A off-label used drug: Gabapentin

Description

Gabapentin might belong to the class of psychoactive drugs, such as antidepressants (eg, tranylcypromine, tianeptine, bupropion), which themselves have no relevant specific addiction potency (sui generis) but could become addictive in patients with another SUD, who look for various options to induce euphoria or improve their affected stress reactivity that occurs following substance addiction.

History

Gabapentin and pregabalin have a long history of use in treating neuropathic pain, having been approved by the Food and Drug Administration (FDA) in 2002 and 2004, respectively, for the indication of neuropathic pain associated with postherpetic neuralgia (PDN; both) and diabetic peripheral neuropathy (DPN; pregabalin only). The first case reports of treatment of refractory neuropathic pain conditions with gabapentin were presented in 1996。 Despite limited supporting evidence and safety concerns, it is widely recommended as a first-line treatment for neuropathic pain, and gabapentin has also become a popular alternative to opioids for pain[1].

Clinical uses

Gabapentin could prevent and control partial seizures. It can be used in adults and children aged 3 and older who have partial seizures. It is also used to treat moderate-too-severe primary restless legs syndrome. Gabapentin is the most commonly prescribed medication for the treatment of chronic musculoskeletal pain in cats. It is used as an adjunct in the treatment of withdrawal symptoms of alcohol, benzodiazepines, cannabis, and opioids or in the treatment of anxiety or agitation in anxiety and affective disorders or dementia.

This drug could relieve nerve pain following shingles in adults. Shingles is a painful rash that develops many years after you've had chickenpox. The virus that causes chickenpox stays dormant in a portion of your spinal nerve root called the dorsal root ganglion[2]. For whatever reason, this otherwise dormant virus gets reactivated — usually by stress — causing a shingles rash. Nerve pain following a case of shingles is called postherpetic neuralgia (PHN).

Renal clearance and hemodialysis

Gabapentin is almost exclusively cleared by the kidney. Therefore, the use of Gabapentin in patients with renal failure is problematic. It could be effectively cleared by hemodialysis. Researchers have found that continuous peritoneal dialysis (PD) provides significant clearance of gabapentin. Gabapentin clearance by PD was estimated at 94% of urea clearance. Hence, intensive PD provides gabapentin clearance that approximates that of urea and is an effective but slow method to treat gabapentin overdose and toxicity[3].

Mechanism of activity

Initially, it was shown that gabapentin acted on neuronal voltage-gated Ca2+ channels (VGCCs), which we now know occurs via the auxiliary α2δ subunit, resulting in decreased presynaptic release of excitatory neurotransmitters. The α2δ-1 subunit is heavily expressed in dorsal root ganglion (DRG) and spinal dorsal horn and is significantly upregulated following nerve injury and correlates with allodynia.26 This key role in neuropathic pain provides a mechanistic rationale for clinical use. Whilst gabapentin also attenuates neurotransmission to inhibitory neurons, preferential inhibition of excitatory neurons has been demonstrated in the substantia gelatinosa of the dorsal horn.

References

[1] Bonnet U, et al. Comment: Gabapentin. Annals of Pharmacotherapy, 2016.

[2 Ibrahim H, et al. Treatment of Gabapentin Toxicity With Peritoneal Dialysis: Assessment of Gabapentin Clearance. American Journal of Kidney Diseases, 2017; 70: 78-880.

[3] Moore A, et al. Gabapentin for Chronic Neuropathic Pain. JAMA, 2018: 285–290.

You may like