If you’ve been diagnosed with major depressive disorder (MDD), the good news is that, along with psychotherapy, there are several classes of drugs that can treat it. If one particular drug doesn’t work for you, there are other choices to try that are often effective.
The bad news is that up to one-third of patients don’t get relief from any of those antidepressants, according to Dan V. Iosifescu MD, MSc, associate professor of psychiatry at NYU School of Medicine.
People with depression who don’t improve after taking at least two different FDA-approved antidepressants at adequate doses for at least six weeks (for each drug) are considered to have treatment-resistant depression (TRD).
Here, Dr. Iosifescu discusses the best therapies that are now available for people with TRD:
Proven therapies for TRD
The order in which these treatments are tried depends on the doctor’s opinion and patient’s preference. These treatments may be used along with psychotherapy, antidepressants, and some of the other natural treatments mentioned below.
Ketamine. Ketamine, a common anesthetic that is also, tragically, used as an illicit street drug, is now being used off-label for treatment of TRD. Over the past decade, research has demonstrated that low doses of ketamine, administered via intravenous or intranasal infusion, can help two-thirds of TRD patients experience significant improvement.
Ketamine works much faster than conventional antidepressants—within days rather than weeks—which can be lifesaving for a patient with suicidal impulses. The effect wears off about one week after treatment, requiring repeated administrations.
At the time of administration, patients can experience an increase in blood pressure or distorted perception of reality, so they need to be monitored in the doctor’s office for two hours after treatment. Ketamine may impair your driving. Additional research is needed on the long-term side effects of multiple therapeutic doses.
In March 2019, the U.S. Food and Drug Administration (FDA) approved a new ketamine formulation called esketamine (Spravato), which comes in the form of a nasal spray, for patients with TRD. Spravato can cost more than $4,700 for the first month of treatment and is covered by only some insurers.
As with standard ketamine, patients’ vital signs need to be monitored in the doctor’s office for several hours after administration, which means additional cost.
Repetitive transcranial magnetic stimulation. With rTMS, brief, magnetic pulses are noninvasively administered via an insulated coil placed over the patient’s scalp near the area of the brain thought to regulate mood.
Treatment sessions vary in length, depending on the type of coil used and the number of pulses delivered, but usually last around 30 to 40 minutes. Patients typically receive rTMS five days a week for four to six weeks. A trained physician needs to determine the dose of rTMS for each patient, but other sessions are generally done by TMS operators. If the initial round is successful, patients may get maintenance treatments for months. The effects wear off when the treatments stop. Side effects can include headaches, hearing loss if there is inadequate ear protection and, very rarely, seizures.
Electroconvulsive therapy (ECT). Although ECT has been used for decades and has about a 75% to 80% success rate, most people view it negatively due to films such as One Flew Over the Cuckoo’s Nest. ECT has been refined over the years and is much safer today, but because ECT works by inducing a seizure and carries a risk of adverse cognitive effects, such as memory gaps, it is used only after multiple other treatments have been unsuccessful.
ECT requires anesthesia and is performed by a trained psychiatrist. It is typically given two to three times weekly for three to four weeks, so that the patient gets a total of six to 12 treatments. After a course of treatment, the patient may need either maintenance treatments or another therapy to prevent recurrence of depression.
Add-on treatments for TRD
The following treatments make sense for some patients with mild forms of depression, but for TRD and MDD, I would use them only in conjunction with more proven treatments for a possible minor boost in symptom relief.
- Acupuncture. There are a few studies that show that acupuncture can help people with mild depression. For these patients, there are no downsides to trying it, but acupuncture has not been shown to be effective for TRD by itself and should not delay the use of more effective treatments.
- Supplements. Research has shown that the supplements S-adenosyl-L-
methionine (SAMe), L-methylfolate, and omega-3 fatty acids can be effective for mild depression, with few side effects. However, for TRD, these supplements should be used only as an addition to other treatments.
- At-home electrical stimulation. The Fisher Wallace Stimulator is a portable, battery-powered micro-electric pulse generator. It was cleared by the FDA with respect to safety, and data suggest that it may be helpful for milder forms of depression as well as insomnia, anxiety, and chronic pain. It is safe to use and can be used at home without medical supervision. There is no data on its effectiveness for TRD.
A problematic treatment
Vagus nerve stimulation (VNS) involves the use of an implantable, pacemaker-like device to stimulate the vagus nerve, one of the cranial nerves that connects the brain to the body, with electrical impulses. The FDA approved VNS for TRD in 2005, but VNS requires the patient to undergo a very expensive neurosurgical procedure for implantation of the device. It works in only a minority of patients, and most insurers don’t cover the procedure. For now, VNS is not a practical option for most people.