Alcohol dependence
Oral naltrexone (ReVia®; DuPont) has been available since 1994. Alkermes was granted priority review of its NDA for Vivitrex®, an intramuscular, once monthly naltrexone formulation. A PDUFA date of Sept. 30, 2005, has been established. Vivitrex has reportedly performed well in clinical trials. In one study, it significantly reduced drinking (vs. placebo) even in the 57% of subjects who did not indicate a desire to become abstinent; 85% of subjects who completed this 6-month study elected to receive the monthly injections for another year. The once monthly injection regimen may improve compliance. If approved, a successful launch of Vivitrex will require significant educational and marketing programs because naltrexone has not been widely accepted as a treatment for alcohol dependence. One presentation at ASAM addressed physicians' reluctance to treat alcoholics with naltrexone; physicians cite doubts about the drug's efficacy in alcohol dependence and concerns about side effects and cost. The reluctance to prescribe medications approved for alcohol dependence extends to acamprosate (Campral®, Forest Laboratories), which was approved in July 2004. Campral has been slow to gain acceptance since its approval, despite consistently positive results in Phase III trials (in >5,000 subjects), no known drug interactions, and minor side effects.

Opioid dependence
The acceptance of buprenorphine (Subutex®; Schering-Plough) and buprenorphine + naltrexone (Suboxone®; Schering-Plough) has been growing rapidly among physicians who treat opioid dependence because it allows a much easier withdrawal than methadone (which, itself, has a protracted, difficult withdrawal period). Furthermore, buprenorphine is effective for detox and maintenance therapy. In the U.S., more than 7,200 physicians have been trained in the use of buprenorphine; 4,700 have received the DEA waiver required to prescribe it for opioid dependence. Buprenorphine is also a very effective analgesic; and off-label use for the treatment of pain is increasing.

Prescription drug abuse
According to the 2003 National Survey on Drug Abuse and Health, 6.3 million Americans aged 12 and older currently use prescription drugs for non-medical purposes:

• Pain medications: 4.7 million;
• Sedatives/ tranquilizers: 2.1 million; and
• Stimulants: 1.2 million.

Prescription opioid use has been increasing, in part because these medications--such as Vicodin® (hydrocodone + acetaminophen), OxyContin® (oxycodone, controlled release) and others--are easily obtained illegally from internet sources outside the U.S. According to some observers, opioid addiction is increasing rapidly in the adolescent population, who may obtain prescription drugs from friends, family, or internet. Adult abusers often obtain prescription opioids from (multiple) physicians as treatment for chronic pain or from internet or street sources.

Marijuana dependence
Marijuana is a gateway drug that may lead to other drug use but likely only in people who are predisposed to addiction/dependence. Cannabis use is associated with increased risk of road, rail, and air traffic accidents. Chronic use causes cognitive deficits, particularly verbal IQ deficits, which appear to be mostly reversible with long-term abstinence. Chronic use is also associated with depression. Recent U.S. findings:

• Prevalence of adult marijuana use: 4%;
• Used marijuana last year: 14 million;
• Prevalence of marijuana use among black and Hispanic populations: has risen sharply;
• Age of first use: continues to decline;
• Potency of marijuana: has continued to rise during the last decade--some cannabis plants exceed 15%-20%;
• THC may be detected in urine up to 2 weeks after the last marijuana use.

See Tables 1 and 2. As shown in Table 2, NIDA and NIAA support much of the alcohol and drug dependence research conducted worldwide; the list provided in Table 2 is not comprehensive.

Table 1

Source: D&MD

Table 2

Source: D&MD