06/9/14

The Dark Side of a Pill to Cure Addiction

On December 23, 2013, The Wall Street Journal published an article with the provocative title: “A Pill to Cure Addiction?” The article was generally upbeat and positive about the research done at the Scripps Research Institute in La Jolla, California—a well known and reputable research institution. The original research article, “Gabapentin Treatment for Alcohol Dependence” is available in JAMA Internal Medicine. A news release by The Scripps Research Institute, “Clinical Trial Indicates Gabapentin Is Safe and Effective for Treating Alcohol Dependence,” is available on their website.

The study found that “gabapentin significantly improved the rates of abstinence and no heavy drinking.” In the placebo group, the abstinence rate was 4.1%, 11.1% in the 900mg dose group, and 17.0% in the 1800mg dose group. The no heavy drinking rate was 22.5% in the placebo group, 29.6% in the 900mg dose group and 44.7% in the 1800mg dose group.  See the JAMA Internal Medicine abstract for the above data. The subjects who took the highest dose of gabapentin either stopped drinking altogether (17%) or refrained from heavy drinking (45%).

Barbara Mason, the lead researcher, reported in the Scripps Research Institute news release that the high-dose group refrained from heavy drinking twice as often (45% to 23%) and entirely abstained four times as often (17% to 4%) as the placebo group. Patients who received the lower, 900mg dose of gabapentin showed intermediate benefits. She concluded: “I think that we can now have confidence in the pharmacological effect of this drug.”

The WSJ article reflected this positive, upbeat attitude towards gabapentin as a treatment alternative for alcoholism. It also elaborated on the neurochemical mechanism gabapentin is theorized to influence—the brain’s stress response system—specifically CRF (corticotropin-releasing factor). Alcohol or drug use is thought to trigger the brain’s release of CRF in order to help the brain return to normal after the heightened sensation of pleasure from the chemical high. So years of drinking or drug taking are thought to make the brain more sensitive to CRF.

CRF is sometimes referred to as a “misery neurotransmitter.” It is thought to cause the anxiousness felt by addicts, which they “treat” by drinking again or taking more drugs. It also is believed to play a role in the difficulties that alcoholics and addicts have when trying to quit, particularly during situations that heighten feelings of tension and stress.

The neurochemical research into CRF and CRF-related neurotransmitters has an exciting and promising future into this so-called “dark side of addiction.” It seems to have something to say about the acute withdrawal and post acute withdrawal symptoms alcoholics and drug addicts must wrestle with and overcome to establish abstinence. But there is a dark side to gabapentin, the drug proposed to treat this dysregulation of the brain’s stress response system.

A previous blog, “Twentieth Century Snake Oil,” related the sordid, illegal history of how gabapentin became such widely prescribed drug for not just epilepsy and pain, but a slew of non-approved uses such as: anxiety, post traumatic stress, headaches and insomnia. In 2008 the FDA also mandated that anticonvulsant drugs such as gabapentin carry warning labels about the increased risk of suicidal thoughts and behaviors.  A 2010 study confirmed that gabapentin and other anitconvulsants could be associated with an increased risk of suicidal acts or violent deaths.

An article in Psychiatric Times, “The Link Between Substance Abuse, Violence, and Suicide,” indicated that individuals with a substance use disorder are almost six times more likely to report a lifetime suicide attempt than those without a substance use disorder. Emerging research also suggested that a greater severity of recent drinking is associated with the greater likelihood of suicide attempts and successes. Co-occurring alcohol and drug use may also predict a greater likelihood of suicide.

The study by the Scripps Howard Research Institute did not report any serious side effects among the treated patients. But was the presence of serious side effects actively assessed within the study or were they simply noted if reported by the subjects? It should also be pointed out that within the group with the most promising response to the gabapentin treatment, 38% of the subjects were still drinking heavily while using high doses of gabapentin; and another 45% were drinking to some extent while using gabapentin. This alone is clearly contraindicated in the FDA approved Medication Guide for Neurontin (gabapentin).

Medication assisted forms of recovery are all the rage in addiction treatment and research these days. My fear is that well meaning researchers and clinicians could be putting the very people they seek to help at risk with the solutions they propose. This study does not alleviate that fear. Let’s stay tuned for future developments.

Do you think that gabapentin should be used as a treatment for addiction?