicide attempt
- screening recommended for adolescents[4]
- refer to psychiatry for:
- significant suicidal or homicidal ideation
- psychotic symptoms
- bipolar disorder[3]
- refractory symptoms
- neuropsychologic testing for cognitive impairment or functional impairment[3]
- failure of initial therapy
- psychiatric comorbidities[3]
- severe depression
- hospitalize if imminent danger of self harm or harm to others
More general terms
More specific terms
Additional terms
- adjustment disorder
- atypical depression
- depression in the elderly
- dysthymia
- seasonal affective disorder
- Sequenced Treatment Alternatives to Relieve Depression (STAR*D)
- treatment-resistant depression
References
- ↑ Medical Knowledge Self Assessment Program (MKSAP) 11, 18, 19. American College of Physicians, Philadelphia 1998, 2018, 2021.
Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022 - ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 Geriatrics Review Syllabus, American Geriatrics Society, 5th edition, 2002-2004;
Geriatric Review Syllabus, 7th edition Parada JT et al (eds) American Geriatrics Society, 2010
Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
Geriatric Review Syllabus, 9th edition (GRS9) Medinal-Walpole A, Pacala JT, Porter JF (eds) American Geriatrics Society, 2016
Geriatric Review Syllabus, 10th edition (GRS10) Harper GM, Lyons WL, Potter JF (eds) American Geriatrics Society, 2019 - ↑ 3.0 3.1 3.2 3.3 3.4 3.5 Kahl KG et al, Bone mineral density, bone turnover and osteoprotegerin in depressed women with and without borderline personality disorder Psychosom Med 2006, 68:669 PMID: https://www.ncbi.nlm.nih.gov/pubmed/17012519
- ↑ 4.0 4.1 4.2 US Preventive Services Task Force Screening and Treatment for Major Depressive Disorder in Children and Adolescents: US Preventive Services Task Force Recommendation Statement PEDIATRICS 2009 123:1223-1228 (doi:10.1542/peds.2008-2381) http://pediatrics.aappublications.org/cgi/content/abstract/123/4/1223
corresponding NGC guideline withdrawn Dec 2014
Williams SB et al Screening for Child and Adolescent Depression in Primary Care Settings: A Systematic Evidence Review for the US Preventive Services Task Force PEDIATRICS 2009, 123:e716-e735 (doi:10.1542/peds.2008-2415) http://pediatrics.aappublications.org/cgi/content/full/123/4/e716 - ↑ Gelenberg AJ et al for the Work Group on Major Depressive Disorder American Psychiatric Association Practice Guideline for the treatment of patients with major depressive disorder, 3rd edition http://www.psych.org/guidelines/mdd2010 corresponding NGC guideline withdrawn Dec 2015
- ↑ 6.0 6.1 Li JZ, Bunney BG, Meng F Circadian patterns of gene expression in the human brain and disruption in major depressive disorder. Proc Natl Acad Sci U S A. 2013 May 13 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23671070
- ↑ 7.0 7.1 Gallo JJ et al. Long term effect of depression care management on mortality in older adults: Follow-up of cluster randomized clinical trial in primary care. BMJ 2013 Jun 5; 346:f2570 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23738992 <Internet> http://www.bmj.com/content/346/bmj.f2570
- ↑ 8.0 8.1 Papakostas GI et al. Ziprasidone augmentation of escitalopram for major depressive disorder: Efficacy results from a randomized, double-blind, placebo-controlled study. Am J Psychiatry 2015 Jun 18; <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/26085041 <Internet> http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2015.14101251
- ↑ 9.0 9.1 Wani A, Trevino K, Marnell P, Husain MM. Advances in brain stimulation for depression. Ann Clin Psychiatry. 2013 Aug;25(3):217-24. Review. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23926577
