When Sertraline Has Failed: Next Steps in Treatment
If sertraline has not worked adequately, switch to a different SSRI (such as fluoxetine, citalopram, or escitalopram) or consider switching to an SNRI, or add cognitive behavioral therapy (CBT) if not already implemented. 1
Optimizing the Current Trial First
Before abandoning sertraline entirely, ensure the trial was adequate:
- Confirm adequate dosing and duration: Sertraline should be titrated to therapeutic doses (typically 100-200 mg/day for anxiety disorders) and maintained for at least 8-12 weeks to assess full efficacy 1
- Verify adherence: Confirm the patient has been taking the medication consistently 1
- Assess for behavioral activation: Initial anxiety or agitation can occur with SSRIs and may be mistaken for treatment failure; this typically improves with continued treatment or dose adjustment 1
Switching Strategies
Switch to Another SSRI
Alternative SSRIs have similar efficacy but different side effect profiles and may work when sertraline has failed:
- Citalopram/escitalopram: May have the least effect on CYP450 enzymes and lower propensity for drug interactions compared to other SSRIs 1
- Fluoxetine: Longer half-life may be beneficial for patients with adherence issues or discontinuation concerns 1
- Avoid paroxetine: Associated with higher risk of suicidal thinking compared to other SSRIs and more significant discontinuation syndrome 1
Consider SNRIs
- While not extensively studied in pediatric anxiety, SNRIs may have greater effect on pain conditions and could be considered in treatment-resistant cases 1
Combination Treatment Approach
For children and adolescents (6-18 years) with anxiety disorders, combination treatment with CBT plus an SSRI is preferentially recommended over monotherapy:
- The American Academy of Child and Adolescent Psychiatry suggests combination treatment could be offered preferentially for social anxiety, generalized anxiety, separation anxiety, or panic disorder 1
- This recommendation is based on evidence showing combination therapy has superior outcomes compared to either treatment alone 1
Alternative Medication Classes
For Anxiety Disorders:
- Tricyclic antidepressants (TCAs): May be considered but have more significant side effects including anticholinergic effects, sedation, and cardiovascular concerns 1
- Clomipramine: For OCD specifically, clomipramine (a non-selective serotonin reuptake inhibitor) may be more efficacious than SSRIs, though it has a less favorable tolerability profile 1
Important Safety Considerations
When switching medications:
- Avoid combining with MAOIs: Allow at least 2 weeks between discontinuing sertraline and starting an MAOI, or vice versa, to prevent serotonin syndrome 1, 2
- Taper sertraline gradually: Sertraline is associated with discontinuation syndrome characterized by dizziness, fatigue, sensory disturbances, and anxiety 1
- Monitor for serotonin syndrome: When combining serotonergic agents, start at low doses and increase slowly, monitoring especially in the first 24-48 hours after dosage changes 1, 2
Treatment-Resistant Cases
For patients who fail multiple SSRI trials:
- Consider augmentation strategies with atypical antipsychotics or other agents, though evidence in pediatric populations is limited 1
- Intensive CBT protocols (multiple sessions over days) may be beneficial for severe, treatment-resistant cases 1
- Ensure screening for bipolar disorder, as treating unrecognized bipolar depression with antidepressants alone may worsen outcomes 2
Common Pitfalls to Avoid
- Premature discontinuation: Many patients show improvement within 2 weeks, but maximal benefit requires 8-12 weeks 1
- Inadequate dosing: Higher SSRI doses are often needed for anxiety disorders compared to depression, though this must be balanced against increased side effects 1
- Ignoring comorbidities: Presence of other psychiatric conditions may require different treatment approaches 1
- Switching too rapidly: Allow adequate washout periods between serotonergic medications to prevent dangerous interactions 1, 2