Nontraditional therapies for treatment-resistant depression
FIRST OF 2 PARTS
Some off-label agents show promise, but carry risks.
A systematic review and meta-analysis of 5 RCTs (N = 574) considered patients with various depression diagnoses who were randomized to adjunctive NAC, 1,000 mg twice a day, or placebo. Over 12 to 24 weeks, there was a significantly greater improvement in mood symptoms and functionality with NAC vs placebo.16
Overall, NAC was well-tolerated. The most common AEs were GI symptoms, musculoskeletal complaints, decreased energy, and headache. While NAC has been touted as a potential adjunct therapy for several psychiatric disorders, including TRD, the evidence for benefit remains limited. Given its favorable AE profile, however, and over-the-counter availability, it remains an option for select patients. It is important to ask patients if they are already taking NAC.
Options beyond off-label medications
There are a multitude of options available for addressing TRD. Many FDA-approved medications are repurposed and prescribed off-label for other indications when the risk/benefit balance is favorable. In Part 1 of this article, we reviewed several off-label medications that have supportive controlled data for treating TRD. In Part 2, we will review other nontraditional therapies for TRD, including herbal/nutraceuticals, anti-inflammatory/immune system therapies, device-based treatments, and other alternative approaches.
Bottom Line
Off-label medications that may offer benefit for patients with treatment-resistant depression (TRD) include pimavanserin, antihypertensive agents, ketamine, scopolamine, botulinum toxin, mifepristone, estrogens, buprenorphine, and N-acetylcysteine. Although some evidence supports use of these agents as adjuncts for TRD, an individualized risk/benefit analysis is required.
Related Resource
- Joshi KG, Frierson RL. Off-label prescribing: How to limit your liability. Current Psychiatry. 2020;19(9):12,39.
Drug Brand Names
Amlodipine • Katerzia, Norvasc
Atenolol • Tenormin
Bisoprolol • Zebeta
Buprenorphine • Sublocade, Subutex
Carvedilol • Coreg
Enalapril • Vasotec
Esketamine • Spravato
Estradiol transdermal • Estraderm
Ketamine • Ketalar
Mifepristone • Mifeprex
Pimavanserin • Nuplazid
Progesterone • Prometrium
Propranolol • Inderal
Ramipril • Altace
Verapamil • Calan, Verelan
