Timothy F. Kirn

SAN DIEGO — Risedronate treatment preserved trabecular bone in patients with advanced medial compartment knee osteoarthritis, and at a high dose even appeared to build it, Christopher Buckland-Wright, Ph.D., said at the annual meeting of the American College of Rheumatology.

Despite the loss of cartilage, “high doses of risedronate appeared to protect joints against bone loss, and preserved the structure and integrity,” said Dr. Buckland-Wright, professor of radiologic anatomy at King's College London.

If the results are confirmed by additional studies, perhaps bisphosphonate treatment will be used to delay the onset of the compartmental collapse in knees affected by osteoarthritis.

Dr. Buckland-Wright presented the results of an analysis of a multicenter, placebo-controlled trial involving three different doses of risedronate in knee osteoarthritis: 5 mg/day, 15 mg/day, and 50 mg once a week. The analysis included 100 patients randomly selected from each of the four groups. Patients were selected from the entire 1,200-patient cohort.

Overall, most of the patients had evidence of vertical and trabecular bone loss during the 2-year course of the study. But among those who had progressive narrowing of the joint space, risedronate at the higher two doses appeared to preserve bone. Patients taking 15 mg/day had stabilizing of both vertical and horizontal trabeculae. In the patients taking 50 mg per week, horizontal trabeculae stabilized, and there was an increase in vertical trabeculae, Dr. Buckland-Wright said.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., Mason, Ohio.

SAN DIEGO — Risedronate treatment preserved trabecular bone in patients with advanced medial compartment knee osteoarthritis, and at a high dose even appeared to build it, Christopher Buckland-Wright, Ph.D., said at the annual meeting of the American College of Rheumatology.

Despite the loss of cartilage, “high doses of risedronate appeared to protect joints against bone loss, and preserved the structure and integrity,” said Dr. Buckland-Wright, professor of radiologic anatomy at King's College London.

If the results are confirmed by additional studies, perhaps bisphosphonate treatment will be used to delay the onset of the compartmental collapse in knees affected by osteoarthritis.

Dr. Buckland-Wright presented the results of an analysis of a multicenter, placebo-controlled trial involving three different doses of risedronate in knee osteoarthritis: 5 mg/day, 15 mg/day, and 50 mg once a week. The analysis included 100 patients randomly selected from each of the four groups. Patients were selected from the entire 1,200-patient cohort.

Overall, most of the patients had evidence of vertical and trabecular bone loss during the 2-year course of the study. But among those who had progressive narrowing of the joint space, risedronate at the higher two doses appeared to preserve bone. Patients taking 15 mg/day had stabilizing of both vertical and horizontal trabeculae. In the patients taking 50 mg per week, horizontal trabeculae stabilized, and there was an increase in vertical trabeculae, Dr. Buckland-Wright said.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., Mason, Ohio.

SAN DIEGO — Risedronate treatment preserved trabecular bone in patients with advanced medial compartment knee osteoarthritis, and at a high dose even appeared to build it, Christopher Buckland-Wright, Ph.D., said at the annual meeting of the American College of Rheumatology.

Despite the loss of cartilage, “high doses of risedronate appeared to protect joints against bone loss, and preserved the structure and integrity,” said Dr. Buckland-Wright, professor of radiologic anatomy at King's College London.

If the results are confirmed by additional studies, perhaps bisphosphonate treatment will be used to delay the onset of the compartmental collapse in knees affected by osteoarthritis.

Dr. Buckland-Wright presented the results of an analysis of a multicenter, placebo-controlled trial involving three different doses of risedronate in knee osteoarthritis: 5 mg/day, 15 mg/day, and 50 mg once a week. The analysis included 100 patients randomly selected from each of the four groups. Patients were selected from the entire 1,200-patient cohort.

Overall, most of the patients had evidence of vertical and trabecular bone loss during the 2-year course of the study. But among those who had progressive narrowing of the joint space, risedronate at the higher two doses appeared to preserve bone. Patients taking 15 mg/day had stabilizing of both vertical and horizontal trabeculae. In the patients taking 50 mg per week, horizontal trabeculae stabilized, and there was an increase in vertical trabeculae, Dr. Buckland-Wright said.

The study was sponsored by Procter & Gamble Pharmaceuticals Inc., Mason, Ohio.

SCOTTSDALE, ARIZ. – Addiction specialists do see chronic pain patients who are so dependent on opiates that they require detoxification, but the question of whether such patients are “addicted” is difficult to determine clinically, two presenters said at a workshop at the annual meeting of the American Academy of Addiction Psychiatry.

One of the presenters said he prefers to detoxify these patients slowly and gently, using codeine. The other said he prefers a rapid method using naltrexone.

Many doctors have attempted to distinguish dependence from addiction, but the most clinically useful determination might be made by asking two questions, said Dr. Carl R. Sullivan of West Virginia University, Morgantown.

Does the patient misuse the medication or take it strictly based on the prescribed regimen? Is the patient honest about using the medication?

“I think that is a nice, easy way to look at it. If you see misuse and deceit, you are usually looking at addiction,” said Dr. Sullivan, who treats many chronic pain patients.

Dr. Sullivan also said he thinks chronic pain patients who truly become addicts are rare, and most who do have had substance abuse issues in the past.

“That seems not to happen very much,” he said. “Usually, if you are seeing addiction, and you think it is iatrogenic addiction, just look into the history a little bit.”

Still, both Dr. Sullivan and the workshop's other presenter, Dr. A. K. Roy, said they have little use for opiates in chronic pain. Other treatments such as tricyclics and physical rehabilitation are better.

Opiates can be somewhat effective at first, but after some patients have taken them for years, things begin to backfire, causing hyperalgesia and impeding functionality, said Dr. Roy, an addiction specialist who practices in Metairie, La.

“I have a concept that opiate use is temporary, though I don't know exactly what the definition of temporary is,” he said. “The liability for harm increases with the length of use.”

Dr. Sullivan said he has heard very articulate discussions on the rationale for switching opiate treatments periodically to avoid dependence and diminished efficacy. “To me, most of the time it just looks like … you are just switching a green M&M for a red one. There's just not that much difference.

“I'm not an opiate guy; I think there are so many better ways to deal with chronic pain.” he added.

More collaboration among pain medication and addiction treatment specialists might reduce the problems that some patients get into, but “some places I go they do everything but shoot guns at each other,” he said.

Of the approaches used for withdrawing a dependent patient from an opiate, Dr. Sullivan said he prefers to use a time-tested regimen using codeine that has mostly fallen into disuse. “I know it is an old-fashioned drug,” he said. “But it is very cheap and very effective, and it is a nice, short-acting agent.”

The advantage of the short-acting agent is that one can more precisely tailor the administration of the drug to symptoms. It also avoids a problem he has seen when longer-acting agents such as buprenorphine or methadone are used. That is, the drug effects can take several days to wear off, so patients who were thought to be fully detoxified start having symptoms days after the drug is stopped.

For the first 24 hours, the patient is given 30 mg of codeine every half hour, as needed, to stave off withdrawal symptoms. They also are given supportive medications, including a benzodiazepine and nonopiates for pain, if needed.

At the end of 24 hours, the total amount of codeine given is counted as the baseline dosage. That amount is then divided for dosing every 3–4 hours. The codeine is gradually scaled back over 10–14 days, Dr. Sullivan said.

Dr. Roy said he often prefers a rapid detox using naltrexone. It lets the patient have symptoms (with supportive benzodiazepine treatment), and results in a complete detoxification in 3–4 days.

It is not the very rapid detoxification that is done with anesthesia, but it is almost as rapid. Instead, it is a newer approach that has been pioneered at Loma Linda University and the Mayo Clinic with good reported results. When the patients are finished, they are no longer dependent and have no cravings, said Dr. Roy.

“This is not something I would do outside of a locked unit,” he said.

After detoxification, patients who are thought to have an addiction problem should then be referred to Alcoholics Anonymous, Narcotics Anonymous, or some other form of psychosocial support, Dr. Sullivan said.

The backbone of a new pain treatment program should be exercise and physical rehabilitation, because the fundamental goal needs to be improving functionality, Dr. Roy stressed.

SCOTTSDALE, ARIZ. – Addiction specialists do see chronic pain patients who are so dependent on opiates that they require detoxification, but the question of whether such patients are “addicted” is difficult to determine clinically, two presenters said at a workshop at the annual meeting of the American Academy of Addiction Psychiatry.

One of the presenters said he prefers to detoxify these patients slowly and gently, using codeine. The other said he prefers a rapid method using naltrexone.

Many doctors have attempted to distinguish dependence from addiction, but the most clinically useful determination might be made by asking two questions, said Dr. Carl R. Sullivan of West Virginia University, Morgantown.

Does the patient misuse the medication or take it strictly based on the prescribed regimen? Is the patient honest about using the medication?

“I think that is a nice, easy way to look at it. If you see misuse and deceit, you are usually looking at addiction,” said Dr. Sullivan, who treats many chronic pain patients.

Dr. Sullivan also said he thinks chronic pain patients who truly become addicts are rare, and most who do have had substance abuse issues in the past.

“That seems not to happen very much,” he said. “Usually, if you are seeing addiction, and you think it is iatrogenic addiction, just look into the history a little bit.”

Still, both Dr. Sullivan and the workshop's other presenter, Dr. A. K. Roy, said they have little use for opiates in chronic pain. Other treatments such as tricyclics and physical rehabilitation are better.

Opiates can be somewhat effective at first, but after some patients have taken them for years, things begin to backfire, causing hyperalgesia and impeding functionality, said Dr. Roy, an addiction specialist who practices in Metairie, La.

“I have a concept that opiate use is temporary, though I don't know exactly what the definition of temporary is,” he said. “The liability for harm increases with the length of use.”

Dr. Sullivan said he has heard very articulate discussions on the rationale for switching opiate treatments periodically to avoid dependence and diminished efficacy. “To me, most of the time it just looks like … you are just switching a green M&M for a red one. There's just not that much difference.

