Discontinuing antidepressants: Pearls and pitfalls

Samantha J. Zwiebel; Adele C. Viguera

doi:10.3949/ccjm.89a.21020

Article Figures & Data

Tables

View popup

TABLE 1

Clinical syndromes after discontinuing antidepressants

Condition	Category	Onset, duration	Symptoms
Discontinuation syndrome	Acute withdrawal	Onset 36–96 hours Duration < 6 weeks	New symptoms not present before antidepressant was started or stopped
	Rebound	Onset 36–96 hours Duration < 6 weeks	Greater severity of original symptoms
	Persistent withdrawal syndrome	Onset 24 hours to 6 weeks Duration > 6 weeks	New symptoms and/or greater severity of original symptoms

New episode	Relapse	Onset < 6 weeks Duration variable	Original symptoms at original severity
New episode	Recurrence	Onset > 6 months Duration variable	Original symptoms at original severity

Based on information in reference 9.

View popup

TABLE 2

Discontinuation symptoms by antidepressant drug class

System	SSRIs	SNRIs	TCAs	MAOIs	Atypicals
General	Flu-like symptoms	Flu-like symptoms	Flu-like symptoms	Flu-like symptoms	Flu-like symptoms
	Fatigue	Fatigue	Fatigue	Fatigue
		Diaphoresis			Fatigue

Cardiovascular	Tachycardia	Tachycardia	Tachycardia	Tachycardia	(Limited data)
	Flushing	Hypertension, hypotension Syncope	Arrhythmia	Arrhythmia

Gastrointestinal	Nausea, vomiting	Nausea, vomiting	Nausea, vomiting	Nausea, vomiting	Nausea, vomiting
	Diarrhea	Diarrhea	Diarrhea	Diarrhea	Diarrhea
	Anorexia	Anorexia	Anorexia	Anorexia	Anorexia (mirtazapine)

Neurologic	Headache	Headache	Headache	Headache	Headache
	Gait instability	Gait instability	Paresthesias	Paresthesias	Dizziness
	Dizziness	Dizziness	Tremor, ataxia	Tremor, ataxia	Paresthesias
	Paresthesias, brain zaps	Parasthesias, brain zaps	Seizure	Seizure, myoclonus, muscle jerking	Tremor
	Tremor, ataxia	Tremor, ataxia	Parkinsonism		Dystonia (bupropion)
	Myclonus, muscle jerking	Stroke-like symptoms		Parkinsonism
	Parkinsonism	Seizure, myoclonus, muscle jerking		Dystonia Catatonia

Psychiatric	Anxiety, panic	Anxiety, panic	Anxiety, panic	Depression, lability	Anxiety, panic
	Depression, mania	Depression, mania	Depression, mania	Suicidal ideation	Depression, mania
	Suicidal ideation	Suicidal ideation	Suicidal ideation	Anger, irritability	Suicidal ideation
	Anger, irritability	Anger, irritability	Anger, irritability	Aggression, agitation	Anger, irritability
	Mood swings	Mood swings	Mood swings		Mood swings
	Depersonalization, derealization	Depersonalization, derealization	Derealization	Hallucinations	Depersonalization, derealization
			Hallucinations	Delusions
	Hallucinations	Hallucinations	Delusions

Cognitive	Confusion, delirium	Confusion, delirium	Confusion, delirium	Confusion, delirium	(Limited data)
	Inattention	Inattention	Inattention	Inattention

Sleep	Sleep disturbances	Sleep disturbances	Sleep disturbances	Sleep disturbances	Sleep disturbances
	Nightmares, vivid dreams	Nightmares, vivid dreams	Nightmares, vivid dreams	Nightmares, vivid dreams	Nightmares, vivid dreams

Visual	Vision changes	Vision changes	Vision changes	Vision changes	(Limited data)
Sexual	Dysfunction	Dysfunction	Dysfunction	Dysfunction	Dysfunction

MAOIs = monoamine oxidase inhibitors; SNRIs = serotonin-norepinephrine reuptake inhibitors; SSRIs = selective serotonin reuptake inhibitors; TCAs = tricyclic and tetracyclic antidepressants
Based on information in references 6,7,13,14.

View popup

TABLE 3

Risk factors for antidepressant discontinuation syndrome

Longer duration of treatment

Higher dose of drug

Shorter half-life of drug

Higher receptor affinity of drug

Younger patient age

History of discontinuation symptoms

Abrupt discontinuation

High-risk medication (see Table 4)

Based on information in references 6,7,14,23,24,26,28–32.

View popup

TABLE 4

Risk of antidepressant discontinuation syndrome (ADS): A summary of antidepressant dosing

Risk of ADS	Name (brand name)	Starting daily dose (mg)	Daily dose range (mg)	Typical dose increment (mg) (conservative dose increment)
Low	Bupropion XL (Wellbutrin XL)^a	150	150–450	150
	Doxepin (Silenor)	3	3–6	3
	Fluoxetine (Prozac)^a	10	10–80	10
	Levomilnacipran (Savella)	20	20–120	40 (20)
	Milnacipran (Fetzima)	25	50–300	25–50 (12.5)
	Vilazodone (Viibryd)	10	10–40	10
	Citalopram (Celexa)	10	10–40	10
	Escitalopram (Lexapro)	5	5–30	10 (5)
	Mirtazapine (Remeron)	7.5–15	7.5–60	15 (7.5)

Intermediate	Sertraline (Zoloft)	25	25–300	50 (12.5–25)
	Trazodone (Deseryl)	25–50	25–400	50 (25)
	Vortioxetine (Trintellix)	5	5–20	5
	Amitriptyline (Elavil)	10–25	10–300	50 (10–25)
	Clomipramine (Anafranil)	25	25–300	50 (25)
	Desipramine (Norpramin)	25	25–300	25–50 (10–25)
	Desvenlafaxine (Pristiq)	25	50–400	50 (25)
	Doxepin (Sinequan)	25	25–300	25–50 (10–25)
	Duloxetine DR (Cymbalta DR)	20–30	30–120	30 (20)

High	Fluvoxamine (Luvox)^b	25	25–300	50 (12.5–25)
	Imipramine (Tofranil)	25	25–300	25–50 (10–25)
	Nortriptyline (Pamelor)	10–50	10–150	25–50 (10–25)
	Paroxetine (Paxil)^a	10	10–50	10 (5)
	Phenelzine (Nardil)	15	7.5–90	15
	Tranylcypromine (Parnate)	10	10–60	10
	Venlafaxine ER (Effexor ER)	37.5	75–375	37.5