AAAP Annual Meeting; the Annual Meeting Of the American Academy Of Addiction Psychiatry

AVENTURA, FLA. – Clinicians interested in providing naloxone for their patients at risk for an opioid overdose should consider the pros and cons of the different formulations, addiction medicine specialists say.

In addition, clinicians should become familiar with legislation affecting how naloxone can be prescribed to lay persons in their state, according to the specialists, who spoke at the annual meeting of the American Academy of Addiction Psychiatry.

During a workshop on expanding access to the opioid antagonist to patients at risk and their families to help prevent opioid overdoses, Dr. Eric D. Collins, physician-in-chief at Silver Hill Hospital, New Canaan, Conn., described naloxone as “an effective and generally safe intervention that requires minimal training” and can be administered by a layperson. “Any prescriber can provide naloxone to persons at risk of opioid overdose” and in some states, can provide naloxone to anyone at risk of witnessing an opioid overdose, he added.

Dr. Seddon R. Savage, director of the Dartmouth Center on Addiction Recovery and Education, Hanover, N.H., said that although providing naloxone is a late intervention, it saves lives. “So clearly, it is critical that we embrace that strategy,” she said.

Providing naloxone is among the current strategies used to address the misuse of prescription opioids and to reduce mortality and morbidity related to opioids. These strategies include the development of tamper-resistant products, public campaigns increasing awareness about the importance of locking up pain medications and disposing of them safely, drug take back programs, and pharmacy-based interventions.

Overdose death rates fall

To date, “good solid evidence for efficacy in reducing mortality and opioid overdoses only exists” for maintenance therapy of opioid dependence and naloxone distribution, said Dr. Savage, who also is medical director of the chronic pain and addiction program at Silver Hill Hospital. She cited a 2013 study that found a significant reduction in opioid overdose deaths rate after a program that provided education about overdoses and nasal naloxone kits to potential bystanders (users, families, and friends) was implemented in 19 communities in Massachusetts with high overdose rates. Training included 10-60 minutes of training in recognizing and intervening in an overdose (BMJ 2013; 346:f174).

For pain medicine specialists, Dr. Savage said, “it is reasonable to consider” providing naloxone to patients at risk for overuse tied to unmet pain needs, accidental overuse, or self-treatment of other symptoms; as well as those with history of recreational drug use or addiction. Primary care clinicians can target their patients being treated with opioids for pain and those with known or a suspected addiction to opioids. Addiction medicine specialists can consider prescribing naloxone to their patients with opioid addiction on or off opioid agonist therapy (OAT), such as buprenorphine.

However, challenges prevail in prescribing naloxone, which include wide variations in naloxone legislation and Good Samaritan laws in states, resources needed to train lay people to administer naloxone, and recent increases in the cost of intranasal naloxone. The latter is the most widely used form of the drug to treat overdoses, said Dr. Savage, who also is affiliated with Dartmouth Medical School in Hanover.

Familiarity with laws advised

Dr. Savage advised clinicians to become familiar with the policies regarding naloxone prescribing and Good Samaritan laws in their jurisdictions. Legislation that exists in some states but not others include protection from possession of controlled substance and paraphernalia (in 22 states and the District of Columbia [D.C.] as of August 2014), protection from criminal liability for lay administration of naloxone (23 states and D.C.), protection from civil liability for lay administration (20 states and D.C.) and protection of prescribers from criminal liability (13 states). In 24 states, third party prescribing is allowed.

Naloxone – which binds to opioid receptors and in patients on opioids, thereby reversing the effects of opioids, including respiratory depression – can precipitate opioid withdrawal symptoms in some patients, said Dr. Collins, who also is affiliated with Columbia University in New York. He referred to a 2004 study that found that the most common adverse events after naloxone was used to treated a suspected opioid overdose outside of the hospital were confusion ( 32%) and headache (22%), nausea and vomiting (9%), and aggressiveness (8%), but serious complications were rare (Eur. J. Emerg. Med. 2004;11:19-23). Seizures were reported in 4% and tachycardia was reported in 6%. Dr. Collins said he has never seen a case of allergy to naloxone, the only contraindication to the drug.

Since aggressiveness might be associated with withdrawal, Dr. Savage said training for naloxone providers often includes how to manage a combative person. The risk of tachycardia has been raised as a concern, particularly in situations where law enforcement personnel who are not medically trained are delivering naloxone, but those patients are transported to medical facilities, she pointed out.

Intranasal (IN) naloxone, which is not approved by the Food and Drug Administration, is the most widely used method of administering naloxone by police and other first responders. They use a standard dose of 0.4 contained in a syringe with an atomizer, delivering one 0.2 mg dose per nostril. Another option is the autoinjector that provides an injection of naloxone with a speaker that provides instructions guiding the user. This option was approved by the FDA in 2014.

Evidence that the intranasal form is effective dates back to 2005, with a study that found a dose of 2 mg/2 cc in a prefilled syringe delivered with an atomizer by Denver paramedics was effective in 43 of 52 (83%) people. IV naloxone was needed in nine individuals who did not respond to the IN dose, including five who had nasal pathology (J. Emerg. Med. 2005; 29:265-71). In a more recent study that randomized 100 patients admitted to an emergency department with an opioid overdose to a lower IN dose (0.4 mg) or IV naloxone, the IN route proved as effective as the IV route in reversing respiratory depression and central nervous system effects (Arch. Med. Sci. 2014;10:309-14).

Courtesy Silver Hill Hospital, New Canaan, Conn.

