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New Medication Formulations Could Quickly Make a Difference for Treating Opioid Addiction

August 22, 2017

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As Francis Collins and I wrote in May, NIH and NIDA are committed to an “all scientific hands on deck” effort to end the opioid crisis in America by halving the time it takes to develop new medications to treat pain and addiction and reverse overdoses. This effort will involve partnerships with pharmaceutical companies and academic institutions, leveraging the diverse benefits that federally funded science, private industry, and academia can bring to bear. Such partnerships have always been important in advancing treatment of addiction, as exemplified by NIDA’s partnership with Lightlake Therapeutics, Inc. (a partner of Adapt Pharma Limited) that led to the approval of nasal Narcan (an intranasal formulation of naloxone) in 2015.

The goals of the new initiative range from innovative and ambitious new treatment approaches that will take some time to develop, such as vaccines or transcranial magnetic stimulation for pain and addiction, to goals that are relatively achievable in the short term, such as improved formulations of existing medications. Effective medications are already available to treat opioid addiction—buprenorphine, methadone, and naltrexone—but only a fraction of people with opioid use disorders are being treated with them, due to limited access and treatment capacity, stigma around their use, lack of provider training, and cost. Also, for those treated, compliance tends to be low and few are retained in treatment for sufficient periods of time. New formulations of these medications that can facilitate access to treatment and improve compliance could be a real game-changer that could quickly make a dent in this crisis.

Buprenorphine and methadone are both highly effective at controlling cravings and withdrawal symptoms when they are administered at sufficient doses for a sufficient length of time. The reality is that these drugs are still not widely available, and are often used at too low a dose and duration when they are available. People who live in rural communities are at particular disadvantage due to logistical challenges associated with accessing treatment. During the first few weeks on the opioid partial agonist buprenorphine, the induction period, the patient must visit the doctor’s office daily or near daily while the dosage is adjusted. Even after the patient’s dosage is adjusted, he or she needs to visit the doctor regularly.

Patients face similar challenges with the opioid agonist methadone, which is only available from opioid treatment programs (OTPs) and is often not covered by insurance. In addition, some states place restrictions on the doses that can be administered or the duration of treatment. Initially, patients are required to visit their OTP daily or, as their treatment progresses, every couple of days. These restrictions are intended to prevent both diversion and overdose. (Methadone overdose is a significant risk for patients who are prescribed it for pain, whose usage is not as closely monitored.) But those who don’t live near an OTP are for this reason not able to take advantage of this medication to treat their addiction.

If extended-release formulations of these drugs were available that allowed patients to get a single injection (depot formulations)—once every few months, or even once a year—it would go a long way toward providing patients a stable, consistent dose and promoting long-term retention in treatment. Developing such formulations is one of the goals for the partnerships NIH is pursuing with industry. A little over a year ago, the FDA approved a six-month buprenorphine implant called Probuphine that Titan Pharmaceuticals had developed with support from NIDA, and this was an important first step. Its dosage is equivalent to 8mg daily, which is relatively low—most people require buprenorphine doses in the 16-24mg range—so the development of higher-dosage formulations, as well as depot injections, would be of great benefit. Multiple pharmaceutical companies are already working to develop new depot formulations of buprenorphine. Implantable formulations of methadone have been evaluated in animal models and also have the potential to be a valuable tool for the treatment of opioid addiction.

Vivitrol, an injectable version of naltrexone that blocks the effects of opioids in the body for four weeks, was approved by FDA in 2006 for treating opioid addiction. Vivitrol makes treatment compliance easier for patients who no longer need to remember to, and choose to, take a pill every day.  The challenge with opioid antagonists like naltrexone is that patients have to be detoxified prior to treatment initiation to avoid withdrawal.  Not all patients tolerate the transition to treatment with an opioid antagonist like Vivitrol, and research is ongoing to evaluate new strategies that can facilitate induction on such medications. Also, patients on naltrexone rapidly lose their opioid tolerance, putting them at risk of overdose if they discontinue treatment—which happens all too often due to lapses in access, insurance coverage, or compliance.   

