Addiction treatment, novel but unproved

The drug treatment first raised eyebrows several months ago with its provocative marketing campaign. Featuring deceased comedian Chris Farley and the message “It wasn’t all his fault,” the billboard, radio and Internet advertisements were a bold departure from the often understated ads used to market addiction treatment.

But since then, it’s been the therapy itself, known as Prometa, that has caught the attention of the public and the medical community alike, drawing both anecdotal reports of success and sharp criticism.

The philosophy of Hythiam, the small Santa Monica company that developed the treatment, is that drug addiction is a brain-based disorder that cannot be overcome by willpower alone. That belief isn’t unusual, but the company maintains that three specific medications -- used in a certain sequence and dosage -- can treat brain dysfunction and break addictions to alcohol, cocaine and methamphetamine.

Doctors using Prometa “have never seen anything this dramatic,” says Terren Peizer, Hythiam’s chairman and chief executive. “This is changing the way we approach this disease.”

The drugs aren’t approved for addiction treatment, and the company makes doctors who use their method sign a disclosure agreement promising not to divulge details. The company also charges up to $15,000 for the two to five outpatient visits that form the core of the treatment.

Critics point out that no randomized studies pitting Prometa against standard treatment or a placebo have been done to show that the method is safe, or useful, in helping addicts achieve sobriety.

“Controlled studies where participants have paid similar amounts of money and have equally high expectations of treatment have not been completed or published,” says Dr. Lori D. Karan, a researcher in the Drug Dependence Research Laboratory at UC San Francisco. She suggests there is a high likelihood of a strong placebo effect.

Prometa’s secrecy and lack of a track record worry doctors.

“They are using a procedure that has yet to be proven effective, charging an inordinate amount of money and making promises they are not able to keep,” says Dr. Rick Chavez, medical director of the Pain Institute in Redondo Beach. He says some of his patients tried the Prometa approach and relapsed.

Hythiam officials and proponents of Prometa say critics are worrying needlessly. Not only are no promises made, they say, more than 1,000 of people in the United States have safely undergone the treatment. They say word-of-mouth reports show it works where most other treatments have failed.

An outpatient treatment

Peizer launched Hythiam three years ago after searching worldwide for a better way to treat drug addictions. Although he has no background in addiction treatment, Peizer was looking for an investment opportunity and was intrigued by the idea that addictions could be treated with medications. Before starting Hythiam, he directed several other science or biotechnology companies.

Prometa is based on research by a Spanish doctor who believed that medications that control the gabaminergic system of the brain could help break addictions. The treatment involves administration of an intravenous medicine, flumazenil, and two oral drugs, gabapentin and hydroxyzine, in an outpatient setting. The patient also receives vitamins and minerals and is urged to begin traditional psychosocial counseling and group support meetings to augment recovery.

The medications, which are approved by the Food and Drug Administration for treating other disorders but not drug addiction, are aimed at quieting cravings and improving mental clarity, Peizer says.

Hythiam has applied for a patent to protect its unique use of the three medications and the specific dosing regimen. The company licenses the protocol to addiction treatment centers or doctors for a fee and, so far, has about 45 licensees nationwide, Peizer says.

Peizer points to data compiled by several doctors using the protocol that show it works. Data from a drug court (a specialized court designed to handle cases involving offenders who abuse substances) in Pierce County, Wash., showed that 98% of methamphetamine and cocaine addicts achieved clean urine screening tests for three months after the Prometa treatment provided by Hythiam. That data was presented in June at the National Assn. of Drug Court Professionals’ annual conference.

Another 12-week nonrandomized study by Research Across America, a clinical research company, on methamphetamine-dependent patients showed that 80% of patients “experienced a significant clinical benefit” with the medication alone (without behavioral therapy). The benefit was defined as decreased cravings, reduction in methamphetamine use and staying in treatment. The study, which was also undertaken and paid for at the request of Hythiam, was presented in June at the annual meeting of the College on Problems of Drug Dependence.

“You have different populations in different regions of the United States all showing the same result,” Peizer says.

People like the treatment, he says, because it jump-starts the recovery process and can be accomplished on an outpatient basis.

“You don’t have the added stress of being away from your friends, family, community and workplace,” he says. “You don’t have the stigma” of hospitalization.

The treatment is based on the belief that the brain becomes depleted of the neurotransmitter gamma aminobutyric acid in people addicted to alcohol, cocaine or methamphetamine. Prometa targets the brain’s receptors for that neurotransmitter, restoring proper function, says Dr. Crescenzo Pisano, medical director of the chemical dependency unit at Little Company of Mary-San Pedro Hospital, who began using the treatment four years ago on his patients.

“The reason why other treatments fail is because the treatments don’t correct the problem in that area of the brain,” says Pisano, who adds that he has no financial ties or stock in Hythiam. “When you see the difference in people, it is really very remarkable.”