Broad effectiveness found

Dr. Collins said the various options have advantages and drawbacks, and if only one option is available for whatever reason, “they all work.” IM and IV formulations have the fastest onset of action, are the least expensive, and are FDA-approved but carry the risk of a needlestick injury. IN naloxone is not FDA-approved, and might have a slightly slower and less predictable effect but has no risk of a needlestick injury. In addition, IN naloxone is inexpensive and easy to use. The recently FDA-approved Evzio autoinjector pre-filled with naloxone solution, administered IM or subcutaneously, has a faster onset with a predictable effect and no risk of a needle stick. It also includes audio instructions that walks the user through its use. But it costs about $400 per kit, which is a drawback, he said.

Dr. Savage pointed out that administering naloxone is only part of intervening in an opioid overdose and that training is needed when naloxone is dispensed or prescribed to patients or their families. Included in such training would be when to call for help, how to identify signs of an overdose, how to position patients for rescue, understanding rescue breathing, and knowing when the admininstration of naloxone is indicated. Since naloxone wears off in about half an hour, depending on the route and other variables, people should be told that they need to call for emergency support and transport for ongoing care because many opioids end up lasting longer than the effects of naloxone.

The FDA is considering making naloxone available over the counter, but such a move will take several years. It can be provided by pharmacies in states that have a collaborative practice agreement in place that supports distribution to people addicted to opioids, their families, and friends, she said. For example, in Rhode Island, a collaborative practice agreement exists allowing Walgreens pharmacies to dispense naloxone without a prescription.

Based on an informal poll taken during the workshop, none of those in attendance had started to prescribe naloxone for their patients, although they were interested in doing so or were figuring out how to make it available. During the discussion period, barriers they cited included the time and resources needed to train people to administer naloxone, the cost, and the lack of awareness among pharmacies about their ability to obtain intranasal kits. Suggestions among participants include having nurses or pain medicine fellows provide training and education, and using videos for training. A physician at the Atlanta Veterans Affairs Medical Center pointed out that naloxone is provided at no charge to all VA hospitals, although patients might have a co-pay.

Among the resources provided by Dr. Savage and Dr. Collins for clinicians interested in providing naloxone to patients at risk of an opioid overdose and to family members of others who might witness an overdose was an American Medical Association webinar on naloxone safety, information on how to start prescribing and dispensing naloxone rescue kits, and patient information videos. More information on how to start a program is available at http://www.naloxoneinfo.org.

Dr. Savage and Dr. Collins said they had no direct commercial interests related to the topic of the workshop.

[email protected]

AVENTURA, FLA. – Clinicians interested in providing naloxone for their patients at risk for an opioid overdose should consider the pros and cons of the different formulations, addiction medicine specialists say.

In addition, clinicians should become familiar with legislation affecting how naloxone can be prescribed to lay persons in their state, according to the specialists, who spoke at the annual meeting of the American Academy of Addiction Psychiatry.

During a workshop on expanding access to the opioid antagonist to patients at risk and their families to help prevent opioid overdoses, Dr. Eric D. Collins, physician-in-chief at Silver Hill Hospital, New Canaan, Conn., described naloxone as “an effective and generally safe intervention that requires minimal training” and can be administered by a layperson. “Any prescriber can provide naloxone to persons at risk of opioid overdose” and in some states, can provide naloxone to anyone at risk of witnessing an opioid overdose, he added.

Dr. Seddon R. Savage, director of the Dartmouth Center on Addiction Recovery and Education, Hanover, N.H., said that although providing naloxone is a late intervention, it saves lives. “So clearly, it is critical that we embrace that strategy,” she said.

Providing naloxone is among the current strategies used to address the misuse of prescription opioids and to reduce mortality and morbidity related to opioids. These strategies include the development of tamper-resistant products, public campaigns increasing awareness about the importance of locking up pain medications and disposing of them safely, drug take back programs, and pharmacy-based interventions.

Overdose death rates fall

To date, “good solid evidence for efficacy in reducing mortality and opioid overdoses only exists” for maintenance therapy of opioid dependence and naloxone distribution, said Dr. Savage, who also is medical director of the chronic pain and addiction program at Silver Hill Hospital. She cited a 2013 study that found a significant reduction in opioid overdose deaths rate after a program that provided education about overdoses and nasal naloxone kits to potential bystanders (users, families, and friends) was implemented in 19 communities in Massachusetts with high overdose rates. Training included 10-60 minutes of training in recognizing and intervening in an overdose (BMJ 2013; 346:f174).

For pain medicine specialists, Dr. Savage said, “it is reasonable to consider” providing naloxone to patients at risk for overuse tied to unmet pain needs, accidental overuse, or self-treatment of other symptoms; as well as those with history of recreational drug use or addiction. Primary care clinicians can target their patients being treated with opioids for pain and those with known or a suspected addiction to opioids. Addiction medicine specialists can consider prescribing naloxone to their patients with opioid addiction on or off opioid agonist therapy (OAT), such as buprenorphine.

However, challenges prevail in prescribing naloxone, which include wide variations in naloxone legislation and Good Samaritan laws in states, resources needed to train lay people to administer naloxone, and recent increases in the cost of intranasal naloxone. The latter is the most widely used form of the drug to treat overdoses, said Dr. Savage, who also is affiliated with Dartmouth Medical School in Hanover.

Familiarity with laws advised

Dr. Savage advised clinicians to become familiar with the policies regarding naloxone prescribing and Good Samaritan laws in their jurisdictions. Legislation that exists in some states but not others include protection from possession of controlled substance and paraphernalia (in 22 states and the District of Columbia [D.C.] as of August 2014), protection from criminal liability for lay administration of naloxone (23 states and D.C.), protection from civil liability for lay administration (20 states and D.C.) and protection of prescribers from criminal liability (13 states). In 24 states, third party prescribing is allowed.

