No "Cookie Cutter" Patients: Managing Treatment-Resistant Depression

Psychiatric TimesVol 38, Issue 11

Treatment-resistant depression: how to diagnose, what treatment options are available, and how to best help patients.


In an installment of Psychiatric TimesTM custom Case Based Psych Perspectives, Lisa Harding, MD, and Angelos Halaris, MD, PhD, APA, ACNP, CINP, provided insight into how to diagnose treatment-resistant depression (TRD), summarized available treatment options, and offered recommendations on how to best help patients with this disorder.

Through examination of 2 case presentations, Harding and Halaris came to the agreement that each patient must be handled as a unique individual. A thorough psychiatric and developmental history must be performed for each patient to ensure the diagnosis of TRD, they said.

“There’s no cookie cutter patient that fits into a scenario [of TRD],” said Harding, who is a board-certified psychiatrist and clinical instructor of psychiatry at the Yale School of Medicine in New Haven, Connecticut.

Treatment Options

Additionally, the experts discussed 2 nonpharmacological modalities for the treatment of TRD, the former “mainstay” electroconvulsive therapy (ECT) and transcranial magnetic stimulation (TMS), which is Halaris’ second top choice.

“[ECT] is very effective, there’s no doubt about it. But again, the effect doesn’t last forever, and the issue of maintenance ECT is acknowledged,” Halaris said. “The potential for some kind of cognitive impairment is still an issue.”

On the other hand, TMS is time consuming. Patients come into the office a minimum of 3 days a week, preferably 5 days a week for Halaris. TMS also requires maintenance.

“The response is generally quite good. Even after the first few treatments, we can get a response. But I have also witnessed the loss of efficacy after termination of the initial acute treatment phase of about 35 sessions,” admitted Halaris, professor of psychiatry at Loyola University Chicago Stritch School of Medicine in Maywood, Illinois. Nonetheless, he considers it a viable and important treatment option in the TRD arsenal.

Intranasal Esketamine

Clinicians can also consider pharmacological treatment options; however, Halaris stressed the importance of ensuring a patient has true TRD, and not presumptive TRD. “In my book, true TRD is the one that has ruled out all potential contributory factors...If all these criteria have been met, then we have a true TRD patient,” he said. “Then I would consider intranasal esketamine.”

Halaris began using intranasal esketamine during phase 3 clinical trials before the US Food and Drug Administration (FDA) approval and still uses it.

“I had a maintenance patient just an hour ago, and another one coming back for maintenance intranasal esketamine right after we’re done with this discussion,” Halaris said. “It’s a very interesting approach, not so much the classic neurotransmitters or serotonin-norepinephrine-dopamine, but at the end NMDA [N-methyl-D-aspartate] receptor blockade that involves predominantly, but not exclusively, glutamatergic transmission.”

Off-label intravenous ketamine is a treatment that Halaris does not use. He cited 3 reasons for this decision: 1) it is not FDA approved, 2) it is costly, and 3) it is not as well-regulated as intranasal esketamine by the Risk Evaluation and Mitigation Strategy (REMS) program.

Halaris, who helped establish REMS-certified treatment centers both in university medical centers and private practice settings, considers the REMS certification process easily achievable. “The process is fairly simple. It takes an application. The company…is very helpful in assisting prospective sites, whether a medical center or a private practice setting to achieve REMS certification. Certain conditions needed to be met; the equipment—there’s no equipment other than a suitable chair for the patient to rest comfortably. Monitoring vital signs, installing a safe, because the medication needs to be under double-lock with limited access with a code that the REMS certified provider,” Halaris explained. “It’s not that cumbersome. I know it sounds scarier than it really is.”

The ideal candidates for intranasal esketamine are those who are on an oral antidepressant concomitantly with some response but not full remission, according to Halaris and Harding. Contraindications include cardiovascular, intracerebral, intraabdominal, and aneurysmal vascular disease, and histories of hemorrhages.

It is also important to have a conversation with patients about substance abuse, Harding said. She asks patients whether they are going to support groups, and if so, what they look like, as well as simply extending the conversation as you would before any schedule III substance prescription.

In terms of costs for intranasal esketamine, the way to obtain reimbursement is still unclear. Getting insurance companies to cover it is a challenge and requires extensive paperwork, Halaris noted. However, there is assistance through CarePath.

“Once we obtain the insurance information with patients’ written consent, their data are passed on to CarePath, and they are amazingly efficient...It saves our staff tons of time,” Halaris stated.

Harding and Halaris shared that patients have had copays as little as $10 to $20.

For clinicians who are considering intranasal esketamine as a therapeutic option for their patients, Halaris shared this advice: “It works as long as you do it right, for the right patient, in the right constellation.”

Dr Harding is a board-certified psychiatrist and clinical instructor of psychiatry at the Yale School of Medicine, in New Haven, Connecticut. She is also part of the Janssen Speaker Bureau. Dr Halaris is a board-certified psychiatrist and professor of psychiatry at Loyola University Chicago Stritch School of Medicine in Maywood, Illinois. He reports no conflicts of interest regarding the subject matter of this article.

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