gabapentin (Neurontin)

see also:

• neuropathic pain

• gabapentin is a gabapentinoid anticonvulsant neuropathic pain modulator commonly used in patients with chronic pain and those with focal seizures
• 1st approved for use in the United Kingdom in 1993
• pregabalin (Lyrica) is related in structure to gabapentin and has a similar activity and use profile

• commonly used medication for the treatment of neuropathic pain caused by diabetic neuropathy, postherpetic neuralgia, and central pain and appears to help 30-40% of those with diabetic neuropathy or postherpetic neuralgia.
• can be used for anxiety, insomnia and restless legs syndrome that are the result of an underlying illness
• can be used for acquired pendular nystagmus, torsional nystagmus, and infantile nystagmus, however, it does not work in periodic alternating nystagmus
• decreases the frequency of hot flushes in both menopausal women and people with breast cancer.
• reduces spasticity in multiple sclerosis
• moderately effective in reducing the symptoms of alcohol withdrawal and associated craving

• reduce dose in renal disease as it undergoes little or no metabolism
• not effective for generalized seizures
• little or no benefit and significant risk in those with chronic low back pain or sciatica
• not effective in HIV-associated sensory neuropathy[35] and neuropathic pain due to cancer
• ineffective in cocaine dependence and methamphetamine use
• does not appear to provide benefit for bipolar disorder, complex regional pain syndrome, post-surgical pain, or tinnitus,
• does not seem to prevent episodic migraine in adults
• see also adverse effects for patients at risk

• pregnancy
• breastfeeding

• usual adult starting dose 100mg tds
  • consider increase to 300mg tds over 7 days, and if needed, increase by 100-300mg every 5 days to max. 3600mg daily.

• acts by decreasing activity of the α2δ-1 protein, coded by the CACNA2D1 gene, first known as an auxiliary subunit of voltage gated calcium channels
• by binding to α2δ-1, gabapentin reduces the release of excitatory neurotransmitters (primarily glutamate) and as a result, reduces excess excitation of neuronal networks in the spinal cord and brain.
• enhances slow-wave sleep in people with primary insomnia - improves sleep quality by elevating sleep efficiency and decreasing spontaneous arousal.
• when taken in excess, gabapentin can induce euphoria, a sense of calm, improved sociability, and reduced alcohol or cocaine cravings - “the gabbies”

• sleepiness
• dizziness
• nystagmus
• ataxia
• myoclonus
• peripheral oedema
• weight gain - usually ~2kg
• may cause anorgasmia and erectile dysfunction
• may cause pancreatitis
• may cause cognitive issues, hallucinations or delirium
• may increase risk of suicide esp. in those with bipolar disorder or epilepsy
• potential for misuse and physical/psychological dependency
• risk of discontinuation and withdrawal symptoms after prolonged use at higher doses
  • withdrawal symptoms typically occur 1–2 days after abruptly stopping gabapentin
  • eg. agitation, confusion, GIT syptoms, sweating and rarely tachycardia, hypertension, insomnia
• may cause resp. depression esp. if taken together with opioids, benzodiazepines, or other depressants, or by people with underlying lung problems such as COPD
• allergic reactions
• appears to significantly increase risks of developing dementia and mild cognitive impairment although this is a retrospective study which didn't account for dose or length of gabapentin use¹⁾
  • those who had received six or more gabapentin prescriptions were 29% more likely to be diagnosed with dementia and 85% more likely to be diagnosed with mild cognitive impairment within 10 years of their initial pain diagnosis.
  • when the records were stratified by age, 18–64 year olds prescribed the drug were more than twice as likely to develop either condition than those who hadn't been prescribed gabapentin; the risks of dementia more than doubled and those of MCI more than tripled among 35–49 year olds prescribed it.