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depression

A mental state marked by feelings of despair, discouragement, & sadness. * also see major depression & depression in the elderly Etiology: 1) psychosocial a) social determinants of health - less education, being unmarried, unemployment, lack of health insurance are associated with higher PHQ-9 scores b) stress 1] medical illness may be a severe form of stress - knee osteoarthritis, risk increases with severity [83] 2] job stress 3] marital discord c) emotional loss 1] death 2] divorce 3] job loss d) family dynamics: - children of depressed fathers at increased risk for depression during adolescence [77] e) religion or spirituality may confer protective effect [20] 2) pharmacologic causes* a) amphetamine withdrawal b) beta blockers c) centrally-acting antihypertensives (e.g. reserpine, methyldopa, clonidine) d) glucocorticoids e) levodopa f) angiotensin-converting enzyme (ACE) inhibitors g) proton pump inhibitors h) gabapentin + cyclobenzaprine [82] 3) heredity 5) prenatal depression & postpartum depression in mothers increases risk of depression during adolescence in offspring [39] 6) young adults with most social media use have more depressive symptoms [61] 7) risk factors in reproductive age women - major depression: government insurance, hypertension - minor depression: education level high school or less 8) nutritional deficiency - scurvy 9) also see depression in the elderly * increasing use of drugs that list depression as possible adverse effect [82] Epidemiology: 1) 10-15% of general medical outpatients [17] 2) female/male ratio is about 2-3/1 3) lifetime incidence of major depression is ~20% in women & about ~12% in men [3] 4) prevalence of depression in reproductive age women - major depression: 4.8%, minor depression: 4.3% [79] 5) prevalence of antidepressant use in reproductive age women with depression - major depression: 32%, minor depression: 20% [79] 6) more common among blacks & Hispanics than whites 7) more common among middle-aged adults than among younger & older adults 8) individuals without health insurance more likely to be depressed than those with coverage [17] 9) common among resident physicians (29%) [58] 10) common in persons with medical disease [3] 11) disconnect of treatment & screening - 29% of adults who screen positive for depression receive treatment [71] - among adults treated for depression, only 30% screened positive for depression [71] Pathology: - resting leukocyte telomerase activity is elevated in major depression a) pretreatment telomerase activity is directly correlated with depression ratings b) lower pretreatment telomerase activity with relatively greater increase in telomerase activty during treatment correlates with better treatment response [23] c) comment: difficult to envision a mechanism - the frontal-striatal network is expanded nearly twofold in the cortex of most individuals with depression [102] Genetics: 1) alleles of serotonin transporter SLC6A4 gene may predispose to depression [10] 2) the A allele of SNP rs7997012 in the HTR2A gene confers likelihood of response to SSRIs 3) associated with variations in CACNA1C & CACNB2 [35] History: (self-report scales for depression) 1) Center for Epidemiological Studies - Depression Scale 2) Beck Depression Inventory 3) Zung self-rating depression scale Clinical manifestations: 1) anhedonia 2) sadness 3) apathy 4) appetite changes 5) fatigue 6) sleep disturbances 7) feelings of worthlessness 8) thoughts of death 9) suicidal ideation 10) anxiety/nervousness 11) difficulty with concentration 12) inappropriate guilt 13) agitation 14) slowness 15) self-effacing 16) demanding behavior 17) irritation 18) anger 19) grumpiness 20) complaints, hypochondriasis 21) natural course of depression is generally 6 months to 2 years 22) also see depression in the elderly Diagnostic criteria: - depression must be present for at least 2 weeks [47] Laboratory: 1) thyroid function tests 2) complete blood count (CBC) 3) chemistry profile a) electrolytes b) renal function tests 1] serum urea nitrogen 2] serum creatinine c) serum calcium d) serum glucose e) liver function tests 1] serum aspartate transaminase (AST) 2] serum lactate dehydrogenase (LDH) 3] serum gamma-glutamyltransferase (GGT) 4] serum albumin 5) serum cortisol or cosyntropin-stimulation test 6) serum folate & serum vitamin B12 7) erythrocyte sedimentation rate (ESR) or serum C-reactive protein (CRP) 8) urinalysis 9) serology for HIV 10) serum homocysteine: - high serum homocysteine associated with increased risk of depression in elderly men (RR=1.6) [31] - may be useful for predicting which patients might benefit from vitamin B6, vitamin B12 & folate supplementation [52] 11) lumbar puncture & CSF catecholamine levels Special laboratory: 1) electrocardiogram (ECG) 2) sleep encephalogram