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to the editor: In 2017, Wilkinson et al. (1) reported on the growing clinical off-label use of racemic ketamine among academic settings and community providers for psychiatric disorders. In 2019, the U.S. Food and Drug Administration (FDA) approved intranasal (IN) esketamine as an adjunctive therapy for treatment-resistant depression, yet esketamine has been challenging to implement (2). Whether approval of esketamine has influenced the characteristics and viability of clinics offering off-label racemic ketamine has not been investigated.
Between September 2020 and May 2021, a web-based survey was sent to U.S. providers identified by an Internet search, membership in various ketamine physician societies, and ketamine social media groups. Providers and clinics were included if they offered intravenous (IV) ketamine treatment for psychiatric disorders and provided a valid e-mail address. Academic institutions were not included in this survey. The study received approval from the Baylor College of Medicine IRB.
Of 154 clinics with valid e-mail addresses, 98 (63.6%) completed surveys. The sample was divided into four U.S. regions (South=35.9%, West=28.1%, Midwest: 25.8%, Northeast=10.1%). Clinics reported treating a wide range of psychiatric disorders, including major depressive disorder (100%), bipolar disorder (98%), anxiety disorders (87%), posttraumatic stress disorder (80%), and obsessive-compulsive disorder (78%). Many clinics offered adjunctive and alternative services to IV ketamine treatment, including hydration or nutritional infusions (37%), medication management (30%), and counseling/psychotherapy (40%). Over half (61%) offered other routes of ketamine administration, including intranasal, intramuscular and sublingual.
A majority of clinics (53%) reported initial weight-based dosing at 0.5 mg/kg. However, the vast majority (88%) titrated infusion dose over the course of acute treatment, with doses ranging from 0.5 to 3.0 mg/kg. The most commonly prescribed infusion courses were 4-6 infusions (57%) or 6-8 infusions (40%). The majority administered infusions on a twice (53%) or three times per week (42%) treatment schedule. Most providers determined maintenance phase treatments according to patient preference and need (73%) rather than a fixed-schedule protocol.
Virtually all providers reported administering a validated self-report scale to assess depressive symptoms (97%), most commonly the PHQ-9 (66%) (3). A majority of providers reported tracking outcomes for anxiety (53%), and some reported tracking outcomes for trauma symptoms (15%) as well.
Compared to Wilkinson et al., similar vital monitoring patterns were noted. Many providers monitored heart rate (HR, 40%), pulse oximetry (PO, 31%) and blood pressure (BP, 30%) at least every 5 minutes during the infusion. Most providers monitored these vitals at least every 15 minutes (HR, 88%; PO, 83%; BP, 85%). Few providers reported no monitoring (HR, 3%; PO, 4%; BP, 1%).
Two-thirds of survey-respondent clinics were owned by physicians, with the other third owned by Certified Registered Nurse Anesthetists (28%) and Nurse Practitioners (3%). Regarding administrating provider types, 68% of clinics reported at least one physician as part of the treatment team, with a wide range of physician specialties reported (Table 1).
TABLE 1. Survey respondents by administrating provider type and physician specialty
Provider or Specialty TypeN%
Administrating providers (N=98)  
 MD or DO only3738
 Combination of providers with at least one MD2930
 Certified registered nurse anesthetist2526
 Registered nurse22
 Combination of providers without a MD55
Physician specialties (N=68)  
 Anesthesiology2441
 Psychiatry1927
 ER medicine1118
 Addiction medicine48
 PM&R23
 Internal medicine23
 Critical care23
 Neurosurgery12
 Palliative care12
 Obesity medicine12
 Neurology12
Although there are limitations to our approach and our sample did not include academic medical centers, we highlight some interesting results. First, a majority of clinics (73% of respondents) did not have a psychiatrist on staff (a change from the earlier report, where two-thirds did). Second, most clinics titrated dosage to optimize patient response, and reported using validated and standardized measures of symptom severity to track outcomes, findings that highlight prior calls to organize a registry of patient data (4). Third, despite FDA approval of esketamine, clinics continue to provide off-label racemic ketamine . These findings indicate several topics worthy of further investigation, including optimal dose titration, the selection of ketamine versus esketamine as a treatment in community clinical practice, and barriers to care (e.g., financial, time commitment, driving restrictions). In summary, with the continued provision of off-label ketamine for psychiatric disorders, partnerships among various stakeholders will be necessary to improve the effectiveness, safety, delivery, and responsible accessibility of this treatment.

References

1.
Wilkinson ST, Toprak M, Turner M, et al: A survey of the clinical, off-label use of ketamine as a treatment for psychiatric disorders. Am J Psychiatry 2017; 174:695–696
2.
Wilkinson ST, Howard DH, Busch SH: Psychiatric practice patterns and barriers to the adoption of esketamine. JAMA 2019; 322:1039–1040
3.
Kroenke K, Spitzer RL, Williams JB: The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med 2001; 16:606–613
4.
Sanacora G, Frye MA, McDonald W, et al: A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry 2017; 74:399–405

Information & Authors

Information

Published In

Go to American Journal of Psychiatry
Go to American Journal of Psychiatry
American Journal of Psychiatry
Pages: 393 - 394
PubMed: 35491568

History

Accepted: 14 December 2021
Published online: 1 May 2022
Published in print: May 2022

Keywords

  1. Ketamine/Esketamine
  2. Psychopharmacology
  3. Depressive Disorders

Authors

Details

Brittany O’Brien, Ph.D. [email protected]
Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston (O’Brien, Mathew); Department of Psychiatry, Yale School of Medicine, New Haven, Conn. (Wilkinson); Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, The Menninger Clinic, Houston (Mathew).
Samuel T. Wilkinson, M.D.
Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston (O’Brien, Mathew); Department of Psychiatry, Yale School of Medicine, New Haven, Conn. (Wilkinson); Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, The Menninger Clinic, Houston (Mathew).
Sanjay J. Mathew, M.D.
Menninger Department of Psychiatry & Behavioral Sciences, Baylor College of Medicine, Houston (O’Brien, Mathew); Department of Psychiatry, Yale School of Medicine, New Haven, Conn. (Wilkinson); Mental Health Care Line, Michael E. Debakey VA Medical Center, Houston, The Menninger Clinic, Houston (Mathew).

Notes

Send correspondence to Dr. O’Brien ([email protected]).

Funding Information

Dr. Wilkinson reports receiving contract funding from Janssen, Sage Therapeutics, and Oui Therapeutics for the conduct of clinical trials administered through Yale University and consulting fees from Janssen, Oui Therapeutics, Sage Therapeutics, and Biohaven Pharmaceuticals. Dr. Mathew is supported through the use of resources and facilities at the Michael E. Debakey VA Medical Center, Houston, and receives salary support from The Menninger Clinic, Houston; he has served as a consultant to Allergan, Alkermes, Axsome Therapeutics, BioXcel Therapeutics, Clexio Biosciences, Eleusis, EMA Wellness, Engrail Therapeutics, Greenwich Biosciences, Intra-Cellular Therapies, Janssen, Levo Therapeutics, Perception Neurosciences, Neurocrine, Relmada Therapeutics, Sage Therapeutics, Seelos Therapeutics, and Signant Health; he has served as an investigator for clinical trials funded by Janssen, Merck, NeuroRx, and Sage Therapeutics; he has received research support from Biohaven Pharmaceuticals and VistaGen Therapeutics. Dr. O'Brien reports no financial relationships with commercial interests.
The authors wish to thank Ashna Karpe, Celine Nguyen, and Jin Yan for their contributions to this research.

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