“I'm not an opiate guy; I think there are so many better ways to deal with chronic pain.” he added.

More collaboration among pain medication and addiction treatment specialists might reduce the problems that some patients get into, but “some places I go they do everything but shoot guns at each other,” he said.

Of the approaches used for withdrawing a dependent patient from an opiate, Dr. Sullivan said he prefers to use a time-tested regimen using codeine that has mostly fallen into disuse. “I know it is an old-fashioned drug,” he said. “But it is very cheap and very effective, and it is a nice, short-acting agent.”

The advantage of the short-acting agent is that one can more precisely tailor the administration of the drug to symptoms. It also avoids a problem he has seen when longer-acting agents such as buprenorphine or methadone are used. That is, the drug effects can take several days to wear off, so patients who were thought to be fully detoxified start having symptoms days after the drug is stopped.

For the first 24 hours, the patient is given 30 mg of codeine every half hour, as needed, to stave off withdrawal symptoms. They also are given supportive medications, including a benzodiazepine and nonopiates for pain, if needed.

At the end of 24 hours, the total amount of codeine given is counted as the baseline dosage. That amount is then divided for dosing every 3–4 hours. The codeine is gradually scaled back over 10–14 days, Dr. Sullivan said.

Dr. Roy said he often prefers a rapid detox using naltrexone. It lets the patient have symptoms (with supportive benzodiazepine treatment), and results in a complete detoxification in 3–4 days.

It is not the very rapid detoxification that is done with anesthesia, but it is almost as rapid. Instead, it is a newer approach that has been pioneered at Loma Linda University and the Mayo Clinic with good reported results. When the patients are finished, they are no longer dependent and have no cravings, said Dr. Roy.

“This is not something I would do outside of a locked unit,” he said.

After detoxification, patients who are thought to have an addiction problem should then be referred to Alcoholics Anonymous, Narcotics Anonymous, or some other form of psychosocial support, Dr. Sullivan said.

The backbone of a new pain treatment program should be exercise and physical rehabilitation, because the fundamental goal needs to be improving functionality, Dr. Roy stressed.

SCOTTSDALE, ARIZ. – Addiction specialists do see chronic pain patients who are so dependent on opiates that they require detoxification, but the question of whether such patients are “addicted” is difficult to determine clinically, two presenters said at a workshop at the annual meeting of the American Academy of Addiction Psychiatry.

One of the presenters said he prefers to detoxify these patients slowly and gently, using codeine. The other said he prefers a rapid method using naltrexone.

Many doctors have attempted to distinguish dependence from addiction, but the most clinically useful determination might be made by asking two questions, said Dr. Carl R. Sullivan of West Virginia University, Morgantown.

Does the patient misuse the medication or take it strictly based on the prescribed regimen? Is the patient honest about using the medication?

“I think that is a nice, easy way to look at it. If you see misuse and deceit, you are usually looking at addiction,” said Dr. Sullivan, who treats many chronic pain patients.

Dr. Sullivan also said he thinks chronic pain patients who truly become addicts are rare, and most who do have had substance abuse issues in the past.

“That seems not to happen very much,” he said. “Usually, if you are seeing addiction, and you think it is iatrogenic addiction, just look into the history a little bit.”

Still, both Dr. Sullivan and the workshop's other presenter, Dr. A. K. Roy, said they have little use for opiates in chronic pain. Other treatments such as tricyclics and physical rehabilitation are better.

Opiates can be somewhat effective at first, but after some patients have taken them for years, things begin to backfire, causing hyperalgesia and impeding functionality, said Dr. Roy, an addiction specialist who practices in Metairie, La.

“I have a concept that opiate use is temporary, though I don't know exactly what the definition of temporary is,” he said. “The liability for harm increases with the length of use.”

Dr. Sullivan said he has heard very articulate discussions on the rationale for switching opiate treatments periodically to avoid dependence and diminished efficacy. “To me, most of the time it just looks like … you are just switching a green M&M for a red one. There's just not that much difference.

“I'm not an opiate guy; I think there are so many better ways to deal with chronic pain.” he added.

More collaboration among pain medication and addiction treatment specialists might reduce the problems that some patients get into, but “some places I go they do everything but shoot guns at each other,” he said.

Of the approaches used for withdrawing a dependent patient from an opiate, Dr. Sullivan said he prefers to use a time-tested regimen using codeine that has mostly fallen into disuse. “I know it is an old-fashioned drug,” he said. “But it is very cheap and very effective, and it is a nice, short-acting agent.”

The advantage of the short-acting agent is that one can more precisely tailor the administration of the drug to symptoms. It also avoids a problem he has seen when longer-acting agents such as buprenorphine or methadone are used. That is, the drug effects can take several days to wear off, so patients who were thought to be fully detoxified start having symptoms days after the drug is stopped.

For the first 24 hours, the patient is given 30 mg of codeine every half hour, as needed, to stave off withdrawal symptoms. They also are given supportive medications, including a benzodiazepine and nonopiates for pain, if needed.

At the end of 24 hours, the total amount of codeine given is counted as the baseline dosage. That amount is then divided for dosing every 3–4 hours. The codeine is gradually scaled back over 10–14 days, Dr. Sullivan said.

Dr. Roy said he often prefers a rapid detox using naltrexone. It lets the patient have symptoms (with supportive benzodiazepine treatment), and results in a complete detoxification in 3–4 days.

It is not the very rapid detoxification that is done with anesthesia, but it is almost as rapid. Instead, it is a newer approach that has been pioneered at Loma Linda University and the Mayo Clinic with good reported results. When the patients are finished, they are no longer dependent and have no cravings, said Dr. Roy.

“This is not something I would do outside of a locked unit,” he said.

After detoxification, patients who are thought to have an addiction problem should then be referred to Alcoholics Anonymous, Narcotics Anonymous, or some other form of psychosocial support, Dr. Sullivan said.

The backbone of a new pain treatment program should be exercise and physical rehabilitation, because the fundamental goal needs to be improving functionality, Dr. Roy stressed.

SCOTTSDALE, ARIZ. – Treating dual diagnosis patients–those with concurrent psychiatric and substance abuse disorders–requires a readiness to use a medication for the substance abuse, perhaps first and foremost, Dr. John W. Tsuang said at the annual meeting of the American Academy of Addiction Psychiatry.

For the substance abusing patient who may have some other psychiatric condition, it is best to wait until the patient is abstinent for some time before making a definitive diagnosis–but without proper treatment, few can get sober, said Dr. Tsuang, who is director of the dual diagnosis program at the Los Angeles County Harbor-UCLA Medical Center.

Dr. Tsuang described a study in which he was once involved to illustrate the conundrum and the difficulty in getting a handle on substance abuse in dual diagnosis patients.

In the study, the patients to be enrolled–presumably with schizophrenia–were actively seeking help and attending a program daily. They also needed to be abstinent for 6 weeks to be given a definitive diagnosis of schizophrenia. Of the candidates, 81% could not stay abstinent long enough, “despite our best intentions,” Dr. Tsuang said.

“I will use whatever I can to help a patient initiate and achieve abstinence,” Dr. Tsuang said in the workshop that he conducted with Dr. Timothy Fong, also with the University of California, Los Angeles.

Buprenorphine is an excellent medication for narcotics abusers, he said. For alcohol abusers, he mostly relies on disulfiram, but he acknowledges that what works and is appropriate for one patient is not necessarily right for everyone. “A lot of clinicians shy away from disulfiram,” he said.

Some drugs that can be used for the mental health diagnosis may also help with substance abuse. Some of the newer atypical antipsychotics, when used in patients with schizophrenia, may reduce drug-high cravings. Clozapine, for example, appears to reduce alcohol use and smoking. Theoretically, it may reduce craving for cocaine, though there is no evidence yet, said Dr. Tsuang.

“Clozapine is one of our best medications,” though it does require close monitoring in substance abusers and may interact badly with methamphetamine use, he said.

In an experiment, risperidone (Risperdal) was given to individuals who were using cocaine, and it was found to interfere with the high, Dr. Tsuang said

Since then, studies have shown that risperidone treatment reduced cravings and relapse in patients with either schizophrenia or bipolar disorder who used cocaine.

Risperidone, however, has been tried in primary cocaine abusers who did not have a dual-diagnosis, and it was not helpful, he said.

Quetiapine (Seroquel) is a popular medication in general, because it reportedly ameliorates anxiety and helps with sleep problems, two difficulties that substance abusers who become abstinent often have.

There have been suggestions that the drug may be of use in bipolar disorder patients who are cocaine dependent. However, there is less evidence of its efficacy than there is for some other drugs, and it has never been given a trial to see if it helped substance abusers with no second diagnosis, Dr. Tsuang pointed out.

Whatever medications are used, psychosocial substance-abuse treatment of some kind is essential for these patients, because no single drug is a panacea. In his experience, most patients will continue at least some substance abuse, Dr. Tsuang said.

Dr. Fong said that despite the conundrum faced by the clinician who has a patient who may have a dual diagnosis but cannot get sober long enough for symptoms to become clear, it is often necessary to make some primary diagnosis to initiate timely treatment.

Delay “may make them harder to treat over the long term,” he said. “Ongoing untreated psychosis is very bad for the brain. That's going to make it more difficult to treat the psychosis and to treat the substance abuse.”

At UCLA, said Dr. Fong, the solution is to take a meticulous history and try to establish a time line. The doctors ask patients if they had psychiatric symptoms or treatments before the substance use started. They also ask about symptoms during periods of abstinence. Finally, they ask about the patient's last use in relation to the most recent symptoms.

SCOTTSDALE, ARIZ. – Treating dual diagnosis patients–those with concurrent psychiatric and substance abuse disorders–requires a readiness to use a medication for the substance abuse, perhaps first and foremost, Dr. John W. Tsuang said at the annual meeting of the American Academy of Addiction Psychiatry.

