The aim - Development of a new long-acting effective medicine for alcoholism treatment.

Alcoholism is the major public health problem facing by many countries. Development of a new effective treatment for alcohol dependence is very important. Worldwide, nearly 140 million people are dependent on or abusing alcohol.

In Europe, about 41 million adults are estimated to abuse or to be dependent on alcohol. Alcohol abuse causes more than 60 types of diseases, the studies say, including liver damage, stomach ulcers and mental health problems. For some European societies, the costs of alcohol abuse and dependence have been calculated to amount to 3% of their gross domestic product.  Based on a scientific review of existing studies the total tangible costs of alcohol to the EU society in 2003 was estimated to be 125 billion Euro,  approximately 1.3% of the EU GDP.

Alcohol abuse and dependence in Russia is a nation-wide problem. Alcohol consumption per capita in Russia is about 14.5 liters of pure ethanol per capita – among the highest in the world.

The total cost of alcohol-related problems is between $10-20 billion a year.There are about 8-9 million people in Russia afflicted with alcoholism.

Methods of treatment of alcohol dependence

The primary objective of the treatment of alcohol dependence is complete abstinence.nAll current methods of treatment of alcohol dependence are largely ineffective: More than 75% of alcoholics relapse within the first year after treatment (begins or ends).

Currently approved pharmacotherapies for alcohol dependence include naltrexone, acamprosate, and disulfiram.

Naltrexone is an opiate receptor antagonist that basically reduces the number of heavy drinking days and the volume of alcohol consumed per drinking day but has a relatively low effect on abstinence. Across studies, only about 30% of alcohol dependent patients medicated with naltrexone remained abstinent within 3 month (of beginning or end).

Acamprosate targets NMDA and GABA receptors in the brain to improve the rate of abstinence. Still, only about 30% of alcohol dependent patients treated with acamprosate remained abstinent withinin 3 months (of beginnig or end of treatment).Disulfiram inhibits acetaldehydedehydrogenase, an enzyme that converts acetaldehyde, the major metabolite of alcohol.     

Disulfiram inhibits acetaldehydedehydrogenase, an enzyme that converts acetaldehyde, the major metabolite of alcohol.  

Supervised disulfiram treatment programs consistently give better outcomes than treatment programs including naltrexone or acamprosate.

Average effect sizes for naltrexone and acamprosate in alcoholism are small - 0.28 and 0.26 respectively, against 0.53 for supervised disulfiram treatment. 
While there are several negative studies of naltrexone and acamprosate, even with good patient compliance, all studies of supervised disulfiram treatment in which patients actually received the planned medication had positive results.

The major problem with disulfiram medication is a poor compliance – that is why disulfiram requires special supervision of taking pills to improve compliance and efficacy of the treatment.

Disulfiram is a medication that makes alcohol effects aversive: Drinking on disulfiram brings about increase of the acetaldehyde concentration in the blood which in its turn causes skin flash, headache, dizziness, hypotension, increased hart rate, breath disturbances, nausea, vomiting, and sometimes even seizures. 

For subjects maintained on disulfiram, drinking alcohol is virtually impossible. nUnlike naltrexone and acamprosate, disulfiram and other similar “aversive” agents provide virtually 100% abstinence if patient compliance is good.

Currently available aversive medications include only oral formulations.

The major problem with the treatment of alcohol dependence with oral aversive medications that must be taken on a daily basis is one of compliance: patients are not taking medication appropriately.

There are also other problems related to the variations of blood levels of medication taken orally and negative effects of the medication on the digestive system.

Primary objective of the project is to develop a sustained release long-acting formulation of aversive medication for alcoholism (medication that inhibits acetaldehydedehydrogenase).

- The rationales for this specific objective are:nAversive medication is the most effective medication for alcohol dependence if properly supervised.

- The major problem with aversive medications for alcoholism is patient compliance.

- There is no long-acting sustained release formulation for disulfiram or any other aversive medication for alcoholism.