Naloxone – which binds to opioid receptors and in patients on opioids, thereby reversing the effects of opioids, including respiratory depression – can precipitate opioid withdrawal symptoms in some patients, said Dr. Collins, who also is affiliated with Columbia University in New York. He referred to a 2004 study that found that the most common adverse events after naloxone was used to treated a suspected opioid overdose outside of the hospital were confusion ( 32%) and headache (22%), nausea and vomiting (9%), and aggressiveness (8%), but serious complications were rare (Eur. J. Emerg. Med. 2004;11:19-23). Seizures were reported in 4% and tachycardia was reported in 6%. Dr. Collins said he has never seen a case of allergy to naloxone, the only contraindication to the drug.

Since aggressiveness might be associated with withdrawal, Dr. Savage said training for naloxone providers often includes how to manage a combative person. The risk of tachycardia has been raised as a concern, particularly in situations where law enforcement personnel who are not medically trained are delivering naloxone, but those patients are transported to medical facilities, she pointed out.

Intranasal (IN) naloxone, which is not approved by the Food and Drug Administration, is the most widely used method of administering naloxone by police and other first responders. They use a standard dose of 0.4 contained in a syringe with an atomizer, delivering one 0.2 mg dose per nostril. Another option is the autoinjector that provides an injection of naloxone with a speaker that provides instructions guiding the user. This option was approved by the FDA in 2014.

Evidence that the intranasal form is effective dates back to 2005, with a study that found a dose of 2 mg/2 cc in a prefilled syringe delivered with an atomizer by Denver paramedics was effective in 43 of 52 (83%) people. IV naloxone was needed in nine individuals who did not respond to the IN dose, including five who had nasal pathology (J. Emerg. Med. 2005; 29:265-71). In a more recent study that randomized 100 patients admitted to an emergency department with an opioid overdose to a lower IN dose (0.4 mg) or IV naloxone, the IN route proved as effective as the IV route in reversing respiratory depression and central nervous system effects (Arch. Med. Sci. 2014;10:309-14).

Courtesy Silver Hill Hospital, New Canaan, Conn.

Broad effectiveness found

Dr. Collins said the various options have advantages and drawbacks, and if only one option is available for whatever reason, “they all work.” IM and IV formulations have the fastest onset of action, are the least expensive, and are FDA-approved but carry the risk of a needlestick injury. IN naloxone is not FDA-approved, and might have a slightly slower and less predictable effect but has no risk of a needlestick injury. In addition, IN naloxone is inexpensive and easy to use. The recently FDA-approved Evzio autoinjector pre-filled with naloxone solution, administered IM or subcutaneously, has a faster onset with a predictable effect and no risk of a needle stick. It also includes audio instructions that walks the user through its use. But it costs about $400 per kit, which is a drawback, he said.

Dr. Savage pointed out that administering naloxone is only part of intervening in an opioid overdose and that training is needed when naloxone is dispensed or prescribed to patients or their families. Included in such training would be when to call for help, how to identify signs of an overdose, how to position patients for rescue, understanding rescue breathing, and knowing when the admininstration of naloxone is indicated. Since naloxone wears off in about half an hour, depending on the route and other variables, people should be told that they need to call for emergency support and transport for ongoing care because many opioids end up lasting longer than the effects of naloxone.

The FDA is considering making naloxone available over the counter, but such a move will take several years. It can be provided by pharmacies in states that have a collaborative practice agreement in place that supports distribution to people addicted to opioids, their families, and friends, she said. For example, in Rhode Island, a collaborative practice agreement exists allowing Walgreens pharmacies to dispense naloxone without a prescription.

Based on an informal poll taken during the workshop, none of those in attendance had started to prescribe naloxone for their patients, although they were interested in doing so or were figuring out how to make it available. During the discussion period, barriers they cited included the time and resources needed to train people to administer naloxone, the cost, and the lack of awareness among pharmacies about their ability to obtain intranasal kits. Suggestions among participants include having nurses or pain medicine fellows provide training and education, and using videos for training. A physician at the Atlanta Veterans Affairs Medical Center pointed out that naloxone is provided at no charge to all VA hospitals, although patients might have a co-pay.

Among the resources provided by Dr. Savage and Dr. Collins for clinicians interested in providing naloxone to patients at risk of an opioid overdose and to family members of others who might witness an overdose was an American Medical Association webinar on naloxone safety, information on how to start prescribing and dispensing naloxone rescue kits, and patient information videos. More information on how to start a program is available at http://www.naloxoneinfo.org.

Dr. Savage and Dr. Collins said they had no direct commercial interests related to the topic of the workshop.

[email protected]

AVENTURA, FLA. – Clinicians interested in providing naloxone for their patients at risk for an opioid overdose should consider the pros and cons of the different formulations, addiction medicine specialists say.

In addition, clinicians should become familiar with legislation affecting how naloxone can be prescribed to lay persons in their state, according to the specialists, who spoke at the annual meeting of the American Academy of Addiction Psychiatry.

During a workshop on expanding access to the opioid antagonist to patients at risk and their families to help prevent opioid overdoses, Dr. Eric D. Collins, physician-in-chief at Silver Hill Hospital, New Canaan, Conn., described naloxone as “an effective and generally safe intervention that requires minimal training” and can be administered by a layperson. “Any prescriber can provide naloxone to persons at risk of opioid overdose” and in some states, can provide naloxone to anyone at risk of witnessing an opioid overdose, he added.

Dr. Seddon R. Savage, director of the Dartmouth Center on Addiction Recovery and Education, Hanover, N.H., said that although providing naloxone is a late intervention, it saves lives. “So clearly, it is critical that we embrace that strategy,” she said.