For the substance abusing patient who may have some other psychiatric condition, it is best to wait until the patient is abstinent for some time before making a definitive diagnosis–but without proper treatment, few can get sober, said Dr. Tsuang, who is director of the dual diagnosis program at the Los Angeles County Harbor-UCLA Medical Center.

Dr. Tsuang described a study in which he was once involved to illustrate the conundrum and the difficulty in getting a handle on substance abuse in dual diagnosis patients.

In the study, the patients to be enrolled–presumably with schizophrenia–were actively seeking help and attending a program daily. They also needed to be abstinent for 6 weeks to be given a definitive diagnosis of schizophrenia. Of the candidates, 81% could not stay abstinent long enough, “despite our best intentions,” Dr. Tsuang said.

“I will use whatever I can to help a patient initiate and achieve abstinence,” Dr. Tsuang said in the workshop that he conducted with Dr. Timothy Fong, also with the University of California, Los Angeles.

Buprenorphine is an excellent medication for narcotics abusers, he said. For alcohol abusers, he mostly relies on disulfiram, but he acknowledges that what works and is appropriate for one patient is not necessarily right for everyone. “A lot of clinicians shy away from disulfiram,” he said.

Some drugs that can be used for the mental health diagnosis may also help with substance abuse. Some of the newer atypical antipsychotics, when used in patients with schizophrenia, may reduce drug-high cravings. Clozapine, for example, appears to reduce alcohol use and smoking. Theoretically, it may reduce craving for cocaine, though there is no evidence yet, said Dr. Tsuang.

“Clozapine is one of our best medications,” though it does require close monitoring in substance abusers and may interact badly with methamphetamine use, he said.

In an experiment, risperidone (Risperdal) was given to individuals who were using cocaine, and it was found to interfere with the high, Dr. Tsuang said

Since then, studies have shown that risperidone treatment reduced cravings and relapse in patients with either schizophrenia or bipolar disorder who used cocaine.

Risperidone, however, has been tried in primary cocaine abusers who did not have a dual-diagnosis, and it was not helpful, he said.

Quetiapine (Seroquel) is a popular medication in general, because it reportedly ameliorates anxiety and helps with sleep problems, two difficulties that substance abusers who become abstinent often have.

There have been suggestions that the drug may be of use in bipolar disorder patients who are cocaine dependent. However, there is less evidence of its efficacy than there is for some other drugs, and it has never been given a trial to see if it helped substance abusers with no second diagnosis, Dr. Tsuang pointed out.

Whatever medications are used, psychosocial substance-abuse treatment of some kind is essential for these patients, because no single drug is a panacea. In his experience, most patients will continue at least some substance abuse, Dr. Tsuang said.

Dr. Fong said that despite the conundrum faced by the clinician who has a patient who may have a dual diagnosis but cannot get sober long enough for symptoms to become clear, it is often necessary to make some primary diagnosis to initiate timely treatment.

Delay “may make them harder to treat over the long term,” he said. “Ongoing untreated psychosis is very bad for the brain. That's going to make it more difficult to treat the psychosis and to treat the substance abuse.”

At UCLA, said Dr. Fong, the solution is to take a meticulous history and try to establish a time line. The doctors ask patients if they had psychiatric symptoms or treatments before the substance use started. They also ask about symptoms during periods of abstinence. Finally, they ask about the patient's last use in relation to the most recent symptoms.

SCOTTSDALE, ARIZ. – Treating dual diagnosis patients–those with concurrent psychiatric and substance abuse disorders–requires a readiness to use a medication for the substance abuse, perhaps first and foremost, Dr. John W. Tsuang said at the annual meeting of the American Academy of Addiction Psychiatry.

For the substance abusing patient who may have some other psychiatric condition, it is best to wait until the patient is abstinent for some time before making a definitive diagnosis–but without proper treatment, few can get sober, said Dr. Tsuang, who is director of the dual diagnosis program at the Los Angeles County Harbor-UCLA Medical Center.

Dr. Tsuang described a study in which he was once involved to illustrate the conundrum and the difficulty in getting a handle on substance abuse in dual diagnosis patients.

In the study, the patients to be enrolled–presumably with schizophrenia–were actively seeking help and attending a program daily. They also needed to be abstinent for 6 weeks to be given a definitive diagnosis of schizophrenia. Of the candidates, 81% could not stay abstinent long enough, “despite our best intentions,” Dr. Tsuang said.

“I will use whatever I can to help a patient initiate and achieve abstinence,” Dr. Tsuang said in the workshop that he conducted with Dr. Timothy Fong, also with the University of California, Los Angeles.

Buprenorphine is an excellent medication for narcotics abusers, he said. For alcohol abusers, he mostly relies on disulfiram, but he acknowledges that what works and is appropriate for one patient is not necessarily right for everyone. “A lot of clinicians shy away from disulfiram,” he said.

Some drugs that can be used for the mental health diagnosis may also help with substance abuse. Some of the newer atypical antipsychotics, when used in patients with schizophrenia, may reduce drug-high cravings. Clozapine, for example, appears to reduce alcohol use and smoking. Theoretically, it may reduce craving for cocaine, though there is no evidence yet, said Dr. Tsuang.

“Clozapine is one of our best medications,” though it does require close monitoring in substance abusers and may interact badly with methamphetamine use, he said.

In an experiment, risperidone (Risperdal) was given to individuals who were using cocaine, and it was found to interfere with the high, Dr. Tsuang said

Since then, studies have shown that risperidone treatment reduced cravings and relapse in patients with either schizophrenia or bipolar disorder who used cocaine.

Risperidone, however, has been tried in primary cocaine abusers who did not have a dual-diagnosis, and it was not helpful, he said.

Quetiapine (Seroquel) is a popular medication in general, because it reportedly ameliorates anxiety and helps with sleep problems, two difficulties that substance abusers who become abstinent often have.

There have been suggestions that the drug may be of use in bipolar disorder patients who are cocaine dependent. However, there is less evidence of its efficacy than there is for some other drugs, and it has never been given a trial to see if it helped substance abusers with no second diagnosis, Dr. Tsuang pointed out.

Whatever medications are used, psychosocial substance-abuse treatment of some kind is essential for these patients, because no single drug is a panacea. In his experience, most patients will continue at least some substance abuse, Dr. Tsuang said.

Dr. Fong said that despite the conundrum faced by the clinician who has a patient who may have a dual diagnosis but cannot get sober long enough for symptoms to become clear, it is often necessary to make some primary diagnosis to initiate timely treatment.

Delay “may make them harder to treat over the long term,” he said. “Ongoing untreated psychosis is very bad for the brain. That's going to make it more difficult to treat the psychosis and to treat the substance abuse.”

At UCLA, said Dr. Fong, the solution is to take a meticulous history and try to establish a time line. The doctors ask patients if they had psychiatric symptoms or treatments before the substance use started. They also ask about symptoms during periods of abstinence. Finally, they ask about the patient's last use in relation to the most recent symptoms.

SCOTTSDALE, ARIZ. – Alcohol abusers who take acamprosate and relapse are still better off continuing to take the drug because they have an improved chance of achieving abstinence, company data show.

Pooled data from three separate, controlled trials of the drug suggest that almost three times more patients treated through a relapse eventually achieve a period of abstinence, compared with controls, Dr. Eugene Schneider said in a poster presentation at the annual meeting of the American Academy of Addiction Psychiatry.

In the studies, most of the participants relapsed at some point. Of the 372 people treated with acamprosate (1,998 mg/day), 72% relapsed, and 85% of 375 placebo-control patients relapsed. One of the trials lasted 13 weeks, one lasted 48 weeks, and the third lasted 52 weeks.

Overall, 13% of the acamprosate-treated individuals who relapsed were subsequently abstinent for the remainder of the study and an additional 20% who relapsed were abstinent at their final study evaluation. The comparable figures for the control patients were 5% and 10%, respectively, said Dr. Schneider, an associate director for medical affairs at Forest Laboratories Inc., New York.

Acamprosate-treated patients who achieved a period of abstinence after relapse had a greater mean number of days of abstinence than did controls: 24 days vs. 14 days. In the patients who relapsed but eventually became abstinent for the remainder of the study, the treated patients were more likely to have had a longer abstinence: a mean of 28 days for the treated patients, compared with 12 days for the control patients.

“It is worthwhile treating patients through a relapse,” Dr. Schneider said in an interview.

SCOTTSDALE, ARIZ. – Alcohol abusers who take acamprosate and relapse are still better off continuing to take the drug because they have an improved chance of achieving abstinence, company data show.

Pooled data from three separate, controlled trials of the drug suggest that almost three times more patients treated through a relapse eventually achieve a period of abstinence, compared with controls, Dr. Eugene Schneider said in a poster presentation at the annual meeting of the American Academy of Addiction Psychiatry.

In the studies, most of the participants relapsed at some point. Of the 372 people treated with acamprosate (1,998 mg/day), 72% relapsed, and 85% of 375 placebo-control patients relapsed. One of the trials lasted 13 weeks, one lasted 48 weeks, and the third lasted 52 weeks.

Overall, 13% of the acamprosate-treated individuals who relapsed were subsequently abstinent for the remainder of the study and an additional 20% who relapsed were abstinent at their final study evaluation. The comparable figures for the control patients were 5% and 10%, respectively, said Dr. Schneider, an associate director for medical affairs at Forest Laboratories Inc., New York.

Acamprosate-treated patients who achieved a period of abstinence after relapse had a greater mean number of days of abstinence than did controls: 24 days vs. 14 days. In the patients who relapsed but eventually became abstinent for the remainder of the study, the treated patients were more likely to have had a longer abstinence: a mean of 28 days for the treated patients, compared with 12 days for the control patients.

“It is worthwhile treating patients through a relapse,” Dr. Schneider said in an interview.

SCOTTSDALE, ARIZ. – Alcohol abusers who take acamprosate and relapse are still better off continuing to take the drug because they have an improved chance of achieving abstinence, company data show.

