Road to recovery: Personalized treatments and technology are helping people free themselves from opioid addiction

This article originally appeared in Genome in July 2017.

In 1998, Rose Palinkas was finally clean. Using heroin recreationally as a twentysomething in the 1980s had spiraled into a lifelong addiction. It cost her three children. She spent years living on the street and never had a career or a stable home. She had spent almost 20 years dependent on heroin or the prescription medications, like methadone, that doctors use to wean people off heroin.

But at 42 years old, on methadone for the second time, she checked into a hospital and asked them to get her off it, too. “I started meeting nice people and doing the right thing,” she says. “I was making money, working out, and I felt good about myself.”

Palinkas loved riding her bike along the beach in Broward County, Florida. Clean for about a year, she was biking along the coast one afternoon, when an 18-wheeler almost killed her. The truck — its driver asleep behind the wheel — crushed her lower spine and sciatic nerve. The pain was unbearable. Anyone in her condition would have received a prescription opioid as soon as he or she arrived at the hospital. “Doctors are very fast to write you that prescription,” she says, “but when you’re a recovering addict, you can’t go on painkillers,” though, people sometimes do.

The doctor who had gotten Palinkas off methadone the year before put her on buprenorphine. While it too is a painkiller, it’s one of only three medications used to treat opioid addiction. It masked her pain, but once again, Palinkas was chained to a drug. Every 30 days she had to fight with Medicaid to refill her prescription. She quit exercising, gained weight, and became depressed.

“I would have to wait two, maybe three weeks [for my prescription to be filled]. Meanwhile my pain is going all the way up, and a few houses down they’re selling oxys,” she says. “That’s really hard when I could get some relief just two doors down.”

More than 2.5 million Americans like Palinkas suffer from opioid use disorder (OUD) involving either prescription painkillers or heroin. Up to 85 percent of heroin users got hooked on opioids via prescription painkillers. In 2015, the most recent year for which data are available, more than 33,000 people died of an opioid overdose. These deaths have quadrupled since 2000. And many of those who try to free themselves from these drugs are failed by the standard treatment options. But a handful of innovative alternatives might better serve the millions of Americans desperate to get their lives back.

Care as Usual

Doctors have three FDA-approved medications available to them to treat opioid addiction: methadone, naltrexone, and buprenorphine. Methadone, an opioid painkiller itself, alleviates the pain of withdrawal while also reducing cravings, which helps opioid addicts avoid illicit drugs and get their lives back on track. Treatment typically lasts at least a year but can continue for many years.

It’s estimated that 60 to 90 percent of people in methadone treatment manage to stay off other opioids. The treatment boasts up to 75 percent retention rates, but critics say retention doesn’t tell the whole story.

In the beginning, the only way to get methadone is to go to a clinic every day for a dose. “You are basically married to the clinic. You can’t get away. Retention just means you got stuck,” says Walter Ling, a professor of psychiatry and the founding director of the Integrated Substance Abuse Programs at the University of California, Los Angeles. “After a certain period, mostly 90 days, you can get some methadone doses to take home — the so-called ‘take home privileges’ if you fulfill certain requirements, like showing no illicit drug use in urine tests and having a job,” says Ling. Still, the most common clinic attendance, even after months and sometimes years of treatment, is three times a week, he adds.

While the drug’s properties might help people restart their lives, the frequent in-person dose administration can be a challenge.

“I got stuck on that monster for years,” says Palinkas. “It was just a different kind of nightmare. You have to go there every day, and they don’t care about you.” She recalls a clinic that didn’t offer counseling and denied her medication on the days when money was scarce. Clinic hours and locations can prevent people from holding down jobs or taking even an overnight trip — not to mention the stigma that surrounds entering or exiting these buildings.

Some research also suggests that certain people are more sensitive to methadone than others, putting them at a greater risk of accidentally overdosing on the drug. Those with a sluggish version of the enzyme encoded by the CYP2B6 gene are thought to metabolize methadone in a way that makes them more susceptible to experiencing respiratory depression or arrhythmias that can lead to death. People with CYP2B6 genetic variations are thought to need far less methadone per day for maintenance treatment than others. For this reason — as well as methadone’s access challenges — healthcare providers might choose a different therapy.

Naltrexone is another option, but patients don’t seem to do as well on it. The drug blocks opioid receptors in the brain. Thus, people who try to use heroin or prescription opioids won’t feel any of the drugs’ effects.

“The idea is, if you make it impossible for them to enjoy opioids, they will stop doing it,” says Ling. “Well, that’s true in animals, but humans don’t always act like animals.”

