Can Lyrica (Pregabalin) Cause Depression as a Side Effect?
Yes, pregabalin can cause depression, suicidal ideation, and mood changes as recognized adverse effects, and the FDA explicitly warns that all antiepileptic drugs including pregabalin approximately double the risk of suicidal thoughts or behavior compared to placebo. 1
FDA-Mandated Warning on Depression and Suicidality
The FDA drug label for pregabalin contains a black box-level warning about psychiatric adverse effects:
Pregabalin increases the risk of suicidal thoughts or behavior approximately 2-fold (adjusted Relative Risk 1.8,95% CI: 1.2.7) based on pooled analysis of 199 placebo-controlled trials involving 27,863 patients treated with antiepileptic drugs. 1
The absolute risk translates to approximately one additional case of suicidal thinking or behavior for every 530 patients treated with antiepileptic drugs including pregabalin. 1
This increased risk appears as early as one week after starting treatment and persists throughout the duration of therapy. 1
The FDA mandates monitoring all patients on pregabalin for "emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior." 1
Clinical Evidence of Depression with Pregabalin
Case reports and clinical series document clear temporal relationships between pregabalin initiation and development of depression:
A published case report describes a 20-year-old male who developed severe depressive syndrome following pregabalin medication that progressed to a suicide attempt. 2
An Australian case series of the first 50 patients started on pregabalin for neuropathic pain identified 5 patients (approximately 10%) who developed changes in mood, depression, and/or suicidal ideation shortly after commencing pregabalin. 3
Critically, these patients had histories of depression but their mood had been stable before starting pregabalin, and symptoms improved with dose reduction or cessation, with all five ultimately discontinuing the medication. 3
Postmarketing Surveillance Data
The most commonly reported adverse events in pregabalin overdose and general use include depression/anxiety, confusional state, agitation, and reduced consciousness. 1
Paradoxical Effects Despite Anxiolytic Properties
This represents a clinical paradox, as pregabalin also demonstrates efficacy in treating depressive symptoms associated with generalized anxiety disorder:
Pregabalin reduced depressive symptoms in patients with GAD across multiple dosing ranges (150 mg/day, 300-450 mg/day, and 600 mg/day). 4
However, this does not negate the risk of inducing or worsening depression in susceptible individuals, particularly those with prior psychiatric history. 3
Clinical Management Recommendations
When prescribing pregabalin, you must:
Warn patients explicitly about the risk of mood deterioration, depression, and suicidal ideation before initiating therapy. 1, 3
Monitor closely for psychiatric symptoms, especially in the first few weeks of treatment when risk is highest. 1, 3
Exercise particular caution in patients with any history of depression or psychiatric illness, even if currently stable, as they appear at higher risk. 3
Instruct patients and caregivers to report immediately any emergence or worsening of depression, unusual mood changes, or suicidal thoughts. 1
Consider dose reduction or discontinuation if depressive symptoms emerge, as symptoms have been shown to improve with these interventions. 3
Taper pregabalin gradually over at least one week rather than abrupt discontinuation to minimize withdrawal symptoms including anxiety and mood changes. 1
Common Clinical Pitfall
The major pitfall is assuming that because pregabalin treats anxiety and associated depressive symptoms in GAD, it cannot cause depression. The reality is that pregabalin carries FDA-mandated warnings for inducing depression and suicidality, with documented cases of severe outcomes including suicide attempts. 1, 2, 3 This risk exists independently of its therapeutic benefits in other contexts.