Providing naloxone is among the current strategies used to address the misuse of prescription opioids and to reduce mortality and morbidity related to opioids. These strategies include the development of tamper-resistant products, public campaigns increasing awareness about the importance of locking up pain medications and disposing of them safely, drug take back programs, and pharmacy-based interventions.

Overdose death rates fall

To date, “good solid evidence for efficacy in reducing mortality and opioid overdoses only exists” for maintenance therapy of opioid dependence and naloxone distribution, said Dr. Savage, who also is medical director of the chronic pain and addiction program at Silver Hill Hospital. She cited a 2013 study that found a significant reduction in opioid overdose deaths rate after a program that provided education about overdoses and nasal naloxone kits to potential bystanders (users, families, and friends) was implemented in 19 communities in Massachusetts with high overdose rates. Training included 10-60 minutes of training in recognizing and intervening in an overdose (BMJ 2013; 346:f174).

For pain medicine specialists, Dr. Savage said, “it is reasonable to consider” providing naloxone to patients at risk for overuse tied to unmet pain needs, accidental overuse, or self-treatment of other symptoms; as well as those with history of recreational drug use or addiction. Primary care clinicians can target their patients being treated with opioids for pain and those with known or a suspected addiction to opioids. Addiction medicine specialists can consider prescribing naloxone to their patients with opioid addiction on or off opioid agonist therapy (OAT), such as buprenorphine.

However, challenges prevail in prescribing naloxone, which include wide variations in naloxone legislation and Good Samaritan laws in states, resources needed to train lay people to administer naloxone, and recent increases in the cost of intranasal naloxone. The latter is the most widely used form of the drug to treat overdoses, said Dr. Savage, who also is affiliated with Dartmouth Medical School in Hanover.

Familiarity with laws advised

Dr. Savage advised clinicians to become familiar with the policies regarding naloxone prescribing and Good Samaritan laws in their jurisdictions. Legislation that exists in some states but not others include protection from possession of controlled substance and paraphernalia (in 22 states and the District of Columbia [D.C.] as of August 2014), protection from criminal liability for lay administration of naloxone (23 states and D.C.), protection from civil liability for lay administration (20 states and D.C.) and protection of prescribers from criminal liability (13 states). In 24 states, third party prescribing is allowed.

Naloxone – which binds to opioid receptors and in patients on opioids, thereby reversing the effects of opioids, including respiratory depression – can precipitate opioid withdrawal symptoms in some patients, said Dr. Collins, who also is affiliated with Columbia University in New York. He referred to a 2004 study that found that the most common adverse events after naloxone was used to treated a suspected opioid overdose outside of the hospital were confusion ( 32%) and headache (22%), nausea and vomiting (9%), and aggressiveness (8%), but serious complications were rare (Eur. J. Emerg. Med. 2004;11:19-23). Seizures were reported in 4% and tachycardia was reported in 6%. Dr. Collins said he has never seen a case of allergy to naloxone, the only contraindication to the drug.

Since aggressiveness might be associated with withdrawal, Dr. Savage said training for naloxone providers often includes how to manage a combative person. The risk of tachycardia has been raised as a concern, particularly in situations where law enforcement personnel who are not medically trained are delivering naloxone, but those patients are transported to medical facilities, she pointed out.

Intranasal (IN) naloxone, which is not approved by the Food and Drug Administration, is the most widely used method of administering naloxone by police and other first responders. They use a standard dose of 0.4 contained in a syringe with an atomizer, delivering one 0.2 mg dose per nostril. Another option is the autoinjector that provides an injection of naloxone with a speaker that provides instructions guiding the user. This option was approved by the FDA in 2014.

Evidence that the intranasal form is effective dates back to 2005, with a study that found a dose of 2 mg/2 cc in a prefilled syringe delivered with an atomizer by Denver paramedics was effective in 43 of 52 (83%) people. IV naloxone was needed in nine individuals who did not respond to the IN dose, including five who had nasal pathology (J. Emerg. Med. 2005; 29:265-71). In a more recent study that randomized 100 patients admitted to an emergency department with an opioid overdose to a lower IN dose (0.4 mg) or IV naloxone, the IN route proved as effective as the IV route in reversing respiratory depression and central nervous system effects (Arch. Med. Sci. 2014;10:309-14).

Courtesy Silver Hill Hospital, New Canaan, Conn.

Broad effectiveness found

Dr. Collins said the various options have advantages and drawbacks, and if only one option is available for whatever reason, “they all work.” IM and IV formulations have the fastest onset of action, are the least expensive, and are FDA-approved but carry the risk of a needlestick injury. IN naloxone is not FDA-approved, and might have a slightly slower and less predictable effect but has no risk of a needlestick injury. In addition, IN naloxone is inexpensive and easy to use. The recently FDA-approved Evzio autoinjector pre-filled with naloxone solution, administered IM or subcutaneously, has a faster onset with a predictable effect and no risk of a needle stick. It also includes audio instructions that walks the user through its use. But it costs about $400 per kit, which is a drawback, he said.

Dr. Savage pointed out that administering naloxone is only part of intervening in an opioid overdose and that training is needed when naloxone is dispensed or prescribed to patients or their families. Included in such training would be when to call for help, how to identify signs of an overdose, how to position patients for rescue, understanding rescue breathing, and knowing when the admininstration of naloxone is indicated. Since naloxone wears off in about half an hour, depending on the route and other variables, people should be told that they need to call for emergency support and transport for ongoing care because many opioids end up lasting longer than the effects of naloxone.

The FDA is considering making naloxone available over the counter, but such a move will take several years. It can be provided by pharmacies in states that have a collaborative practice agreement in place that supports distribution to people addicted to opioids, their families, and friends, she said. For example, in Rhode Island, a collaborative practice agreement exists allowing Walgreens pharmacies to dispense naloxone without a prescription.

