Archive for the ‘Controlled Substances’ Category

Tramadol and Nucynta

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Tramadol, the generic for the brand name Ultram, is a messy drug. It’s a pain reliever that has actions on several types of brain receptors: the mu opioid, serotonin, norepinephrine, NMDA, and other receptors.

Because it stimulates the mu opioid receptors, it can cause feelings of pleasure as well as pain relief. Tramadol is far less active at the mu opioid receptors than its metabolite, and it takes time for the tramadol to be metabolized in the liver to its first metabolite. Because of this delay, some experts thought it wouldn’t appeal to addicts, who prefer an immediate high. Overall this is probably true, and tramadol has a much lower rate of addiction than other opioids, but it still causes addiction in some patients.

Some of tramadol’s pain relieving properties may also be produced by its actions on serotonin and norepinephrine receptors, since tramadol’s pain relieving capability is only partially reversed by a pure opioid antagonist like naloxone.

When this medication was first released, it wasn’t a controlled substance. That is, the DEA didn’t control it strictly like medications that can cause addiction. Now, it’s a Schedule IV drug, in some states. It does have some benefit for pain relief, but also some risk of addiction, though lower than that of hydrocodone, for example.

Tramadol is usually dosed in 50mg pills, one or two every six hours, giving the maximum dose of 400mg per day. Recreational use of this medication (to get high) is dangerous, since it causes seizures at doses higher than 400mg. In susceptible patients, it can even cause seizures at lower prescribed doses.

I’ve seen patients in tramadol withdrawal who were so sick it frightened me. This drug can produce a severe withdrawal. If a patient taking high doses stops taking tramadol suddenly, some patients have opioid withdrawal symptoms like sweating, nausea, diarrhea, high blood pressure and heart rate, and severe muscle and joint pains. The sickest patient I’ve ever seen in opioid withdrawal had been using only tramadol, in doses of around 600mg per day. She had fever to 103 degrees, and dehydration from the diarrhea and vomiting. That patient needed hospitalization.

Besides the opioid-withdrawal symptoms, some of these patients also have withdrawal symptoms similar to those seen when certain serotonin-affecting antidepressants, like Paxil and Celexa, are stopped suddenly. They can have fairly severe anxiety, depression, mood swings, and restlessness. Many times they have weird sensory experiences, often called “brain zaps,” or the sensation of electric shocks throughout the body. They can have seizures during this withdrawal.

If the patient had only physical dependency and no addiction, the dose of tramadol can usually be tapered slowly over a few weeks to months, as an outpatient. But if the patient has not only physical dependency but also the disease of addiction, the obsession and craving for the medication will usually prevent a successful outpatient taper, unless a dependable non-addict holds the pill bottle, and dispenses it as prescribed.

Traditional treatment for tramadol addiction starts with detoxification. As above, that can rarely be done as an outpatient, so medical inpatient detoxification admissions for five to seven days can be helpful. However, since tramadol acts so much like an opioid, patients ready to leave detox probably need to go on to an inpatient residential treatment center for at least thirty days. Intensive outpatient treatment probably isn’t enough support for these addicts. But that’s only my opinion, since I haven’t found any studies describing success rates with tramadol addicts.

Opioid maintenance medications like methadone and buprenorphine do stop the opioid-type withdrawal symptoms from tramadol, but there’s no information about the use of maintenance medications in these patients. Most doctors working in clinics won’t start a patient on maintenance medications unless the patient is also using other opioids.

Often, methadone patients at the opioid treatment centers where I work are given tramadol by their primary care doctors who think it’s a low risk medication for opioid addicts. It probably is lower in its risk for abuse, but it can cause withdrawal in patients on stable, blocking doses of methadone. [1]

Tramadol is a synthetic, pared-down version of codeine. Interestingly, a structurally similar medication, tapentadol, has just been released, and is now being sold under the brand name Nucynta. That medication is a schedule II drug, presumably because of a higher abuse potential than we’ve seen with tramadol. Tapentadol stimulates opioid mu receptors, and also acts as a norepinephrine re-uptake inhibitor, like some antidepressants.

I saw my first patient who was addicted to Nucynta earlier this year. He had a history of opioid addiction in the past, had successfully tapered off methadone maintenance, but became re-addicted to opioids during a bout of back pain. He couldn’t stop taking Nucynta without abusing other illicit opioids to ease his withdrawal symptoms. Because he was using other opioids, I did admit him to methadone maintenance and he continues to do well on our program.

The bottom line is this: if you are in recovery from addiction (alcohol or drugs, this medication should be used with caution. Let your doctor know that you’re in recovery from addiction. If you must take a potentially addicting medication, talk to your sponsor and your support network. Go to extra meetings. Let a dependable non-addict hold the pill bottle and dispense as prescribed. If you have to take the medication for more than a few weeks, have your doctor taper your dose instead of stopping suddenly.