Pooled data from three separate, controlled trials of the drug suggest that almost three times more patients treated through a relapse eventually achieve a period of abstinence, compared with controls, Dr. Eugene Schneider said in a poster presentation at the annual meeting of the American Academy of Addiction Psychiatry.

In the studies, most of the participants relapsed at some point. Of the 372 people treated with acamprosate (1,998 mg/day), 72% relapsed, and 85% of 375 placebo-control patients relapsed. One of the trials lasted 13 weeks, one lasted 48 weeks, and the third lasted 52 weeks.

Overall, 13% of the acamprosate-treated individuals who relapsed were subsequently abstinent for the remainder of the study and an additional 20% who relapsed were abstinent at their final study evaluation. The comparable figures for the control patients were 5% and 10%, respectively, said Dr. Schneider, an associate director for medical affairs at Forest Laboratories Inc., New York.

Acamprosate-treated patients who achieved a period of abstinence after relapse had a greater mean number of days of abstinence than did controls: 24 days vs. 14 days. In the patients who relapsed but eventually became abstinent for the remainder of the study, the treated patients were more likely to have had a longer abstinence: a mean of 28 days for the treated patients, compared with 12 days for the control patients.

“It is worthwhile treating patients through a relapse,” Dr. Schneider said in an interview.

In his adult cystic fibrosis clinic in Denver, Dr. Jerry A. Nick has patients who were not diagnosed until they were 40 years of age or older.

These patients represent the tip of an iceberg of unrecognized patients, and clinicians need to be on the lookout for these individuals, Dr. Nick suggests.

His patients reflect the fact that the clinical presentation of cystic fibrosis can vary along a spectrum of severity. This has become clearer as more and more specific genetic mutations causing cystic fibrosis have been identified.

With that awareness, patients who were once just considered a curious aberration are now recognized as representing something significant, said Dr. Nick, director of the Adult Cystic Fibrosis Clinic of the National Jewish Medical and Research Center.

“These cases have shown up sporadically for years,” he said in an interview.

Dr. Nick recently published a paper on 27 of his late-diagnosis patients (Am. J. Respir. Crit. Care Med. 2005;171:621–6), comparing them with 28 patients diagnosed early who have survived into their 40s. He has also published a review article on long-term survival with cystic fibrosis (Curr. Opin. Pulm. Med. 2005;11:513–8).

Dr. Nick's patients are some of the oldest cystic fibrosis patients yet reported. The median age of his late-diagnosis patients is at present more than 52 years.

They may not be an exclusive group for long, however. Adult diagnosis is already becoming more common, Dr. Nick noted in his article. In 1982, only 3% of patients enrolled in the Cystic Fibrosis Foundation patient registry had been diagnosed after the age of 18 years. By 2002, 10% of the new patients added to the registry that year were diagnosed during adulthood.

Many of the late-diagnosis patients that Dr. Nick described in his article had been seeing physicians for years for recurrent and chronic lung infections, or similar symptoms. They were thought to have asthma, or chronic obstructive pulmonary disease, or something else.

But there is no question about their cystic fibrosis diagnosis, Dr. Nick said. The patients all meet Cystic Fibrosis Foundation diagnostic criteria, and they have had genetic analysis, sweat chloride testing, and/or nasal potential difference testing.

European centers also have begun to take note of late-diagnosis patients, but most of the European patients have been diagnosed in their 20s and 30s.

The importance of Dr. Nick's older patients is that they may help to identify factors associated with long-term survival. The median survival of cystic fibrosis patients is still only 35 years of age, despite improvements in cystic fibrosis treatment.

Dr. Nick has not uncovered any notable clues yet. But there are intriguing, observed differences between the early-diagnosed and late-diagnosed patients. The late-diagnosed patients were less likely to have pancreatic insufficiency, so they tended to have better lung function and nutritional status. They were also less likely to have cystic fibrosis-related diabetes.

One unexpected difference was that 74% of the late-diagnosis patients were women. In the early-diagnosis group, most older patients were male (64%), which is consistent with data in cystic fibrosis patient registries in general, Dr. Nick said. Males also tend to have a longer median survival, by 3–5 years on average.

In addition, a large proportion of the late-diagnosis patients carried nontuberculous mycobacteria. These findings may be the most interesting, Dr. Nick said, as they may indicate something about the airway environment that could be a clue to the patients' long-term survival.

That is also the sole finding so far that might be helpful in identifying the patients who go without a diagnosis for so long. Physicians who see a patient with a nontuberculous mycobacteria infection should have a strong suspicion of cystic fibrosis, he said.

The comparison study found that only 4 of the 27 early-diagnosis patients had at least one positive culture for nontuberculous mycobacteria, whereas 14 of the 28 late-diagnosis patients did. None of the early-diagnosis patients met criteria for an infection, while six of the late-diagnosis patients did.

In contrast, Pseudomonas aeruginosa was found less frequently in cultures from the late-diagnosis patients, although mucoid and nonmucoid strains were still found in more than 50% of cultures.

In general, the late-diagnosis patients had less severe manifestations, but not all of them had mild disease, Dr. Nick noted in the interview. Four of the patients have died. Two required lung transplant. Some had the same genotypes as early-diagnosis patients.

In his adult cystic fibrosis clinic in Denver, Dr. Jerry A. Nick has patients who were not diagnosed until they were 40 years of age or older.

These patients represent the tip of an iceberg of unrecognized patients, and clinicians need to be on the lookout for these individuals, Dr. Nick suggests.

His patients reflect the fact that the clinical presentation of cystic fibrosis can vary along a spectrum of severity. This has become clearer as more and more specific genetic mutations causing cystic fibrosis have been identified.

With that awareness, patients who were once just considered a curious aberration are now recognized as representing something significant, said Dr. Nick, director of the Adult Cystic Fibrosis Clinic of the National Jewish Medical and Research Center.

“These cases have shown up sporadically for years,” he said in an interview.

Dr. Nick recently published a paper on 27 of his late-diagnosis patients (Am. J. Respir. Crit. Care Med. 2005;171:621–6), comparing them with 28 patients diagnosed early who have survived into their 40s. He has also published a review article on long-term survival with cystic fibrosis (Curr. Opin. Pulm. Med. 2005;11:513–8).

Dr. Nick's patients are some of the oldest cystic fibrosis patients yet reported. The median age of his late-diagnosis patients is at present more than 52 years.

They may not be an exclusive group for long, however. Adult diagnosis is already becoming more common, Dr. Nick noted in his article. In 1982, only 3% of patients enrolled in the Cystic Fibrosis Foundation patient registry had been diagnosed after the age of 18 years. By 2002, 10% of the new patients added to the registry that year were diagnosed during adulthood.

Many of the late-diagnosis patients that Dr. Nick described in his article had been seeing physicians for years for recurrent and chronic lung infections, or similar symptoms. They were thought to have asthma, or chronic obstructive pulmonary disease, or something else.

But there is no question about their cystic fibrosis diagnosis, Dr. Nick said. The patients all meet Cystic Fibrosis Foundation diagnostic criteria, and they have had genetic analysis, sweat chloride testing, and/or nasal potential difference testing.

European centers also have begun to take note of late-diagnosis patients, but most of the European patients have been diagnosed in their 20s and 30s.

The importance of Dr. Nick's older patients is that they may help to identify factors associated with long-term survival. The median survival of cystic fibrosis patients is still only 35 years of age, despite improvements in cystic fibrosis treatment.

Dr. Nick has not uncovered any notable clues yet. But there are intriguing, observed differences between the early-diagnosed and late-diagnosed patients. The late-diagnosed patients were less likely to have pancreatic insufficiency, so they tended to have better lung function and nutritional status. They were also less likely to have cystic fibrosis-related diabetes.

One unexpected difference was that 74% of the late-diagnosis patients were women. In the early-diagnosis group, most older patients were male (64%), which is consistent with data in cystic fibrosis patient registries in general, Dr. Nick said. Males also tend to have a longer median survival, by 3–5 years on average.

In addition, a large proportion of the late-diagnosis patients carried nontuberculous mycobacteria. These findings may be the most interesting, Dr. Nick said, as they may indicate something about the airway environment that could be a clue to the patients' long-term survival.

That is also the sole finding so far that might be helpful in identifying the patients who go without a diagnosis for so long. Physicians who see a patient with a nontuberculous mycobacteria infection should have a strong suspicion of cystic fibrosis, he said.

The comparison study found that only 4 of the 27 early-diagnosis patients had at least one positive culture for nontuberculous mycobacteria, whereas 14 of the 28 late-diagnosis patients did. None of the early-diagnosis patients met criteria for an infection, while six of the late-diagnosis patients did.

In contrast, Pseudomonas aeruginosa was found less frequently in cultures from the late-diagnosis patients, although mucoid and nonmucoid strains were still found in more than 50% of cultures.

In general, the late-diagnosis patients had less severe manifestations, but not all of them had mild disease, Dr. Nick noted in the interview. Four of the patients have died. Two required lung transplant. Some had the same genotypes as early-diagnosis patients.

In his adult cystic fibrosis clinic in Denver, Dr. Jerry A. Nick has patients who were not diagnosed until they were 40 years of age or older.

These patients represent the tip of an iceberg of unrecognized patients, and clinicians need to be on the lookout for these individuals, Dr. Nick suggests.

His patients reflect the fact that the clinical presentation of cystic fibrosis can vary along a spectrum of severity. This has become clearer as more and more specific genetic mutations causing cystic fibrosis have been identified.

With that awareness, patients who were once just considered a curious aberration are now recognized as representing something significant, said Dr. Nick, director of the Adult Cystic Fibrosis Clinic of the National Jewish Medical and Research Center.

“These cases have shown up sporadically for years,” he said in an interview.

Dr. Nick recently published a paper on 27 of his late-diagnosis patients (Am. J. Respir. Crit. Care Med. 2005;171:621–6), comparing them with 28 patients diagnosed early who have survived into their 40s. He has also published a review article on long-term survival with cystic fibrosis (Curr. Opin. Pulm. Med. 2005;11:513–8).