a) reduced slow-wave sleep* b) reduced REM sleep latency* c) increased awakenings* * changes in sleep also seen with aging; effects may be additive Radiology: 1) positron-emission tomography 2) single-photon-emission tomography 3) functional MRI (fMRI) [72] - 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 [72] - absence or reversal of this pattern yields opposite results Differential diagnosis: 1) dysthymia 2) situational adjustment disorder with depressed mood 3) bipolar affective disorder (assess for episodes of mood elevation) 4) seasonal affective disorder 5) grief reaction (bereavement) - helplessness, hopelessness, worthlessness, guilt & anhedonia are consistent with depression rather than normal grief [3] 6) personality disorder - borderline personality disorder - volatile interpersonal relationships - episodes of intense anger [47] - attributes problems to others - complains about healthcare providers 7) neurologic disorders a) dementia 1] Alzheimer's disease 2] multi-infarct dementiaa b) stroke c) Parkinson's disease d) multiple sclerosis e) temporal lobe epilepsy 8) endocrine disorder a) menses-related mood changes b) hypothyroidism c) hyperthyroidism d) diabetes mellitus e) parathyroid disorders f) Cushing's disease g) Addison's disease h) post-partum endocrine changes 9) infectious or inflammatory processes a) may present or be accompanied by depression b) pneumonia c) arthritis d) systemic lupus erythematosus (SLE) e) infectious mononucleosis f) hepatitis g) tuberculosis h) viral infections 10) drug-induced (see etiology) 11) cardiopulmonary disease a) especially with hypoxia &/or anemia b) congestive heart failure (CHF) c) myocardial infarction 12) cancer 13) uremia 14) sleep apnea 15) head injury 16) vitamin deficiencies a) folate deficiency b) vitamin B12 deficiency c) thiamine deficiency 17) depression associated with medical illness 18) hypoactive delirium [47] 19) also see dementia vs delirium vs depression Complications: 1) increased death rate from all causes 2) up to 15% incidence of suicide 3) increased risk of stroke morbidity & mortality [19] 4) shorter telomeres [42]; significance unknown 5) children of depressed fathers at increased risk for depression during adolescence [77] 6) serotonin syndrome in patients taking SSRI in combination with other medications [3] Management: 1) ensure the safety of the suicidal depressed patient - assess suicide risk in all patients - refer to a psychiatrist those patients with a plan - hospitalize if patient is a imminent risk to themselves or others (place hold on patient if necessary) - 1 week follow-up patients with passive suicidal ideation 2) aggressively treat contributing medical problems - ask about episodes of mania or hypomania before starting antidepressant [3] - antidepressant alone in patient with bipolar disorder can precipitate mania [3] - comormid depression & anxiety is more treatment-resistant than either alone [47] 3) combination of psychotherapy (cognitive behavorial therapy) & antidepressant results in best outcomes [3,47,60,86] - combination of antidepressant & psychotherapy for persistent depressive disorder 4) psychotherapy [13,15] - 1st line treatment in adolescents - cognitive behavioral therapy (CBT) - treatment-resistant depression 3 times more likely to respond with adjunctive CBT [32,33] - CBT delivered to depressed adolescents by computer is effective [28] - web-based psychotherapy may help prevent depression [65] - effective in youth declining pharmaceutical treatment [63] - long-term benefits of CBT 3 years after therapy has stopped, but depressive symptoms still common [59] - cognitive behavioral therapy & psychodynamic psychotherapy with equally poor response rates of 23% [38] - treatment of insomnia with cognitive behavioral therapy improves symptoms of depression [41] - mindfullness-based cognitive behavioral therapy (MBCT) - may aid in maintenance of remission [16] - as effective as antidepressants & may be superior in depressed patients with histories of severe childhood abuse [54] - relapse less frequent when antidepressant combined with continuation of antidepressant (54-69% vs 39-46%) [62] - behavioral activation non-inferior to CBT for mild depression ((PHQ-9 5-9) [98] - can be delivered in a primary care office [87] - life review therapy for older adults - psychodynamic therapy [3] - short-term (16 weeks) dynamic psychotherapy ineffective [22] - interpersonal therapy [3] - cognitive therapy can help prevent recurrence [80] - therapy via telehealth by lay counselor or licensed clinician of benefit [91] 5) 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 6) pharmacologic agents (PHQ-9 >= 10) - pharmacologic therapy indicated for severe depression [98] - be alert for increased risk of suicide associated with initiation of drug therapy for depression [3] - antidepressants