When patients fail to respond to a particular antidepressant, or exhibit side effects, and a trial of another antidepressant is indicated, the clinician must be familiar with the pharmacology of the drug that is being discontinued, the potential for drug-drug interactions, and the time to onset of effectiveness of the new medication. Similarly, when antidepressants are being discontinued after a therapeutic course, care must be taken to avoid precipitating an antidepressant withdrawal syndrome. These issues are addressed in this topic. Indications for switching or stopping antidepressants, general information about the treatment of depression and individual medications, and the prognosis of depression are discussed separately (see "Unipolar major depression in adults: Choosing initial treatment" and "Serotonin-norepinephrine reuptake inhibitors (SNRIs): Pharmacology, administration, and side effects" and "Tricyclic and tetracyclic drugs: Pharmacology, administration, and side effects" and "Monoamine oxidase inhibitors (MAOIs) for treating depressed adults" and "Unipolar depression in adults: Course of illness" and "Unipolar depression in adults: Treatment of resistant depression").
SWITCHING ANTIDEPRESSANT MEDICATION
There are several issues to consider when switching a patient from one antidepressant to another, to avoid drug toxicity or re-emergence of depression symptoms.
Cross-tapering — For many drug switches, cross-tapering is the best technique to assure that the patient's depression is not unmasked from rapid drug withdrawal, while minimizing the risk of drug-drug interactions. In a cross-taper, the dose of the current antidepressant is gradually reduced, over a one to two week period or longer, while the dose of the antidepressant being initiated is gradually increased to therapeutic range over the same time period.
Switching between SSRIs — This is generally the simplest antidepressant switch. Selective serotonin reuptake inhibitors (SSRIs) overlap in their mechanism of action, and the new SSRI will usually prevent discontinuation symptoms that may occur when the first SSRI is stopped. Substituting a new SSRI at the relatively equivalent dose of the former SSRI is typically well-tolerated (table 1), though starting the new SSRI at a lower dose may also be considered since patients occasionally have idiosyncratic side effects to particular SSRIs.
Switching from SSRI to TCA — The most common method used to switch from an SSRI to a tricyclic antidepressant (TCA) is a cross-taper (see 'Cross-tapering' above). It is important to remember that fluoxetine and paroxetine are strong inhibitors of the p450 enzyme 2D6 (sertraline, citalopram, and escitalopram are significantly milder inhibitors). This enzyme is involved in the metabolism of many TCAs and inhibition will cause an increased TCA blood level (in some cases, several-fold higher), which can result in toxicity. Because of this, TCAs should be started at low doses when cross-tapering with an SSRI, particularly with fluoxetine and paroxetine; TCA blood levels can be checked during this period for added safety.