Treatment-Resistant Depression Care in North Carolina
I’m a board-certified psychiatrist. I treat adults with treatment-resistant depression anywhere in North Carolina by secure video.
Treatment-resistant depression is depression that hasn’t improved after 2 or more antidepressants, each taken at an adequate dose for an adequate length of time (PMID 31638723). At least 30% of people with depression meet that definition (PMID 37713549).
If you haven’t tried 2 antidepressants yet, my page on depression treatment in North Carolina covers how I approach first-line care.
My care is a flat $250 a month. It starts with a free 15-minute consultation.
- You see me at every visit.
- Visits run 45 to 60 minutes.
- I don’t bill insurance for my monthly practice. Labs and medications are paid separately.
- I treat adults, and you need to be physically in North Carolina at the time of each visit.
What I Offer for Treatment-Resistant Depression
I provide the evaluation and the medication treatment myself. When TMS is a better fit, I’ll tell you and help you get a referral.
| Treatment | Through my practice |
|---|---|
| Review of your medication history, diagnosis, and medical contributors | Yes |
| Dose changes, switching medications, and adding a second medication | Yes |
| Lithium, thyroid hormone (T3), and FDA-approved add-on antipsychotics | Yes |
| MAOIs and tricyclic antidepressants | Yes |
| Ketamine | Planned for my Wilmington office |
| TMS | Referral to a TMS provider |
| ECT | Not offered |
Adding an antipsychotic to an antidepressant that partly worked has the strongest trial evidence of the add-on medications. A 2026 meta-analysis of 45 trials found a consistent benefit over placebo (PMID 42532626).
The gain is modest. In a 2013 analysis of aripiprazole, quetiapine, and risperidone trials, for every 9 people who added one, about 1 more reached remission than on placebo (PMID 23554581).
The FDA has approved 5 antipsychotics as add-ons for depression: aripiprazole, quetiapine XR, brexpiprazole, cariprazine, and lumateperone. The most recent was lumateperone, in November 2025.
These medications can cause restlessness (akathisia) and weight gain (PMID 23554581), so I check your weight, glucose, and lipids while you take one.
In the VA’s VAST-D trial of 1,522 veterans, most of them men, adding aripiprazole did better than switching to bupropion. Remission rates were 28.9% and 22.3% (PMID 28697253).
Most of lithium’s add-on trials were done before today’s definition of treatment-resistant depression. In the same 2026 meta-analysis, its benefit was no longer significant after adjusting for publication bias (PMID 42532626).
I still prescribe it. In randomized trials, people with mood disorders who took lithium had fewer suicides than those who took placebo (PMID 23814104).
Lithium is FDA-approved for bipolar disorder, so using it for depression is off-label. It requires regular blood tests. You can get them at a lab near you.
The evidence that T3 adds benefit is weak (PMID 42532626). Using it for depression is also off-label. I offer it when other add-ons don’t suit you.
You can also add a second antidepressant from a different class, such as mirtazapine with an SSRI. The evidence for that is limited (PMID 26246787), so I use it less often than an antipsychotic add-on.
The FDA label for the MAOI tranylcypromine covers adults who haven’t responded well to other antidepressants.
MAOIs require avoiding high-tyramine foods and checking every other medication for interactions. Before you start one, I go through both precautions with you.
If you’ve tried 2 or more antidepressants without enough relief, book a free 15-minute consultation.
Why Depression Can Persist Through Several Medications
There’s no agreed number of weeks for an adequate trial (PMID 31638723). In my experience, side effects and cost often end trials early. A trial that ends early can’t show whether the drug would have worked.
Depression can also persist for reasons that have little to do with which antidepressant you took:
- A medical condition is contributing, such as low thyroid, low testosterone, or sleep apnea.
- The depression is part of bipolar II, which can look like major depression during a depressive episode.
- ADHD, PTSD, or an anxiety disorder is present alongside the depression.
- Ongoing stress, such as job stress or caregiving, is keeping symptoms going.
For men whose workup confirms low testosterone, I walk through the augmentation decision in testosterone augmentation for depression.
What STAR*D Reported, and What a Reanalysis Found
STAR*D is the best-known study of what happens when people try one antidepressant after another. It enrolled outpatients with nonpsychotic major depression and moved them through up to 4 treatment steps. The published remission rates were 36.8% at step 1, 30.6% at step 2, 13.7% at step 3, and 13.0% at step 4, with a cumulative remission rate of 67% (PMID 17074942).
I think the 67% figure is inflated. In 2023, Pigott and colleagues reanalyzed STAR*D’s patient-level data using the outcome measure the study’s own protocol specified. The original summary had used a non-blinded, clinic-administered scale.