Dr. Nick's patients are some of the oldest cystic fibrosis patients yet reported. The median age of his late-diagnosis patients is at present more than 52 years.

They may not be an exclusive group for long, however. Adult diagnosis is already becoming more common, Dr. Nick noted in his article. In 1982, only 3% of patients enrolled in the Cystic Fibrosis Foundation patient registry had been diagnosed after the age of 18 years. By 2002, 10% of the new patients added to the registry that year were diagnosed during adulthood.

Many of the late-diagnosis patients that Dr. Nick described in his article had been seeing physicians for years for recurrent and chronic lung infections, or similar symptoms. They were thought to have asthma, or chronic obstructive pulmonary disease, or something else.

But there is no question about their cystic fibrosis diagnosis, Dr. Nick said. The patients all meet Cystic Fibrosis Foundation diagnostic criteria, and they have had genetic analysis, sweat chloride testing, and/or nasal potential difference testing.

European centers also have begun to take note of late-diagnosis patients, but most of the European patients have been diagnosed in their 20s and 30s.

The importance of Dr. Nick's older patients is that they may help to identify factors associated with long-term survival. The median survival of cystic fibrosis patients is still only 35 years of age, despite improvements in cystic fibrosis treatment.

Dr. Nick has not uncovered any notable clues yet. But there are intriguing, observed differences between the early-diagnosed and late-diagnosed patients. The late-diagnosed patients were less likely to have pancreatic insufficiency, so they tended to have better lung function and nutritional status. They were also less likely to have cystic fibrosis-related diabetes.

One unexpected difference was that 74% of the late-diagnosis patients were women. In the early-diagnosis group, most older patients were male (64%), which is consistent with data in cystic fibrosis patient registries in general, Dr. Nick said. Males also tend to have a longer median survival, by 3–5 years on average.

In addition, a large proportion of the late-diagnosis patients carried nontuberculous mycobacteria. These findings may be the most interesting, Dr. Nick said, as they may indicate something about the airway environment that could be a clue to the patients' long-term survival.

That is also the sole finding so far that might be helpful in identifying the patients who go without a diagnosis for so long. Physicians who see a patient with a nontuberculous mycobacteria infection should have a strong suspicion of cystic fibrosis, he said.

The comparison study found that only 4 of the 27 early-diagnosis patients had at least one positive culture for nontuberculous mycobacteria, whereas 14 of the 28 late-diagnosis patients did. None of the early-diagnosis patients met criteria for an infection, while six of the late-diagnosis patients did.

In contrast, Pseudomonas aeruginosa was found less frequently in cultures from the late-diagnosis patients, although mucoid and nonmucoid strains were still found in more than 50% of cultures.

In general, the late-diagnosis patients had less severe manifestations, but not all of them had mild disease, Dr. Nick noted in the interview. Four of the patients have died. Two required lung transplant. Some had the same genotypes as early-diagnosis patients.

SAN FRANCISCO — For patients undergoing Roux-en-Y gastric bypass surgery, concurrent cholecystectomy or treatment with ursodiol is more cost-effective than leaving patients alone and waiting to see if they develop gallstones, Dr. Brent C. White reported.

The combined intervention also provides a better quality of life, according to an analysis that he presented at the annual clinical congress of the American College of Surgeons.

Dr. White and his colleagues performed a cost analysis that compared three treatment strategies for patients undergoing Roux-en-Y gastric bypass surgery: Giving ursodiol treatment for 6 months post operatively, performing concurrent cholecystectomy, and watchful waiting for possible gallstones. The analysis assumed that patients who developed gallstones during watchful waiting or while being treated with ursodiol would undergo cholecystectomy.

After culling information from the peer-reviewed literature, the investigators incorporated into the analysis data on the likelihood of a patient developing gallstones after a Roux-en-Y bypass, on the effectiveness of ursodiol treatment, and on the likelihood of complications with any of the strategies.

In their payer-perspective analysis, the investigators found that concurrent cholecystectomy was the least expensive treatment, with an average cost of $1,046 per patient, followed by ursodiol at $2,623 and watchful waiting at $3,964, said Dr. White of the surgery department at Dartmouth Hitchcock Medical Center, Lebanon, N.H.

The three treatments showed almost the same number of quality-adjusted life-years achieved: 21.39 years for concurrent cholecystectomy, 21.44 years for ursodiol, and 21.43 years for watchful waiting.

When the cost per quality-adjusted life-year of watchful waiting was computed for a population of patients, it was found to exceed the benchmark of what is considered a cost-effective strategy. Ursodiol, on the other hand, was cost-effective, as long as one considered it to be at least 60% effective in preventing gallstones.

On the basis of these findings, Dr. White and his associates concluded that “surgeons who currently employ a watchful waiting approach should consider either using ursodiol or performing a concurrent cholecystectomy.”

Studies have suggested that anywhere from 32% to 71% of patients who have a Roux-en-Y bypass will develop gallstones, he noted.

In a 2002 survey of surgeons who perform bariatric procedures, 30% said they use ursodiol treatment after a Roux-en-Y procedure, 15% remove the gallbladder routinely, and the remainder watch and wait, Dr. White said.

The landmark clinical trial of ursodiol treatment found that it reduced the rate of gallstone formation to 2%, from 32% in untreated controls.

In commenting on the analysis, Dr. David Flum said he thought the study was a timely piece of work, given the variations in practice, but that physicians perhaps should not put too much stock in a study that looked at the issues primarily from a cost perspective.

“We have to be very careful about the message we are sending when you only look at cost and quality-adjusted life-years,” said Dr. Flum of the University of Washington, Seattle. Bile duct injury may occur with gallbladder removal, and it has a devastating impact on the patient, he cautioned. And the situation may be changing as more procedures are done laparoscopically, when removing the gallbladder is more difficult.

Moreover, it is not clear how effective ursodiol treatment is, even when patients are compliant. Studies have shown that patients dislike taking it so much that at least half of them stop.

“I think that a lot of people will take this study and interpret it in different ways,” Dr. Flum added.

SAN FRANCISCO — For patients undergoing Roux-en-Y gastric bypass surgery, concurrent cholecystectomy or treatment with ursodiol is more cost-effective than leaving patients alone and waiting to see if they develop gallstones, Dr. Brent C. White reported.

The combined intervention also provides a better quality of life, according to an analysis that he presented at the annual clinical congress of the American College of Surgeons.

Dr. White and his colleagues performed a cost analysis that compared three treatment strategies for patients undergoing Roux-en-Y gastric bypass surgery: Giving ursodiol treatment for 6 months post operatively, performing concurrent cholecystectomy, and watchful waiting for possible gallstones. The analysis assumed that patients who developed gallstones during watchful waiting or while being treated with ursodiol would undergo cholecystectomy.

After culling information from the peer-reviewed literature, the investigators incorporated into the analysis data on the likelihood of a patient developing gallstones after a Roux-en-Y bypass, on the effectiveness of ursodiol treatment, and on the likelihood of complications with any of the strategies.

In their payer-perspective analysis, the investigators found that concurrent cholecystectomy was the least expensive treatment, with an average cost of $1,046 per patient, followed by ursodiol at $2,623 and watchful waiting at $3,964, said Dr. White of the surgery department at Dartmouth Hitchcock Medical Center, Lebanon, N.H.

The three treatments showed almost the same number of quality-adjusted life-years achieved: 21.39 years for concurrent cholecystectomy, 21.44 years for ursodiol, and 21.43 years for watchful waiting.

When the cost per quality-adjusted life-year of watchful waiting was computed for a population of patients, it was found to exceed the benchmark of what is considered a cost-effective strategy. Ursodiol, on the other hand, was cost-effective, as long as one considered it to be at least 60% effective in preventing gallstones.

On the basis of these findings, Dr. White and his associates concluded that “surgeons who currently employ a watchful waiting approach should consider either using ursodiol or performing a concurrent cholecystectomy.”

Studies have suggested that anywhere from 32% to 71% of patients who have a Roux-en-Y bypass will develop gallstones, he noted.

In a 2002 survey of surgeons who perform bariatric procedures, 30% said they use ursodiol treatment after a Roux-en-Y procedure, 15% remove the gallbladder routinely, and the remainder watch and wait, Dr. White said.

The landmark clinical trial of ursodiol treatment found that it reduced the rate of gallstone formation to 2%, from 32% in untreated controls.

In commenting on the analysis, Dr. David Flum said he thought the study was a timely piece of work, given the variations in practice, but that physicians perhaps should not put too much stock in a study that looked at the issues primarily from a cost perspective.

“We have to be very careful about the message we are sending when you only look at cost and quality-adjusted life-years,” said Dr. Flum of the University of Washington, Seattle. Bile duct injury may occur with gallbladder removal, and it has a devastating impact on the patient, he cautioned. And the situation may be changing as more procedures are done laparoscopically, when removing the gallbladder is more difficult.

Moreover, it is not clear how effective ursodiol treatment is, even when patients are compliant. Studies have shown that patients dislike taking it so much that at least half of them stop.

“I think that a lot of people will take this study and interpret it in different ways,” Dr. Flum added.

SAN FRANCISCO — For patients undergoing Roux-en-Y gastric bypass surgery, concurrent cholecystectomy or treatment with ursodiol is more cost-effective than leaving patients alone and waiting to see if they develop gallstones, Dr. Brent C. White reported.

The combined intervention also provides a better quality of life, according to an analysis that he presented at the annual clinical congress of the American College of Surgeons.

Dr. White and his colleagues performed a cost analysis that compared three treatment strategies for patients undergoing Roux-en-Y gastric bypass surgery: Giving ursodiol treatment for 6 months post operatively, performing concurrent cholecystectomy, and watchful waiting for possible gallstones. The analysis assumed that patients who developed gallstones during watchful waiting or while being treated with ursodiol would undergo cholecystectomy.

After culling information from the peer-reviewed literature, the investigators incorporated into the analysis data on the likelihood of a patient developing gallstones after a Roux-en-Y bypass, on the effectiveness of ursodiol treatment, and on the likelihood of complications with any of the strategies.

