How precision psychiatry helped my patient; Ketamine: The next ‘opioid crisis’?

Ketamine: The next ‘opioid crisis’?

The chief of the FDA, Scott Gottlieb, MD, recently discussed the need to learn from the mistakes that contributed to the current opioid epidemic¹ and how to curb this crisis. Understanding some of the potential pitfalls could help us prevent, or better manage, the next crisis. Despite the bad press about the opioid crisis,² there seems to be growing promise of another: ketamine. Although ketamine is classified as a Schedule III drug by the Drug Enforcement Agency³ and has a well-documented potential for dependency,⁴ this medication is now being considered a potential treatment for acute suicidality and depression.

There are many similarities between the use of opioids to treat pain and the potential use of ketamine to treat suicidality. Physical and mental pain are subjective, qualitative, and difficult to quantify, which makes it difficult to develop accurate measurements of symptom severity. Chronic physical pain and suicidality are not illnesses, but symptoms of myriad types of pathologies with differing etiologies and treatment options.⁵ Due to the ambiguous and subjective experience of physical and mental pain, we tend to lump them together as 1 pathological category without understanding pathophysiologic differences. The most commonly reported types of pain include low back pain, migraine/headache, neck pain, and facial pain.⁶ However, each of these pain types would likely have a different pathophysiology and treatment. Likewise, suicide can be associated with various psychiatric conditions,⁷ and suicidality resulting from these conditions may require a different etiology and treatment.

We already know that both opioids and ketamine are addictive. For example, there is a report of a nurse stealing a hospital’s supply of ketamine and self-treating for depression, which led to an inpatient detox admission after she developed toxicity and addiction.⁸ Some ketamine research supports its safe use, but it may be biased due to conflicts of interest. For example, several authors of a recent study proclaiming the effectiveness of a single dose of ketamine in treating suicidal ideation are named on patents or are employed by companies named on patents related to ketamine and would financially benefit from FDA-approval of ketamine for the treatment of psychiatric disorders.⁹

Warnings stating how both opioid and ketamine should be used were published years ago but have since been ignored. For example, a 1977 article advocated that opioids should only be used for a “short duration and limited to patients with acute diseases or inoperable or metastatic cancer who require long-term relief.”¹⁰ The rationale for this distinction was foretelling of the current opioid epidemic: “Continued and prolonged use of narcotics in patients with chronic benign pain is not recommended because of serious behavioral consequences, the development of tolerance, and addiction liability. Long-term use of analgesic drugs in chronic pain usually produces negative behavioral complications that are more difficult to manage than the pain it was desired to eliminate.”¹⁰ We knew better then.

The earliest report of ketamine dependency I could find was published in 1987, which predates its classification as a controlled substance.¹¹ More recently, ketamine dependency has been associated with adverse effects that are similar to “not only cocaine and amphetamine but also with opiates, alcohol and cannabis, as well as the psychological attractions of its distinctive psychedelic properties.”¹² We should consider ourselves warned.

Michael Shapiro, MD
Assistant Professor
Department of Psychiatry
University of Florida
Gainesville, Florida

References
1. Jayne O’Donnell. FDA chief supports opioid prescription limits, regrets agency’s prior inaction. USA TODAY. https://www.usatoday.com/story/news/politics/2017/10/23/fda-chief-supports-opioid-prescription-limits-regrets-agencys-prior-inaction/774007001. Published October 23, 2017. Accessed January 25, 2018.
2. Bill Whitaker. Ex-DEA agent: opioid crisis fueled by drug industry and Congress. CBS News. https://www.cbsnews.com/news/ex-dea-agent-opioid-crisis-fueled-by-drug-industry-and-congress. Published October 15, 2017. Accessed January 25, 2018.
3. Drug Enforcement Administration. Diversion of Control Division. Ketamine. https://www.deadiversion.usdoj.gov/drug_chem_info/ketamine.pdf. Published August 2013. Accessed January 25, 2018.
4. Bell RF. Ketamine for chronic noncancer pain: concerns regarding toxicity. Curr Opin Support Palliat Care. 2012;6(2):183-187.
5. Barzilay S, Apter A. Psychological models of suicide. Arch Suicide Res. 2014;18(4):295-312.
6. American Academy of Pain Medicine. AAPM facts and figures on pain. http://www.painmed.org/patientcenter/facts_on_pain.aspx.
7. Diagnostic and Statistical Manual of Mental Disorders, 5th ed. Washington, DC: American Psychiatric Association; 2013.
8. Bonnet U. Long-term ketamine self-injections in major depressive disorder: focus on tolerance in ketamine’s antidepressant response and the development of ketamine addiction. J Psychoactive Drugs. 2015;47(4):276-85.
9. Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry 2017. https://doi.org/10.1176/appi.ajp.2017.17040472
10. Halpern LM. Analgesic drugs in the management of pain. Arch Surg. 1977;112(7):861-869.
11. Kamaya H, Krishna PR. Anesthesiology. 1987;67(5):861-862.
12. Jansen KL, Darracot-Cankovic R. The nonmedical use of ketamine, part two: a review of problem use and dependence. J Psychoactive Drugs. 2001;33(2):151-158.