SSRI Discontinuation and Switching to a Different Class
SSRIs like sertraline should never be discontinued abruptly when switching to a different antidepressant class such as bupropion; instead, the SSRI must be tapered gradually to prevent discontinuation syndrome, and appropriate timing must be observed before initiating the new medication. 1, 2
Why Abrupt Discontinuation is Contraindicated
Discontinuation syndrome occurs frequently with abrupt SSRI cessation, particularly with shorter-acting agents like sertraline, paroxetine, and fluvoxamine. 1 The syndrome manifests with:
- Physical symptoms: Dizziness, fatigue, lethargy, myalgias, chills, headaches, nausea, vomiting, diarrhea, insomnia, imbalance, vertigo, sensory disturbances, and paresthesias 1, 3
- Psychological symptoms: Anxiety, irritability, agitation, crying spells, and confusion 1, 4
Research demonstrates that abrupt discontinuation causes significantly more discontinuation symptoms than tapering (12.0 versus 5.9 DESS events), with symptoms emerging even after missed doses. 5, 6
Proper Tapering Protocol for Sertraline
When discontinuing sertraline at 300 mg daily, reduce to 150 mg once daily before complete discontinuation. 2 For lower doses, the FDA label for bupropion (the switching target) specifies gradual dose reduction rather than abrupt cessation. 2
The taper should occur over at least 1 week for most patients, though some may require longer tapers depending on duration of treatment and individual sensitivity. 1, 5
Critical Timing When Switching to Bupropion
After discontinuing sertraline, no specific washout period is required before starting bupropion, as bupropion is not an MAOI and does not carry the same interaction risks. 2 However, the taper period itself provides natural spacing between medications.
Important contraindication: If the patient were switching to or from an MAOI, at least 14 days must elapse between medications. 2 This does not apply to the sertraline-to-bupropion switch.
Serotonin Syndrome Risk During Transition
Monitor carefully for serotonin syndrome during any overlap period, as bupropion can inhibit cytochrome P450 2D6, potentially increasing SSRI blood levels if medications overlap. 1, 7 Key warning signs include:
- Mental status changes (confusion, agitation, anxiety) 1
- Neuromuscular hyperactivity (tremors, clonus, hyperreflexia, muscle rigidity) 1
- Autonomic hyperactivity (hypertension, tachycardia, tachypnea, diaphoresis) 1
- Advanced symptoms: fever, seizures, arrhythmias, unconsciousness 1
Symptoms typically emerge within 24-48 hours of combining serotonergic medications. 1
Special Considerations for Bupropion Initiation
Start bupropion at 150 mg once daily in the morning, increasing to 300 mg after 4 days if tolerated. 2 The medication should be:
- Swallowed whole (not crushed, divided, or chewed) 2
- Taken in the morning with or without food 2
- Dose-escalated gradually to minimize seizure risk 2
Bupropion is contraindicated in patients with seizure disorders, eating disorders (bulimia/anorexia), or those undergoing abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs. 2
Clinical Advantages of This Switch
Bupropion can reverse SSRI-associated sexual side effects, making it a particularly advantageous choice for patients experiencing sexual dysfunction on sertraline. 3 Additionally, bupropion has a different mechanism (norepinephrine and dopamine reuptake inhibition) that may benefit patients who have not responded adequately to serotonergic agents. 1
Common Pitfalls to Avoid
- Never allow patients to abruptly stop their SSRI, even if they feel well—younger patients are particularly prone to this error 6
- Do not misinterpret early serotonin syndrome symptoms as depression worsening—this can lead to inappropriate medication escalation 7
- Patients who experienced adverse effects early in SSRI treatment are at higher risk for discontinuation syndrome and require extra vigilance during tapering 6
- Ensure patient education about discontinuation symptoms before initiating the taper—lack of knowledge correlates with more severe symptoms 5