What is the preferred treatment between lithium (lithium carbonate) and lamictal (lamotrigine) for a patient with post-traumatic stress disorder (PTSD) symptoms?

Neither Lithium Nor Lamotrigine Are Recommended for PTSD Treatment

Neither lithium nor lamotrigine should be used as primary treatment for PTSD symptoms, as trauma-focused psychotherapy (Prolonged Exposure, Cognitive Processing Therapy, or EMDR) is the evidence-based first-line treatment, with SSRIs (sertraline or paroxetine) as the only medications with established efficacy for PTSD. 1

Why These Medications Are Not Appropriate for PTSD

Lithium Has No Evidence for PTSD Treatment

• Lithium is FDA-approved only for bipolar disorder (mania and maintenance therapy), not for PTSD or anxiety disorders 2
• The only published study on lithium for PTSD is a theoretical hypothesis paper from 2013 proposing its use immediately after trauma to prevent PTSD development—this has never been tested in clinical trials and represents speculation, not evidence 3
• Lithium carries significant cardiac risks including bradycardia, T-wave changes, and AV-block, requiring close monitoring 2
• Lithium requires routine laboratory monitoring and is only appropriate when such monitoring is reliably available 2

Lamotrigine Has Minimal and Weak Evidence for PTSD

• Lamotrigine is FDA-approved only for bipolar disorder maintenance treatment, not for PTSD 2
• The evidence for lamotrigine in PTSD consists of one small preliminary study from 1999 with only 14 patients (10 on lamotrigine, 4 on placebo) showing a non-significant trend 4
• Subsequent publications are limited to case reports of 1-2 patients describing effects on anger and aggression, not core PTSD symptoms 5, 6
• The proposed mechanism through glutamate modulation remains theoretical and unproven in PTSD 7

Evidence-Based Treatment Algorithm for PTSD

First-Line Treatment: Trauma-Focused Psychotherapy

• Offer trauma-focused psychotherapy as primary treatment, with 40-87% of patients no longer meeting PTSD criteria after 9-15 sessions 1
• The three therapies with strongest evidence are Prolonged Exposure (PE), Cognitive Processing Therapy (CPT), and Eye Movement Desensitization and Reprocessing (EMDR) 1
• Trauma-focused therapy provides more durable benefits than medication, with lower relapse rates after treatment completion compared to medication discontinuation 1

When to Consider Medication

• Add pharmacotherapy when psychotherapy is unavailable, ineffective, or the patient strongly prefers medication 1
• The only medications with established efficacy are SSRIs: sertraline, paroxetine, or the SNRI venlafaxine 1
• Continue SSRI treatment for 6-12 months minimum after symptom remission, as discontinuation leads to relapse rates of 26-52% 1

Adjunctive Treatment for Specific Symptoms

• For PTSD-related nightmares specifically, add prazosin (starting 1 mg at bedtime, titrating to average effective dose of 3 mg) 1
• Prazosin has Level A evidence specifically for nightmare reduction from the American Academy of Sleep Medicine 1

Critical Medications to Avoid in PTSD

Benzodiazepines Are Contraindicated

• The 2023 VA/DoD guideline strongly recommends AGAINST benzodiazepines for PTSD treatment 1
• Evidence shows 63% of patients receiving benzodiazepines developed PTSD at 6 months compared to only 23% receiving placebo 1
• Benzodiazepines worsen PTSD outcomes and should be avoided entirely 1

Common Pitfalls to Avoid

• Do not use psychological debriefing within 24-72 hours after trauma, as it may be harmful 1
• Do not prescribe medications off-label for PTSD without first attempting evidence-based treatments 1
• Do not assume mood stabilizers used for bipolar disorder will be effective for PTSD—the pathophysiology and treatment response differ fundamentally 2
• Relapse is common after medication discontinuation, requiring longer-term treatment planning 1