The original summary also counted 99 patients who already scored as remitted when they entered the study and 125 who scored as remitted when they started their next step. With those problems corrected, the cumulative remission rate was 35.0%, about half of what was reported (PMID 37491091).
The original report did show that each additional step produced a lower remission rate, and that people who needed more steps relapsed more often during follow-up (PMID 17074942).
What I Review First
Before I choose the next medication, I review your past trials and look for anything else keeping the depression going.
Your Medication History
For each medication you’ve taken, I ask about the highest dose, how long you stayed at it, whether it helped at all, and why you stopped. When a medication partly helped, a higher dose or a second drug sometimes helps more. One stopped for side effects can sometimes be restarted at a lower dose and increased more slowly.
My post on when an antidepressant isn’t working covers when to switch and when to add a second medication.
The Diagnosis
Most people with bipolar II seek help during a depressive episode. In my experience, the high periods often feel good, so people rarely bring them up.
I ask about any period of 4 or more days (the DSM-5 threshold for hypomania) with less need for sleep, more energy, faster speech, or impulsive decisions. The evidence that antidepressants help in bipolar depression is weak. They can also trigger a switch into hypomania or a mixed state. That risk appears lower in bipolar II than in bipolar I (PMID 24030475).
ADHD, PTSD, and anxiety disorders can occur alongside depression, and each one needs its own treatment. I ask about all three at the first visit.
Medical Contributors
Thyroid. Hypothyroidism, including subclinical hypothyroidism, may contribute to fatigue, slowed thinking, and low mood. I check TSH, and I add free T4 and free T3 when TSH is borderline or doesn’t match the symptoms.
Testosterone in men. Low testosterone overlaps with depression on fatigue, low motivation, irritability, and low libido. A meta-analysis of 27 randomized trials in 1,890 men found that testosterone treatment reduced depressive symptoms compared with placebo, with a small average effect (PMID 30427999). In the 2024 TRAVERSE analysis of 5,204 middle-aged and older men with low testosterone and heart disease or heart risk, treatment produced small improvements in mood and energy (PMID 38205962).
I measure testosterone in men with depression and low-T symptoms. When a morning level is under roughly 300 ng/dL, I’ll talk with you about whether testosterone replacement makes sense.
Sleep. Obstructive sleep apnea can cause fatigue, irritability, and poor concentration. In my experience, antidepressants rarely help much until the sleep problem is treated. Snoring, pauses in breathing that someone else has noticed, or heavy daytime sleepiness lead me to recommend a sleep study. I cover treating sleep problems separately.
Vitamins. Low B12, vitamin D, and folate are worth checking and cheap to treat. I test for each one.
Metabolic health. When obesity is present, I treat it alongside the depression, sometimes with GLP-1 medications. I cover the connection in metabolic psychiatry.
What Is Happening in Your Life
Job stress, a failing marriage, caregiving, or unresolved trauma can keep symptoms going whatever medication you take. Medication can reduce the symptoms. Therapy and practical changes address the situation itself.
Among psychotherapies, cognitive behavioral therapy has the strongest evidence in treatment-resistant depression (PMID 24314926).
Exercise and Supplements Alongside Treatment
Exercise can reduce depression on its own. A 2024 review of 218 trials in people with major depression found moderate reductions in symptoms with walking or jogging, yoga, and strength training (PMID 38355154). The authors rated the certainty of that evidence as low to very low. I include exercise in your treatment plan.
When your labs show a deficiency, I recommend an over-the-counter supplement to correct it. I also consider other supplements when your history points to them.
ECT, TMS, and Ketamine
TMS and ketamine make the most sense once I’ve reviewed your medication history, diagnosis, and medical contributors. If a condition such as sleep apnea or low thyroid is contributing, that gets treated first.
ECT remains one of the most effective treatments for depression. A Lancet meta-analysis pooling 18 trials and 1,144 participants found it more effective than medication in the short term (PMID 12642045). Its main downside is short-term memory loss (PMID 37224232).
Ketamine was compared directly with ECT in a 2023 randomized trial of 403 people with nonpsychotic treatment-resistant depression who had been referred for ECT. IV ketamine given twice weekly for 3 weeks produced a response in 55.4% of patients, compared with 41.2% for ECT. The trial tested whether ketamine was at least as effective as ECT, and it met that standard (PMID 37224232).
ECT was associated with more short-term memory loss, which recovered over follow-up. Ketamine was associated with dissociation (PMID 37224232).
Since 2008, TMS has been FDA-cleared for depression that hasn’t responded to at least 1 antidepressant (FDA 510(k) K083538; Psychiatric News, 2008). It delivers magnetic pulses through the scalp in daily sessions over several weeks, with no anesthesia. I don’t offer TMS, and I refer patients when it fits.
I’m preparing to offer IV ketamine and Spravato at my Wilmington office. Neither is available yet. You can join the waitlist on my ketamine therapy page.