In their payer-perspective analysis, the investigators found that concurrent cholecystectomy was the least expensive treatment, with an average cost of $1,046 per patient, followed by ursodiol at $2,623 and watchful waiting at $3,964, said Dr. White of the surgery department at Dartmouth Hitchcock Medical Center, Lebanon, N.H.

The three treatments showed almost the same number of quality-adjusted life-years achieved: 21.39 years for concurrent cholecystectomy, 21.44 years for ursodiol, and 21.43 years for watchful waiting.

When the cost per quality-adjusted life-year of watchful waiting was computed for a population of patients, it was found to exceed the benchmark of what is considered a cost-effective strategy. Ursodiol, on the other hand, was cost-effective, as long as one considered it to be at least 60% effective in preventing gallstones.

On the basis of these findings, Dr. White and his associates concluded that “surgeons who currently employ a watchful waiting approach should consider either using ursodiol or performing a concurrent cholecystectomy.”

Studies have suggested that anywhere from 32% to 71% of patients who have a Roux-en-Y bypass will develop gallstones, he noted.

In a 2002 survey of surgeons who perform bariatric procedures, 30% said they use ursodiol treatment after a Roux-en-Y procedure, 15% remove the gallbladder routinely, and the remainder watch and wait, Dr. White said.

The landmark clinical trial of ursodiol treatment found that it reduced the rate of gallstone formation to 2%, from 32% in untreated controls.

In commenting on the analysis, Dr. David Flum said he thought the study was a timely piece of work, given the variations in practice, but that physicians perhaps should not put too much stock in a study that looked at the issues primarily from a cost perspective.

“We have to be very careful about the message we are sending when you only look at cost and quality-adjusted life-years,” said Dr. Flum of the University of Washington, Seattle. Bile duct injury may occur with gallbladder removal, and it has a devastating impact on the patient, he cautioned. And the situation may be changing as more procedures are done laparoscopically, when removing the gallbladder is more difficult.

Moreover, it is not clear how effective ursodiol treatment is, even when patients are compliant. Studies have shown that patients dislike taking it so much that at least half of them stop.

“I think that a lot of people will take this study and interpret it in different ways,” Dr. Flum added.

VANCOUVER, B.C. — Malignant melanoma is associated with Parkinson's disease, Dr. Darrell S. Rigel reported at the Sixth World Congress on Melanoma.

A case control study of 862 melanoma patients culled from 10 academic centers found that 3% also had Parkinson's disease, compared with only 1% of 862 age- and sex-matched controls, Dr. Rigel, of New York University, New York, said in a poster presentation.

Of the 351 subjects over the age of 60 years, 7% had Parkinson's disease, compared with 3% of the controls.

The study is the first to report an increased prevalence of any nonneoplastic disease in malignant melanoma patients, and it is consistent with reports that have suggested an increased incidence of melanoma in Parkinson's disease patients, Dr. Rigel said.

Parkinson's disease patients have been reported to have a lower rate of cancer overall, except for thyroid cancer and melanoma.

Possible reasons for the association include the fact that melanocytes and dopaminergic neurons are derived from the same embryonic tissue, that a particular cytochrome P450 polymorphism is associated with both diseases, and that neuromelanin and cutaneous melanin are similar.

It also has been suggested by some that levodopa plays a role, since there are shared pathways between the synthesis of dopamine and melanin, and the Physicians' Desk Reference lists levodopa as a contraindication in patients with suspicious skin lesions or a history of melanoma.

However, case control studies have suggested that the drug is not responsible for the association between melanoma and Parkinson's disease.

VANCOUVER, B.C. — Malignant melanoma is associated with Parkinson's disease, Dr. Darrell S. Rigel reported at the Sixth World Congress on Melanoma.

A case control study of 862 melanoma patients culled from 10 academic centers found that 3% also had Parkinson's disease, compared with only 1% of 862 age- and sex-matched controls, Dr. Rigel, of New York University, New York, said in a poster presentation.

Of the 351 subjects over the age of 60 years, 7% had Parkinson's disease, compared with 3% of the controls.

The study is the first to report an increased prevalence of any nonneoplastic disease in malignant melanoma patients, and it is consistent with reports that have suggested an increased incidence of melanoma in Parkinson's disease patients, Dr. Rigel said.

Parkinson's disease patients have been reported to have a lower rate of cancer overall, except for thyroid cancer and melanoma.

Possible reasons for the association include the fact that melanocytes and dopaminergic neurons are derived from the same embryonic tissue, that a particular cytochrome P450 polymorphism is associated with both diseases, and that neuromelanin and cutaneous melanin are similar.

It also has been suggested by some that levodopa plays a role, since there are shared pathways between the synthesis of dopamine and melanin, and the Physicians' Desk Reference lists levodopa as a contraindication in patients with suspicious skin lesions or a history of melanoma.

However, case control studies have suggested that the drug is not responsible for the association between melanoma and Parkinson's disease.

VANCOUVER, B.C. — Malignant melanoma is associated with Parkinson's disease, Dr. Darrell S. Rigel reported at the Sixth World Congress on Melanoma.

A case control study of 862 melanoma patients culled from 10 academic centers found that 3% also had Parkinson's disease, compared with only 1% of 862 age- and sex-matched controls, Dr. Rigel, of New York University, New York, said in a poster presentation.

Of the 351 subjects over the age of 60 years, 7% had Parkinson's disease, compared with 3% of the controls.

The study is the first to report an increased prevalence of any nonneoplastic disease in malignant melanoma patients, and it is consistent with reports that have suggested an increased incidence of melanoma in Parkinson's disease patients, Dr. Rigel said.

Parkinson's disease patients have been reported to have a lower rate of cancer overall, except for thyroid cancer and melanoma.

Possible reasons for the association include the fact that melanocytes and dopaminergic neurons are derived from the same embryonic tissue, that a particular cytochrome P450 polymorphism is associated with both diseases, and that neuromelanin and cutaneous melanin are similar.

It also has been suggested by some that levodopa plays a role, since there are shared pathways between the synthesis of dopamine and melanin, and the Physicians' Desk Reference lists levodopa as a contraindication in patients with suspicious skin lesions or a history of melanoma.

However, case control studies have suggested that the drug is not responsible for the association between melanoma and Parkinson's disease.

SAN DIEGO — Febuxostat was more effective than allopurinol for management of gout, even in patients with moderate renal impairment, according to data from a company-sponsored trial.

The 28-week trial, Febuxostat vs. Allopurinol and Placebo in Subjects With Hyperuricemia and Gout, known as APEX, revealed that 4 of 9 gout patients with moderate renal impairment (serum creatinine between 1.6 and 2 mg/dL) who received febuxostat at a dose of 80 mg/day achieved a serum urate level less than 6 mg/dL in their final three measurements, as did 5 of 11 patients who received 120 mg/day and 3 of 5 patients who received 240 mg/day.

None of the 10 patients with moderate renal impairment who received allopurinol, at 100 mg a day, achieved that goal, Dr. H. Ralph Schumacher said at the annual meeting of the American College of Rheumatology.

Phase III results from the company-sponsored trial on febuxostat for gout were first reported at last year's annual meeting of the American College of Rheumatology. The presentation at the most recent ACR annual meeting included data on more patients as well as on those with renal impairment; the trial was shorter than the earlier investigation. Dr. Schumacher's new report included data on 1,067 patients with gout and a serum urate level greater than 8 mg/dL followed for 28 weeks. Last year's report was on 760 patients, followed for 52 weeks.

The new results were very similar to last year's. Febuxostat at a dose of 80 mg a day decreased serum urate levels below 6 mg/dL in the last three measurements in 48% of patients. A dose of 120 mg a day reduced the last three measurements below 6 mg/dL in 65% of patients, and 240 mg a day reduced the last three measurements below 6 mg/dL in 69%.

The patients without renal impairment who received allopurinol received a dose of 300 mg a day, and, in those patients, the allopurinol reduced the last three measurements below 6 mg/dL in 20% of the group. No such decrease occurred in patients on placebo.

Noting that the study's primary requirement that patients have all three of their final serum urate measurements below 6 mg/dL to be considered a success is a “rigorous and demanding end point,” Dr. Schumacher also noted that 90% of the patients on febuxostat had at least one serum urate measurement below 6 mg/dL during the trial. That compared with 40% of those on allopurinol and none on placebo. Seventy-five percent of the subjects on 240 mg a day of febuxostat got at least one serum urate measurement below 4 mg/dL.

Tophi of the hands and feet decreased in size in patients on either active treatment, but the change was more significant among patients taking febuxostat, said Dr. Schumacher, professor of medicine at the University of Pennsylvania, Philadelphia.

Types of adverse events were similar in the patients with and without moderate renal impairment; dose of febuxostat did not have an effect on adverse events, Dr. Schumacher added.

Gastrointestinal adverse events were most common and included diarrhea in 2%–4% of the patients on febuxostat and 7% of those on allopurinol.

Liver function abnormalities occurred in some patients and were deemed to be the result of colchicine use, used to manage gout flares and of little clinical concern, Dr. Schumacher said. Patients in all the groups had flares, particularly those on the highest dose of febuxostat, though the flares decreased over time.

Serum creatinine levels did increase slightly with febuxostat treatment. But those levels did not increase to any greater degree in the patients with moderate renal impairment than they did in those without renal impairment, added Dr. Schumacher, who reported receiving funding from the company that makes febuxostat, TAP Pharmaceutical Products Inc., Lake Forest, Ill.

SAN DIEGO — Febuxostat was more effective than allopurinol for management of gout, even in patients with moderate renal impairment, according to data from a company-sponsored trial.

The 28-week trial, Febuxostat vs. Allopurinol and Placebo in Subjects With Hyperuricemia and Gout, known as APEX, revealed that 4 of 9 gout patients with moderate renal impairment (serum creatinine between 1.6 and 2 mg/dL) who received febuxostat at a dose of 80 mg/day achieved a serum urate level less than 6 mg/dL in their final three measurements, as did 5 of 11 patients who received 120 mg/day and 3 of 5 patients who received 240 mg/day.

