Long-term opioid prescription use jumps threefold over 16-year period, study suggests

Long-term use, which is associated with greater risk for addiction and overdose, increased threefold during the study's time frame. In 1999-2000, less than half of the people who were taking prescription opioids were taking them for 90 days or more. By 2013-2014, more than 70 percent were taking opioid medication on a long-term basis.
The findings come as the U.S. grapples with a worsening opioid epidemic that on average is killing nearly 100 people a day, some from prescription opioids and others from illegal forms, primarily heroin. Last month, the Trump administration declared the opioid epidemic a public health emergency, a step that will allow the government to dispense additional federal funds for treatment.
The study, published online in the journal Pharmacoepidemiology and Drug Safety, draws from survey data gathered by the National Health and Nutritional Examination Survey, which the National Center for Health Statistics has conducted every two years since 1999-2000. Prescription opioid use, the paper found, rose from 4.1 percent of U.S. adults in 1999-2000 to 6.8 percent in 2013-2014, an increase of 60 percent. Long-term prescription opioid use, defined as 90 days or more, increased from 1.8 percent in 1999-2000 to 5.4 percent in 2013-2014.
"What's especially concerning is the jump in long-term prescription opioid use, since it's linked to increased risks for all sorts of problems, including addiction and overdoses," says study author Ramin Mojtabai, MD, PhD, MPH, a professor in the Department of Mental Health at the Bloomberg School. "The study also found that long-term use was associated with heroin use as well as the concurrent use of benzodiazepines, a class of widely prescribed drugs that affect the central nervous system," he says.
This is one of the paper's more worrisome findings, Mojtabai notes, since combining opioids and benzodiazepines significantly increases the risk of overdose, even if the patient is taking a moderate dosage of opioid medication. Combining these drugs can also cause respiratory suppression, he says.
For the paper, Mojtabai examined eight consecutive biannual surveys, each of which included over 5,000 adults living throughout the U.S. Interviews were conducted via computer in participants' homes. Participants were asked to identify prescription medication they'd taken in the past 30 days, and for what length of time. A total of 47,356 adults participated in the eight surveys, and the response rate ranged from 71 percent to 84 percent. If participants were taking more than one opioid medication, the study logged the duration for the longest-used medication.
Opioid medication use overall and long-term use were more common among participants on Medicaid and Medicare versus private insurance.
Despite the upward trend, there is scant evidence supporting benefits of longer-term prescription opioid use, Mojtabai says, with no randomized clinical trials that support their extended use, given the risks.
Prescription opioids were originally designed for shorter-term use, which involves fewer patient risks. Many patients who take opioid medication for weeks or months develop a tolerance that over time requires higher dosages for the medication to relieve pain. As a result, patients will take more medication to reduce their pain, setting them on the path to possible addiction. While there is no clear delineation as to when addiction kicks in, longer-term use is thought to be a risk factor.
The Centers for Disease Control and Prevention issued new guidelines last year, recommending that physicians prescribe opioids for chronic pain only after other options have been proven ineffective. The guidelines also recommend short-term use (three days instead of seven) and lower dosages. The impact of these new guidelines is not yet known, Mojtabai says.
The 2013-2014 survey asked participants for the first time to identify the main reason they were taking prescription opioid medication. Back pain was the leading reason, with over 42 percent, or 167 of 402 participants taking these medications in 2013-2014, reporting they were seeking relief for back pain. This was followed by arthritis and other joint pain, with 102, or 25.3 percent, identifying them as the reason for taking prescription opioids.
For those with back pain, nearly one half had been taking medication for over 90 days, while among those with arthritis or other joint pain, a quarter had been taking opioid medication for over 90 days. Other leading reasons for prescription opioid use included injury-related pain (14.4 percent) and muscle and soft tissue pain (11.4 percent).