Based on an informal poll taken during the workshop, none of those in attendance had started to prescribe naloxone for their patients, although they were interested in doing so or were figuring out how to make it available. During the discussion period, barriers they cited included the time and resources needed to train people to administer naloxone, the cost, and the lack of awareness among pharmacies about their ability to obtain intranasal kits. Suggestions among participants include having nurses or pain medicine fellows provide training and education, and using videos for training. A physician at the Atlanta Veterans Affairs Medical Center pointed out that naloxone is provided at no charge to all VA hospitals, although patients might have a co-pay.

Among the resources provided by Dr. Savage and Dr. Collins for clinicians interested in providing naloxone to patients at risk of an opioid overdose and to family members of others who might witness an overdose was an American Medical Association webinar on naloxone safety, information on how to start prescribing and dispensing naloxone rescue kits, and patient information videos. More information on how to start a program is available at http://www.naloxoneinfo.org.

Dr. Savage and Dr. Collins said they had no direct commercial interests related to the topic of the workshop.

[email protected]

AVENTURA, FLA. – Treatment with naltrexone* was associated with reductions in drinking over 3 months in a study of alcohol-dependent adults, but whether these individuals had a polymorphism that has been associated with better responses to the drug in previous studies did not affect outcomes, Dr. David W. Oslin reported at the annual meeting of the American Academy of Addiction Psychiatry.

“We did not find that naltrexone ... was moderated by genotype in this prospective trial,” said Dr. Oslin, professor of medicine at the University of Pennsylvania, Philadelphia.

Naltrexone, an opioid antagonist approved by the Food and Drug Administration for treating alcohol dependence, acts principally on the mu opioid receptor.

Elizabeth Mechcatie/Frontline Medical News

Various types of studies have shown that the Asp40 allele of OPRM1, the gene that encodes for the mu-opioid receptor, is functionally active and might predict response to treatment with naltrexone , Dr. Oslin said. Studies have found that individuals with the Asp40 allele had better responses to naltrexone . A preliminary study led by Dr. Oslin found that those who had one or two copies of the Asp40 allele had significantly lower relapse rates and a longer time to return to heavy drinking than did those who had only the Asn40 allele (Neuropsychopharmacology 2003;28:1546-52). A meta-analysis of observational clinical studies of patients treated with naltrexone found that those patients with the Asp40 allele were twice as likely not to relapse than were those who were homozygous for the Asn40 allele.

In another study, the COMBINE trial, which found a “robust” effect of treatment with naltrexone over placebo among those with the Asp40 allele, “naltrexone seemed to be moderated by the presence of the Asp40 allele,” with “essentially no effect” of naltrexone in the homozygous (Asn40/Asn40) group, he noted Arch Gen Psychiatry 2008;65:135-44). In all these studies, Dr. Oslin pointed out that genotyping was performed retrospectively.

But in the study he presented, genotyping was performed as part of the study, a prospective, double-blind, placebo-controlled study of 221 alcohol-dependent adults, mostly men (mean age 46-51 years). Most had undergone addiction treatment previously. Patients with one or two copies of the Asp40 allele and those who were homozygous for the Asn40 allele were randomized to naltrexone 50 mg a day or placebo and the primary outcome measured was relapse to heavy drinking during treatment.

In the group overall, there was a “moderate to small” effect of naltrexone on the primary outcome over 12 weeks of treatment, but no statistically significant differences on responses by genotype, Dr. Oslin said. There was also no effect of genotype on craving, abstinence, or percent days of drinking, or any drinking.

Some differences in adverse events were found by genotype: Among those with the Asn40 allele, fatigue, nausea, sensory problems, and upper respiratory infections were more for those who received naltrexone than for those who received placebo. Among those with the Asp40 allele, nausea and upper GI problems were more common for those on naltrexone than for those on placebo. Adverse events were slightly more common in the N/ASP40 group, he said.

Overall, the results of the study supported a moderate effect of naltrexone, similar to that seen in previous studies, but the lack of a genotype effect is not an indication it does not exist, Dr. Oslin said.

As to why the results were not what they expected, he speculated that age could be an explanation and that “the Asp40 dopamine release cascade may be more relevant “on cravings in younger people with alcohol dependence. The individuals in this study were in their 40s and 50s on average, most had been alcoholics for years, and they had more severe addictions to drinking than in some of the other studies, so “the dopamine response to craving may not be as relevant.”

While the study does not indicate that this single nucleotide polymorphism is not “robustly functional,” based on the current literature, it “doesn’t add to our clinical management” at this time, Dr. Oslin said. “We are in our infancy really in understanding how genetics influences treatment.”

The study received funding from the National Institutes of Health and the Department of Veterans Affairs. Dr. Oslin and five coinvestigators reported no conflicts; another investigator received funding from Alkermes at the time of the grant as a consultant on depot naltrexone.

[email protected]

*Correction, 12/19/2014: An earlier version of this article incorrectly identified the drug naltrexone. 

AVENTURA, FLA. – Treatment with naltrexone* was associated with reductions in drinking over 3 months in a study of alcohol-dependent adults, but whether these individuals had a polymorphism that has been associated with better responses to the drug in previous studies did not affect outcomes, Dr. David W. Oslin reported at the annual meeting of the American Academy of Addiction Psychiatry.

“We did not find that naltrexone ... was moderated by genotype in this prospective trial,” said Dr. Oslin, professor of medicine at the University of Pennsylvania, Philadelphia.

Naltrexone, an opioid antagonist approved by the Food and Drug Administration for treating alcohol dependence, acts principally on the mu opioid receptor.

