Switching from Imipramine 200 mg to Lexapro (Escitalopram) in Adolescents
Critical Safety Consideration
Imipramine should be tapered and discontinued in favor of escitalopram, as tricyclic antidepressants have high lethal potential in overdose and are explicitly contraindicated in suicidal adolescents, while SSRIs like escitalopram are the preferred first-line treatment with superior efficacy and safety profiles in this population. 1
Rationale for the Switch
- Tricyclic antidepressants should not be prescribed to suicidal children and adolescents because of their greater lethal potential, particularly dangerous given that youth may have access to their own medications 1
- SSRIs are recommended as the preferred first-line pharmacological treatment for adolescent depression and anxiety, not tricyclic antidepressants, due to superior efficacy and lower toxicity in overdose 1
- Escitalopram is FDA-approved for adolescents aged 12-17 years with depression and has demonstrated significant improvement in depression symptoms compared to placebo in this age group 1, 2
- Tricyclic antidepressants have been shown to be less effective than SSRIs in treating adolescent depression in placebo-controlled studies 1
- Imipramine showed only 44% response rates in adolescents with major depression despite adequate dosing (mean 246 mg/day), suggesting poor efficacy in this population 3
Recommended Taper Schedule
Week 1-2: Initial Imipramine Reduction
- Reduce imipramine from 200 mg to 150 mg daily (25% reduction) 4
- Simultaneously start escitalopram 10 mg daily 1, 2
- Monitor for withdrawal symptoms including dysphoria, irritability, insomnia, anhedonia, or vague sense of being unwell 5
Week 3-4: Continue Imipramine Taper
- Reduce imipramine from 150 mg to 100 mg daily 4
- Continue escitalopram 10 mg daily 2
- Schedule appointments every 2-4 weeks to assess for withdrawal symptoms and potential relapse 5
Week 5-6: Further Imipramine Reduction
- Reduce imipramine from 100 mg to 50 mg daily 4
- Continue escitalopram 10 mg daily 2
- If intolerable symptoms occur, consider extending the time between dose reductions to 4-6 weeks 5
Week 7-8: Final Imipramine Discontinuation
- Reduce imipramine from 50 mg to 25 mg daily for 3-4 days, then discontinue 4
- Continue escitalopram 10 mg daily 2
- Consider smaller dose reductions (5% instead of 10%) if withdrawal symptoms are problematic 5
Week 8 and Beyond: Escitalopram Optimization
- After imipramine is fully discontinued, assess response to escitalopram 10 mg 2
- If inadequate response after 4-6 weeks on escitalopram alone, may increase to 20 mg daily 2
- Continue monitoring for several months after complete imipramine discontinuation for protracted withdrawal symptoms 5
Critical Monitoring During the Switch
- Assess within 1 week of initiation and regularly thereafter, evaluating depressive symptoms, suicide risk, adverse effects, adherence, and environmental stressors 1
- Use the Columbia-Suicide Severity Rating Scale (C-SSRS) to monitor for suicidal ideation and behavior 6, 2
- Document baseline symptoms and functioning before initiating the taper 5
- Be prepared to adjust the tapering schedule based on individual patient response 5
Managing Withdrawal Symptoms
- Consider symptomatic treatments as needed: trazodone or mirtazapine for insomnia, NSAIDs or acetaminophen for headaches and muscle aches, and anti-nausea medications for gastrointestinal symptoms 5
- If severe withdrawal symptoms occur, slow the taper or temporarily increase the imipramine dose before resuming a slower taper 4
Important Caveats
Do not use alternate-day dosing when tapering either medication, as this approach causes pronounced increases in receptor occupancy variation and likely increases the risk of severe withdrawal symptoms 7
The gradual cross-taper approach minimizes both withdrawal symptoms from imipramine discontinuation and allows time for escitalopram to reach therapeutic effect, while prioritizing patient safety by moving away from a medication with high overdose lethality 4, 1.