Phil Newton

From Mouse to Man

Potential Treatments for Alcoholism and Drug Addiction

An introduction to new treatments.

Posted Jan 12, 2009

A lot of work, in both the public and private sectors, is being put into the development of medications to treat alcohol and drug addiction. Here I will give you an overview of ongoing research and highlight some of the most exciting developments.

I recently disagreed with fellow blogger Stanton Peele about the nature of addiction as a treatable disease. I pointed out that there are a couple of medications available to addicts, but had to concede that these don't work for everyone. In summary, I wrote, "these addiction treatments are not perfect, but they do help some patients and form the basis of further research aimed at developing more effective treatments". I thought I would bring you an overview of that research to highlight some of the progress that is being made. In future posts I'll come back to some of these experimental treatments and go over them in detail.

A search of using the keywords "alcoholism" and "treatment" reveals 312 clinical trials. Of these, 137 are currently recruiting participants. A large number of medications are being tested in these trials. To highlight this number and demonstrate their diversity; here's a list of the drugs, with the trade name given in brackets; gabapentin (Neurontin), topiramate (Topamax), varenicline (Chantix), quetiapine (Seroquel), prazosin, zonisamide (Zonegran), mecamylamine (Inversine), LY2196044, modafinil (Provigil), sertaline (Zoloft and others), fluoxetine (Prozac and others), aripiprazole (Abilify), ondansetron (Zofran), nalmefene (Revex), olanzapine (Zyprexa) and others), n-acetylcysteine, org25935, vitamin B1, levetiracetam (keppra), baclofen (Lioresal and Kemstro), Lamotrigine (Lamictal), flumazenil, vanlafaxine (Effexor and others), vigabatrin, clozapine (Clozaril), d-cycloserine, lisdexamfetamine (Vyvanse), SYN115 and amlodipine (Norvasc and others). Thats a lot.

There are also new trials with the established medications; naltrexone (Revia), acamprosate (Campral), methadone, buprenorphine (Subutex) and disulfiram (Antabuse). I should also mention that there are a number of behavioral therapies being tested in clinical trials, including variations on existing therapies and more novel approaches, including yoga. I am a basic scientist tho', so I'll leave discussion of the behavioral therapies to those experts.

Alcoholism and drug addiction are complex, heterogeneous diseases with many different symptoms that affect people in different ways. This heterogeneity is reflected in the nature of the trials being conducted; some are for straight-up heavy drug use, some are specifically designed to treat the alcoholism or drug abuse of patients who have co-occuring disorders such as depression, anxiety, schizophrenia and posttraumatic stress disorder. Other trials are to treat patients who are addicted multiple substances, most commonly to alcohol and another substance such as nicotine or cocaine. There are also trials which are testing combinations of these different test medications together and also combining medications with behavioral therapies.

From this overview we can see some common themes, despite the large number and wide variety of treatments being tested. First, as you can tell by the number of familiar names, a lot of these medications are already approved by the US Food and Drug administration for the treatment of other diseases. This is a plus because it means a lot of the hard/expensive work has already been done for these compounds and positive results obtained in these clinical trials could be rapidly applied.

Secondly, along similar lines, many of these medications are being tested because a patients drug and alcohol problems may be inextricably linked to another disorder against which that medication has shown efficacy. An example of this is the SSRI anti-depressants, which have not shown much promise in the treatment of alcoholism alone, despite extensive testing. However, where that alcoholism occurs with depression, treatment of the depression can have a significant impact on the alcoholism symptoms. The same can be true of anxiety and schizophrenia.

A third common theme is that many of these trials have arisen as a result of positive results obtained in basic science research. As we begin to understand more about the neuroscience of addiction, new treatments suggest themselves. These can be tested in the laboratory and positive results form the basis of proposing clinical trials in people. There are still more questions than answers though.

As a neuroscientist, perhaps the most interesting feature is the abundance of epilepsy medications that are being tested as potential treatments for addiction. From the list above we have Zonisamide (Zonegran), levetiracetam (Keppra), gabapentin (Neurontin), topiramate (Topamax) and lamotrigine (Lamictal). Positive results have also been obtained studies with older drugs like carbamazepine and valropate. Unlike the aforementioned depression/anxiety/schizophrenia drugs which appear to work by treating a disorder that is co-occuring with the addiction, these epilepsy medications appear to work directly on the addiction itself, providing a window into the neuroscience behind addictive disorders. As I said above, scientists gazing through this window currently see more questions than answers; why are epilepsy medications effective? Most of these anticonvulsant treatments seem to work best for alcoholism, where they reduce craving as well as being effective in treating the alcohol withdrawal syndrome. Epilepsy sufferers know that anything more than a few drinks can be dangerous; during their hangover, the risk of seizures is greatly increased as the brain goes through a mild version of withdrawal. In detoxifying alcoholics, this process is more extreme; many need to have their withdrawal managed ina hospital setting as they will suffer full blown seizures (even if they do not also have epilepsy). The fact that epilepsy medications are effective against alcoholism has some scientists speculating that the intense neural activity seen during epilepsy and alcohol withdrawal may also drive the relentless craving that is such a debilitating symptom of drug and alcohol addiction. This neural activity may be "calmed" by treatment with epilepsy medications. The ability of these anticonvulsant drugs to act as mood stabilizers and anxiety medications may also be beneficial in the treatment of addiction.

Hopefully we'll hear a lot more about these drugs in the future. I'll highlight some more of them as new results come out and go into some depth about the neuroscientific basis for their actions. Until then; fingers crossed.

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