None of the 10 patients with moderate renal impairment who received allopurinol, at 100 mg a day, achieved that goal, Dr. H. Ralph Schumacher said at the annual meeting of the American College of Rheumatology.

Phase III results from the company-sponsored trial on febuxostat for gout were first reported at last year's annual meeting of the American College of Rheumatology. The presentation at the most recent ACR annual meeting included data on more patients as well as on those with renal impairment; the trial was shorter than the earlier investigation. Dr. Schumacher's new report included data on 1,067 patients with gout and a serum urate level greater than 8 mg/dL followed for 28 weeks. Last year's report was on 760 patients, followed for 52 weeks.

The new results were very similar to last year's. Febuxostat at a dose of 80 mg a day decreased serum urate levels below 6 mg/dL in the last three measurements in 48% of patients. A dose of 120 mg a day reduced the last three measurements below 6 mg/dL in 65% of patients, and 240 mg a day reduced the last three measurements below 6 mg/dL in 69%.

The patients without renal impairment who received allopurinol received a dose of 300 mg a day, and, in those patients, the allopurinol reduced the last three measurements below 6 mg/dL in 20% of the group. No such decrease occurred in patients on placebo.

Noting that the study's primary requirement that patients have all three of their final serum urate measurements below 6 mg/dL to be considered a success is a “rigorous and demanding end point,” Dr. Schumacher also noted that 90% of the patients on febuxostat had at least one serum urate measurement below 6 mg/dL during the trial. That compared with 40% of those on allopurinol and none on placebo. Seventy-five percent of the subjects on 240 mg a day of febuxostat got at least one serum urate measurement below 4 mg/dL.

Tophi of the hands and feet decreased in size in patients on either active treatment, but the change was more significant among patients taking febuxostat, said Dr. Schumacher, professor of medicine at the University of Pennsylvania, Philadelphia.

Types of adverse events were similar in the patients with and without moderate renal impairment; dose of febuxostat did not have an effect on adverse events, Dr. Schumacher added.

Gastrointestinal adverse events were most common and included diarrhea in 2%–4% of the patients on febuxostat and 7% of those on allopurinol.

Liver function abnormalities occurred in some patients and were deemed to be the result of colchicine use, used to manage gout flares and of little clinical concern, Dr. Schumacher said. Patients in all the groups had flares, particularly those on the highest dose of febuxostat, though the flares decreased over time.

Serum creatinine levels did increase slightly with febuxostat treatment. But those levels did not increase to any greater degree in the patients with moderate renal impairment than they did in those without renal impairment, added Dr. Schumacher, who reported receiving funding from the company that makes febuxostat, TAP Pharmaceutical Products Inc., Lake Forest, Ill.

SAN DIEGO — Febuxostat was more effective than allopurinol for management of gout, even in patients with moderate renal impairment, according to data from a company-sponsored trial.

The 28-week trial, Febuxostat vs. Allopurinol and Placebo in Subjects With Hyperuricemia and Gout, known as APEX, revealed that 4 of 9 gout patients with moderate renal impairment (serum creatinine between 1.6 and 2 mg/dL) who received febuxostat at a dose of 80 mg/day achieved a serum urate level less than 6 mg/dL in their final three measurements, as did 5 of 11 patients who received 120 mg/day and 3 of 5 patients who received 240 mg/day.

None of the 10 patients with moderate renal impairment who received allopurinol, at 100 mg a day, achieved that goal, Dr. H. Ralph Schumacher said at the annual meeting of the American College of Rheumatology.

Phase III results from the company-sponsored trial on febuxostat for gout were first reported at last year's annual meeting of the American College of Rheumatology. The presentation at the most recent ACR annual meeting included data on more patients as well as on those with renal impairment; the trial was shorter than the earlier investigation. Dr. Schumacher's new report included data on 1,067 patients with gout and a serum urate level greater than 8 mg/dL followed for 28 weeks. Last year's report was on 760 patients, followed for 52 weeks.

The new results were very similar to last year's. Febuxostat at a dose of 80 mg a day decreased serum urate levels below 6 mg/dL in the last three measurements in 48% of patients. A dose of 120 mg a day reduced the last three measurements below 6 mg/dL in 65% of patients, and 240 mg a day reduced the last three measurements below 6 mg/dL in 69%.

The patients without renal impairment who received allopurinol received a dose of 300 mg a day, and, in those patients, the allopurinol reduced the last three measurements below 6 mg/dL in 20% of the group. No such decrease occurred in patients on placebo.

Noting that the study's primary requirement that patients have all three of their final serum urate measurements below 6 mg/dL to be considered a success is a “rigorous and demanding end point,” Dr. Schumacher also noted that 90% of the patients on febuxostat had at least one serum urate measurement below 6 mg/dL during the trial. That compared with 40% of those on allopurinol and none on placebo. Seventy-five percent of the subjects on 240 mg a day of febuxostat got at least one serum urate measurement below 4 mg/dL.

Tophi of the hands and feet decreased in size in patients on either active treatment, but the change was more significant among patients taking febuxostat, said Dr. Schumacher, professor of medicine at the University of Pennsylvania, Philadelphia.

Types of adverse events were similar in the patients with and without moderate renal impairment; dose of febuxostat did not have an effect on adverse events, Dr. Schumacher added.

Gastrointestinal adverse events were most common and included diarrhea in 2%–4% of the patients on febuxostat and 7% of those on allopurinol.

Liver function abnormalities occurred in some patients and were deemed to be the result of colchicine use, used to manage gout flares and of little clinical concern, Dr. Schumacher said. Patients in all the groups had flares, particularly those on the highest dose of febuxostat, though the flares decreased over time.

Serum creatinine levels did increase slightly with febuxostat treatment. But those levels did not increase to any greater degree in the patients with moderate renal impairment than they did in those without renal impairment, added Dr. Schumacher, who reported receiving funding from the company that makes febuxostat, TAP Pharmaceutical Products Inc., Lake Forest, Ill.

SCOTTSDALE, ARIZ. — Alcohol abusers who take acamprosate and relapse are still better off continuing to take the drug because they have an improved chance of achieving abstinence, company data show.

Pooled data from three separate, controlled trials of the drug suggest that almost three times more patients treated through a relapse eventually achieve a period of abstinence, compared with controls, Dr. Eugene Schneider said in a poster presentation at the annual meeting of the American Academy of Addiction Psychiatry.

In the studies, most of the participants relapsed at some point. Of the 372 people treated with acamprosate (1,998 mg/day), 72% relapsed, and 85% of 375 placebo-control patients relapsed. One of the trials lasted 13 weeks, one lasted 48 weeks, and the third lasted 52 weeks.

Overall, 13% of the acamprosate-treated individuals who relapsed were subsequently abstinent for the remainder of the study and an additional 20% who relapsed were abstinent at their final study evaluation. The comparable figures for the control patients were 5% and 10%, respectively, said Dr. Schneider, an associate director for medical affairs at Forest Laboratories Inc., New York.

Acamprosate-treated patients who achieved a period of abstinence after relapse had a greater mean number of days of abstinence than did controls: 24 days vs. 14 days. In the patients who relapsed but eventually became abstinent for the remainder of the study, the treated patients were more likely to have had a longer abstinence: a mean of 28 days for the treated patients, compared with 12 days for the control patients.

“It is worthwhile treating patients through a relapse,” Dr. Schneider said in an interview.

SCOTTSDALE, ARIZ. — Alcohol abusers who take acamprosate and relapse are still better off continuing to take the drug because they have an improved chance of achieving abstinence, company data show.

Pooled data from three separate, controlled trials of the drug suggest that almost three times more patients treated through a relapse eventually achieve a period of abstinence, compared with controls, Dr. Eugene Schneider said in a poster presentation at the annual meeting of the American Academy of Addiction Psychiatry.

In the studies, most of the participants relapsed at some point. Of the 372 people treated with acamprosate (1,998 mg/day), 72% relapsed, and 85% of 375 placebo-control patients relapsed. One of the trials lasted 13 weeks, one lasted 48 weeks, and the third lasted 52 weeks.

Overall, 13% of the acamprosate-treated individuals who relapsed were subsequently abstinent for the remainder of the study and an additional 20% who relapsed were abstinent at their final study evaluation. The comparable figures for the control patients were 5% and 10%, respectively, said Dr. Schneider, an associate director for medical affairs at Forest Laboratories Inc., New York.

Acamprosate-treated patients who achieved a period of abstinence after relapse had a greater mean number of days of abstinence than did controls: 24 days vs. 14 days. In the patients who relapsed but eventually became abstinent for the remainder of the study, the treated patients were more likely to have had a longer abstinence: a mean of 28 days for the treated patients, compared with 12 days for the control patients.

“It is worthwhile treating patients through a relapse,” Dr. Schneider said in an interview.

SCOTTSDALE, ARIZ. — Alcohol abusers who take acamprosate and relapse are still better off continuing to take the drug because they have an improved chance of achieving abstinence, company data show.

Pooled data from three separate, controlled trials of the drug suggest that almost three times more patients treated through a relapse eventually achieve a period of abstinence, compared with controls, Dr. Eugene Schneider said in a poster presentation at the annual meeting of the American Academy of Addiction Psychiatry.

In the studies, most of the participants relapsed at some point. Of the 372 people treated with acamprosate (1,998 mg/day), 72% relapsed, and 85% of 375 placebo-control patients relapsed. One of the trials lasted 13 weeks, one lasted 48 weeks, and the third lasted 52 weeks.

Overall, 13% of the acamprosate-treated individuals who relapsed were subsequently abstinent for the remainder of the study and an additional 20% who relapsed were abstinent at their final study evaluation. The comparable figures for the control patients were 5% and 10%, respectively, said Dr. Schneider, an associate director for medical affairs at Forest Laboratories Inc., New York.

