Wendy Leith



Document Type


Degree Name



Department of Public Health and Preventive Medicine


Oregon Health & Science University


Importance: Gabapentin is an antiepileptic drug (AED) commonly used in the treatment of bipolar disorder (BPD). In 2008, the US Food and Drug Administration (FDA) concluded that it is associated with an increased risk of suicidality; however, published studies have arrived at conflicting conclusions.

Objective: To assess the association between the use of gabapentin and suicidality in a cohort of adult patients diagnosed with bipolar disorder (BPD), and to determine if the risk is greater relative to patients prescribed lithium.

Design: This is a retrospective observational study utilizing US population-based claims data assembled by PharMetrics, Inc. between 2000 and 2006.

Setting: Data were collected from US insurance claims data, and comprise patients treated in both clinical and hospital settings.

Participants: The database comprises 47,918 patients diagnosed with BPD who had two years of continuous healthcare coverage (one year before and after BPD diagnosis). Subjects were included in this analysis if they were at least 18 years old and initiated a new monotherapy prescription of either gabapentin (n=2,421) or lithium (n=3,101). For this analysis, subjects were followed for up to one year after medication initiation.

Main Outcome and Measure: Suicide attempt or self-harm (SA/SH) as defined by ICD-9 codes E950-E959.

Results: Gabapentin patients contributed 915.8 person-years (PY), while lithium patients contributed 1,421.3 PY. A total of 37 SA/SH events were identified; 21 (0.9%) in the gabapentin group and 16 (0.5%) in the lithium group (p=0.13). The unadjusted incidence rates were 22.9 and 11.3 per 1,000 PY in the gabapentin and lithium groups, respectively (p=0.03). After adjusting for concomitant medications, comorbid diagnoses, age, sex, and history of SA/SH, the hazard ratio (HR) was 2.3 (95% CI [1.2, 4.5]). Sensitivity analyses support this finding, with an adjusted HR of 1.9 (95% CI [0.9, 3.8]) among patients without a history of SA/SH, and 2.1 (95% CI [1.02, 4.5]) in a propensity score-matched analysis accounting for pre-existing illnesses and medications.

Conclusions and Relevance: The use of gabapentin is significantly associated with suicidality in patients diagnosed with bipolar disorder. Even after adjusting for significant confounders, bipolar patients treated with gabapentin have twice the risk of suicidality as compared to patients treated with lithium. Sensitivity analyses support this conclusion. Gabapentin should not be prescribed for the treatment of bipolar disorder.




School of Medicine

Available for download on Friday, December 28, 2018