Neurontin (Gabapentin) and Benzodiazepine Withdrawal
By
Dr. Reg Peart
Victims of Tranquilizers
The attached information indicates that the pharmacological properties of neurontin (therapeutic actions, adverse reactions, and withdrawal symptoms) are similar to those of benzodiazepine and other sedative/hypnotic drugs. Neurontin and the benzodiazepines are cross dependent and cross tolerant drugs and therefore neurontin will alleviate adverse reactions and withdrawal symptoms produced by the benzodiazepines.*
Neurontin does not meet all of the criteria needed for use in tapering from benzodiazepine withdrawals. (See the notes on Diazepam vs. Clonazepam) Firstly, it has no active metabolites; secondly, the elimination half life is short and; thirdly, the drug equivalence is not reported for the various therapeutic actions.
The range of the short half life i.e. 5 – 7 hours is small compared with most CNS depressant drugs. For most the upper value is 3 to 5 times the lower value. The limited range quoted may be the result of few studies and could very well be significantly larger. The problem of a short half-life is to some extent overcome by three divided doses/day. With a half life of 7 hours or more accumulation of about times 2 or more can be expected, but with half-lives of 5 hours or less very little accumulation is produced and may cause interdose withdrawals, especially if tolerance occurs.
I have been unable to find the drug equivalence between benzodiazepines and neurontin for the different therapeutic actions but, I have estimated the value from the anticonvulsant action for neurontin and klonopin. This value is 1 gram neurontin is equivalent to about 5 mgs. of klonopin.
From a few reports I’ve had, patients have been prescribed the anticonvulsant dose of neurontin for benzodiazepine withdrawals. This is cause for concern because such a dose is equivalent to high levels of klonopin (5-15mgs) and could lead to difficulty in tapering from neurontin. It would be helpful to have reports of the doses used and any difficulty or otherwise in tapering from neurontin.
Neurontin (Gabapentin)
This information is a summary of that given in about six references including the data sheets published by Parke Davis, the manufacturer of neurontin.
This drug was first marketed in the U.S. in 1981 and in the U.K. in the early 1990’s. It appears that it was marketed after a limited number of controlled clinical trials (a total of only 543 patients) and a series of uncontrolled studies.
Indications/Uses
For treatment of epileptic convulsions and neuropathic pain. Some of the studies reported anxiolytic, muscle relaxant, hypnotic, and amnesic actions.
Cautions
Special procedures are required for diabetics taking neurontin and extreme care if used for patients with renal insufficiency.
Dose
As an anticonvulsant – 900 mgs. – 2,400 mgs./day reached gradually over a few days and given in three divided doses/day (U.K.) Maximum value of 3,600 mgs. (U.S.)
For neuropathic pain – maximum of 1,800 mgs/day reached gradually over a few days given in three divided doses/day (U.K.). Same dose as for anticonvulsant use (U.S.)
Mechanism of Action
Neurontin is structurally related to GABA. Its mechanism of action is unknown, but it appears to increase GABA turnover in several regions of the brain.
Absorption and Fate
Neurontin is not metabolized by the body, i.e., it does not produce active or inactive metabolites. It is eliminated solely by renal excretion. For elderly patients and those with renal insufficiency, the elimination half-life is up to 52 hours. For others it is quoted as 5 – 7 hours.
Adverse Reactions
Drowsiness, dizziness, fatigue, muscle tremor, vision disturbances, indigestion, weight gain, mood changes, hallucinations, decreased kidney function in over 60s, diarrhea, dry mouth, nausea, vomiting, peripheral oedema, anxiety, abnormal gait, amnesia, nystagmus, asthenia, parathesia, abnormal thinking, emotional lability, hyperkinesia, infections (urinary and upper respiratory tract), dysarthria, arthralgia, diplopia, amblyopia, constipation, flatulence, impotence, leucopenia, depression, psychosis, headache, pancreatitis, incontinence, alopecia, allergic reactions, rashes and angioedema, chest pain, palpitations, movement disorders, thrombocytopenia, tinnitus, acute renal failure, purpura, changes in blood pressure, seizures, confusion, impairment of mental alertness, coordination problems, ataxia, coughing, rhinitis, pharyngitis, nervousness, myalgia, back pain, dental abnormalities, puritis, twitching, fever, abdominal pain, confusion, acne, vertigo, decreased or absent reflexes, hostility, variations in blood glucose level.
Dependency Potential and Withdrawal Symptoms
All references warn of avoiding abrupt withdrawal and the use of a tapered withdrawal. Some references suggest the dependency potential is low, but this generally refers to short-term use and that it can significantly increase with long-term use.
Withdrawal symptoms reported include – anxiety, insomnia, nausea, pain, sweating, vomiting, severe and repeated seizures, ataxia, nystagmus, fatigue and dizziness.
*Subject to the limitation that inter-individual response could vary widely.
N.B. 1 gram = 1,000 milligrams