The Clinical Moment: Antidepressant Withdrawal Syndrome
At least one-third of patients who stop antidepressants experience withdrawal symptoms. Symptoms may occur within a few days of stopping or dose reduction. Most symptoms resolve within 2 weeks but prolonged and severe symptoms have been reported to last up to months.
Most Common Symptoms | Common Symptoms | Less Common |
Dizziness Fatigue Headache Nausea |
Agitation Anxiety Chills Diaphoresis Insomnia Irritability Myalgias Paresthesias Rhinorrhea Tremor |
Ataxia Electric Shocks Hallucinations - Auditory Halucinations - Visual Hypertension |
Unfortunately, few studies have looked at optimal discontinuation methods. One study compared a taper to abrupt stop and found tapering reduced the rates but did not eliminate the symptoms. Another trial found no difference between a short taper and a long taper. Despite this, most guidelines recommend a slow taper approach.
Considerations that favor tapering could include: anxiety symptoms at onset of antidepressant treatment, higher doses, longer duration at therapeutic doses (> 5 to 8 weeks),no toxicity from current antidepressant treatment, patient prefers self-regulated taper, if withdrawal symptoms occurred previously and short half-life of drug and/or metabolites (<24 hours).
Paroxetine and Venlafaxine carry a greater risk of discontinuation symptoms while citalopram, escitalopram and sertraline have intermediate risks. Fluoxetine has the least risk of symptoms due to its long elimination half life.
Considerations that favor abrupt stopping may be: important new drug may have significant interactions with antidepressant, troubling toxicity related to antidepressant, short treatment duration (<6-8 weeks), pregnancy and the safety profile of antidepressant not established, tapering is prolonging discomfort of withdrawal symptoms and long half-life of drug and/or metabolites.
Before starting antidepressants, patients should be informed of the possibility of withdrawal symptoms. Informed consent would be analogous to initiating long-term opioid therapy as antidepressants are associated with tolerance, dependence and withdrawal symptoms.
Drug | Strategy |
Fluoxetine | Taper over 1-2 weeks |
Citalopram, escitalopram, sertraline | Taper over 2-4 weeks |
Paroxetine | Taper over 3-4 weeks; if difficult taper, switch to fluoxetine 20mg for 1-2weeks, then 10mg 1-2 weeks |
Desvenlafaxine, Duloxetine | Taper over 2-4 weeks |
Venlafaxine | Over 4 weeks, seekly decrease by 37.5-75mg; consider switch to fluoxetine if difficult taper |
Bupropion | Discontinuation symptom uncommon, taper over 2 weeks |
Mirtazapine | Taper over 2-4 weeks |
Trazodone | Taper over 2-4 weeks |
TCAs | Over 2-4 weeks |