Because it brings no additional feel-good effects, naltrexone is a hard sell for someone who’s come to depend on opioids to induce or reduce euphoria. Studies show relatively low rates of adherence to the medication and high rates of relapse.

Buprenorphine brings both the feel-better effects of methadone and the opioid-blocking effects of naltrexone. While opioids cause their high by latching onto opioid receptors in the brain, buprenorphine is less effective as doses increase, causing milder, albeit pain-relieving, effects. And it latches on to the receptor tightly enough to block other opioids from causing their euphoric effects. The medication, which can be taken at home, can allow people to move on with their lives without suffering withdrawal and cravings.

“It’s been a lifesaver. It’s made a huge difference,” says Richard Rosenthal, a professor of psychiatry at Mount Sinai’s Icahn School of Medicine in New York.

Studies are mixed as to whether it works as well as methadone. But while it’s not without access issues, buprenorphine doesn’t present the same barriers as methadone treatment; patients don’t have to go to a clinic each day for their dose.

Still, physicians must receive training before they can treat patients with the drug. The reason, says Mitra Ahadpour, is that medical schools don’t provide sufficient training in substance use disorder treatment or screening. Ahadpour is a physician and the director of the Division of Pharmacologic Therapies in the Center for Substance Abuse Treatment at the Substance Abuse and Mental Health Services Administration in Rockville, Maryland.

Even trained physicians are limited in the number of patients they can treat with buprenorphine. That’s to reduce the risk of patients diverting the drug, says Ahadpour. Some people believe that the more legally prescribed buprenorphine that’s out there, the greater the chance it can be diverted. Along with buprenorphine, physicians must provide psychotherapy or a referral for it.

According to Ling of UCLA, no other Food and Drug Administration-approved medication comes with such stringent requirements. “Not even highly dangerous cardiovascular and anti-cancer drugs,” he says. “There is absolutely no reason for those requirements except to appease those opposing [buprenorphine’s] approval. It reflects the mindset of law enforcement people and the general attitude of our society toward addicts and, by extension, the doctors who treat them.”

The requirements can, in some ways, prevent those in recovery from feeling that they’ve gotten their lives back. “It’s great if you don’t want to travel — if you just want to stay living in one state,” says Palinkas, who longs to visit her 93-year-old father in Puerto Rico but sticks close to home to attend therapy and keep her prescription refills on schedule.

Some people take buprenorphine indefinitely. Those who want to stop the medication must go through withdrawal just as they would with any other opioid. “It’s hell,” says 27-year-old Brian Comer of St. Charles, Missouri.

Comer’s wisdom tooth extraction during college earned him a prescription painkiller, which led to recreational use of opioids and eventual dependence. Comer didn’t even realize he’d become dependent until he came down with what felt like the flu when he tried to quit the first time. After four more years on opioids, Comer started buprenorphine treatment. When he decided to stop the treatment last year, he had to go through the sickness all over again.

“Your skin is crawling. You can hardly wear clothes,” Comer recalls. “I couldn’t lie on the couch because the material made me uncomfortable. You can’t sleep. You’re contorting your body to try and get comfortable. It’s like extreme restless leg syndrome.” Comer had flu-like symptoms, fogginess, chills, and sweating.

The physical symptoms are worst during the first three days. But cravings, depression, and discomfort can last a month or more.

Electronic Acupuncture

But Comer only had to suffer for a few days. The psychiatrist who managed his buprenorphine treatment, Arturo Taca, offered Comer something called “the Bridge,” an electrical nerve-stimulation device. FDA-cleared as an electro-acupuncture device for the treatment of pain, the Bridge isn’t approved for detoxification. That’s why Comer had to wait for the buprenorphine to leave his system first.

The gadget fits behind the ear like a hearing aid, secured with adhesive tape. Four wires with tiny needles at the ends are taped to specific spots on the ear, stimulating several cranial nerves. “These nerves project to the central pain complex,” says Carrie Peterson, a surgeon at Froedtert & Medical College of Wisconsin. She is currently recruiting patients for a clinical trial that will test the benefits of the Bridge in addressing pain after colon surgery. If successful, the device could help reduce opioid prescribing to begin with. (Neither Peterson nor Taca and his co-authors have financial ties to Innovative Health Solutions, the makers of the Bridge.)

The central pain complex, Peterson says, controls your interpretation of pain and your emotional response to it. “We think the Bridge works by changing the way you perceive painful stimuli.” It might not be that the pain goes away, but rather that it doesn’t matter as much anymore.

