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major depression

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: 1) depression with psychotic features a) delusions or hallucinations b) generally concurrent & logically consistent with the depressed mood 2) depression with melancholic features a) prominent psychomotor retardation or agitation b) loss of interest c) worsening in the morning d) early morning awakening 3) depression with atypical features a) overeating b) oversleeping c) weight gain d) sensitivity to personal rejection e) mood that responds to external events Etiology: 1) independent risk factors a) social isolation b) caregiver status c) bereavement [2] 2) 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] 3) cardiovascular events a) myocardial infarction b) stroke [2] 4) risk factors in reproductive age women [16] - government insurance, hypertension Epidemiology: 1) most often begins in mid 20's 2) less common in community-dwelling elderly 3) more prevalent in specific groups of elderly a) hospitalized patients (12%) b) patients with chronic illness c) nursing home residents (16%) 4) prevalence is 9-21% in adolescents [4] 5) prevalence in reproductive age women is 4.8% [16] 6) 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 Diagnostic criteria: Minimal criteria: 1) a depressed mood or anhedonia resulting in impaired function 2) symptoms should be present every day or nearly every day for at least 2 weeks 3) at least 4 additional symptoms must be present: a) unintentional weight loss or decreased appetite or weight gain b) insomnia or hypersomnia c) psychomotor agitation or retardation with slow speach d) fatigue e) feeling or inappropriate sense of worthlessness or guilt f) indecisiveness or inability to concentrate g) suicidal ideation or recurrent thoughts of death h) loss of interest 4) symptoms should NOT be due to bereavement Clinical manifestations: - see depression & depression in the elderly - fatigue - anhedonia - sadness - irritabilty - poor sleep - hopelessness - pervasive dysphoria - feelings of guilt or worthlessness - changes in sleep or appetite - 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] 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: 1) other depressed mood disorders a) dysthymia b) adjustment disorder with depressed mood c) seasonal affective disorder d) bipolar disorder (assess for episodes of mood elevation) 2) bereavement 3) normal sadness 4) 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] 5) persistent depressive disorder - presence of symptoms for >= 2 years without remission lasting > 2 months - symptoms generally less severe than major depression 6) psychotic/delusional depression Management: 1) general - see suicidal ideation - hospitalize if imminent danger of self harm or harm to others - 1 week follow-up for passive suicidal ideation - see depression, see STAR*D - pharmacologic therapy indicated for severe depression [29] 2) shared decision making improves treatment adherence [12] 3) 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] 4) major depression with psychotic features (includes delusions) a) responds poorly to antidepressants alone b) cognitive behavioral therapy improves response to antidepressant in the elderly (GRS9) [2] c) 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) - discontinuation due to adverse effects 14%, NNH=10 [8] d) patients with anhedonia, abulia, fatigue, or psychomotor retardation should receive treatment with an SNRI rather than SSRI [24] e) addition of lithium carbonate may improve response to antidepressant in the elderly (GRS9) [2] f) a single dose of psilocybin 25 mg reduces depression scores with 8 days & over a period of 3-6 weeks [31] g) gepirone (Exxua) FDA approve for treatment of major depression h) electroconvulsive therapy for treatment-resistant depression [2,18] or delusional depression [22] i) 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] - ketamine infusions comparable or more effective than ECT [28] - adverse effects differ between ketamine & ECT - ketamine: lower risks for headache & muscle pain - ECT: lower risks for blurred vision, vertigo, diplopia/nystagmus, & transient dissociative/depersonalization symptoms [23,28] j) 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] k) folinic acid (1-2 mg/kg/day) may be of benefit in treatment-resistant depression [10] 5) anti-inflammatory agents might be helpful as monotherapy or add-on [20] - omega-3 fatty acids, celecoxib, statins, minocycline, modafinil, pioglitazone, N-acetylcysteine [20] 6) adjunctive treatment with probiotics may improve symptoms of depression & anxiety [30] 7) prognosis a) early response of irritability symptoms to antidepressants might predict subsequent treatment outcomes [17] b) partial response at 4 weeks increases the likelihood of full remission [2] - also holds true for major depression with comorbid anxiety [2] c) comorbidity of anxiety & major depression in the elderly predicts more severe & treatment-resistant disease than either alone [2] d) presence of a personality disorder is a negative indicator for return to full function [2] e) 8-year mortality for patients managed in primary care is the same as for the general population [7] f) 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] g) lifetime therapy for patients with > 2 episodes of major depression [25,26,27]; including recurrence within 1 year of treatment & suicide attempt 8) screening recommended for adolescents [4] 9) refer to psychiatry for: a) significant suicidal or homicidal ideation b) psychotic symptoms c) bipolar disorder [3] d) refractory symptoms e) neuropsychologic testing for cognitive impairment or functional impairment [3] f) failure of initial therapy g) psychiatric comorbidities [3] h) severe depression

Interactions

disease interactions

Related

adjustment disorder atypical depression depression in the elderly dysthymia seasonal affective disorder Sequenced Treatment Alternatives to Relieve Depression (STAR*D) treatment-resistant depression

Specific

major depression with psychosis; psychotic/delusional depression

General

depression

References

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