Elizabeth Mechcatie/Frontline Medical News

Various types of studies have shown that the Asp40 allele of OPRM1, the gene that encodes for the mu-opioid receptor, is functionally active and might predict response to treatment with naltrexone , Dr. Oslin said. Studies have found that individuals with the Asp40 allele had better responses to naltrexone . A preliminary study led by Dr. Oslin found that those who had one or two copies of the Asp40 allele had significantly lower relapse rates and a longer time to return to heavy drinking than did those who had only the Asn40 allele (Neuropsychopharmacology 2003;28:1546-52). A meta-analysis of observational clinical studies of patients treated with naltrexone found that those patients with the Asp40 allele were twice as likely not to relapse than were those who were homozygous for the Asn40 allele.

In another study, the COMBINE trial, which found a “robust” effect of treatment with naltrexone over placebo among those with the Asp40 allele, “naltrexone seemed to be moderated by the presence of the Asp40 allele,” with “essentially no effect” of naltrexone in the homozygous (Asn40/Asn40) group, he noted Arch Gen Psychiatry 2008;65:135-44). In all these studies, Dr. Oslin pointed out that genotyping was performed retrospectively.

But in the study he presented, genotyping was performed as part of the study, a prospective, double-blind, placebo-controlled study of 221 alcohol-dependent adults, mostly men (mean age 46-51 years). Most had undergone addiction treatment previously. Patients with one or two copies of the Asp40 allele and those who were homozygous for the Asn40 allele were randomized to naltrexone 50 mg a day or placebo and the primary outcome measured was relapse to heavy drinking during treatment.

In the group overall, there was a “moderate to small” effect of naltrexone on the primary outcome over 12 weeks of treatment, but no statistically significant differences on responses by genotype, Dr. Oslin said. There was also no effect of genotype on craving, abstinence, or percent days of drinking, or any drinking.

Some differences in adverse events were found by genotype: Among those with the Asn40 allele, fatigue, nausea, sensory problems, and upper respiratory infections were more for those who received naltrexone than for those who received placebo. Among those with the Asp40 allele, nausea and upper GI problems were more common for those on naltrexone than for those on placebo. Adverse events were slightly more common in the N/ASP40 group, he said.

Overall, the results of the study supported a moderate effect of naltrexone, similar to that seen in previous studies, but the lack of a genotype effect is not an indication it does not exist, Dr. Oslin said.

As to why the results were not what they expected, he speculated that age could be an explanation and that “the Asp40 dopamine release cascade may be more relevant “on cravings in younger people with alcohol dependence. The individuals in this study were in their 40s and 50s on average, most had been alcoholics for years, and they had more severe addictions to drinking than in some of the other studies, so “the dopamine response to craving may not be as relevant.”

While the study does not indicate that this single nucleotide polymorphism is not “robustly functional,” based on the current literature, it “doesn’t add to our clinical management” at this time, Dr. Oslin said. “We are in our infancy really in understanding how genetics influences treatment.”

The study received funding from the National Institutes of Health and the Department of Veterans Affairs. Dr. Oslin and five coinvestigators reported no conflicts; another investigator received funding from Alkermes at the time of the grant as a consultant on depot naltrexone.

[email protected]

*Correction, 12/19/2014: An earlier version of this article incorrectly identified the drug naltrexone. 

AVENTURA, FLA. – Treatment with naltrexone* was associated with reductions in drinking over 3 months in a study of alcohol-dependent adults, but whether these individuals had a polymorphism that has been associated with better responses to the drug in previous studies did not affect outcomes, Dr. David W. Oslin reported at the annual meeting of the American Academy of Addiction Psychiatry.

“We did not find that naltrexone ... was moderated by genotype in this prospective trial,” said Dr. Oslin, professor of medicine at the University of Pennsylvania, Philadelphia.

Naltrexone, an opioid antagonist approved by the Food and Drug Administration for treating alcohol dependence, acts principally on the mu opioid receptor.

Elizabeth Mechcatie/Frontline Medical News

Various types of studies have shown that the Asp40 allele of OPRM1, the gene that encodes for the mu-opioid receptor, is functionally active and might predict response to treatment with naltrexone , Dr. Oslin said. Studies have found that individuals with the Asp40 allele had better responses to naltrexone . A preliminary study led by Dr. Oslin found that those who had one or two copies of the Asp40 allele had significantly lower relapse rates and a longer time to return to heavy drinking than did those who had only the Asn40 allele (Neuropsychopharmacology 2003;28:1546-52). A meta-analysis of observational clinical studies of patients treated with naltrexone found that those patients with the Asp40 allele were twice as likely not to relapse than were those who were homozygous for the Asn40 allele.

In another study, the COMBINE trial, which found a “robust” effect of treatment with naltrexone over placebo among those with the Asp40 allele, “naltrexone seemed to be moderated by the presence of the Asp40 allele,” with “essentially no effect” of naltrexone in the homozygous (Asn40/Asn40) group, he noted Arch Gen Psychiatry 2008;65:135-44). In all these studies, Dr. Oslin pointed out that genotyping was performed retrospectively.

But in the study he presented, genotyping was performed as part of the study, a prospective, double-blind, placebo-controlled study of 221 alcohol-dependent adults, mostly men (mean age 46-51 years). Most had undergone addiction treatment previously. Patients with one or two copies of the Asp40 allele and those who were homozygous for the Asn40 allele were randomized to naltrexone 50 mg a day or placebo and the primary outcome measured was relapse to heavy drinking during treatment.

In the group overall, there was a “moderate to small” effect of naltrexone on the primary outcome over 12 weeks of treatment, but no statistically significant differences on responses by genotype, Dr. Oslin said. There was also no effect of genotype on craving, abstinence, or percent days of drinking, or any drinking.