The results for Comer were nothing short of miraculous. He dragged himself to Taca’s office to get the device after three days of suffering. “It literally took 10 minutes for me to start feeling better,” he says. He recognized that the device was manipulating his perception of pain. “It was like, ‘Wait, am I still feeling withdrawal or am I not?’”

Taca, who specializes in addiction treatment, offers the Bridge to any eligible patients interested in getting off buprenorphine. “Eighty-five percent of the symptoms are managed within 30 minutes,” Taca says. Taca and co-author Adrian Miranda, a pediatrician at Children’s Hospital of Wisconsin, reported these findings from their small, uncontrolled, open-label study in March in the American Journal of Drug and Alcohol Abuse. Miranda will also collaborate with Peterson on the postoperative pain study.

In Taca and Miranda’s study, patients knew they were receiving the treatment, and the researchers didn’t use an untreated control group for comparison. So it’s hard to know whether patients’ results can be attributed to the device or the placebo effect.

Aside from this small, open-label study, scientific evidence of the benefits of the nerve stimulation device is limited. A randomized, double-blind, placebo-controlled study would provide more robust evidence of the device’s efficacy. Peterson’s upcoming trial, which will include about 60 patients, is a start.

“I think there is potential for it to be helpful as an adjunct to the treatments that we have, which, unfortunately, are not the greatest,” says Tim Mariano, a psychiatrist at Brigham and Women’s Hospital in Boston, who studies neuromodulation devices to treat the effects of chronic pain on mood. “But we need more data before we can make a firm recommendation to patients. We want to offer all the treatments that we think would potentially be useful, even if they’re experimental, but we don’t want to give people a false sense of hope.”

Comer has no doubt that the device worked for him. He wore the Bridge for five days, “and that was it,” he says. Withdrawal was over. “I couldn’t believe it was real. I got a better job, leased my own apartment for the first time, and I can go out with my friends because I’m not worried about getting home before the [buprenorphine] wears off.”

He was, he says, finally free.

Handheld, Portable Therapy

Prescription digital therapeutics might also give those fighting opioid dependence more of the freedom they long for, while at the same time dramatically enhancing rates of abstinence. Standard guidelines for addiction treatment recommend psychotherapy or cognitive behavioral therapy (CBT), in conjunction with medication. A prescription smartphone app called reSET-O, currently under review by the FDA, might bring some benefits of face-to-face psychotherapy to patients’ smartphones.

Designed for combined use with methadone or buprenorphine to treat opiate use disorder, the app includes CBT principles delivered via five- to 10-minute interactive, multimedia learning modules that test for understanding at the end. “It’s really easy to sit in face-to-face therapy and nod your head without actually mastering therapeutic concepts, whereas here, the patient is not able to advance to the next module unless mastery is demonstrated,” says Corey McCann, the president and CEO of Pear Therapeutics, the developer of the app.

ReSET-O also offers a platform for logging cravings, triggers, and opioid use, which clinicians can monitor for reduction. In three randomized, controlled clinical trials, patients using reSET-O had better drug abstinence rates, better treatment retention, and less need for clinician intervention than their peers receiving standard care.

But would people stick to their treatment plan as well in real life as they do in the controlled setting of a clinical trial, asks John Torous, a psychiatrist and the co-director of the digital psychiatry program at Beth Israel Deaconess Medical Center in Boston. People have to use the app for it to work, and clinical trials might not indicate how well a smartphone app will work in real life.

McCann attributes part of the program’s success to its standardization and its immediate accessibility. “Face-to-face therapy is highly variable, and when you have a craving, it may be days before your next therapy session.”

But a certain type of person will turn to a phone app in the face of a mighty drug craving. “Who are the people that are going to reach for their phone in a time of crisis, and how do we learn from them?” Torous asks. “It may be a perfect solution for some people and an ineffective one for others.”

Medication Under Your Skin

As for Palinkas, now 61 years old, she has regained her freedom through an implant in her arm called Probuphine. The implant provides a steady flow of buprenorphine for six months, and it’s indicated for use for a year. Palinkas was among the first people to receive the implant after the FDA approved it in May 2016.

Early clinical trials show that people with implants do a little better at avoiding illicit opioids than people taking oral buprenorphine. The implants may perform better, in part, because there’s no room for user error. With oral therapy, says Rosenthal, who ran a clinical trial of the implant, “there’s no guarantee that the patient is going to take it. They can forget a dose, sell a dose, lose a dose, or have it stolen.”

Not only does the implant ensure a consistent release of medication, but it also sets Palinkas free from monthly battles with Medicaid and the temptation to buy relief two doors down. She’s investing that freedom in herself. “I know it’s working, because I’m working out again,” she says. “Now I can go to Puerto Rico and see my father.”

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