Therapists can now prescribe ketamine

In the past few decades, ketamine has garnered increasing attention for its ability to help people recover from treatment-resistant depression, PTSD, and other severe mental health concerns. Originally a veterinarian analgesic turned street drug, ketamine is a dissociative anesthetic and hallucinogenic with a controversial presence in mental healthcare.  

Its dissociative properties are key; the goal is to separate yourself from traumatic memories and depressive thoughts temporarily and in a state of peace create new neural synapses that, long after the drug, may have long-lasting positive effects on the brain and in the patient.  

The FDA approved the first ketamine-derived medication, Spravato (esketamine), as a Schedule III controlled substance  for treatment-resistant depression in 2019 after almost 20 years of clinical research that produced varied and complicated results.  

The approval came with a set of restrictions intended to protect the patient from the known side effects like change in state of consciousness. For example, patients had to take the medication in a healthcare setting and be monitored by a healthcare professional for two hours after administration.  

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To avoid the tight safety measures and the difficult approval-process to get esketamine covered by insurance, patients and doctors flocked to an alternative: “off-label” prescribing. Instead of giving patients a prescription for Spravato (esketamine), doctors would write prescriptions for FDA-approved ketamine anesthetic (ketamine hydrochloride) with the intention of treating depression.  

This practice only increased when the Drug Enforcement Administration lifted the requirements for doctors to see patients in-person in order to prescribe controlled substances, paving the way for an explosion in “off-label” ketamine prescription based businesses.  

Since 2020, an onslaught of ketamine clinics that provide intravenous infusions in a spa-like setting have quickly appeared on the market and investors have poured cash into these businesses showing an expected rise in ketamine demand. 

Ketamine-based telehealth startup Nue Life Health has raised $23 million to scale its ketamine distribution services. Their business has a single goal: to offer ketamine prescriptions through telehealth and send ketamine pills directly to your door. They’ve also raised serious concerns from psychiatrists who are alarmed at the lack of medical professional involvement.  

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And there are a growing number of companies like Journey Clinical that want to empower non-clinicians like therapists and even chaplains to provide ketamine to people suffering from depression. They operate by connecting clinicians with prescribing authority to approve prescriptions for ketamine that are distributed through non-clinicians in what’s called Ketamine-Assisted Therapy (KAP).  

Many of these businesses are making sweeping promises to patients with little medical oversight, and some medical professionals argue ketamine needs to be better regulated.  

“I’m very concerned about treatments that deviate too far from the standard recommendations given by the FDA,” said Gerard Sanacora, MD, who has studied ketamine treatment for depression at the Yale Depression Research Program. “We have to be very careful to continue to develop this responsibly.” 

Ketamine studies vary 

Ketamine assisted therapy is often lumped in with unconventional psychedelic treatments for depression like LSD and psilocybin, but it is not a psychedelic. It is also not an opioid, though its effect on the brain is remarkably similar, which might be why there is a higher risk of addiction.  

Researchers at Stanford studied Ketamine’s opioid-like effect on the brain. They took two groups of people suffering from depression. Both groups were given a ketamine infusion but the second group was given Naltrexone, an opioid blocker, before treatment.  

In the first group, 7 out of 12 patients felt their depression symptoms decrease by 50%. The group that took Naltrexone felt no change in their depression at all, but still experienced the dissociative and hallucinogenic effects that many patients experience.  

The study found that patients receiving ketamine treatment could be vulnerable to addiction – in addition to operating like an opioid, ketamine also had stimulant effects, similar to cocaine and methamphetamine.  

Ketamine’s effect on the brain’s opioid receptors is not as strong as say, oxycodone, but “that doesn’t mean it’s safer,” says Alan Schatzberg, MD, professor of psychiatry and behavioral sciences at Stanford, told NPR.  

Schatzberg is dubious if the risk is worth the reward, and he has questioned the FDA approval of esketamine. In one of the studies the FDA used in its review of the drug, 40% of patients relapsed into a major depressive episode after treatment ended.  

Even more alarming, three patients died by suicide four to 20 days after their last dose, two of which had not previously had suicidal ideation. None of these patients were in the placebo group. The results suggested that ketamine (in the form of esketamine) is associated with “a protracted withdrawal reaction.” 

“Given the small number of cases, the severity of the patients’ underlying illness, and the lack of a consistent pattern among these cases, it is difficult to consider these deaths as drug-related,” the FDA said in their briefing, but Schatzberg found that conclusion “misguided.”  

In total, six patients died. The other patients’ deaths were attributed to high blood pressure, hyperlipidemia, and for one, a motorcycle accident. 

The off-label prescribing prevalence caused the FDA to issue a warning to prescriber and patients. One concern is that animal studies showed racemic ketamine causes lesions in the brain and “the relevance of this finding in humans is unknown.”  

The DEA wants to return to pre-pandemic prescribing practices in the case of narcotics which may throw a wrench in ketamine telehealth companies’ progress, but it might not make a difference if they can leverage non clinicians to satisfy in-person requirements.   

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