1. Leavitt, MA, PhD, “Methadone-Drug Interactions,” Pain Treatment Topics, Addiction Treatment Forum, January 2006

Opioid Use in the Veteran’s Administration System

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Recent news reports have denounced rates of opioid prescribing for war veterans. According to the Center for Investigative Reporting, rates of opioid prescribing by VA doctors have increased two hundred and seventy percent over the last twelve years. The VA is now prescribing more than one opioid prescription for each patient it treats. (1)

The dramatically different opioid prescribing rates between different VA systems are concerning. For example, doctors at a VA hospital in Oklahoma prescribed 160.7 opioid prescriptions for every one hundred patients, compared to doctors at a VA hospital in Manhattan, who prescribed 19.8 opioid prescriptions for every one hundred VA patients treated. That’s more than an eight-fold difference.

Of particular interest, out of the 130 VA systems evaluated, Mountain Home, Tennessee, ranked as the sixth most frequent prescriber of opioids. Located in Johnson City, TN, this VA system had a rate of 138.8 opioid prescriptions per 100 patients for 2012. The worst system was Muskogee, OK, with 160.7 per 100 patients, followed closely by Beckley WV, Lexington, KY, and Huntington, WV. (But remember, Tennessee’s Department of Mental Health said there was no need for an opioid treatment center to be located in Johnson City. Nope. No problem there.)

We already know that in some states, the numbers of U.S. citizens who die from drug overdoses outnumber deaths from motor vehicle accidents. But veterans treated by VA doctors die from prescription drug overdoses at almost twice the rate of civilians. (1)

To be fair, we need to consider the changing nature of war injuries. Soldiers are surviving catastrophic injuries which would have been fatal in the past. This is partly due to better body armor and partly because of better and quicker medical care at the time of the injury. Some experts say some Iraq and Afghanistan soldiers have survived severe burns and amputations that killed Vietnam-era soldiers.

These patients surely need heavy opioids, at least early in their treatment. No compassionate doctor would skimp on pain medication for an acutely injured person. But acute pain is different from chronic pain. As the patient recovers, it’s time to consider backing off on opioids, and consider trials of non-opioid means of pain control. Patients often need help getting off prescribed opioids, which may mean tapering them over weeks to months, in order to prevent opioid withdrawal. This often takes more time and patience than writing another opioid prescription.

Due to the nature of the Iraq and Afghanistan wars, thousands of veterans have been diagnosed with traumatic brain injury (TBI). We are only beginning to understand the relationship between TBI and the risk for developing addiction. Similarly, war veterans have higher rates of PTSD (post-traumatic stress disorder) and depression. These mental disorders increase the risk for developing addiction to drugs including alcohol in all people, including war veterans.

I’ve admitted a few war veterans to the opioid treatment programs where I work. I dread trying to coordinate care with their VA doctors. Many times, after getting a release from the patient, I’ve called the VA to talk with their doctor. I can’t think of one time when I’ve reached the doctor to whom I wanted to speak. Sometimes I got a nurse, and left a message for the doctor to call me back, knowing I’d never hear from them.

I don’t have any way to know what those VA doctors are prescribing for my patients. Often, at least in my area, it’s a heavy benzodiazepine or two, and one or more opioids. Because the VA doesn’t report medication to my state’s prescription monitoring program, I’m left in the dark. I hear that’s supposed to change, but not soon enough for me.

The VA can fix this problem of inappropriate prescribing. I’ve been at ASAM (American Society of Addiction Medicine) conferences, and have met knowledgeable VA physicians. I’ve heard them lecture at these meetings. The VA must allow these experts teach their colleagues who are dated or oblivious in their prescribing habits.

I hope to see the time come when it’s as easy for a war veteran to access treatment for addiction as it is to get opioid prescriptions. These treatments should, of course, include medication-assisted treatments with buprenorphine and methadone.

Our veterans deserve the best care possible.

1. http://cironline.org/node/5261

FDA Approves Zubsolv, New Brand of Sublingual Buprenorphine

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Suboxone is getting competition from the generic preparations of buprenorphine/naloxone, and now another name-brand preparation has just been approved by the FDA.

It’s called Zubsolv, and the manufacturer, Orexo, says it takes less time to dissolve, is a smaller tablet, and tastes better. The company added a menthol taste. They also say their preparation has higher bioavailability, and the tablets come in two strengths: 5.7/1.4 buprenorphine to naloxone ratio, and 1.4/.36 ratio. The lower doses of buprenorphine per tablet are due to the higher bioavailability. Also, each tablet is contained in unit dose packaging, to reduce the risk of pediatric exposures.

Interestingly, the package insert says not to switch from one buprenorphine preparation to another, because other tablets have different amounts of buprenorphine than Zubsolv. That’s a problem for established patients. I’d like the manufacturer to give prescribers some information on how blood levels of their tablets compare to blood levels of other preparations of buprenorphine. I guess new patients could be started on Zubsolv.

On the company’s website, they claim that nine out of ten people prefer Zubsolv to Suboxone.

This medication should be available in pharmacies by September of this year.

I’m glad for every new buprenorphine product that’s released to the market, because I hope it brings the price down. Lower cost of medication means more opioid addicts could afford treatment.

I’m curious to see how this new preparation will be greeted by patients on buprenorphine.

