Pregabalin (Lyrica) Has No Established Role in Treating Depression
Pregabalin is not indicated for depression treatment and carries FDA warnings about increased risk of suicidal thoughts and behavior. 1
FDA-Approved Indications and Depression Risk
Pregabalin is FDA-approved exclusively for neuropathic pain conditions (diabetic peripheral neuropathy, postherpetic neuralgia) and fibromyalgia—not for any psychiatric indication including depression. 2, 1
The FDA drug label explicitly warns that pregabalin, as an antiepileptic drug (AED), approximately doubles the risk of suicidal thinking or behavior compared to placebo (adjusted Relative Risk 1.8). 1 This increased risk:
- Appears as early as one week after starting treatment 1
- Persists throughout treatment duration 1
- Applies across all AED indications regardless of mechanism 1
Clinical Evidence on Mood Effects
Case reports and clinical observations document that pregabalin can precipitate or worsen depression and suicidal ideation, even in patients with previously stable mood. 3, 4
- A case series of five patients with stable pre-existing depression developed new or worsening depression and suicidal ideation after starting pregabalin for neuropathic pain, which improved only after dose reduction or discontinuation 4
- A documented case of severe depressive syndrome leading to suicide attempt occurred following pregabalin initiation 3
Animal studies show pregabalin is ineffective for depressive symptoms: chronic pregabalin treatment ameliorated pain but failed to improve depressive-like behaviors in a validated myalgia model. 5 Only acute (not chronic) administration showed any antidepressant-like effects, which is clinically irrelevant for depression treatment requiring sustained response 5
Guideline-Recommended Alternatives
For patients with co-occurring chronic pain and depression, guidelines specifically recommend antidepressants with dual analgesic properties—not pregabalin. 2
The evidence-based approach prioritizes:
- SNRIs (duloxetine) for neuropathic pain, fibromyalgia, and comorbid depression 2
- Tricyclic antidepressants for neuropathic pain with depression (though use cautiously in older adults due to anticholinergic effects) 2
These antidepressants provide documented benefit for both pain and mood, whereas pregabalin addresses only pain while potentially worsening psychiatric symptoms 2
Critical Clinical Pitfall
The most dangerous error is assuming pregabalin's anxiolytic properties translate to antidepressant effects—they do not. 6, 7 While pregabalin has proven anxiolytic activity for generalized anxiety disorder 7, this mechanism does not confer antidepressant efficacy and may paradoxically increase depression risk 1, 3, 4
Monitoring Requirements If Pregabalin Is Used
When pregabalin is prescribed for its approved pain indications in patients with any psychiatric history, mandatory monitoring includes assessment for emergence or worsening of depression, suicidal thoughts, or unusual mood changes at every visit. 1