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NEW ORLEANS – Gabapentin heads the short list of prescription drugs other than opioids and benzodiazepines with substantial black-market abuse potential, according to Alexander Y. Walley, MD.
“At least in Massachusetts, where I see patients, these are the pills that people are using and trading on the street. Your part of the country might have others,” noted Dr. Walley, director of the addiction medicine fellowship program at Boston Medical Center.
“I’m not telling you to never prescribe these medications – they are clinically indicated in certain cases and should certainly be used,” Dr. Walley said at the annual meeting of the American College of Physicians. “But now that you know that they might be misused, you should use safeguards.
“A lot of these medications – gabapentin is an example – are a problem primarily in people with other substance use disorders,” he added. “That’s really where I think you need to have the greatest caution.”
Gabapentinoids
Gabapentin and pregabalin are not addictive in the sense that it’s easy to get laboratory animals or healthy volunteers to self-administer them. However, gabapentinoid use disorder is extremely common among people with opioid use disorder, who report that the combination boosts the euphoric effects of opioids and reduces opioid withdrawal symptoms without causing side effects.
Indeed, a recent systematic review of 106 studies found that gabapentinoid use disorder was present in up to 26% of opioid users (Eur Neuropsychopharmacol. 2017 Dec;27[12]:1185-1215).
Overdoses involving gabapentinoids alone are uncommon because they require consumption at up to 25 times the maximum recommended dose. Moreover, these overdoses are rarely fatal.
“You almost can’t overdose on a gabapentinoid, because you have to take lots and lots of it to do so, and you’ll usually survive. But if you add it to an opioid or other sedative, then you’re really in dangerous territory. That’s where all the deaths are clustered,” Dr. Walley explained.
A recent Canadian/Dutch population-based, nested, case-control study concluded that concomitant prescription of opioids and gabapentin was associated with a 49% greater chance of fatal overdose, compared with opioid prescription alone, in an analysis extensively adjusted for potential confounders. A dose-response effect was noted, such that coprescription of high-dose gabapentin was linked to an adjusted 58% increased risk (PLoS Med. 2017 Oct 3;14[10]:e1002396).
Complicating the picture, however, is solid evidence from a randomized, placebo-controlled, crossover trial that gabapentin and opioids are synergistic for relief from neuropathic pain, which can be notoriously difficult to control (N Engl J Med. 2005 Mar 31;352[13]:1324-34).
“It’s tricky, because you can potentially spare having to use high-dose opioids by adding gabapentin,” Dr. Walley observed. “So, as prescribers, you’re in a difficult position, because there’s a mixed message here: When gabapentin is combined with opioids, that’s when it’s dangerous – but that’s also when they’re potentially more effective for pain.”
Promethazine
This drug has a host of neurobiologic actions, which collectively provide sedative and antiemetic effects. Promethazine jacks up opioid-induced euphoria and alleviates withdrawal symptoms. It’s commonly detected in toxicology testing of patients on prescription opioids for chronic pain or on methadone therapy for opioid use disorder.
National Poison Data System figures show an unwelcome trend: A sharp uptick in promethazine abuse/misuse beginning in 2008, even while the total number of poisoning events of all kinds reported to the system began a steady decline (J Addict Med. 2015 May-Jun;9[3]:233-7).
Clonidine
This centrally acting alpha2-adrenoreceptor and imidazoline-receptor agonist is indicated for treatment of hypertension. However, it’s also extensively used off-label to treat anxiety, as well as for alcohol and opioid withdrawal symptoms. The problem is, clonidine boosts opioid-induced euphoria.
A retrospective study of clonidine-overdose patients characterized the clonidine overdose syndrome as marked by sedation, hypotension, bradycardia, and excessive pupillary constriction (Clin Toxicol [Phila]. 2017 Mar;55[3]:187-92).
“The combination of clonidine and opioids is particularly dangerous,” according to Dr. Walley. “Even though it mimics what an opioid overdose looks like, a clonidine overdose is not responsive to naloxone.”
Stimulants
One-quarter of patients who are prescribed methylphenidate or amphetamine for ADHD report being asked to divert their medication, and 11%-29% sell or give it to others seeking to use it recreationally or as a performance aid.
It’s common for prescription seekers to misrepresent symptoms of ADHD, and this play-acting is often tough to detect. In contrast, the nonstimulant atomoxetine (Strattera) and the alpha-adrenergic agonists prescribed for ADHD aren’t linked to misuse or diversion (Postgrad Med. 2014 Sep;126[5]:64-81).
