Lexapro (Escitalopram) for Depersonalization-Derealization Disorder
Lexapro (escitalopram) is not recommended as a treatment for depersonalization-derealization disorder (DPD), as there is no evidence supporting the efficacy of SSRIs, including escitalopram, for this condition.
Evidence Base for Treatment
The evidence for treating depersonalization-derealization disorder with any pharmacotherapy is extremely limited, and what exists does not support the use of SSRIs like Lexapro:
SSRI Efficacy in DPD
- Fluoxetine, the only SSRI studied in a randomized controlled trial for DPD, showed no efficacy compared to placebo 1
- There was only a trend toward benefit in patients with comorbid anxiety disorder, but this did not reach statistical significance 1
- Conventional antidepressants, including SSRIs, have been found to be of little value in treating depersonalization disorder 2
What Has Limited Evidence
The most promising pharmacological approaches, though still with inconsistent evidence, include:
- Lamotrigine as add-on therapy with SSRIs (not as monotherapy): Open-label trials suggest benefit when combined with SSRIs in a substantial number of patients, though RCT evidence is inconsistent 2, 1
- Opioid receptor antagonists (naltrexone, naloxone): Studies suggest usefulness in at least a subgroup of patients 3, 2
- Clonazepam combined with SSRI antidepressants: Appears beneficial in patients with high levels of background anxiety 2
Clinical Context
If you are considering escitalopram because the patient has comorbid depression or anxiety disorders, then treatment of those conditions is appropriate 4. However, do not expect improvement in the depersonalization-derealization symptoms themselves from the SSRI 2, 1.
Important Caveats
- DPD has a prevalence of 0.8-2% in the general population and typically begins around age 16 with a chronic, continuous course 3
- The disorder is often precipitated by severe stress, depression, panic, or substance use (marijuana, hallucinogens) 3
- Mood and anxiety disorders are commonly comorbid but do not predict symptom severity 3
- No FDA-approved treatments exist for DPD 5
Treatment Approach
Given the lack of evidence-based interventions:
Address comorbid conditions first: If depression or anxiety disorders are present, treat these with standard approaches (SSRIs may be appropriate for these comorbidities) 4, 3
Consider combination therapy if SSRI is used: If an SSRI is initiated for comorbid conditions, consider adding lamotrigine or clonazepam for the depersonalization symptoms specifically 2
Explore alternative pharmacological options: Opioid antagonists (naltrexone) may be considered, though evidence is limited to case series and open-label trials 3, 2
Psychotherapy approaches: Trauma-focused therapy and cognitive-behavioral techniques have been used, though none have established efficacy 3, 6
The quality and quantity of treatment studies for DPD are generally low despite its relatively high prevalence, making this a particularly challenging condition to treat 6.