Ketamine Clinics Attract Patients Despite Unknowns

Even as researchers continue to investigate how a single dose of the anesthetic ketamine reduces symptoms of treatment-resistant depression within hours and what the risks of long-term, repeated ketamine infusions might be, a growing number of patients are turning to ketamine clinics in the United States.

The most recent issue of Psychiatric News PsychoPharm features an article exploring the off-label use of this medication in special clinics. The piece describes what patients can expect at ketamine centers, including the physicians running them and the course and cost of standard treatment regimens.

The majority of the ketamine clinics in the United States are run by anesthesiologists, who tend to have firsthand experience with using ketamine and managing side effects. Psychiatric News spoke with anesthesiologists at ketamine clinics in New York and Arizona, where patients are initially given four infusions of ketamine within about two weeks.

Such procedures can be expensive, with most clinics charging $400 to $800 for a single infusion of ketamine, Dennis Hartman of the Ketamine Advocacy Network told Psychiatric News. (The Ketamine Advocacy Network is a website whose mission is to spread awareness about ketamine therapy for treatment-resistant depression.)

Although ketamine works for many patients, an estimated one-third of all patients in clinical trials do not respond to the medication.

“We need to find particular characteristics that can predict response,” APA President Maria A. Oquendo, M.D., Ph.D., told Psychiatric News. Oquendo is involved with a clinical trial evaluating the safety and effectiveness of ketamine in patients with refractory depression.

Anesthesiologists Glen Brooks, M.D., medical director of the New York Ketamine Infusions LLC, and Mark Murphy, M.D., the medical director of the Ketamine Wellness Centers in Mesa, Ariz., noted that patients at their clinics undergo mental health screening before receiving ketamine infusion, and they recommend that patients receive ongoing psychiatric or psychological care during treatment. Additionally, staff at the clinics routinely communicate with referring psychiatrists.

For related information, see “APA Task Force to Address ‘What’s Next?’ for Ketamine.”

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CSF Metabolic Abnormalities May Contribute to Treatment-Refractory Depression

Metabolic abnormalities in cerebrospinal fluid (CSF) may be an unrecognized contributor to treatment-refractory depression, according to a study in AJP in Advance.

The findings, if replicated, suggest that early identification and treatment of an underlying metabolic abnormality early in the course of psychiatric illness could prevent long-term emotional and cognitive complications, say Lisa Pan, M.D., of the University of Pittsburgh Medical Center and colleagues at several other institutions.

In the study, participants aged 14 to 40 with depression who had not responded to at least three maximum-dose medication trials of at least six weeks each were recruited by advertisement through the Clinical and Translational Science Institute’s Research Participant Registry at the University of Pittsburgh or by clinical referral.

CSF metabolic testing was compared in 33 adolescent and young adult patients with histories of treatment-refractory depression (at least three maximum-dose, adequate-duration medication treatments) and 16 healthy comparison subjects. Testing for CNS-specific metabolic abnormalities included 5-methyltetrahydrofolate, tetrahydrobiopterin, neopterin, pyridoxal-5-phosphate, 5-hydroxyindoleacetic acid, homovanillic acid, and amino-adipic semialdehyde.

CSF metabolite abnormalities were identified in 21 of the 33 participants with treatment-refractory depression. Cerebral folate deficiency (n=12) was most common, with normal serum folate levels and low CSF 5-methyltetrahydrofolate levels. All patients with cerebral folate deficiency showed improvement in depression symptom inventories after treatment with folinic acid. None of the healthy comparison subjects had a metabolite abnormality.

The study was prompted by the case of a young adult with treatment-refractory depression and multiple suicide attempts who was found to have a severe deficiency of CSF tetrahydrobiopterin, a critical cofactor for monoamine neurotransmitter synthesis. After treatment with sapropterin, a tetrahydrobiopterin analogue, the patient experienced a dramatic and long-lasting remission of depression.

“If these findings are replicated, they suggest that the identification of new inborn errors of metabolism or secondary disorders of metabolism contributing to psychiatric illness may allow repurposing of currently approved orphan drugs,” the researchers stated.

For related information, see the Psychiatric News article "Metabolites Offer New Clues About Medication Response."

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