Nejm 2008;358:55; Ann IM 2001;134:47; 2000;343:1942
Cause:Partially genetic—monozygotic twin concordance studies indicate heritability of ~37%.
Pathophys:Polymorphic variation at serotonin transporter region confers some predisposition. Various neurotransmitters involved: serotonin, norepinephrine, inositol
Increased incidence in postpartum female, late middle age and elderly, pts w family h/o alcoholism. Major depressive disorder onset in teens and 20s w recurrence in adulthood in 2/3 (Jama 1999;281:1707). Lifetime incidence 12-20%
Sx:
Major depressive d/o (MDD): >2 wk of depressed mood or loss of interest with 4 other neurovegetative sx—appetite change, sleep disturbance, guilt, decreased energy, decreased concentration, or suicidal ideation, withsignificant impairment in functioning. In children and adolescents, depression usually irritable.
Depressive d/o not otherwise specified (NOS): Some of the above depressive features, but does not meet criteria for MDD
Somatic complaints alone or w complaints of depression, guilt, and other psychological sx (Nejm 1999;341:1329)
Ask re suicidal thoughts (no incr risk of precipitating those thoughts if ask—Jama 2005;293:1635), previous suicide attempts, sleep disturbance lasting 
2 wk, guilt feelings 2 wk, hopelessness (1 or more such sx have an 84% sens—Jama 1994;272:1757)
Si:Flat affect, sad, irritable, panic attacks; psychomotor retardation or agitation, weight changes, disheveled
50-85% have a recurrence (APA Practice Guideline, 2000)
Suicide in up to 15% (Ann IM 2002;136:302); alcoholism or other substance abuse, mania; lower bone mineral density in women (Nejm 1996;335:1176), job/familial disruptions.
r/o secondary causes like prescription drug side effects (long list—Med Let 2002;44:59), stress, bereavement, illness, alcohol/illicit drug use; SEASONAL AFFECTIVE DISORDER (SAD) (Jama 1993;270:2717) and vit D deficiency (Jama 1993;270:2717); M/F = 1:3-4, esp in northern climes in winter; sx of lethargy, increased sleep, decreased libido, weight and appetite changes; rx w 30 min tid 10 000 lux light box ($400), or × 2 h qd (Can J Psych 1995;40:457; Am Fam Phys 1988;38:173), or get outdoors at noon. Found to be equally efficacious to pharmacotherapy (Am J Psych 2005;162:656). Many pts may have latent bipolar d/o and rx may precipitate mania
Rx:
Preventive evaluation and rx of alcohol use, suicidality (Jama 2004;291:1887; Nejm 1997:337:910)
Psychotherapy as good as meds and provides additive benefit to drug rx (Jama 2004;292:807 [adolescents]; Nejm 2000;342:1462; Arch Gen Psych 1999;56:829), meds needed for moderate to severe.
Medications (Ann IM 2001;134:47) (Antidepressants); rx for 6 mos after remit (Am J Psych 1998;155:1247):
- 1st: SSRIs, 1st-line, acute phase rx 6-12 wk, continuation phase rx 4-9 mos, maintenance rx 1+ years (Ann IM 2008;149:725); after 6-9 mo successful rx, maintenance reduces recurrence from 25% to 5% (NNT-1 = 5 by DBRCT—Jama 1998;280:1665); adjunctive benzos for 1st 4-6 wk helpful (J Affect Disord 2001;65:173); work in children and adolescents too (Jama 2004;292:807; 2003;290:1033) but FDA Black Box warning regarding suicide
- 2nd: Venlafaxine (Effexor), Buproprion (Wellbutrin)
- 3rd: TCAs or MAOIs
- 4th: Electroshock therapy q 2-3 d × 2-3 wk is most effective antidepressant, esp if suicidal or elderly (Nejm 2007;357:1939); very safe; follow w lithium + nortriptyline to maintain (Jama 2001;285:1299); only relative contraindication is intracranial mass; adv effects: transient memory loss
- others: T3 (Cytomel) 25-50 µg po qd as adjunct to SSRIs or TCAs
- in menopausal women: Estrogens; NNT = 3 (Arch Gen Psych 2001;58:529)
- in postpartum depression: SSRIs or TCAs (Nejm 2002;347:196) in pregnancy: careful weighing of risk/benefit, avoid paroxetine, all SSRI may induce neonatal withdrawal syndrome when used in 3rd trimester (Jama 2005; 293:2372)