- ↑ 10.0 10.1 10.2 10.3 Pan LA, Martin P, Zimmer T et al. Neurometabolic disorders: Potentially treatable abnormalities in patients with treatment-refractory depression and suicidal behavior. Am J Psychiatry 2016 Aug 13; PMID: https://www.ncbi.nlm.nih.gov/pubmed/27523499
- ↑ 11.0 11.1 Judd LL, Schettler PJ, Rush AJ et al. A new empirical definition of major depressive episode recovery and its positive impact on future course of illness. J Clin Psychiatry 2016 Aug; 77:1065. PMID: https://www.ncbi.nlm.nih.gov/pubmed/26580150
- ↑ 12.0 12.1 12.2 12.3 Dunlop BW et al. Functional connectivity of the subcallosal cingulate cortex and differential outcomes to treatment with cognitive- behavioral therapy or antidepressant medication for major depressive disorder. Am J Psychiatry 2017 Mar 24; http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2016.16050518
Dunlop BW et al. Effects of patient preferences on outcomes in the Predictors of Remission in Depression to Individual and Combined Treatments (PReDICT) Study. Am J Psychiatry 2017 Mar 24; http://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2016.16050517 - ↑ American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder -- third edition. Oct 2010 http://psychiatryonline.org/pb/assets/raw/sitewide/practice_guidelines/guidelines/mdd.pdf
- ↑ Bentley SM, Pagalilauan GL, Simpson SA. Major depression. Med Clin North Am. 2014 Sep;98(5):981-1005 PMID: https://www.ncbi.nlm.nih.gov/pubmed/25134869
- ↑ 15.0 15.1 Swift Yasgur M Major Depression Tied to Reduced Arginine Levels. Medscape - Mar 06, 2018. https://www.medscape.com/viewarticle/893513
- ↑ 16.0 16.1 16.2 16.3 Guo N, Robakis T, Miller C, Butwick A. Prevalence of depression among women of reproductive age in the United States. Obstet Gynecol 2018 Apr; 131:671 PMID: https://www.ncbi.nlm.nih.gov/pubmed/29528926 https://insights.ovid.com/crossref?an=00006250-900000000-98125
- ↑ 17.0 17.1 Jha MK, Minhajuddin A, South C, Rush AJ, Trivedi MH. Irritability and its clinical utility in major depressive disorder: Prediction of individual-level acute-phase outcomes using early changes in irritability and depression severity. Am J Psychiatry 2019 Mar 29; PMID: https://www.ncbi.nlm.nih.gov/pubmed/30922100 https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2018.18030355
- ↑ 18.0 18.1 18.2 18.3 Mutz J, Vipulananthan V, Carter B, Hurlemann R, Fu CHY, Young AH. Comparative efficacy and acceptability of non-surgical brain stimulation for the acute treatment of major depressive episodes in adults: Systematic review and network meta-analysis. BMJ 2019 Mar 27; 364:l1079 PMID: https://www.ncbi.nlm.nih.gov/pubmed/30917990 Free PMC Article https://www.bmj.com/content/364/bmj.l1079
- ↑ 19.0 19.1 Ross EL, Vijan S, Miller EM, Valenstein M, Zivin K. The Cost-Effectiveness of Cognitive Behavioral Therapy Versus Second- Generation Antidepressants for Initial Treatment of Major Depressive Disorder in the United States: A Decision Analytic Model. Ann Intern Med. 2019. Oct 29 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31658472 https://annals.org/aim/article-abstract/2753801/cost-effectiveness-cognitive-behavioral-therapy-versus-second-generation-antidepressants-initial
- ↑ 20.0 20.1 20.2 Bai S, Guo W, Feng Y et al Efficacy and safety of anti-inflammatory agents for the treatment of major depressive disorder: a systematic review and meta-analysis of randomised controlled trials. BMJ. Neurology, Neurosurgery & Psychiatry. Oct 28, 2019 PMID: https://www.ncbi.nlm.nih.gov/pubmed/31658959 https://jnnp.bmj.com/content/early/2019/08/29/jnnp-2019-320912
- ↑ NEJM Knowledge+ Question of the Week. Nov 5, 2019 https://knowledgeplus.nejm.org/question-of-week/1802
- ↑ 22.0 22.1 Talebraza S et al Geriatrics Evaluation & Management Tools American Geriatrics Society. 2021 https://geriatricscareonline.org/ProductAbstract/geriatrics-evaluation-management-tools/B007/
