Are We Making Any Progress in Treatment and Attitudes?

Psychiatry 20/20• Series Editor H. Steven Moffic, MD

About 50 years ago (1968) in an early edition of Resident Physician, a progenitor of Psychiatric Times, Herbert Berger, MD (Chairman of the Committee on Alcoholism and Narcotic Addiction, New York State Medical Society) wrote about the “Physicians’ Retreat from Management of Addictions” and blamed physician attitudes for turning over this major medical challenge to non-medical personnel and the criminal justice system. This retreat from potential patients was not just active rejection from physicians’ offices but an omission of responsibility to counter the prevalent argument that these individuals were willfully evil rather than sick.

Berger went on to discuss the 1919 interpretation of the Harrison Act of 1915-that keeping an opioid dependent patient “comfortable by maintaining his customary [opioid] use was not a prescription, within the meaning of the law . . . .” As a result, physicians became targets for arrest and imprisonment for prescribing narcotics to control withdrawal symptoms in attempt to make their patients comfortable. Had any progress been made from 1919 to 1968, when Dr Berger wrote his appeal?

Interestingly, on this very same page of the article in 1968 was an advertisement from Smith, Kline, and French Laboratories stating in bold type, “To reduce pain-narcotics” followed on the next page by the statement, “To reduce narcotics-Thorazine.”

As some of us may remember, chlorpromazine was used for opioid withdrawal in the late 1960s through the 1980s (and even into the 1990s in some settings), when going cold turkey was the option. In fact, chlorpromazine was frequently given to opioid dependent arrestees during incarceration, although they did not like its effects. It was never FDA approved for this purpose. Other off-label medications also were used for reducing opioid withdrawal symptoms, including the use of clonidine for opioid withdrawal along with other non-opioid medications. However, off-label marketing was quite common at that time and continued with a vengeance for opioids such as oxycontin for chronic pain, with the subsequent problems and fines against manufacturers that bring us to modern day.

Overall, the two components of the Smith, Kline, and French Laboratories (and other pharmaceutical) advertising campaign were problematic. First, reducing pain was generalized to any pain, including benign chronic pain such as backaches, headaches, peripheral neuropathies, fibromyalgia pain, and other chronic pain conditions that do not benefit from long-term opioids. Second, reducing opioids was not easy and could not be simply treated with essentially aversive medications such as chlorpromazine, which did not target the underlying neurobiology driving opioid withdrawal symptoms. Thus, little progress with the pharmaceutical industry was evident in 1968, but plenty of future problems were starting, which the next 50 years-from 1968 to the present-began addressing.

Strides in clinical research

Progress has been more evident during these more recent 50 years, moving us further away from the 1919 decisions that made it illegal to provide medical help to people with an opioid addiction. While medical progress has been slow, it has been steady. In the 1970s, because of the discovery by Vincent Dole, MD, and Marie Nyswander, MD, and the efforts of the federal government led by Jerome Jaffee, MD, the national Drug Czar, the introduction of methadone maintenance provided a wide-spread agonist treatment. Parallel work led to two important milestones: naltrexone as a blocker for opioids and its evolution to an injectable long-acting formulation as well as the development of buprenorphine as a partial agonist maintenance agent. In addition, the Data2000 legislation provided more relaxed prescribing restrictions. In addition to these maintenance approaches to treatment, aids for managing the symptoms of opioid discontinuation, such as clonidine and most recently lofexidine, also became available.

We have made significant progress in moving addiction into the medical treatment area and away from the social stigma that led to widespread incarceration of those with substance use disorders. Current treatments show good efficacy for opioids and promising research is ongoing for alcohol and stimulants.

Market influences still persist

However, along with the more humane treatments for addiction, an opposing trend began from the pharmaceutical industry to increase sales of opioids for managing “insufficiently treated” chronic pain syndromes. This trend during the 1990s resulted in the lawsuits and ongoing settlements for damages that began in 2007.

We have arrived at a time for financial settlements with some of the pharmaceutical companies that derived substantial profits from what resulted in an epidemic of death and destruction as a result of opioid overuse and dependence. Based on recent court settlements of single state cases, negotiations for national settlements might reach $10 billion for each company.

In Ohio and in a recent Oklahoma case, the judge stated that one company “engaged in false and misleading marketing of both their drugs and opioids generally, and the law makes clear that such conduct is more than enough to serve as the act or omission necessary to establish the first element of Oklahoma’s public nuisance law.”

