How to Start a Patient on Another Antidepressant
When switching antidepressants, discontinue the current medication over 10-14 days to limit withdrawal symptoms, then initiate the new antidepressant using the starting dose and titrate upward every 5-7 days until therapeutic benefits or significant side effects appear. 1
Discontinuation Strategy for Current Antidepressant
- Taper the current antidepressant over 10-14 days to minimize withdrawal symptoms, which is the standard approach recommended for all antidepressant discontinuations 1
- Gradual tapering is particularly important for SSRIs and benzodiazepines to avoid withdrawal symptoms, and for antipsychotics and lithium to prevent rebound worsening of symptoms 1
- The tapering schedule should account for the medication's half-life and receptor profile when transitioning between agents 1
Initiation of New Antidepressant
- Start with the initial recommended dose of the new antidepressant rather than jumping to higher doses 1
- Increase dosage using increments of the initial dose every 5-7 days until therapeutic benefits or significant side effects become apparent 1
- This gradual titration approach prevents excessive dosing and reduces side effect burden 1
Timeline for Adequate Trial
- A full therapeutic trial requires at least 4-8 weeks at an adequate dose before determining efficacy 1
- Do not make premature medication changes, as this prevents adequate assessment of response 2
- The actual antidepressant effects become apparent only after the first week or two of therapy 2
Selection of the New Antidepressant
Base selection on previous treatment response, tolerance, and the advantage of potential side effects (e.g., sedation versus activation) 1
For Patients with Insomnia:
- Consider mirtazapine (starting 7.5 mg at bedtime, maximum 30 mg) as it promotes sleep, is potent and well-tolerated 1
- Alternatively, trazodone (starting 25 mg daily, maximum 200-400 mg in divided doses) can be used 1
- Nefazodone (starting 50 mg twice daily, maximum 150-300 mg twice daily) is effective especially with associated anxiety, though monitor for hepatotoxicity 1
For Patients with Apathy or Low Energy:
- Consider bupropion (starting 37.5 mg every morning, maximum 150 mg twice daily) as it is activating and may produce rapid improvement in energy level 1
- Give the second dose before 3 PM to minimize insomnia risk 1
- Desipramine (starting 10-25 mg in morning, maximum 150 mg) tends to be activating and reduces apathy 1
For Patients with Agitated Depression:
- Consider nortriptyline (starting 10 mg at bedtime, maximum 40 mg daily) as it is more sedating and useful in agitated depression with insomnia 1
Evidence for Second-Step Treatment Strategies
- Switching to another antidepressant, switching to cognitive therapy, or augmenting with medication or cognitive therapy are all reasonable options with similar efficacy 1
- The evidence supports that simply trying a different evidence-based approach is more important than the specific second-step strategy chosen 1
- For augmentation strategies, buspirone or bupropion SR have moderate certainty evidence supporting similar efficacy to switching antidepressants 1
Common Pitfalls to Avoid
- Do not use excessively high starting doses, as this does not hasten recovery and more often results in excessive doses and side effects 2
- Do not assess efficacy before 4-8 weeks at therapeutic dose, as premature changes prevent adequate response assessment 1, 2
- Do not abruptly discontinue the current antidepressant, as this increases withdrawal symptoms compared to gradual tapering 1
- Do not assume all patients need indefinite treatment—after 9 months, dosage reduction can be used to reassess the need to medicate 1