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Author: Admin | 2025-04-28
High treatment failure rates make it critical for prescribers to know how to safely and effectively switch antidepressants to ensure patient-treatment targets are met.TABLE 1. Receptor activities and symptoms of abrupt discontinuationTABLE 2. Advantages and disadvantages of various switching strategiesTABLE 3. Guide for switching antidepressantsOne of the most common questions regarding antidepressants involves strategies for switching medications. This is not surprising, considering that results from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial drew attention to the high rates of initial treatment failure with first-line agents.1 More specifically, up to 65% of patients fail to achieve remission, and approximately half of all patients fail to achieve an adequate response from their first antidepressant medication trial. High treatment failure rates make it critical for prescribers to know how to safely and effectively switch antidepressants to ensure patient-treatment targets are met.Understanding drug interactionsThere is limited guidance on the efficacy and tolerability of various switch strategies, which makes it essential that providers have a strong foundation in the pharmacological properties of antidepressants to understand how pharmacokinetic and pharmacodynamic drug interactions affect patients during the switch period. For example, if a patient is completing a cross-taper to transition from an antidepressant that is a potent inhibitor of the cytochrome 450 metabolizing enzyme 2D6 (CYP2D6) (eg, bupropion, fluoxetine, paroxetine) to a new antidepressant metabolized primarily by CYP2D6, the serum concentration of the new medication will be elevated by the CYP2D6 inhibitor until the first medication is eliminated. This leads to slower titration of the second antidepressant.An example of a pharmacodynamic drug interaction is the required 2-week antidepressant-free period after stopping an MAOI because of the risk of serotonin syndrome and hypertensive crisis from accumulated synaptic monoamines. Furthermore, providers must consider the severity of their patient’s mood symptoms and weigh it against the concern of adverse drug events. This may lead to a more rapid switch in the hope of realizing benefit from the new medication as quickly as possible.Discontinuation syndromeDiscontinuation syndrome can occur upon abruptly stopping or rapidly lowering the dose of an antidepressant. Symptoms of discontinuation syndrome associated with various neurotransmitter and receptor systems are summarized in Table 1. Withdrawal phenomena need to be considered based on the pharmacology of how specific antidepressant medications affect serotonergic, adrenergic, histaminergic, and cholinergic activity. For example, TCAs have significant anticholinergic properties. Therefore, rapid withdrawal of these agents may precipitate cholinergic rebound, which can be associated with vomiting, nausea, headache, sweating, and muscle spasms. Cholinergic rebound can also apply to other antidepressants with anticholinergic properties that may be discontinued abruptly, such as paroxetine.2Prescribers should focus on the pharmacology involved rather than on specific medication classes, as differences in pharmacology of drugs in the same class can be significant enough to induce disparate withdrawal syndromes. Another example of this might be abrupt discontinuation of SNRIs, which can result in serotonergic withdrawal in addition to increased gastrointestinal motility and urinary urgency due to loss of noradrenergic effects.In the case of rapid discontinuation of mirtazapine, reports include hypertension, tachycardia, insomnia,
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