Guiding settlement funds>

Guiding settlement funds

Having such massive infusions of funding into public coffers can bring great benefits to treatment of substance use disorders, damage reparations, and new treatment discoveries. However, we need to look back at the Master Settlement Agreement (MSA) from the tobacco lawsuits that were settled 20 years ago in 1998.What happened with those billions of dollars? States collected an estimated $27.3 billion from the MSA and taxes in fiscal year 2019, yet today no state funds tobacco prevention at the level recommended by the Centers for Disease Control and Prevention (CDC). Overall, states spend less than 3% of MSA funds on programs that would help prevent smoking in youth and help smoking cessation. Twenty-nine states and the District of Columbia spend less than 20% of the CDC recommendation. On the other hand, Alaska and California spend more than 70% of the CDC recommended funding-$655 million annually-on prevention and cessation programs. In contrast, tobacco companies spend more than $14 to market tobacco products for every $1 the states spend to reduce tobacco use.¹

Because there are new challenges in reducing tobacco and nicotine use since the agreement, the MSA funds could have been better directed to detecting and addressing future threats than to the many other conditions unrelated to health care for which they were used. Among the new challenges is e-cigarette use by youths, which has skyrocketed to epidemic levels; the CDC and FDA show that from 2017 to 2018 e-cigarette use increased by 78% among high school students (to 20.8%) and by 48% among middle school students (to 4.9%).

The associated morbidity and mortality attributed to vaping with e-cigarettes has been startling and led to dramatically quick actions by Federal government standards, but with no benefit from the MSA funds. Similarly, the legalization of cannabis and its widespread smoking and vaping in many parts of the US has brought with it many health burdens in psychiatric and medical comorbidity, which have not been addressed with any portion of the MSA funds.

This lack of vision and missed opportunities associated with MSA funds should not be repeated with the accumulating opioid epidemic settlement funds. The obvious parallel for opioids with comorbid abuse of other DEA scheduled medications such as stimulants and sedatives strongly argues that these opioid settlement funds need essential investments in prevention, treatment, and research into related types of addictive substances and their delivery systems. However, such an investment is not likely to happen without substantial effort from the medical community.

To jump start these future opioid settlement funds, the federal government currently has allocated funding for the Helping to End Addiction Long-term (HEAL) initiative for the ongoing epidemic of deaths, which are now primarily from fentanyl. These HEAL funds are very welcome in the field and should provide some significant help for our patients, but these funding sources are not sustained and even their re-authorization in Congress will only carry for another year. Thus, the upcoming challenge will not be in the courts, but in the state legislatures, which are likely to get a substantial influx of financial resources for sustained periods from the opioid settlements.

These funds can help address the current opioid epidemic, but perhaps more importantly, these sustained funds need to be directed toward the rapidly growing epidemic of stimulants, particularly methamphetamine. While the fatalities associated with this opioid epidemic have indeed shifted to an illicit market of heroin and fentanyl and away from the original challenges with marketed commercial opioids, fentanyl is not only mixed with opioids, it is also being mixed with stimulants and causing increased mortality among drug users.

Stimulant abusers are also fueled by pharmaceutical companies who market stimulants for adults and children with attention-deficit/hyperativity disorder; however, many adults are getting stimulants for such off-label uses as depression, anxiety, and improved concentration. College campuses are awash in illicit stimulant use, and many young adults are becoming addicted to stimulants. Moreover, there is now the added risk of illicit fentanyl adulteration and overdose.

The financial resources that are clearly on their way to states and communities from both pharmaceutical company settlements and the more immediate federal HEAL grants need appropriate planning for wise spending-not wasting these resources by missing the mark for which they were intended.

So, have we made progress since that article was published in 1968 or are we on a two-steps forward, one backward pattern? Let us hope a future psychiatrist will be able to write a more positive article.

Disclosures:

Dr Kosten is Jay H. Waggoner Endowed Chair, Co-Founder, Institute for Clinical and Translational Research, and Professor of Psychiatry, Neuroscience, Pharmacology, and Immunology, Baylor College of Medicine, Houston, TX.

References:

1. Campaign for Tobacco-Free Kids. A State-by-State Look at the 1998 Tobacco Settlement 21 Years Later. January 16, 2020.