Case example
You’re treating a 15-year-old girl with Major Depressive Disorder. She has moderate benefit from a combination of weekly therapy and sertraline. The sertraline dose has had to be titrated slowly because of nausea as a side effect. When the dose was recently increased to 200mg she complained of such severe nausea that she does not want to take it anymore. She is requesting to change medications. Because she had significant symptoms impacting school attendance and academic performance in the past and is now attending school and doing better academically, you are hesitant to taper off sertraline before starting another antidepressant medication.
Switching medications
Not infrequently, a patient does not tolerate or respond to an initial antidepressant trial, leading to a need to change to a different medication. Although the most conservative approach for changing from one antidepressant medication to another is to taper and stop one medication before starting another, most patients who are taking antidepressant medication can be safely cross titrated off the current medication and onto a different antidepressant concurrently, especially if both medications are in the same class. When switching from one selective serotonin reuptake inhibitor (SSRI) to another, it is important to consider the risk of serotonin syndrome. This risk increases when two serotonergic medications are used simultaneously. However, careful dose management during cross-titration can reduce the risk while also preventing withdrawal symptoms and relapse of depressive symptoms.
Withdrawal symptoms are rare in medications with long half-lives and more common in medications with short half-lives. If withdrawal symptoms occur, they typically occur within hours to days of a dosage decrease, abruptly stopping the medication or missing a dose of medication. The most common symptoms related to withdrawal from SSRI and serotonin norepinephrine reuptake inhibitor (SNRI) medications are flu-like symptoms, nausea, lethargy, dizziness, ataxia, “electric shock” sensations also called “brain zaps”, anxiety, irritability, insomnia and vivid dreams.
Certain factors increase the risk of discontinuation symptoms:
· A history of withdrawal symptoms during past medication changes
· Increased anxiety when starting or increasing medication doses
· Taking the medication for longer than six weeks
· Medications with short half-lives (e.g. paroxetine, venlafaxine). Fluoxetine carries a lower risk of discontinuation syndrome because of its long half-life.
The recommendation is to taper the first medication over 4 weeks and reduce the dose by 25% per week if the medication being tapered was taken for an extended time period. The medication can be reduced more slowly if discontinuation symptoms are encountered. The new medication can be titrated up at the same cadence, monitoring the overall dose of both medications. It is important to know the available dose formulations in order to prescribe doses that are achievable. When switching between medications, it is also important to know the pharmacokinetic and pharmacodynamic drug interactions between the two medications. For example, fluoxetine has a long half-life, therefore it can be decreased to 20mg then stopped and still remain in the system for a couple weeks, allowing for a natural taper. For cross-titration from medications that are strong CY2D6 inhibitors (for example fluoxetine and paroxetine) to medications that are primarily metabolized by CY2D6 (for example duloxetine and venlafaxine), a slower titration of the new medication might be needed.
A cross taper from one antidepressant to another can be achieved over the course of 2-4 weeks. From that point it will be important to give enough time to assess for response to the new medication.
Return to case example:
Your patient is at risk for relapse of depressive symptoms and is experiencing side effects from sertraline, therefore a cross-taper is recommended. The recommended cross titration schedule to change to escitalopram is:
Week 1: sertraline 150mg and escitalopram 2.5mg daily
Week 2: sertraline 100mg and escitalopram 5mg daily
Week 3: sertraline 50mg and escitalopram 10mg daily
Week 4: discontinue sertraline and increase escitalopram to 15mg daily. Consider increasing to 20mg over time if needed and tolerated.
References:
1. Keks, N., Hope, J., & Keogh, S. Switching and stopping antidepressants. Aust Prescr. 2016 Jun 1;39(3):76–83.
https://pmc.ncbi.nlm.nih.gov/articles/PMC4919171/ Accessed March 4, 2026.
2. Soreide, K., Ward, K., Bostwick, J. Strategies and Solutions for Switching Antidepressant Medications. Psychiatric Times.
https://www.psychiatrictimes.com/view/strategies-and-solutions-switching-antidepressant-medications. Accessed March 11, 2026
3. Ogle NK, Akkerman SR. Guidance for the discontinuation or switching of antidepressant therapies in adults. J Pharm Pract. 2013;26:389-396.
AUTHOR:
Dr. Melissa Lorang, MD
Child, Adolescent and Adult Psychiatrist
Vista Hill Foundation