can trigger a manic attack in patients with bipolar-affective disorder [3] - do not stop antidepressant abruptly [3] - selective serotonin reuptake inhibitors (1st line agents) - sertraline (Zoloft) - start 25 mg QD - increase after 4-7 days (minimal adverse reaction) - effective dose: 50-200 mg QD - well tolerated in the elderly [95] - safe for patients with cardiovascular disease [3] - ineffective in patients with moderate depression & chronic renal failure (GFR 28 mL/min/1.73 m2) [78] - paroxetine (Paxil) - paroxetine is ineffective, & even harmful, for treating major depression in adolescents [55] - highest rate of sexual dysfunction among SSRI [3] - highest rate of discontinuation among SSRI [3] - classified as pregnancy category D [3] - fluoxetine (Prozac) - SSRI are preferred agents during pregnancy; no apparent risk to fetus [4] - not 1st line in adolescents because of increased riskmfor suicidality in this age group; use only with 'judicious clinical monitoring' [15] - SSRI modestly better than placebo in children & adolecents [75] - escitalopram for treatment of maternal depression, anxiety, irritability & distress may improve children's mood [53] - augmentation of SSRI with lisdexamfetamine somewhat effective [76] - alternative agents - serotonin & norepinephrine reuptake inhibitor (SNRI) - SNRI modestly better than placebo in children & adolecents [75] - augmentation of SNRI with lisdexamfetamine less effective than augumentation of SSRI [76] - patients with anhedonia, abulia, fatigue, or psychomotor retardation should receive treatment with an SNRI rather than an SSRI [96] - atypical antidepressants - venlafaxine (Effexor) - mirtazapine (Remeron) - no sexual dysfunction, stimulates appetite, weight gain [3] - bupropion (Wellbutrin) - no sexual dysfunction, good for overweight [3] - ok to switch from SSRI to bupropion for sexual dysfunction [3] - tricyclic antidepressants (TCA) - therapeutic monitoring may be indicated - non-responders or partial responders - patients at risk for adverse effects include elderly, pregnant, African or Asian descent - desipramine (Norpramine)* - nortriptyline (Aventyl, Pamelor)* - imipramine (Tofranil) - imipramine is ineffective, & even harmful, for treating major depression in adolescents [55] - MAO inhibitors - lithium carbonate diminishes risk of suicide (odds ratio = 0.13) & all-cause mortality (odds ratio = 0.38) in patients with bipolar disease or unipolar depression [36] - intranasal esketamine as adjunctive treatment for treatment-resistant depression (expensive) [3] - aspirin may reduce risk of depression in elderly menwith hyperhomocysteinemia (RR=0.57) [31] - alternative medicine - Hypericum perforatum (St John's Wort) 900-1800 mg/day (divided TID) at least as effective as paroxetine [8,69] - SAMe may be of benefit [70] - in a single trial, curcumin benefit for major depression not statistically significant - no trials of valerian [47] - psilocybin has rapid & long-lasting antidepressant effects [97] - continue medications >= 6 months before tapering - cognitive behavioral therapy (CBT) may aid in maintenance of remission [16] - no reason to add CBT to pharmacologic therapy if in remission (PHQ-9 < 5) - chronic antidepressant therapy - duration of therapy with 1st recurrence of depression: 18-36 months if 2nd episode occurw 18 months after 1st episode [3] - lifetime therapy for patients with > 2 episodes of major depression [5]; including recurrence within 1 year of treatment & suicide attempt - patients > 50 years of age: > 3 years - among patients who felt well enough to discontinue antidepressant therapy, discontinuation associated with higher risk of relapse within 1 year than continuation of therapy (RR=2.1) [92] - 1/3 of patients don't fully respond to standard antidepressant therapy [7] - for partial responders, maximize dose over 4-8 weeks, then add a second agent after 2-3 months only if needed [47] - a partial response does predict increased likelihood of full remission [47] - for non-responders, change to a different agent after 4-8 weeks at optimal dose of single agent [3,29] - of SSRI initial non-responders, number needed to treat for full remission at 16 weeks is 14 [29] - combination therapy for partial-responders - SSRI + bupropion [47] - SSRI + atypical antidepressant - addition of mirtazapine to SSRI or SNRI of no benefit in treatment-resistant depression [85] - SSRI + atypical antipsychotic - best for patients with insomnia, weight loss, anxiety or agitation - no better than SSRI + bupropion [74] - SSRI + anticonvulsant - lamotrigine, carbamazepine, valproate, gabapentin - used as mood stabilizers for bipolar disorder & may be helpful in patients with unipolar depression - SSRI + Li+ may benefit 20-50% of patients - stimulants such as methylphenidate - may help fatigue - may be beneficial for sexual dysfunction - indicated at end of life if prognosis < 6 weeks [3] - fast onset of action - see guidelines for switching antidepressants - benefits of antidepressants - may fall below accepted criteria for clinical significance [14] - effectiveness in demented patients is controversial [25] - escitalopram of no benefit in heart failure [68] - SSRI may have limited or no benefit in patients with chronic renal failure [78] - short-term (16 weeks) antidepressants ineffective [22] - fluoxetine & venlafaxine effective in children & adults, number needed to treat: 4-6 [24]; less so for geriatric patients, number needed to treat: 17-39 [24] - thyroxine may be useful for patients with subclinical hypothyroidism - low-dose estrogen may improve mood in post-menopausal women (see menopause) - refer to psychiatry - lack of response to two or more antidepressants [3] - suicidal or homicidal ideation - psychotic symptoms - evidence of bipolar disorder [3] - decreased depressive facial expression through use of Botox in the glabellar region may be of benefit [26] - vitamin D supplementation does not reduce risk of depression in elderly women [30] - vitamin B6, vitamin B12, & folate supplementation in addition to antidepressants may diminish relapses in depressed patients with elevated serum homocysteine [52] 7) collaborative care administered by depression care managers including an education, engagement & a choice among treatment with medication, cognitive behavioral therapy, or both with regular follow-up superior to usual care [49] - intervention cost roughly $1400 per patient (2014) - centralized data support essential for workflows & quality improvement across multiple sites [67] 8) phototherapy - bright light therapy - alleviates depression +/- seasonal affective disorder - superior to fluoxetine (study in Canada) [57] - adjunctive therapy for non-seasonal depressive disorders [105] - may improve response time to initial therapy 9) pet/animal therapy [9] 10) acupuncture may be of benefit [40] 11) electroconvulsive therapy for refractory depression 12) transcranial magnetic stimulation (TMS) - application of magnetic fields strong enough to alter cerebral cortex neuron firing patterns - applied over left dorsal frontal cortex - effective in controlled trials - repetitive transcranial magnetic stimulation may be effective in depressed patients not responding to initial antidepressant therapy [103,104] 13) transcranial direct current stimulation (tDCS) - in combination with SSRI - more effective than placebo, but alone less effective than escitalopram 14) dietary meausures - Mediterranean diet may reduce risk of depression [84] - coffee with caffeine reduces risk for depression in women - omega-3 fatty acids may be useful 2-9 g/day - a healthy diet may improve symptoms of depression [88] - dietary creatine may lower risk for depression [90] - probiotics may augment effects of antidepressants [99] 15) exercise - of little or no benefit [27,50] - at least moderate benefit [100] - active adults are less likely to be depressed [51] & becoming active may reduce risk of depression - relatively litte physical activity associated with lower risks of depression - 4.4 marginal metabolic equivalent task hours per week ((mMET-h/wk) reduced depression by 18% - 8.8 mMET-h/wk reduced depression by 25% - resistance exercise training could help improve symptoms of depression [81] 16) integrated mental health & primary care can improve overall function [43] 17) prognosis: - 30% of patients in pharmacologically-induced remission reported diminished quality of life, 9% reported severe impairment [48] 18) patient education - daycare for children of depressed mothers may improve emotional well-being of children [37] 19) see screening for depression * 2nd line agents during pregnancy; monitor levels once each trimester [4] 20) Follow-up: - within 1 week of initial presentations - weekly or biweekly for 6 weeks - 3 times within 3 months, one face to face - monthly or bimonthly if patient improving - at least quarterly while patient still on anti-depressant medications

Interactions

disease interactions

Related

adjustment disorder dementia vs delirium vs depression Depression: What Every Woman Should Know diagnostic criteria for depression (DSM IV) dysthymia screening for depression (includes depression assessment tools) Sequenced Treatment Alternatives to Relieve Depression (STAR*D)

Specific

atypical depression depression during pregnancy depression in children & adolescents depression in patients with substance abuse depression in the elderly depression not otherwise specified (DNOS) depressive pseudodementia major depression perinatal depression persistent depressive disorder treatment-resistant depression

General

chronic mental disorder mood disorder sign/symptom

References

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