Gabapentin circulates in the blood largely unbound and is not appreciably metabolized in humans. It is eliminated unchanged by renal excretion and can be removed by hemodialysis. Food only moderately affects the rate and extent of absorption. Clearance is decreased in elderly persons, requiring dosage adjustments. Gabapentin appears to increase cerebral GABA and may inhibit glutamate synthesis as well. It increases human whole blood serotonin and modulates calcium channels to reduce monoamine release. It has antiseizure as well as antispastic activity and antinociceptive effects in pain.

In neurology, gabapentin is used for the treatment of both general and partial seizures. It is effective in reducing the pain of postherpetic neuralgia and other pain syndromes associated with diabetic neuropathy, neuropathic cancer pain, fibromyalgia, meralgia paresthetica, amputation, and headache. It has been found to be effective in some cases of chronic pruritus.

In psychiatry, gabapentin is used as a hypnotic agent because of its sedating effects. It has anxiolytic properties and benefits patients with social anxiety and panic disorder. It may decrease the craving for alcohol in some patients and improve mood as well; hence, it may have some use in depressed patients. Some bipolar patients have benefited when gabapentin is used adjunctively with mood stabilizers.

Adverse effects are mild with the most common being daytime somnolence, ataxia, and fatigue, which are usually dose related. Overdose (over 45 g) has been associated with diplopia, slurred screech, lethargy, and diarrhea, but all patients recovered. The drug is classified as pregnancy category C and is excreted in breast milk, so it is best to avoid it in pregnant women and nursing mothers.

Gabapentin does not interfere with any laboratory tests, although spontaneous reports of false-positive or positive drug toxicology screenings for amphetamines, barbiturates, benzodiazepines, and marijuana have been reported.

Gabapentin is well tolerated, and the dosage can be increased to the maintenance range within a few days. A general approach is to start with 300 mg on day 1, increase to 600 mg on day 2, 900 mg on day 3, and subsequently increase up to 1800 mg per day in divided doses as needed to relieve symptoms. Final total daily doses tend to be between 1,200 and 2,400 mg per day but occasionally results may be achieved with dosages as low as 200 to 300 mg per day, especially in elderly persons. Sedation is usually the limiting factor in determining the dosage. Some patients have taken dosages as high a 4800 mg per day.

Gabapentin is available as 100-, 300-, and 400-mg capsules and as 600- and 800-mg tablets. A 250-mg/5-mL oral solution is also available. Although abrupt discontinuation of gabapentin does not cause withdrawal effects, use of all anticonvulsant drugs should be gradually tapered.

Topiramate has GABAergic effects and increases cerebral GABA in humans. It has 80% oral bioavailability and is not significantly altered by food. It is 15% protein bound, and about 70% of the drug is eliminated by renal excretion. With renal insufficiency topiramate clearance decreases about 50%, so the dosage needs to be decreased. It has a half-life of around 24 hours.

Topiramate is used mainly as an antiepileptic medication and has been found superior to placebo as monotherapy in patients with seizure disorders. It is also used in the prevention of migraine, smoking cessation, pain syndromes (e.g., low back pain), posttraumatic stress disorder (PTSD), and essential tremor. The drug has been associated with weight loss, and that fact has been used to counteract the weight gain caused by many psychotropic drugs. It has also been used in general obesity and in the treatment of bulimia and binge-eating disorder. Self-mutilating behavior may be decreased in borderline personality disorder. It is of little or no benefit in the treatment of psychotic disorders. In one study, the combination of topiramate with bupropion (Wellbutrin) showed some efficacy in bipolar depression, but double-blind, placebo-controlled trials failed to demonstrate topiramate monotherapy efficacy in acute mania in adults.

The most common adverse effects of topiramate include paresthesias, weight loss, somnolence, anorexia, dizziness, and memory problems. Sometimes disturbances in the sense of taste occur. In many cases, the adverse effects are mild to moderate and can be attenuated by decreasing the dose. No deaths have been reported during overdose. The drug affects acid–base balance (low serum bicarbonate), which can be associated with cardiac arrhythmias, and the formation of renal calculi in about 1.5% of cases. Patients taking the drug should be encouraged to drink plenty of fluids. It is not known if the drug passes through the placenta or is present in breast milk, and it should be avoided by pregnant women or nursing mothers.