Bupropion
This norepinephrine and dopamine reuptake inhibitor is generally assumed to have low abuse potential. That’s usually true – except in jail and prisons.
“In my patient population, where I have a keen eye to what’s being used on the street, bupropion is not one of the medications that I see very often in my patients who are not incarcerated,” Dr. Walley said. “But in incarcerated settings, it does have a street value.”
Consider safeguards
None of the prescription drugs on Dr. Walley’s problem list is included in prescription monitoring programs, nor are they detectable with standard toxicology testing. This poses a challenge for prescribing physicians.
Before prescribing any of these potentially abusable medications for a given patient, therefore, Dr. Walley considers the underlying risks. For example, an addiction history is a big red flag. So is coprescription of an opioid or another drug that might have synergistic adverse effects. Dr. Walley makes sure there is a solid indication for the medication, and, having prescribed the drug, he wants to see and document clear functional benefit.
Drug-specific toxicology screening is worthy of consideration as a means of confirming the presence of the prescribed medication, along with the absence of opioids or other drugs that shouldn’t be on board.
“I do this with gabapentin, because I see a lot of diversion,” he explained. “If gabapentin doesn’t show up in the toxicology screen, I stop prescribing it. Or if I detect it and it hasn’t been prescribed, that allows me to have a safety discussion with the patient.”
Dr. Walley reported no financial conflicts of interest regarding his presentation.
NEW ORLEANS – Gabapentin heads the short list of prescription drugs other than opioids and benzodiazepines with substantial black-market abuse potential, according to Alexander Y. Walley, MD.
“At least in Massachusetts, where I see patients, these are the pills that people are using and trading on the street. Your part of the country might have others,” noted Dr. Walley, director of the addiction medicine fellowship program at Boston Medical Center.
“I’m not telling you to never prescribe these medications – they are clinically indicated in certain cases and should certainly be used,” Dr. Walley said at the annual meeting of the American College of Physicians. “But now that you know that they might be misused, you should use safeguards.
“A lot of these medications – gabapentin is an example – are a problem primarily in people with other substance use disorders,” he added. “That’s really where I think you need to have the greatest caution.”
Gabapentinoids
Gabapentin and pregabalin are not addictive in the sense that it’s easy to get laboratory animals or healthy volunteers to self-administer them. However, gabapentinoid use disorder is extremely common among people with opioid use disorder, who report that the combination boosts the euphoric effects of opioids and reduces opioid withdrawal symptoms without causing side effects.
Indeed, a recent systematic review of 106 studies found that gabapentinoid use disorder was present in up to 26% of opioid users (Eur Neuropsychopharmacol. 2017 Dec;27[12]:1185-1215).
Overdoses involving gabapentinoids alone are uncommon because they require consumption at up to 25 times the maximum recommended dose. Moreover, these overdoses are rarely fatal.
“You almost can’t overdose on a gabapentinoid, because you have to take lots and lots of it to do so, and you’ll usually survive. But if you add it to an opioid or other sedative, then you’re really in dangerous territory. That’s where all the deaths are clustered,” Dr. Walley explained.
A recent Canadian/Dutch population-based, nested, case-control study concluded that concomitant prescription of opioids and gabapentin was associated with a 49% greater chance of fatal overdose, compared with opioid prescription alone, in an analysis extensively adjusted for potential confounders. A dose-response effect was noted, such that coprescription of high-dose gabapentin was linked to an adjusted 58% increased risk (PLoS Med. 2017 Oct 3;14[10]:e1002396).
Complicating the picture, however, is solid evidence from a randomized, placebo-controlled, crossover trial that gabapentin and opioids are synergistic for relief from neuropathic pain, which can be notoriously difficult to control (N Engl J Med. 2005 Mar 31;352[13]:1324-34).
“It’s tricky, because you can potentially spare having to use high-dose opioids by adding gabapentin,” Dr. Walley observed. “So, as prescribers, you’re in a difficult position, because there’s a mixed message here: When gabapentin is combined with opioids, that’s when it’s dangerous – but that’s also when they’re potentially more effective for pain.”
Promethazine
This drug has a host of neurobiologic actions, which collectively provide sedative and antiemetic effects. Promethazine jacks up opioid-induced euphoria and alleviates withdrawal symptoms. It’s commonly detected in toxicology testing of patients on prescription opioids for chronic pain or on methadone therapy for opioid use disorder.
