Can Lyrica (pregabalin) cause low mood or depression?

Can Lyrica Cause Low Mood or Depression?

Yes, Lyrica (pregabalin) can cause low mood and depression, and in some cases may even lead to suicidal thoughts or behavior. 1 The FDA drug label explicitly warns that pregabalin, like other antiepileptic drugs, increases the risk of suicidal thoughts or behavior in patients taking these drugs for any indication.

Evidence from Drug Label and Case Reports

The FDA label for pregabalin 1 includes specific warnings about:

• Suicidal behavior and ideation: Patients taking pregabalin have approximately twice the risk of suicidal thinking or behavior compared to placebo
• Monitoring requirements: Patients should be monitored for emergence or worsening of depression, suicidal thoughts/behavior, or unusual changes in mood
• Warning signs: Symptoms to watch for include thoughts about suicide, new or worse depression, new or worse anxiety, feeling agitated or restless, and other unusual changes in behavior or mood

Several case reports document mood-related adverse effects:

• A review of five patients with neuropathic pain reported changes in mood, depression, and suicidal ideation after starting pregabalin, which improved after dose reduction or discontinuation 2
• A case report described a 20-year-old male who developed severe depression leading to a suicide attempt following pregabalin treatment 3

Risk Factors and Mechanisms

Patients with certain risk factors may be more vulnerable to pregabalin-induced mood changes:

• History of depression or mood disorders (even if stable before starting pregabalin) 2
• Concurrent use of other medications that affect the central nervous system
• Higher doses of pregabalin

Management Recommendations

If a patient on pregabalin develops low mood or depression:

1. Assess severity and safety: Evaluate for suicidal ideation or behavior
2. Consider dose reduction: Lower doses may reduce mood-related side effects while maintaining therapeutic benefit 2
3. Consider discontinuation: If symptoms are severe or persistent, gradual discontinuation may be necessary
   • Important: Do not stop pregabalin abruptly as this can cause withdrawal symptoms including anxiety, insomnia, nausea, headache, and diarrhea 1
   • Taper gradually over at least one week

Alternative Approaches

For patients who need treatment but experience mood-related side effects from pregabalin:

• Consider alternative medications for neuropathic pain such as duloxetine, which has antidepressant properties
• For anxiety disorders, SSRIs or SNRIs may be appropriate alternatives 4
• For seizure disorders, consult with neurology for alternative anticonvulsants

Monitoring Recommendations

For patients taking pregabalin:

• Educate about potential mood-related side effects
• Monitor for changes in mood, especially during the initial treatment period and with dose changes
• Schedule more frequent follow-ups for patients with a history of depression
• Involve family members in monitoring for mood changes when appropriate

Conclusion

While pregabalin is effective for several indications including neuropathic pain, generalized anxiety disorder, and epilepsy, clinicians should be aware of its potential to cause low mood and depression. Careful patient selection, appropriate dosing, and vigilant monitoring can help minimize these risks while maximizing therapeutic benefits.