"Given the urgency, it's critical that we continue to try and understand what benefits, if any, exist for prescribing opioids for both short- but especially for longer-term consumption," says Mojtabai, "There may be alternative treatments. We also need to understand what other factors contribute to the considerable risks of prescription opioid medication among different groups, especially those with other drug or alcohol use in their profiles."

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Serotonin is a neurotransmitter which helps brain cells communicate with one another, playing important roles in stabilising mood and regulating stress. Despite its importance, current models to explain serotonin's function in the brain remain incomplete. Now, in a review paper published this month in the Journal of Psychopharmacology, researchers from Imperial College London suggest that serotonin pathways are more nuanced than previously thought. They argue that the existing view should be updated to incorporate a 'two-pronged' model of how serotonin acts. The researchers believe their updated model could have implications for treating recalcitrant mental health conditions, including depression, obsessive compulsive disorder and addiction, and could exploit the therapeutic potential of psychedelic drugs. In the brain, serotonin acts via a number of sites called 'receptors' and serotonin has at least 14 of these. Brain drugs such antidepressants, antipsychotics and psychedelics are known to interact with serotonin receptors and two of these are thought to be particularly important -- the so-called serotonin 1A and 2A receptors. For patients with depression, commonly prescribed drugs called SSRIs (Selective Serotonin Reuptake Inhibitors) can help to relieve symptoms by boosting levels of serotonin in the brain. Evidence suggests an important part of how they work is to increase activity at the serotonin 1A receptor, which reduces brain activity in important stress circuitry, thereby helping a person cope better. In contrast, psychedelic compounds such as LSD and psilocybin (the psychoactive component of magic mushrooms), are thought to act primarily on the serotonin 2A receptor. Accumulating evidence suggests that psychedelics with psychotherapy can be an effective treatment for certain mental illnesses and, with a focus on the 2A receptor, the authors' paper attempts to explain why. Writing in the review paper, the researchers say that while the traditional view of developing psychiatric treatments has been focused on promoting 1A activity and often blocking the 2A, the therapeutic importance of activating the 2A pathway -- the mechanism by which psychedelics have their effect -- has been largely overlooked. "We may have got it wrong in the past," said Dr Robin Carhart-Harris, Head of Psychedelic Research at Imperial and lead author on the paper. "Activating serotonin 2A receptors may be a good thing, as it makes individuals very sensitive to context and to their environment. Crucially, if that is made therapeutic, then the combination can be very effective. This is how psychedelics work -- they make people sensitive to context and 'open' to change via activating the 2A receptor." According to the researchers, the 1A and 2A pathways form part of a two-pronged approach which may have evolved to help us adapt to adversity. By triggering the 1A pathway, serotonin can make situations less stressful, helping us to become more resilient. However, they argue that this approach may not always be enough, and that in extreme crises, the 2A pathway may kick in to rapidly open a window of plasticity in which fundamental changes in outlook and behaviour can occur. Growing evidence shows that in conditions such as treatment-resistant depression, obsessive compulsive disorder and addiction, certain brain circuitry may become 'stamped in' and resistant to change. The researchers suggest that in such cases, activating the 2A pathway -- such as through psychedelics -- could potentially offer a way to break the cycle, helping patients to change negative behaviours and thought patterns which have become entrenched. By enabling the brain to enter into a more adaptive or 'plastic' state and providing patients with a suitably enriched clinical environment when they receive a drug treatment, clinicians could create a window for therapy, effectively making patients more receptive to psychotherapy. According to the authors, their updated model of how serotonin acts in the brain could lead to a shift in psychiatric care, with the potential to move patients from enduring a condition using current pharmacological treatments, to actively addressing their condition by fundamentally modifying behaviours and thinking. Professor David Nutt, Director of Neuropsychopharmacology in Imperial's Division of Brain Sciences, explained: "This is an exciting and novel insight into the role of serotonin and its receptors in recovery from depression that I hope may inspire more research into develop 5-HT2A receptor drugs as new treatments." 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