New Opioids

I’ve blogged about states that have passed new laws addressing the prescribing of opioids, but the manufacturers of prescription opioids medications also have made changes to help reduce the potential for medication misuse. Of course, opioids will never be misuse-proof, but at least it’s a little harder to misuse some of the newer ones.

Oxecta is a new immediate-release brand of the drug oxycodone. It’s formulated so that it breaks into chunks when crushed, instead of a powder. When it’s mixed with water, it forms a gel so that it can’t be injected. This pill contains sodium laurel sulfate, a substance that irritates the nose if snorted.

Lazanda is a new delivery form of a very potent opioid, fentanyl. This brand is designed to be used as a nasal spray, which I would expect to be very addictive. The preparation itself has no anti-abuse features, but in order to distribute, dispense, prescribe, or be prescribed this medication, parties have to sign an agreement and be enrolled with the drug company. This extra scrutiny is hoped to deter diversion by distributor, pharmacy, doctor, or patient. Physicians must take a training program specific for this brand, and be enrolled with the drug company as a prescriber, or pharmacies can’t dispense to the patient.

Patients also need to complete a patient-prescriber agreement. Many people (like me) think doctors aren’t likely to jump through these extra hoops to prescribe this particular brand, when other brands of the same medication are already on the market, though not in the form of nasal spray.

Remoxy, another brand of oxycodone, hasn’t yet been FDA approved. Supposedly, it’s resistant to injection or snorting, and also has been formulated to be resistant to alcohol extraction.

Drug companies are now required by the FDA to have plans to evaluate and mitigate the risks associated with the opioid drugs they manufacture, particularly if they make sustained release or long-acting opioid preparations. This cooperation by drug manufacturers is a necessary part of turning the tide of opioid addiction in this country.

Last year, Purdue Pharma re-formulated OxyContin, making it more difficult to crush to snort or inject.  I noticed a sudden drop-off in patients entering treatment for pain pill addiction who said OxyContin was their drug of choice. During the years 2002 through 2007, nearly all of the opioid addicts I admitted to treatment said OxyContin was their preferred drug. It became obvious that the re-formulation made a big difference.

Addicts can and will still abuse these medications orally to get high, but the new formulations really do reduce abuse by making pills less likely to be snorted or injected.

So Long Soma

Soma, a well-known brand name of the drug carisoprodol, is prescribed by doctors in the U.S. as a muscle relaxant. However, it does have the potential to cause addiction. Soma is now a Schedule III or Schedule IV controlled substance in about twenty states, and the DEA may soon make it a Schedule IV drug in all states. Carisoprodol has been removed from the market in other nations, due to its potential for addiction.

 All potentially addicting drugs are scheduled, meaning the physician has to have a DEA number to legally prescribe them. Non-scheduled drugs (antibiotics, antidepressants, blood pressure or diabetes medication) aren’t addicting, and the doctor doesn’t need a DEA number to prescribe these. They aren’t tracked by the DEA. Drugs are scheduled I through V, depending on the potential for addiction and the degree of therapeutic usefulness. Schedule I drugs have very high potential for addiction, and very little therapeutic use. Other medications are more beneficial with less risk of addiction. Heroin and Ecstasy are two examples of Schedule I drugs. At the other extreme, Schedule V drugs have some risk of addiction, though fairly low. Examples are low-dose codeine and other low-dose opioids.

 I hate Soma. I can’t remember the last time I wrote a prescription for it. I see too many people who have become addicted to it, or who use it with opioids. There are other better and safer muscle relaxants.

Soma gets metabolized to meprobamate, an old-timey barbiturate. Doctors used barbiturates as sedatives before the safer benzodiazepines came on the market.

 Some addicts say they like the high that they get when they mix Soma with opioids. Since I treat opioid addicts, I see the dangers of mixing Soma with maintenance medications like methadone and buprenorphine. Just like benzodiazepines, Soma has a synergistic effect with opioids, causing more sedation than expected. This is how it can kill. The user takes opioids with Soma, it turns into a barbiturate, and the combination puts the person into a deep sleep. In fact, this combination can make them sleep so deeply that the respiratory center of the brain, which tells us to breathe when we sleep, turns off. The person stops breathing, and without oxygen, vital organs like the brain and heart die, and the person never wakes up.

 At the recent ASAM conference in Washington, D.C., one presenter reminded us of how addicting carisoprodol can be: in one study, around 65% of patients with a personal history of a substance use disorder misused carisoprodol when it was prescribed to them for over three months. And even worse, only 18% of the prescribing doctors knew that this medication is metabolized to meprobamate. (1)

 If you have a history of any sort of addiction disorder and your doctor is prescribing Soma, talk to her. It’s likely that another safer and more effective medication can be found. Soma is only FDA approved for two or three weeks of continuous use, anyway.

  1. Reeves, RR; Carter, S; Pinkofsky, HB; Struve, FA; Bennett, DM; “Carisoprodol (Soma) Abuse Potential and Physician Unawareness; Journal of Addictive Diseases, Vol. 18 (2), 1999, pp 51-56.
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