Monitoring and addressing adverse responses to starting antidepressants

	Suicidality	Akathisia*	Manic switching^¶	Discontinuation syndrome	Serotonergic syndrome^Δ	Apathy
Symptoms	Thoughts or acts of self-harm	Inner restlessness; sense of being "driven": pacing or movements usually bilateral, symmetrical, often specific muscle groups	Silliness, giggling, angry outbursts, lack of sleep	Fear, dizziness, lethargy, parasthesias, nausea, vivid dreams, insomnia, increased irritability or depression	Confusion, restlessness, agitation, fever, hyperthermia, diaphoresis, hypertonia/clonus (usually symmetrical), tremor, shivering, hyper-reflexia	Disinterest, confusion, lack of enjoyment in previously enjoyed activities; NOT depressed
Incidence	2 percent	5-25 percent	2-70 percent in bipolar depression, but 1-10 percent in unipolar depression (TCA >SSRI)	4-18 percent; shorter half-live antidepressants >longer half-life agents	Rare (<1 percent)
When most commonly occurs	1-4 weeks	2-6 weeks	2-4 weeks, or within weeks of dose increases	Within 1-7 days of stopping, decreasing antidepressant	When multiple serotonergic medications are added or combined	24-78 weeks
Response	Discontinue, monitor resolution of suicidality, consider alternative antidepressant	Consider switch to alternative agent; if very positive response for depression, consider propanolol, or <4 weeks augmentation with clonazapam	Discontinue antidepressant; consider mood stablizers if impairing mania (vs milder hypomanic symptoms); after manic symptoms resolve, if prominent depression, consider alternative antidepressants, but titrate slowly and attempt low doses	Resume antidepressant and titrate down slowly; consider switching/adding long half-life antidepressant (fluoxetine) to allow more gradual taper	Hospital management of hyperthermia, benzodiazepines for seizures or muscle hyperactivity; serotonin antagonists such as cyproheptadine 4-8 mg up to four times a day	Consider augmentation with additional antidepressant, but at low dose (eg, bupropion SR 100 mg every morning)

* Hansek L. A critical review of akathisia, and its possible association with suicidal behavior. Hum Psychopharm Clin Exp 2001; 16:495-505.
¶ Martin A, Young C, Leckman JF, Mukonoweshuro C, Rosenheck R, Leslie D. Age effects on antidepressant-induced manic conversion. Arch Pediatr Adolesc Med 2004;158:773-780.
Δ Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-20.

Reproduced with permission from: Rappaport, N, Bostic, JQ, Prince JB, Jellinek, M. Treating pediatric depression in primary care: Coping with the patients' blue mood and the FDA's black box. J Pediatr 2006; 148:567. Copyright ©2006 Elsevier.

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Monitoring and addressing adverse responses to starting antidepressants