- ↑ 23.0 23.1 23.2 23.3 Rhee TG, Shim SR, Forester BP et al Efficacy and Safety of Ketamine vs Electroconvulsive Therapy Among Patients With Major Depressive Episode. A Systematic Review and Meta-analysis. JAMA Psychiatry. Published online October 19, 2022 PMID: https://www.ncbi.nlm.nih.gov/pubmed/36260324 https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2797209
Nikayin S, Rhee TG, Cunningham ME et al Evaluation of the Trajectory of Depression Sever.ity With Ketamine and Esketamine Treatment in a Clinical Setting JAMA Psychiatry. 2022 Jul 1;79(7):736-738. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35544190 PMCID: PMC9096687 (available on 2023-05-11) https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2792407 - ↑ 24.0 24.1 Bennabi D, Charpeaud T, Yrondi A et al Clinical guidelines for the management of treatment-resistant depression: French recommendations from experts, the French Association for Biological Psychiatry and Neuropsychopharmacology and the fondation FondaMental. BMC Psychiatry. 2019 Aug 28;19(1):262. PMID: https://www.ncbi.nlm.nih.gov/pubmed/31455302 PMCID: PMC6712810
- ↑ 25.0 25.1 UCLA Intensive Course in Geriatric Medicine & Board Review, Marina Del Ray, CA, Sept 12-15, 2001
- ↑ 26.0 26.1 Frank C Pharmacologic treatment of depression in the elderly. Can Fam Physician. 2014:60(2):121-126 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24522673 PMCID: PMC3922554 Free PMC article
- ↑ 27.0 27.1 Kok RM, Heeren TJ, Nolen WA. Continuing treatment of depression in the elderly: a systematic review and meta-analysis of double-blinded randomized controlled trials with antidepressants. Am J Geriatr Psychiatry. 2011;19(3):249-255 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21425505
- ↑ 28.0 28.1 28.2 Anand A et al. Ketamine versus ECT for nonpsychotic treatment-resistant major depression. N Engl J Med 2023 May 24; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37224232 https://www.nejm.org/doi/10.1056/NEJMoa2302399
Freedman R. Ketamine and ECT in depression - Risks and rewards. N Engl J Med 2023 May 24; [e-pub] PMID: https://www.ncbi.nlm.nih.gov/pubmed/37224235 https://www.nejm.org/doi/10.1056/NEJMe2305130 - ↑ 29.0 29.1 29.2 29.3 29.4 29.5 NEJM Knowledge+ Psychiatry
- ↑ 30.0 30.1 Bender E Probiotics an Effective Adjunct to Antidepressants for Major Depression. Medscape. June 16, 2023 https://www.medscape.com/viewarticle/993330
Nikolova VL, Cleare AJ, Young AH et al Acceptability, Tolerability, and Estimates of Putative Treatment Effects of Probiotics as Adjunctive Treatment in Patients With Depression. A Randomized Clinical Trial. JAMA Psychiatry. Published online June 14, 2023. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37314797 PMCID: PMC10267847 Free PMC article https://jamanetwork.com/journals/jamapsychiatry/fullarticle/2806011 - ↑ 31.0 31.1 Goodwin GM, Aaronson ST, Alvarez O et al Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med 2022; 387:1637-1648. Nov 3. PMID: https://www.ncbi.nlm.nih.gov/pubmed/36322843 https://www.nejm.org/doi/full/10.1056/NEJMoa2206443
Raison CL, Sanacora G, Woolley J et al Single-Dose Psilocybin Treatment for Major Depressive Disorder. A Randomized Clinical Trial. JAMA. Published online August 31, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/37651119 https://jamanetwork.com/journals/jama/fullarticle/2808950 - ↑ 32.0 32.1 Alexopoulos GS, Raue PJ, Banerjee S et al Modifiable predictors of suicidal ideation during psychotherapy for late-life major depression. A machine learning approach. Transl Psychiatry. 2021 Oct 18;11(1):536. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34663787 Free PMC article. Clinical Trial.