Gabapentin and pregabalin

Common indications

• Both drugs are used for focal epilepsies (with or without secondary generalisation), usually as an add-on treatment when other antiepileptic drugs (e.g. carbamazepine) provide inadequate control.
• Both drugs are used for neuropathic pain; pregabalin in particular is recommended as a second-line option in painful diabetic neuropathy (after duloxetine) and as a first-line option in other painful neuropathies.
• Gabapentin is used in migraine prophylaxis.
• Pregabalin is used in generalised anxiety disorder.

 

Mechanisms of action

• From a structural point of view, gabapentin is closely related to γ-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the brain. 
• However, its mechanism of action, although not completely understood, appears largely unrelated to GABA. It binds with voltage-sensitive calcium (Ca2+) channels, where it presumably prevents inflow of Ca2+ and, in so doing, inhibits neurotransmitter release. 
• This interferes with synaptic transmission and reduces neuronal excitability. 
• Pregabalin is a structural analogue of gabapentin that probably has a similar mechanism of action.

 

Important adverse effects

• Gabapentin and pregabalin are generally better tolerated than other antiepileptic drugs. 
• Their main side effects are drowsiness, dizziness and ataxia, which usually improve over the first few weeks of treatment.

 

Warnings

• Both drugs depend on the kidneys for their elimination, so their doses should be reduced in renal impairment.

 

Important interactions

• The sedative effects of gabapentin and pregabalin may be enhanced when combined with other sedating drugs (e.g. benzodiazepines). 
• Other than this, gabapentin and pregabalin are notable in having relatively few drug interactions – in stark contrast to most other antiepileptic drugs. 
• This makes them particularly useful where combination regimens are considered necessary.