National Poison Data System figures show an unwelcome trend: A sharp uptick in promethazine abuse/misuse beginning in 2008, even while the total number of poisoning events of all kinds reported to the system began a steady decline (J Addict Med. 2015 May-Jun;9[3]:233-7).
Clonidine
This centrally acting alpha2-adrenoreceptor and imidazoline-receptor agonist is indicated for treatment of hypertension. However, it’s also extensively used off-label to treat anxiety, as well as for alcohol and opioid withdrawal symptoms. The problem is, clonidine boosts opioid-induced euphoria.
A retrospective study of clonidine-overdose patients characterized the clonidine overdose syndrome as marked by sedation, hypotension, bradycardia, and excessive pupillary constriction (Clin Toxicol [Phila]. 2017 Mar;55[3]:187-92).
“The combination of clonidine and opioids is particularly dangerous,” according to Dr. Walley. “Even though it mimics what an opioid overdose looks like, a clonidine overdose is not responsive to naloxone.”
Stimulants
One-quarter of patients who are prescribed methylphenidate or amphetamine for ADHD report being asked to divert their medication, and 11%-29% sell or give it to others seeking to use it recreationally or as a performance aid.
It’s common for prescription seekers to misrepresent symptoms of ADHD, and this play-acting is often tough to detect. In contrast, the nonstimulant atomoxetine (Strattera) and the alpha-adrenergic agonists prescribed for ADHD aren’t linked to misuse or diversion (Postgrad Med. 2014 Sep;126[5]:64-81).
Bupropion
This norepinephrine and dopamine reuptake inhibitor is generally assumed to have low abuse potential. That’s usually true – except in jail and prisons.
“In my patient population, where I have a keen eye to what’s being used on the street, bupropion is not one of the medications that I see very often in my patients who are not incarcerated,” Dr. Walley said. “But in incarcerated settings, it does have a street value.”
Consider safeguards
None of the prescription drugs on Dr. Walley’s problem list is included in prescription monitoring programs, nor are they detectable with standard toxicology testing. This poses a challenge for prescribing physicians.
Before prescribing any of these potentially abusable medications for a given patient, therefore, Dr. Walley considers the underlying risks. For example, an addiction history is a big red flag. So is coprescription of an opioid or another drug that might have synergistic adverse effects. Dr. Walley makes sure there is a solid indication for the medication, and, having prescribed the drug, he wants to see and document clear functional benefit.
Drug-specific toxicology screening is worthy of consideration as a means of confirming the presence of the prescribed medication, along with the absence of opioids or other drugs that shouldn’t be on board.
“I do this with gabapentin, because I see a lot of diversion,” he explained. “If gabapentin doesn’t show up in the toxicology screen, I stop prescribing it. Or if I detect it and it hasn’t been prescribed, that allows me to have a safety discussion with the patient.”
Dr. Walley reported no financial conflicts of interest regarding his presentation.
NEW ORLEANS – Gabapentin heads the short list of prescription drugs other than opioids and benzodiazepines with substantial black-market abuse potential, according to Alexander Y. Walley, MD.
“At least in Massachusetts, where I see patients, these are the pills that people are using and trading on the street. Your part of the country might have others,” noted Dr. Walley, director of the addiction medicine fellowship program at Boston Medical Center.
“I’m not telling you to never prescribe these medications – they are clinically indicated in certain cases and should certainly be used,” Dr. Walley said at the annual meeting of the American College of Physicians. “But now that you know that they might be misused, you should use safeguards.
“A lot of these medications – gabapentin is an example – are a problem primarily in people with other substance use disorders,” he added. “That’s really where I think you need to have the greatest caution.”
Gabapentinoids
Gabapentin and pregabalin are not addictive in the sense that it’s easy to get laboratory animals or healthy volunteers to self-administer them. However, gabapentinoid use disorder is extremely common among people with opioid use disorder, who report that the combination boosts the euphoric effects of opioids and reduces opioid withdrawal symptoms without causing side effects.
Indeed, a recent systematic review of 106 studies found that gabapentinoid use disorder was present in up to 26% of opioid users (Eur Neuropsychopharmacol. 2017 Dec;27[12]:1185-1215).
Overdoses involving gabapentinoids alone are uncommon because they require consumption at up to 25 times the maximum recommended dose. Moreover, these overdoses are rarely fatal.