Some differences in adverse events were found by genotype: Among those with the Asn40 allele, fatigue, nausea, sensory problems, and upper respiratory infections were more for those who received naltrexone than for those who received placebo. Among those with the Asp40 allele, nausea and upper GI problems were more common for those on naltrexone than for those on placebo. Adverse events were slightly more common in the N/ASP40 group, he said.

Overall, the results of the study supported a moderate effect of naltrexone, similar to that seen in previous studies, but the lack of a genotype effect is not an indication it does not exist, Dr. Oslin said.

As to why the results were not what they expected, he speculated that age could be an explanation and that “the Asp40 dopamine release cascade may be more relevant “on cravings in younger people with alcohol dependence. The individuals in this study were in their 40s and 50s on average, most had been alcoholics for years, and they had more severe addictions to drinking than in some of the other studies, so “the dopamine response to craving may not be as relevant.”

While the study does not indicate that this single nucleotide polymorphism is not “robustly functional,” based on the current literature, it “doesn’t add to our clinical management” at this time, Dr. Oslin said. “We are in our infancy really in understanding how genetics influences treatment.”

The study received funding from the National Institutes of Health and the Department of Veterans Affairs. Dr. Oslin and five coinvestigators reported no conflicts; another investigator received funding from Alkermes at the time of the grant as a consultant on depot naltrexone.

[email protected]

*Correction, 12/19/2014: An earlier version of this article incorrectly identified the drug naltrexone. 

AVENTURA, FLA.– A single nucleotide polymorphism might help identify heavy drinkers who are most likely to respond to treatment with topiramate, but more studies are needed before testing patients is recommended, Dr. Henry R. Kranzler reported at the annual meeting of the American Academy of Addiction Psychiatry.

In a 12-week placebo-controlled, randomized study of 138 heavy drinkers, the number of days people drank heavily was significantly reduced among those treated with topiramate, compared with those on placebo. But genotyping results indicated that the effect occurred only among those with the polymorphism, according to Dr. Kranzler, the lead author of the study, who is professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania, Philadelphia.

At baseline, the study participants drank about 80% of the days each week. They were randomized to treatment with 200 mg of topiramate a day, in two divided doses, or placebo, with the goal of reducing drinking to safe levels. Brief behavioral counseling was provided at each visit. Over 12 weeks, the number of days participants drank heavily dropped from about 5 days at baseline to about 1.5 days a week among those treated with topiramate, a significant reduction, and to about 3 days a week among those on placebo. In addition, the number of days participants abstained from alcohol increased among those treated with topiramate, from about 1 to almost 3 days per week. Among those on placebo, the number of abstinent days per week increased from about 1 to 1.5 days per week.

Patients were genotyped for the single nucleotide polymorphism (rs2832407) in GRIK1 (glutamate receptor, ionotropic, kainate1), a large gene on chromosome 21, which “encodes the Gluk1 subunit of the kainate (glutamate) receptor” to evaluate its impact as a moderator of topiramate’s effects on drinking and on the adverse effects of the drug. Topiramate affects multiple receptor systems, and the drug’s effects on glutamate (kainate) receptors “are most potent and selective for those containing the GluK1 and GluK2 subunits,” he said.

Genotyping was done in the 122 European Americans in the study to avoid confounding, because the frequency of the allele for the polymorphism varies widely in different populations. In this group, the significant effects over placebo was evident only among the 51 individuals who were “rs2832407 C-allele homozygotes.” They had “a substantially greater response to topiramate, compared to placebo,” and 3 and 6 months after treatment ended, evidence of a beneficial effect of topiramate in this group remained, he added.

However, unlike a small study published in 2009, conducted by different investigators, which found that individuals with this genotype were less likely to experience adverse effects of topiramate therapy, they did not see a pharmacogenetic effect on adverse events associated with topiramate.

Genotyping might help predict which patients may respond to topiramate, testing is not currently recommended, and these results need to be replicated and evaluated in other populations, Dr. Kranzler added.

These findings will also be helpful in identifying targets for more specific medications to treat alcohol abuse, he noted.

Topiramate, marketed as Topamax, also is available in generic formulations; it is not approved for treating alcohol abuse. He referred to a recently published meta-analysis indicating that topiramate had a greater effect than acamprosate or naltrexone in people with alcohol use disorders (Alcohol Clin. Exp. Res. 2014;38:1481-8).

Dr. Kranzler disclosed having received honoraria from the Alcohol Clinical Trials Initiative (ACTIVE) of the American Society of Clinical Psychopharmacology, which is supported by AbbVie, Ethypharm, Lilly, Lundbeck, and Pfizer. He also is a consultant to or advisory board member of Alkermes, Lilly, Lundbeck, Otsuka, Pfizer, and Roche. He said that industry had no role in the data he presented.

[email protected]

AVENTURA, FLA.– A single nucleotide polymorphism might help identify heavy drinkers who are most likely to respond to treatment with topiramate, but more studies are needed before testing patients is recommended, Dr. Henry R. Kranzler reported at the annual meeting of the American Academy of Addiction Psychiatry.

In a 12-week placebo-controlled, randomized study of 138 heavy drinkers, the number of days people drank heavily was significantly reduced among those treated with topiramate, compared with those on placebo. But genotyping results indicated that the effect occurred only among those with the polymorphism, according to Dr. Kranzler, the lead author of the study, who is professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania, Philadelphia.

At baseline, the study participants drank about 80% of the days each week. They were randomized to treatment with 200 mg of topiramate a day, in two divided doses, or placebo, with the goal of reducing drinking to safe levels. Brief behavioral counseling was provided at each visit. Over 12 weeks, the number of days participants drank heavily dropped from about 5 days at baseline to about 1.5 days a week among those treated with topiramate, a significant reduction, and to about 3 days a week among those on placebo. In addition, the number of days participants abstained from alcohol increased among those treated with topiramate, from about 1 to almost 3 days per week. Among those on placebo, the number of abstinent days per week increased from about 1 to 1.5 days per week.

