Switching from Lexapro to Zoloft: Tapering Recommendations
You should gradually taper Lexapro (escitalopram) before starting Zoloft (sertraline) rather than switching abruptly, to minimize discontinuation symptoms and reduce the risk of serotonin syndrome during the transition period. 1, 2
Rationale for Tapering
Discontinuation Syndrome Risk
Both escitalopram and sertraline are associated with discontinuation syndrome, characterized by dizziness, sensory disturbances (paresthesias, electric shock sensations), anxiety, irritability, confusion, headache, nausea, and emotional lability. 1
Escitalopram discontinuation syndrome occurs frequently (observed in 56% of patients in one study) and can include dizziness, muscle tension, chills, confusion, amnesia, and crying. 3
Abrupt discontinuation of SSRIs produces withdrawal symptoms that are often not tolerated by patients, and these symptoms can be mistaken for relapse of the underlying condition, potentially leading to unnecessary long-term medication use. 4
The FDA label for escitalopram explicitly warns that discontinuation symptoms occur "particularly when abrupt" and recommends "a gradual reduction in the dose rather than abrupt cessation is recommended whenever possible." 2
Serotonin Syndrome Considerations
When combining two serotonergic drugs (including switching between SSRIs), caution is required with starting the second drug at a low dose, increasing slowly, and monitoring for symptoms especially in the first 24 to 48 hours after dosage changes. 1
Serotonin syndrome symptoms include mental status changes (agitation, confusion, delirium), autonomic instability (tachycardia, hypertension, diaphoresis, hyperthermia), and neuromuscular symptoms (tremor, rigidity, hyperreflexia), which can progress to seizures and unconsciousness. 1, 5
Recommended Switching Strategy
Conservative Taper Approach
Gradually reduce escitalopram over several weeks rather than using the commonly recommended 2-4 week taper, as short tapers show minimal benefits over abrupt discontinuation and are often not tolerated. 4
Taper to doses much lower than minimum therapeutic doses before complete cessation, as studies show tapers over months down to very low doses have greater success in reducing withdrawal symptoms. 4
Very slow tapering is recommended for all patients, particularly those on higher doses or with lower drug clearance, as these factors increase the risk of discontinuation syndrome. 3
Avoid alternate-day dosing during tapering, as this approach causes pronounced increases in receptor occupancy variation and likely increases the risk of withdrawal symptoms. 6
Initiating Sertraline
After completing the escitalopram taper, start sertraline at a low dose (25 mg daily as per standard starting dose) and increase gradually. 1
Monitor closely for the first 24-48 hours after starting sertraline for any signs of serotonin syndrome, particularly if there is any overlap between medications. 1
If intolerable discontinuation symptoms occur during the taper, resuming the previously prescribed escitalopram dose may be necessary, followed by a more gradual rate of decrease. 2
Clinical Pitfalls to Avoid
Do not use cross-tapering (simultaneously decreasing one SSRI while increasing another) without clinical expertise, as inappropriate co-administration can result in drug toxicity including serotonin syndrome. 7
Do not mistake discontinuation symptoms for relapse of the underlying depression or anxiety disorder, as this can lead to unnecessary testing and inappropriate treatment decisions. 8, 4
Do not recommend dosing every other day as a tapering strategy, as this creates significant fluctuations in drug levels and receptor occupancy that increase withdrawal risk. 6