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Ketamine can serve as remedy for treatment-resistant depression
Roger Selvage 1843

Ketamine can serve as remedy for treatment-resistant depression

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Loren Bonner

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For individuals with suicidal thoughts or who don’t respond to any therapies for depression, ketamine offers a treatment choice, according to Megan Ehret, PharmD, BCPP, from the University of Maryland School of Pharmacy.

“Personally, I’m supportive of it for treatment-resistant depression. It’s efficacious and it works quickly,” Ehret said.

Ketamine—an unusual type of psychedelic drug called a dissociative—was FDA-approved in 2019 as a prescription nasal spray, esketamine (Spravato–Janssen Pharmaceuticals, Inc.), for treatment-resistant depression (TRD). According to the official medication guidelines, it must be ad ministered to patients under the supervision of a trained medical professional.

As more patients experience the benefits of ketamine—or want to—pop-up ketamine clinics have proliferated, as well as prescribers offering it via telehealth. But experts like Ehret, who support the use of ketamine, worry about the motivations behind some of these clinics.

Typically, ketamine clinics are for-profit, and Ehret said many of them simply see money in the enterprise. Most of these clinics will offer I.V. ketamine infusions off-label to patients for an out-of-pocket cost. I.V. ketamine is not FDA-approved like eskatamine and does not fall under a REMS program, meaning there are fewer hurdles for clinicians to go through if they administer I.V. ketamine.

“I worry about pop-up clinics and if people are self-referring,” said Ehret. “Who is there to verify the criteria? Ketamine isn’t for everyone.”

To receive esketamine, patients have to meet certain criteria, like failing other treatment options. TRD is defined as a patient not responding to two or more combinations of pharmacological products. The labeling for esketamine also says that patients with cardiovascular and cerebrovascular conditions may be at increased risk for associated adverse effects.

“The more medically ill someone is, the more we need to think carefully about using it,” said Charles Caley, PharmD, BCPP, from the College of Pharmacy & Health Sciences at Western New England University in Springfield, MA. “We’d do the same thing with ECT [electroconvulsive therapy]. There’s a very controlled, careful process to receive these treatments.”

Patients also need to be monitored 2 hours after administration of the drug.


Caley said ketamine is an important treatment option to have available for patients.

“The state of affairs with depression is dismal,” he said. SSRIs—even treatment options going back further—have not produced the outcomes needed for patients, and they necessitate a lot of treatment trials, according to Caley.

About one-third of patients with depression fail to achieve remission despite treatment with multiple antidepressants.

Study findings published May 21, 2019, in the American Journal of Psychiatry first demonstrated the effectiveness of ketamine for TRD. Ketamine versus placebo resulted in clinically and statistically significant decreases in depression scores. In both groups, patients continued taking antidepressants out of concern of not treating TRD. In another study from September 1, 2019, published in JAMA Psychiatry, researchers found that nasal ketamine had longer-term efficacy and helped patients stay in stable remission 16 weeks into treatment.

A possible pathway

Especially with TRD or even PTSD, ketamine may offer patients a springboard to an antidepressant or other treatment, according to Ehret.

Relief from TRD with ketamine can happen quickly—within 40 minutes—whereas it can take weeks for patients to feel any benefit from an SSRI.

“Ketamine might allow us to understand the pathophysiology of depression, which may lead to better treatment interventions for depression,” said Caley.

Ehret said more research needs to be done with ketamine, especially for its use longer-term (data to support it don’t go beyond a year), as well as for how it could treat other mental illnesses, such as PTSD.

Caley points out that there is a clear tie-in for community pharmacists and ambulatory care pharmacists as well.

“Depression is prevalent and has an adverse effect on a patient’s life function and on comorbid conditions like diabetes,” said Caley. “When you think about that, it sets up a picture of a complex set of illnesses that require persistence and follow-up on their behalf. Naturally that’s an opportunity for community pharmacists to screen patients and refer them.” ■

Spravato REMS

Spravato (Janssen Pharmaceuticals, Inc.) is available only through the Spravato REMS because of the risks of serious adverse outcomes from sedation, dissociation, and abuse and misuse. Important requirements of the Spravato REMS include the following.

  • Health care settings must be certified in the program and ensure that Spravato is only dispensed and administered in health care settings.
  • Patients treated in outpatient settings (e.g., medical offices and clinics) must be enrolled in the program.
  • Spravato is administered to patients under the direct observation of a health care provider and patients must be monitored by a health care provider for at least 2 hours after administration of Spravato.
  • Pharmacies must be certified in the REMS and must only dispense Spravato to health care settings that are certified in the program.

Further information, including a list of certified pharmacies, is available at or 1-855-382-6022. The REMS is available at

Ketamine is avoided or used with extreme caution in the following groups:

  • People with a history of psychosis or schizophrenia, as there is concern that the dissociation ketamine produces can make psychotic disorders worse
  • People with a history of substance use disorder, because ketamine can cause euphoria (likely by triggering the opioid receptors) and some people can become addicted to it (which is called ketamine use disorder)
  • Teenagers, as there are some concerns about the long-term effects of ketamine on the still-developing adolescent brain
  • People who are pregnant or breastfeeding
  • Older adults who have symptoms of dementia

Reach out

If you or someone you know is experiencing a crisis concerning mental health, suicide, substance use, or emotional distress, reach out 24/7 by dialing or texting 988 to the 988 Suicide and Crisis Lifeline (formerly known as the National Suicide Prevention Lifeline) or using chat services at to connect to a trained crisis counselor. ■



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