Patients were genotyped for the single nucleotide polymorphism (rs2832407) in GRIK1 (glutamate receptor, ionotropic, kainate1), a large gene on chromosome 21, which “encodes the Gluk1 subunit of the kainate (glutamate) receptor” to evaluate its impact as a moderator of topiramate’s effects on drinking and on the adverse effects of the drug. Topiramate affects multiple receptor systems, and the drug’s effects on glutamate (kainate) receptors “are most potent and selective for those containing the GluK1 and GluK2 subunits,” he said.

Genotyping was done in the 122 European Americans in the study to avoid confounding, because the frequency of the allele for the polymorphism varies widely in different populations. In this group, the significant effects over placebo was evident only among the 51 individuals who were “rs2832407 C-allele homozygotes.” They had “a substantially greater response to topiramate, compared to placebo,” and 3 and 6 months after treatment ended, evidence of a beneficial effect of topiramate in this group remained, he added.

However, unlike a small study published in 2009, conducted by different investigators, which found that individuals with this genotype were less likely to experience adverse effects of topiramate therapy, they did not see a pharmacogenetic effect on adverse events associated with topiramate.

Genotyping might help predict which patients may respond to topiramate, testing is not currently recommended, and these results need to be replicated and evaluated in other populations, Dr. Kranzler added.

These findings will also be helpful in identifying targets for more specific medications to treat alcohol abuse, he noted.

Topiramate, marketed as Topamax, also is available in generic formulations; it is not approved for treating alcohol abuse. He referred to a recently published meta-analysis indicating that topiramate had a greater effect than acamprosate or naltrexone in people with alcohol use disorders (Alcohol Clin. Exp. Res. 2014;38:1481-8).

Dr. Kranzler disclosed having received honoraria from the Alcohol Clinical Trials Initiative (ACTIVE) of the American Society of Clinical Psychopharmacology, which is supported by AbbVie, Ethypharm, Lilly, Lundbeck, and Pfizer. He also is a consultant to or advisory board member of Alkermes, Lilly, Lundbeck, Otsuka, Pfizer, and Roche. He said that industry had no role in the data he presented.

[email protected]

AVENTURA, FLA.– A single nucleotide polymorphism might help identify heavy drinkers who are most likely to respond to treatment with topiramate, but more studies are needed before testing patients is recommended, Dr. Henry R. Kranzler reported at the annual meeting of the American Academy of Addiction Psychiatry.

In a 12-week placebo-controlled, randomized study of 138 heavy drinkers, the number of days people drank heavily was significantly reduced among those treated with topiramate, compared with those on placebo. But genotyping results indicated that the effect occurred only among those with the polymorphism, according to Dr. Kranzler, the lead author of the study, who is professor of psychiatry and director of the Center for Studies of Addiction at the University of Pennsylvania, Philadelphia.

At baseline, the study participants drank about 80% of the days each week. They were randomized to treatment with 200 mg of topiramate a day, in two divided doses, or placebo, with the goal of reducing drinking to safe levels. Brief behavioral counseling was provided at each visit. Over 12 weeks, the number of days participants drank heavily dropped from about 5 days at baseline to about 1.5 days a week among those treated with topiramate, a significant reduction, and to about 3 days a week among those on placebo. In addition, the number of days participants abstained from alcohol increased among those treated with topiramate, from about 1 to almost 3 days per week. Among those on placebo, the number of abstinent days per week increased from about 1 to 1.5 days per week.

Patients were genotyped for the single nucleotide polymorphism (rs2832407) in GRIK1 (glutamate receptor, ionotropic, kainate1), a large gene on chromosome 21, which “encodes the Gluk1 subunit of the kainate (glutamate) receptor” to evaluate its impact as a moderator of topiramate’s effects on drinking and on the adverse effects of the drug. Topiramate affects multiple receptor systems, and the drug’s effects on glutamate (kainate) receptors “are most potent and selective for those containing the GluK1 and GluK2 subunits,” he said.

Genotyping was done in the 122 European Americans in the study to avoid confounding, because the frequency of the allele for the polymorphism varies widely in different populations. In this group, the significant effects over placebo was evident only among the 51 individuals who were “rs2832407 C-allele homozygotes.” They had “a substantially greater response to topiramate, compared to placebo,” and 3 and 6 months after treatment ended, evidence of a beneficial effect of topiramate in this group remained, he added.

However, unlike a small study published in 2009, conducted by different investigators, which found that individuals with this genotype were less likely to experience adverse effects of topiramate therapy, they did not see a pharmacogenetic effect on adverse events associated with topiramate.

Genotyping might help predict which patients may respond to topiramate, testing is not currently recommended, and these results need to be replicated and evaluated in other populations, Dr. Kranzler added.

These findings will also be helpful in identifying targets for more specific medications to treat alcohol abuse, he noted.

Topiramate, marketed as Topamax, also is available in generic formulations; it is not approved for treating alcohol abuse. He referred to a recently published meta-analysis indicating that topiramate had a greater effect than acamprosate or naltrexone in people with alcohol use disorders (Alcohol Clin. Exp. Res. 2014;38:1481-8).

Dr. Kranzler disclosed having received honoraria from the Alcohol Clinical Trials Initiative (ACTIVE) of the American Society of Clinical Psychopharmacology, which is supported by AbbVie, Ethypharm, Lilly, Lundbeck, and Pfizer. He also is a consultant to or advisory board member of Alkermes, Lilly, Lundbeck, Otsuka, Pfizer, and Roche. He said that industry had no role in the data he presented.

[email protected]