Citation

Lavigne JE, Mathews J, Knox KL. J. Pharm. Health Serv. Res. 2010; 1(2): 47-51.

Copyright

(Copyright © 2010)

DOI

10.1111/j.1759-8893.2010.00013.x

PMID

unavailable

Abstract

OBJECTIVES: To describe the challenges in measurement of suicidal thoughts and behaviours and any causal relationship to prescription drug exposures. Recent US Food and Drug Administration (FDA) investigations of potential provocation of suicidal ideation and behaviour have led to black-box warnings of suicidal thoughts and behaviour on drugs ranging from smoking cessation to urinary incontinence agents. We describe the challenges faced in studying the effects of specific drug exposures on suicidal thoughts and behaviours using gabapentin (Neurontin) as an example because it has been implicated by the FDA as a drug that may induce suicidal thoughts or behaviours, offers more than 20 diverse indications including several known to be associated with an increase in suicide risk, and derives its clinical effect from 2 divergent mechanisms. Key findings: Gabapentin has two primary mechanisms: GABAergic neurotransmission and interruption of sodium and calcium channels. An increase in GABAergic neurotransmission is expected to improve anxiety and essential tremor, but to have no effect on pain, specifically migraine and neuropathic pain. Improvements in pain after gabapentin exposure are likely the result of the interruption of calcium and sodium channels. Neither mechanism is expected to affect bipolar disorder or schizophrenia, serious mental illnesses associated with a risk of suicide.

CONCLUSIONS: These two independent mechanisms are expected to have mutually exclusive effects on a wide range of indications, only some of which are associated with increased risk of suicide. This very complexity and heterogeneity may present fertile ground for research aimed at not only improving our understanding of drug action, but also at expanding our knowledge of suicidal thoughts and behaviours. © 2010 The Authors Journal compilation © 2010 Royal Pharmaceutical Society of Great Britain.

Language: en

Keywords

human; suicide; Suicide; bipolar disorder; suicidal ideation; anxiety; chronic pain; suicide attempt; suicidal behavior; Gabapentin; review; substance abuse; priority journal; anxiety disorder; drug mechanism; nonhuman; convulsion; drug safety; seizure; drug efficacy; postherpetic neuralgia; gabapentin; side effect; drug surveillance program; Pharmacology; neuropathic pain; drug exposure; behavioral risk factor surveillance system; off label drug use; provocation; essential tremor; comparative effectiveness; Anti-epileptics; GABAergic transmission; Off-label indications; Post-market surveillance; sodium calcium exchange; US department of veterans Affairs