Longer-acting formulations of naltrexone or other opioid antagonists could provide greater protection against relapse and overdose, the risk of which is particularly high during the first few months of treatment.  Such formulations will make it easier for patients who have difficulty with medication compliance, and thus will help prevent relapse. The benefits of depot formulations for opioid agonists and partial agonists would be just as great, and would also eliminate diversion and misuse, which are concerns with the use of immediate-release opioid medications.   

Bringing an end to the opioid crisis, which continues to claim more than 91 American lives every day, is a top priority for NIDA and NIH. Some solutions are still on the drawing boards and will take many years to come to fruition. But other solutions like improved formulations of existing medications could be developed in a much shorter time frame to help the millions of Americans currently suffering with opioid addiction achieve and maintain a stable recovery. The partnerships that NIH is currently forging between government-funded institutions and private industry aim to accelerate the translation of scientific solutions to help end the opioid crisis.

This page was last updated August 2017

Comments

Suboxone Abuse

You made no mention of the abuse potential of Suboxone and the fact that the current office-based model lacks the many safeguards built into methadone clinics. Is the widespread distribution of Suboxone by individual providers any different from the office-base pain management model that got us into this mess in the first place?

While there is some abuse

While there is some abuse potential with Suboxone (buprenorphine-naloxone), it is less than other opioids, and research suggests those risks are outweighed by its great benefits in treating opioid use disorders. Data also suggest that most misuse is for controlling withdrawal and cravings, rather than obtaining euphoria. Research on the question of treatment need versus diversion risk for buprenorphine and methadone is summarized in our report Medications to Treat Opioid Addiction. The depot formulations discussed in the above post (i.e., getting a shot every few months or longer) would further lessen the possibility of misuse and diversion.

TOO Easy

Opioid deaths drop by 25%+ in areas where cannabis is legal. (Source Johns Hopkins University)
WE COULD REDUCE OPIOID DEATHS BY 25% SIMPLY BY LEGALIZING CANNABIS.
So what's stopping the NIDA from mitigating this "EPIDEMIC" by 1/4?

The new addiction drugs

This writer is just someone who tries to sound scientific but is really nothing more than a pharmaceutical sales rep. These Bentley compounds being pushed on people have a very serious and problematic profile. I hope people who take these drugs are given accurate, honest information. Is it correct information to say Perdue is highly involved with manufacturing and distributing these drugs? I saw where this was going 15 years ago.

response to Dr.Boris re The new addiction drugs

No. Purdue is not involved in the manufacture of addiction treatment medications. They make Butrans, a buprenorphine patch which is used for pain control, but not for treatment of opioid use disorder. I agree it is critical that the public receive "honest, accurate" information. Suboxone is a life-saving medication and the best currently available treatment for those addicted to heroin and/or prescription pain medications. NIDA is working hard to educate those who need help and reduce overdose death rates. Please get your facts straight.

Use of Buprenorphine

It should be approved as a use of a painkiller for those with chronic pain as was it's original purpose. Believe me when I say, it is by the lessor of the two evils.

Over-Regulations create barriers to effective treatment

As a DEA certified provider with a rural health clinic in South Carolina, it has been difficult to get a "supervising" physician that is also DEA certified to provide suboxone without paying $1000-month... As a health care provider I have had to watch patients forgo treatment because they can't get to another facility and sadly are lost to this disease of despair. South Carolina continues to have draconian laws that prevent access to health care providers. Legislation is slow to change even with conclusive evidence and the vicious cycle continues. We need to bend the cost of healthcare with more providers not less. Competition is good in any industry, why is SC so slow to change its outdated laws?

Find Help Near You

The following website can help you find substance abuse or other mental health services in your area: www.samhsa.gov/Treatment. If you are in an emergency situation, people at this toll-free, 24-hour hotline can help you get through this difficult time: 1-800-273-TALK. Or click on: www.suicidepreventionlifeline.orgExternal link, please review our disclaimer.. We also have step by step guides on what to do to help yourself, a friend or a family member on our Treatment page.

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