Lyrica (Pregabalin) for Depression
Lyrica (pregabalin) is not recommended as a treatment for depression and is not included in any clinical practice guidelines for managing depressive disorders. The standard of care for depression involves second-generation antidepressants (SSRIs, SNRIs, SSNRIs), not anticonvulsants like pregabalin 1.
Why Pregabalin Should Not Be Used for Depression
Lack of Guideline Support
- The American College of Physicians clinical practice guideline for treating depressive disorders specifically recommends second-generation antidepressants (selective serotonin reuptake inhibitors, serotonin norepinephrine reuptake inhibitors, and selective serotonin norepinephrine reuptake inhibitors) as the pharmacologic treatment of choice 1.
- Pregabalin is not mentioned in any established depression treatment algorithms or guidelines 1, 2.
Serious Safety Concerns
- Pregabalin has been associated with worsening depression, development of suicidal ideation, and suicide attempts 3, 4.
- Case reports document patients with previously stable mood who developed depression and suicidal thoughts after starting pregabalin, which improved only after dose reduction or discontinuation 4.
- One case report describes a 20-year-old male who developed severe depressive syndrome and attempted suicide while on pregabalin therapy 3.
Limited and Contradictory Evidence
- The only positive evidence for pregabalin in depression comes from low-quality sources: a single case report suggesting it might work as an augmenting agent 5, and post-hoc analyses showing it reduced depressive symptoms in patients with generalized anxiety disorder (not primary depression) 6.
- One study in lumbar disease patients with comorbid depression showed improvement, but this was in the context of pain management, not primary depression treatment 7.
What Should Be Used Instead
First-Line Treatment
- Start with second-generation antidepressant monotherapy (SSRIs, SNRIs, or SSNRIs), selected based on adverse effect profiles, cost, and patient preferences 1, 8.
Monitoring and Adjustment
- Assess response within 6-8 weeks of optimized therapy at adequate doses 8.
- If inadequate response persists, consider augmentation with FDA-approved agents like aripiprazole 2-20 mg/day 8.
Treatment Duration
Critical Caveat
If a patient is already taking pregabalin for another indication (neuropathic pain, seizures) and develops mood changes or suicidal thoughts, consider pregabalin as a potential cause and monitor closely for deterioration 4.