“You almost can’t overdose on a gabapentinoid, because you have to take lots and lots of it to do so, and you’ll usually survive. But if you add it to an opioid or other sedative, then you’re really in dangerous territory. That’s where all the deaths are clustered,” Dr. Walley explained.
A recent Canadian/Dutch population-based, nested, case-control study concluded that concomitant prescription of opioids and gabapentin was associated with a 49% greater chance of fatal overdose, compared with opioid prescription alone, in an analysis extensively adjusted for potential confounders. A dose-response effect was noted, such that coprescription of high-dose gabapentin was linked to an adjusted 58% increased risk (PLoS Med. 2017 Oct 3;14[10]:e1002396).
Complicating the picture, however, is solid evidence from a randomized, placebo-controlled, crossover trial that gabapentin and opioids are synergistic for relief from neuropathic pain, which can be notoriously difficult to control (N Engl J Med. 2005 Mar 31;352[13]:1324-34).
“It’s tricky, because you can potentially spare having to use high-dose opioids by adding gabapentin,” Dr. Walley observed. “So, as prescribers, you’re in a difficult position, because there’s a mixed message here: When gabapentin is combined with opioids, that’s when it’s dangerous – but that’s also when they’re potentially more effective for pain.”
Promethazine
This drug has a host of neurobiologic actions, which collectively provide sedative and antiemetic effects. Promethazine jacks up opioid-induced euphoria and alleviates withdrawal symptoms. It’s commonly detected in toxicology testing of patients on prescription opioids for chronic pain or on methadone therapy for opioid use disorder.
National Poison Data System figures show an unwelcome trend: A sharp uptick in promethazine abuse/misuse beginning in 2008, even while the total number of poisoning events of all kinds reported to the system began a steady decline (J Addict Med. 2015 May-Jun;9[3]:233-7).
Clonidine
This centrally acting alpha2-adrenoreceptor and imidazoline-receptor agonist is indicated for treatment of hypertension. However, it’s also extensively used off-label to treat anxiety, as well as for alcohol and opioid withdrawal symptoms. The problem is, clonidine boosts opioid-induced euphoria.
A retrospective study of clonidine-overdose patients characterized the clonidine overdose syndrome as marked by sedation, hypotension, bradycardia, and excessive pupillary constriction (Clin Toxicol [Phila]. 2017 Mar;55[3]:187-92).
“The combination of clonidine and opioids is particularly dangerous,” according to Dr. Walley. “Even though it mimics what an opioid overdose looks like, a clonidine overdose is not responsive to naloxone.”
Stimulants
One-quarter of patients who are prescribed methylphenidate or amphetamine for ADHD report being asked to divert their medication, and 11%-29% sell or give it to others seeking to use it recreationally or as a performance aid.
It’s common for prescription seekers to misrepresent symptoms of ADHD, and this play-acting is often tough to detect. In contrast, the nonstimulant atomoxetine (Strattera) and the alpha-adrenergic agonists prescribed for ADHD aren’t linked to misuse or diversion (Postgrad Med. 2014 Sep;126[5]:64-81).
Bupropion
This norepinephrine and dopamine reuptake inhibitor is generally assumed to have low abuse potential. That’s usually true – except in jail and prisons.
“In my patient population, where I have a keen eye to what’s being used on the street, bupropion is not one of the medications that I see very often in my patients who are not incarcerated,” Dr. Walley said. “But in incarcerated settings, it does have a street value.”
Consider safeguards
None of the prescription drugs on Dr. Walley’s problem list is included in prescription monitoring programs, nor are they detectable with standard toxicology testing. This poses a challenge for prescribing physicians.
Before prescribing any of these potentially abusable medications for a given patient, therefore, Dr. Walley considers the underlying risks. For example, an addiction history is a big red flag. So is coprescription of an opioid or another drug that might have synergistic adverse effects. Dr. Walley makes sure there is a solid indication for the medication, and, having prescribed the drug, he wants to see and document clear functional benefit.
Drug-specific toxicology screening is worthy of consideration as a means of confirming the presence of the prescribed medication, along with the absence of opioids or other drugs that shouldn’t be on board.
“I do this with gabapentin, because I see a lot of diversion,” he explained. “If gabapentin doesn’t show up in the toxicology screen, I stop prescribing it. Or if I detect it and it hasn’t been prescribed, that allows me to have a safety discussion with the patient.”
Dr. Walley reported no financial conflicts of interest regarding his presentation.
EXPERT ANALYSIS FROM ACP INTERNAL MEDICINE