Peptides and Psychedelics for Depression
Semax and Selank have been studied for mood and cognition, mostly in animals and in small Russian trials. The BPC-157 data comes almost entirely from animal studies. None of them is FDA-approved for depression. Peptide therapy is offered when legally available, which it isn’t yet.
Psilocybin and MDMA aren’t FDA-approved. In August 2024, the FDA declined to approve MDMA-assisted therapy for PTSD. According to an August 2026 statement from MAPS, the developer has resubmitted its application. I explain the 2024 decision in how MDMA-assisted therapy works.
The FDA has agreed to a rolling review of Compass Pathways’ application to use psilocybin in treatment-resistant depression, according to an April 2026 company press release. In August 2026, the company said it expects to finish submitting the application by the end of 2026 (company release). I track where federal review stands in my breakdown of the psychedelic therapy executive order.
If the FDA approves psilocybin for depression, I’ll consider offering it once it’s legally available and I can deliver it safely.
Psilocybin was studied in U.S. medical research in the 1950s and 1960s. I cover that period in the history of psilocybin. From 1953 to 1973, the CIA’s MKUltra program tested LSD and other drugs on Americans without their consent. My post on the CIA’s MKUltra experiments covers that program.
How I Work With Treatment-Resistant Depression
At the first evaluation, I review every prior medication trial, order the labs your history calls for, and set a baseline with the PHQ-9, a 9-question depression questionnaire.
I change one medication at a time, so we know which change helped. I repeat the PHQ-9 at every visit.
The $250 monthly fee covers your visits and messaging between them.
If you’re taking more than one antidepressant and would rather take fewer, we can talk about a slow taper through my supervised antidepressant tapering service. My post on HHS’s May 2026 deprescribing plan explains what it means for tapering.
Book a free 15-minute consultation to start.
Frequently Asked Questions
What counts as treatment-resistant depression?
It’s depression that hasn’t improved after 2 or more antidepressants, each at an adequate dose and duration. That’s the most common definition (PMID 31638723).
What is the most effective treatment for treatment-resistant depression?
Among add-on medications, an antipsychotic such as aripiprazole has the strongest trial evidence (PMID 42532626). In a meta-analysis of 18 trials, ECT worked better than antidepressant medication in the short term (PMID 12642045).
Do you offer TMS?
I don’t offer TMS. Since 2008, it has been FDA-cleared for depression that hasn’t responded to at least 1 antidepressant. When it fits, I refer you to a TMS provider.
Why would antidepressants not work for me?
Common reasons include a medical problem such as low thyroid, low testosterone, or sleep apnea. The depression may be part of bipolar II, or ADHD or an anxiety disorder may be present alongside it. Ongoing stress can also keep depression going. An evaluation can help show which of these apply to you.
Is ECT still used for depression?
Yes. It remains one of the most effective treatments for depression (PMID 12642045). In a 2023 trial, IV ketamine was tested against ECT and worked at least as well (PMID 37224232). ECT’s main downside is short-term memory loss (PMID 37224232).
Do you offer ketamine?
I don’t offer it yet. IV ketamine and Spravato are planned for my Wilmington office, and you can join the ketamine waitlist.
Can low testosterone cause depression symptoms?
Low testosterone overlaps with depression on fatigue, low motivation, irritability, and low libido. In a meta-analysis of 27 randomized trials, testosterone treatment reduced depressive symptoms in men compared with placebo, with a small average effect (PMID 30427999). I measure it in men whose depression includes these symptoms.
What labs should be checked for treatment-resistant depression?
My usual starting panel is TSH, a CBC (complete blood count), a comprehensive metabolic panel, vitamin D, B12, and folate, plus total testosterone and SHBG (the protein that carries testosterone) in men. I add free T4, free T3, or CRP (an inflammation marker) when your history suggests a need. I recommend a sleep study when your symptoms point to sleep apnea.
How do I know if I have bipolar II instead of major depression?
Bipolar II involves episodes of depression and episodes of hypomania. Hypomania is a period of at least 4 days with high or irritable mood, less need for sleep, more energy, faster speech, and often impulsive decisions. If you’ve had periods like that, bring them up at your evaluation, even if they felt good.
Still Depressed After Two Antidepressants?
Book a free 15-minute consultation to review your treatment history and plan the next step.
Baghel Psychiatry, PLLC | Shantanu Baghel, DO | (910) 612-6015 | sbaghel@thebh.us
The monthly plan covers Dr. Baghel’s clinical services only (evaluation, monitoring, medication management, ongoing care). Labs and medications are paid separately by the patient. This page is for educational purposes only and is not medical advice. Do not start, stop, or modify any medication without consulting your prescribing clinician. If you’re thinking about suicide, call or text 988.
References (16)
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