Acamprosate-treated patients who achieved a period of abstinence after relapse had a greater mean number of days of abstinence than did controls: 24 days vs. 14 days. In the patients who relapsed but eventually became abstinent for the remainder of the study, the treated patients were more likely to have had a longer abstinence: a mean of 28 days for the treated patients, compared with 12 days for the control patients.

“It is worthwhile treating patients through a relapse,” Dr. Schneider said in an interview.

SCOTTSDALE, ARIZ. — Most physicians who treat alcohol-dependent patients know that studies have shown that depressed patients are much less likely to quit, or reduce, their drinking.

It is less well known that treating depression in these patients can improve alcohol treatment results, Dr. Edward V. Nunes said at the annual meeting of the American Academy of Addiction Psychiatry.

“The evidence shows if you do careful diagnosis—preferably in the setting of abstinence, but not absolutely so—treatment works,” said Dr. Nunes, research director at the Substance Treatment and Research Service, New York.

Until recently, treating depression in alcoholic patients has not been a standard practice, because researchers have had difficulty proving its benefit, said Dr. Nunes, who reviewed the history of the research.

Studies conducted before the 1980s were mostly inconsistent, largely because of the absence of a standardized depression diagnosis that differentiated the effects of heavy alcohol use from primary depression in an alcohol abuser, said Dr. Nunes, who also is a psychiatrist at the New York State Psychiatric Institute.

Then the use of selective serotonin reuptake inhibitors (SSRIs) came into practice. But studies with SSRIs were generally seen as disappointing. Researchers interpreted study results to mean that the drugs appeared to reduce drinking behavior but had little impact on mood.

So, for a while it was thought that depression treatment was irrelevant to people seeking help with an alcohol problem.

One study that helped rekindle the idea of addressing depression in alcohol abusers was one that Dr. Nunes conducted.

He gave imipramine to a group of alcoholic patients who appeared to have depression. He then continued the study with the patients who responded to the treatment to potentially identify only those who had a true primary depression. These patients were randomized to continued treatment or to placebo.

Patients who were switched to placebo tended to get worse and relapse, whereas those who remained on imipramine continued to respond (Am. J. Psychiatry 1993;150:963–5).

The study has since been replicated, using a newly available diagnostic tool that helps identify primary depression from alcohol-induced depression, he said (Arch. Gen. Psychiatry 1996;53:232–40).

The more recent study suggested a response rate of 50% with imipramine treatment, compared with 25% for patients on placebo. Though the number of patients who achieved complete abstinence from alcohol was low, the study was able to show that drinking decreased and that mood was correlated with drinking behavior.

Recently, Dr. Nunes conducted a literature review and an analysis of 14 of the most rigorously conducted trials of depression treatment in substance abusers (mostly alcoholics), out of the 44 placebo-controlled trials identified in the review (JAMA 2004;291:1887–96).

Overall, the data from those studies suggest that depression drug treatment has a significant benefit, as measured by Hamilton Depression Scale scores. Not surprisingly, the benefit is similar in degree to that in drug studies for general depression: 50% of treated patients showed improvement, compared with 30% of placebo controls.

Deeper analysis showed that the six studies that failed to show a benefit from treatment tended to have high placebo response rates, in the range of 40%–60%.

These six studies also tended to have patients receive structured alcohol treatment psychotherapy, Dr. Nunes said.

Although his analysis could not show that SSRI treatment was effective, two of the four studies that used an SSRI did show treatment benefit. The other two appeared to be compromised by confounding problems the metaanalysis found, he added.

“I'm not sure the problem with [selective] serotonin reuptake inhibitors is the medication itself so much as it is the placebo response,” he said.

SCOTTSDALE, ARIZ. — Most physicians who treat alcohol-dependent patients know that studies have shown that depressed patients are much less likely to quit, or reduce, their drinking.

It is less well known that treating depression in these patients can improve alcohol treatment results, Dr. Edward V. Nunes said at the annual meeting of the American Academy of Addiction Psychiatry.

“The evidence shows if you do careful diagnosis—preferably in the setting of abstinence, but not absolutely so—treatment works,” said Dr. Nunes, research director at the Substance Treatment and Research Service, New York.

Until recently, treating depression in alcoholic patients has not been a standard practice, because researchers have had difficulty proving its benefit, said Dr. Nunes, who reviewed the history of the research.

Studies conducted before the 1980s were mostly inconsistent, largely because of the absence of a standardized depression diagnosis that differentiated the effects of heavy alcohol use from primary depression in an alcohol abuser, said Dr. Nunes, who also is a psychiatrist at the New York State Psychiatric Institute.

Then the use of selective serotonin reuptake inhibitors (SSRIs) came into practice. But studies with SSRIs were generally seen as disappointing. Researchers interpreted study results to mean that the drugs appeared to reduce drinking behavior but had little impact on mood.

So, for a while it was thought that depression treatment was irrelevant to people seeking help with an alcohol problem.

One study that helped rekindle the idea of addressing depression in alcohol abusers was one that Dr. Nunes conducted.

He gave imipramine to a group of alcoholic patients who appeared to have depression. He then continued the study with the patients who responded to the treatment to potentially identify only those who had a true primary depression. These patients were randomized to continued treatment or to placebo.

Patients who were switched to placebo tended to get worse and relapse, whereas those who remained on imipramine continued to respond (Am. J. Psychiatry 1993;150:963–5).

The study has since been replicated, using a newly available diagnostic tool that helps identify primary depression from alcohol-induced depression, he said (Arch. Gen. Psychiatry 1996;53:232–40).

The more recent study suggested a response rate of 50% with imipramine treatment, compared with 25% for patients on placebo. Though the number of patients who achieved complete abstinence from alcohol was low, the study was able to show that drinking decreased and that mood was correlated with drinking behavior.

Recently, Dr. Nunes conducted a literature review and an analysis of 14 of the most rigorously conducted trials of depression treatment in substance abusers (mostly alcoholics), out of the 44 placebo-controlled trials identified in the review (JAMA 2004;291:1887–96).

Overall, the data from those studies suggest that depression drug treatment has a significant benefit, as measured by Hamilton Depression Scale scores. Not surprisingly, the benefit is similar in degree to that in drug studies for general depression: 50% of treated patients showed improvement, compared with 30% of placebo controls.

Deeper analysis showed that the six studies that failed to show a benefit from treatment tended to have high placebo response rates, in the range of 40%–60%.

These six studies also tended to have patients receive structured alcohol treatment psychotherapy, Dr. Nunes said.

Although his analysis could not show that SSRI treatment was effective, two of the four studies that used an SSRI did show treatment benefit. The other two appeared to be compromised by confounding problems the metaanalysis found, he added.

“I'm not sure the problem with [selective] serotonin reuptake inhibitors is the medication itself so much as it is the placebo response,” he said.

SCOTTSDALE, ARIZ. — Most physicians who treat alcohol-dependent patients know that studies have shown that depressed patients are much less likely to quit, or reduce, their drinking.

It is less well known that treating depression in these patients can improve alcohol treatment results, Dr. Edward V. Nunes said at the annual meeting of the American Academy of Addiction Psychiatry.

“The evidence shows if you do careful diagnosis—preferably in the setting of abstinence, but not absolutely so—treatment works,” said Dr. Nunes, research director at the Substance Treatment and Research Service, New York.

Until recently, treating depression in alcoholic patients has not been a standard practice, because researchers have had difficulty proving its benefit, said Dr. Nunes, who reviewed the history of the research.

Studies conducted before the 1980s were mostly inconsistent, largely because of the absence of a standardized depression diagnosis that differentiated the effects of heavy alcohol use from primary depression in an alcohol abuser, said Dr. Nunes, who also is a psychiatrist at the New York State Psychiatric Institute.

Then the use of selective serotonin reuptake inhibitors (SSRIs) came into practice. But studies with SSRIs were generally seen as disappointing. Researchers interpreted study results to mean that the drugs appeared to reduce drinking behavior but had little impact on mood.

So, for a while it was thought that depression treatment was irrelevant to people seeking help with an alcohol problem.

One study that helped rekindle the idea of addressing depression in alcohol abusers was one that Dr. Nunes conducted.

He gave imipramine to a group of alcoholic patients who appeared to have depression. He then continued the study with the patients who responded to the treatment to potentially identify only those who had a true primary depression. These patients were randomized to continued treatment or to placebo.

Patients who were switched to placebo tended to get worse and relapse, whereas those who remained on imipramine continued to respond (Am. J. Psychiatry 1993;150:963–5).

The study has since been replicated, using a newly available diagnostic tool that helps identify primary depression from alcohol-induced depression, he said (Arch. Gen. Psychiatry 1996;53:232–40).

The more recent study suggested a response rate of 50% with imipramine treatment, compared with 25% for patients on placebo. Though the number of patients who achieved complete abstinence from alcohol was low, the study was able to show that drinking decreased and that mood was correlated with drinking behavior.

Recently, Dr. Nunes conducted a literature review and an analysis of 14 of the most rigorously conducted trials of depression treatment in substance abusers (mostly alcoholics), out of the 44 placebo-controlled trials identified in the review (JAMA 2004;291:1887–96).

Overall, the data from those studies suggest that depression drug treatment has a significant benefit, as measured by Hamilton Depression Scale scores. Not surprisingly, the benefit is similar in degree to that in drug studies for general depression: 50% of treated patients showed improvement, compared with 30% of placebo controls.

Deeper analysis showed that the six studies that failed to show a benefit from treatment tended to have high placebo response rates, in the range of 40%–60%.

These six studies also tended to have patients receive structured alcohol treatment psychotherapy, Dr. Nunes said.

Although his analysis could not show that SSRI treatment was effective, two of the four studies that used an SSRI did show treatment benefit. The other two appeared to be compromised by confounding problems the metaanalysis found, he added.

“I'm not sure the problem with [selective] serotonin reuptake inhibitors is the medication itself so much as it is the placebo response,” he said.