Gabapentin is Effective in Alcohol Use Disorder in Patients with Alcohol Withdrawal Symptoms

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Researcher Raymond F. Anton and colleagues reported in the journal JAMA Internal Medicine that compared with placebo, the anticonvulsant medication gabapentin helped people with alcohol use disorders reduce their drinking or abstain from drinking, especially those who had more withdrawal symptoms before treatment.

Ninety-six participants were randomized to receive either placebo or 1200mg/day of gabapentin for 16 weeks.

In the study, 27% of participants who took gabapentin had no heavy drinking days (compared to 9% among those who took placebo) and 18% achieved total abstinence (compared to 4% among those who took placebo). Gabapentin was most effective in those with a history of alcohol withdrawal symptoms. An impressive 41% of participants with high alcohol withdrawal symptoms who took gabapentin achieved total abstinence compared with 1% of participants in the placebo group.

Gabapentin, which is used to treat epilepsy, influences GABA and glutamate transmitters and inhibits the alpha 2gamma-1 voltage sensitive calcium channel, which is upregulated in chronic alcohol exposure.

Alcohol Use Disorders That Begin Before Age 21 May Cause Lasting Changes to Amygdala

October 29, 2019 · Posted in Risk Factors · Comment 

prefrontal cortex and amygdalaIn a 2019 article in the journal Translational Psychiatry, researcher John Peyton Bohnsack and colleagues report that people with alcohol use disorders that began before they were 21 years of age show amygdala changes that people with alcohol use disorders that began after the age of 21 do not appear to have.

The amygdalas of those who began abusing alcohol in adolescence showed greater expression of the long non-coding RNA known as BDNF-AS. The increased BDNF-AS was associated with decreased levels of brain-derived neurotrophic factor (BDNF) in the amygdala. BDNF protects neurons and is important for learning and memory.

According to Bohnsack and colleagues, “Adolescence is a critical period in brain development and adolescent drinking decreases orbitofrontal cortex activity and increases amygdala activity leading to less executive control, more emotional impulsivity, alterations in decision-making, and [a higher risk of engaging] in risky behaviors and develop[ing] mental health problems later in life.”

NAC Reduces Alcohol Cravings, If Not Use

May 23, 2016 · Posted in Potential Treatments · Comment 

alcohol dependence

The antioxidant N-acetylcysteine (NAC) has been found to reduce many types of habitual behavior, from gambling to drug use to compulsive hair-pulling. A recent study by researcher Gihyun Yoon and colleagues, which was presented at a 2015 scientific meeting, found that while NAC and placebo reduced days of heavy drinking by about the same rates, NAC significantly reduced alcohol cravings and quality of life compared to placebo among participants with alcohol dependence.

In the 8-week study, 44 participants aged 18–65 received either 3600mg/day of NAC or a placebo. This dose of NAC was higher than the 600mg–2400mg doses that have typically been used in research settings, and there were few side effects, confirming that NAC is a safe treatment.

The authors are not sure how NAC produces this effect, but it may be by regulating the neurotransmitter glutamate.

New Research on Ketamine

November 4, 2013 · Posted in Current Treatments · Comment 

IV ketamineThe drug ketamine can produce antidepressant effects within hours when administered intravenously.

Finding an Appropriate Control

Comparing ketamine to placebo has challenges because ketamine produces mild dissociative effects (such as a feeling of distance from reality) that are noticeable to patients. At the 2013 meeting of the Society of Biological Psychiatry, James W. Murrough and collaborators at the Mount Sinai School of Medicine reported their findings from the first controlled trial of intravenous ketamine in depression that uses an active control, the short-acting benzodiazepine midazolam, which has sedative effects and decreases anxiety, but is not known as an antidepressant. On virtually all measures intravenous ketamine was a more effective antidepressant following 2 infusions per week.

These data help dispel one of the criticisms of intravenous ketamine, that studies of the drug have not been sufficiently blinded (when patients and medical staff are kept from knowing which patients receive an active treatment and which are in the placebo control group) and that the lack of an appropriate active placebo contributed to the dramatic findings about ketamine’s antidepressant effects. It now appears that these criticisms have been appropriately answered and that intravenous ketamine is highly effective not only in comparison to placebo but also to an active comparator.

This research was presented as a poster at the meeting and published as abstract #442 in the meeting supplement to the journal Biological Psychiatry, Volume 73, Number 9S, and was also published in the Archives of General Psychiatry in 2013.

Slowing Down Ketamine Infusions to Reduce Side Effects

Ketamine is commonly given in 40-minute intravenous infusions. Timothy Lineberry from the Mayo Clinic reported in Abstract #313 from the meeting that slower infusions of ketamine over 100 minutes were also effective in producing antidepressant effects in patients with treatment-resistant depression. Lineberry’s research group used the slower infusion in order to increase safety and decrease side effects, such as the dissociative effects discussed above. In the 10 patients the group studied, they observed a response rate of 80% and a remission rate of 50% (similar to ketamine’s effects with 40-minute infusions).

Family or Personal History of Alcohol Dependence Predicts Positive Response to Ketamine in Depression

Mark J. Niciu and collaborators at the NIMH reported in Abstract #326 that a personal or family history of alcohol dependence predicted a positive response to IV ketamine in patients with unipolar depression.

Ketamine Acts on Monoamines in Addition to Glutamate

Ketamine’s primary action in the nervous system is to block glutamate NMDA receptors in the brain. In addition to its effects on glutamate, it may also affect the monoamines norepinephrine and dopamine. Kareem S. El Iskandarani et al. reported in Abstract #333 that in a study of rats, ketamine increased the firing rate of norepinephrine neurons in a part of the brain called the locus coeruleus and also increased the number of spontaneous firing dopamine cells in the ventral tegmental area of the brain.

Editor’s Note: These data showing that ketamine increased the activity of two monoamines could help explain ketamine’s ability to induce rapid onset of antidepressant effects, in addition to its ability to immediately increase brain-derived neurotrophic factor (BDNF, important for long-term memory and the creation of new synapses) and to restore healthy mushroom-shaped spines on the dendrites of neurons in the prefrontal cortex.

Anticonvulsant Zonisamide (Zonegran) May Treat Alcohol Abuse

April 29, 2010 · Posted in Potential Treatments · Comment 

Albert Arias and collaborators from the University of Connecticut Health Center presented a study of zonisamide in which the drug provided significant benefits over placebo in patients with primary alcoholism (i.e., not with comorbid bipolar illness).  Treatments began at 100 mg/day and increased to a maximum of 500 mg/day.

EDITOR’S NOTE:  If replicated, this study would place zonisamide in a category with topiramate (Topamax), which has also been shown to decrease alcohol intake and craving. Both drugs also share the ability to cause minor weight loss as a potentially positive side effect, and both drugs have also proven effective in double-blind studies in the treatment of bulimia.

However, four double-blind, placebo-controlled studies found that topiramate did not have acute antimanic efficacy. Zonisamide has not been studied in a systematic fashion, but open studies suggest its potential utility in mania and, to a lesser degree, in depression.


Since zonisamide may have positive effects on mood in patients with bipolar disorder, and there is now placebo-controlled documentation of its efficacy in primary alcohol abuse disorders, its ultimate potential utility in patients with bipolar disorder and comorbid alcoholism deserves consideration.

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