Posted by SLS on June 3, 2009, at 12:32:21
If anyone has read my reposts, they will recall that I posited that withdrawal from SSRIs might include a kindling phenomenon, and that using an anticonvulsant might mitigate withdrawal symptoms.
The first abstract is an example of the successful use of an anticonvulsant - gabapentin (Neurontin) to mitigate alcohol withdrawal.
The second abstract bolsters the theories I laid out in posts which can be reviewed in the reposts.
The importance of these two abstracts combined with my theories is that a kindling phenomenon might be involved with SSRI and SNRI withdrawal syndromes, and would explain a great deal of what we observe upon the discontinuation of these drugs, especially if it occurs multiple times. In addition, it provides a rationale for using anticonvulsant drugs to mitigate withdrawal symptoms.
- Scott
*********************************************************************************A Double-Blind Trial of Gabapentin Versus Lorazepam in the Treatment of Alcohol Withdrawal
Hugh Myrick, Robert Malcolm, Patrick K. Randall, Elizabeth Boyle, Raymond F. Anton, Howard C. Becker, and Carrie L. Randall
From the Ralph H. Johnson Department of Veterans Affairs Medical Center (HM, HCB), Research and Development Service, Charleston, South Carolina; and Department of Psychiatry and Behavioral Sciences, Alcohol Research Center, Medical University of South Carolina (HM, RM, PKR, EB, RFA, CLR), Charleston, South Carolina.
Correspondence to Reprint requests: Hugh Myrick, MD, Institute of Psychiatry 4N, MUSC, 67 President Street, Charleston, SC 29425; Fax: 843-792-7353; E-mail: myrickh@musc.edu
Copyright © 2009 Research Society on Alcoholism
KEYWORDS
Gabapentin Alcohol Dependence Alcohol Withdrawal Lorazepam
ABSTRACTIntroduction: Some anticonvulsants ameliorate signs and symptoms of alcohol withdrawal, but have an unacceptable side effect burden. Among the advantages of using anticonvulsant agents in this capacity is their purported lack of interaction with alcohol that could increase psychomotor deficits, increase cognitive impairment, or increase intoxication. The aim of this study was to evaluate alcohol use and symptom reduction of gabapentin when compared with lorazepam in the treatment of alcohol withdrawal in a double-blinded randomized clinical trial.
Methods: One hundred individuals seeking outpatient treatment of alcohol withdrawal with Clinical Institute Withdrawal Assessment for AlcoholRevised (CIWA-Ar) ratings =10 were randomized to double-blind treatment with 2 doses of gabapentin (900 mg tapering to 600 mg or 1200 tapering to 800 mg) or lorazepam (6 mg tapering to 4 mg) for 4 days. Severity of alcohol withdrawal was measured by the CIWA-Ar on days 1 to 4 of treatment and on days 5, 7, and 12 post-treatment and alcohol use monitored by verbal report and breath alcohol levels.
Results: CIWA-Ar scores decreased over time in all groups; high-dose gabapentin was statistically superior but clinically similar to lorazepam (p = 0.009). During treatment, lorazepam-treated participants had higher probabilities of drinking on the first day of dose decrease (day 2) and the second day off medication (day 6) compared to gabapentin-treated participants (p = 0.0002). Post-treatment, gabapentin-treated participants had less probability of drinking during the follow-up post-treatment period (p = 0.2 for 900 mg and p = 0.3 for 1200 mg) compared to the lorazepam-treated participants (p = 0.55). The gabapentin groups also had less craving, anxiety, and sedation compared to lorazepam.
Conclusions: Gabapentin was well tolerated and effectively diminished the symptoms of alcohol withdrawal in our population especially at the higher target dose (1200 mg) used in this study. Gabapentin reduced the probability of drinking during alcohol withdrawal and in the immediate postwithdrawal week compared to lorazepam.
Received for publication September 10, 2008; accepted April 8, 2009.
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1: Alcohol Health Res World. 1998;22(1):25-33.Links
Kindling in alcohol withdrawal.
Becker HC.Department of Psychiatry and Behavioral Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
In many alcoholics, the severity of withdrawal symptoms increases after repeated withdrawal episodes. This exacerbation may be attributable to a kindling process. Kindling is a phenomenon in which a weak electrical or chemical stimulus, which initially causes no overt behavioral responses, results in the appearance of behavioral effects, such as seizures, when it is administered repeatedly. Both clinical and experimental evidence support the existence of a kindling mechanism during alcohol withdrawal. Withdrawal symptoms, such as seizures, result from neurochemical imbalances in the brain of alcoholics who suddenly reduce or cease alcohol consumption. These imbalances may be exacerbated after repeated withdrawal experiences. The existence of kindling during withdrawal suggests that even patients experiencing mild withdrawal should be treated aggressively to prevent the increase in severity of subsequent withdrawal episodes. Kindling also may contribute to a patient's relapse risk and to alcohol-related brain damage and cognitive impairment.
poster:SLS
thread:899208
URL: http://www.dr-bob.org/babble/wdrawl/20081229/msgs/899208.html