But other addiction treatment specialists say there is scant scientific evidence that the gamma aminobutyric, or GABA, system is altered by addiction.

“When they talk about resetting receptors in the brain, there is no evidence for that,” says Richard Rawson, a psychologist and associate director of UCLA’s Integrated Substance Abuse Programs. “I don’t know if anyone has ever had the idea to package a bunch of medications off-label, patent it and then go out and sell it as a unique indication. That is a strategy many people in the field feel is of concern.”

Chavez, who resigned last year from the chemical dependency treatment staff at Little Company of Mary-San Pedro Hospital, says one or more of the drugs in the Prometa protocol may be helpful in the withdrawal and recovery process -- but only in a limited way.

“I believe there is a place for the chemical treatment of alcohol addiction,” he says. “But that is not the way they are using this. They are using it as a one-shot deal. I don’t think it will work beyond two to four weeks.”

No ‘magic’ drug cure yet

Many neuroscientists are studying the biological basis for addiction in hopes of finding medications that might augment recovery, but no drugs have been found that can cure addiction.

For alcoholism, the FDA has approved three medications as adjuncts to psychosocial treatment. Disulfiram is a decades-old medication that produces a sensitivity to alcohol and an unpleasant reaction when the patient under treatment drinks even small amounts of alcohol. Naltrexone and acamprosate are used to decrease the cravings for alcohol.

“None of these is a magic bullet,” Karan says.

The FDA has not approved any medications specifically for the treatment of cocaine or methamphetamine addiction.

In contrast with Prometa’s emphasis on medications to treat addiction, standard treatment for substance abuse typically involves education, family therapy, behavioral and psychosocial counseling and support groups. This type of therapy can occur in hospitals, residential programs, outpatient classes or free self-help groups. Costs range widely, but insurance typically covers such care.

Some physicians who use Prometa say it works in patients for whom standard approaches have failed.

The use of a new, untested remedy is justified when it’s safe and when there is little else to help addicts, says Dr. Matthew Torrington, medical director of the Prometa Center, an outpatient clinic in Santa Monica founded to provide the treatment.

“I don’t expect anyone to believe me until there is [randomized, controlled] data,” Torrington says. “But for people who are suffering today, this really helps. What else is there?”

Prometa costs between $12,000 and $15,000 for self-paying patients, although Peizer says the company offers discounts to insurers, Medicaid recipients and the criminal justice system. No insurers have covered the treatment as yet.

Stephen Beebe, 44, was treated with Prometa in June for methamphetamine addiction. “After the first infusion, I felt like somebody had cracked open my head and shined a flashlight into my brain,” he says. “I had mental clarity right away. I knew I was going to make it.” He said he experienced no desire for meth and has been free of the drug while undergoing counseling and attending support meetings.

Another man, who asked that his name not be used because he fears his history of addiction may jeopardize his employment, said he spent $8,000 on the treatment several years ago. The San Pedro longshoreman, 55, was addicted to cocaine and heroin when the treatment was recommended. He relapsed one month later even though he was participating in after-care counseling and group support meetings.

“They said it would help me stay clean and sober,” he says. “I paid $8,000 to be a guinea pig. But when you’re desperate and they tell you this stuff, you’ll do it. I got no benefit from it.”

Studies now underway

Some of the questions surrounding Prometa may be resolved by more rigorous studies. Two randomized, controlled clinical trials funded by Hythiam are underway at UCLA and the Medical University of South Carolina. Results from the studies are expected in a year or two.

The trials are being conducted by highly regarded scientists and, says Rawson, “that is absolutely to [Hythiam’s] credit. But they should wait for the results before they do all the marketing. Between now and 2008, there is a lot of marketing going on. What if the results show it’s no better than placebo?”

shari.roan@latimes.com

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The Prometa regimen

Prometa can be used to treat alcohol, cocaine and methamphetamine addictions, says Hythiam, the company that licenses the treatment regimen.

For alcohol dependence, patients receive the prescription drug flumazenil intravenously over two to three visits on consecutive days followed by oral administration of the prescription drugs gabapentin and hydroxyzine.

For cocaine and methamphetamine dependence, patients receive intravenous flumazenil doses on three consecutive days followed by a second treatment about three weeks later. They also receive gabapentin and hydroxyzine.

Flumazenil, gabapentin and hydroxyzine are not approved by the FDA for the treatment of addiction.

The accepted use for Flumazenil is to help reverse the effects of benzodiazepine drugs, such as drowsiness, after surgery or a drug overdose. Gabapentin is used to help control some types of epileptic seizures. Hydroxyzine is used to relieve itching caused by allergies and to control nausea. It is also used for anxiety and to treat symptoms of alcohol withdrawal.

Hythiam does not reveal the dosages and precise sequencing of the medications that are used and even requires its licensees to sign nondisclosure forms protecting the information. Patients are also prescribed vitamins, minerals and amino acids and are encouraged to attend after-care counseling and group support meetings.

-- Shari Roan