Nontraditional therapies for treatment-resistant depression
FIRST OF 2 PARTS
Some off-label agents show promise, but carry risks.
The use of estrogens as an adjunctive therapy for women with treatment-resistant perimenopausal depression should only be undertaken when standard strategies have failed, and in consultation with an endocrine specialist who can monitor for potentially serious AEs.
Opioid medications
Buprenorphine is used to treat opioid use disorder (OUD) as well as acute and chronic pain. The opioid system is involved in the regulation of mood and may be an appropriate target for novel antidepressants. The use of buprenorphine in combination with samidorphan (a preferential mu-opioid receptor antagonist) has shown initial promise for TRD while minimizing abuse potential.
Although earlier results were mixed, a pooled analysis of 2 recent large RCTs (N = 760) of patients with MDD who had not responded to antidepressants reported greater reduction in Montgomery-Åsberg Depression Rating Scale scores from baseline for active treatment (buprenorphine/samidorphan; 2 mg/2 mg) vs placebo at multiple timepoints, including end of treatment (-1.8; P < .010).15
The most common AEs included nausea, constipation, dizziness, vomiting, somnolence, fatigue, and sedation. There was minimal evidence of abuse, dependence, or opioid withdrawal. Due to the opioid crisis in the United States, the resulting relaxation of regulations regarding prescribing buprenorphine, and the high rates of depression among patients with OUD, buprenorphine/samidorphan, which is an investigational agent that is not FDA-approved, may be particularly helpful for patients with OUD who also experience comorbid TRD.
Antioxidant agents
N-acetylcysteine (NAC) is an amino acid that can treat acetaminophen toxicity and moderate hepatic damage by increasing glutathione levels. Glutathione is also the primary antioxidant in the CNS. NAC may protect against oxidative stress, chelate heavy metals, reduce inflammation, protect against mitochondrial dysfunction, inhibit apoptosis, and enhance neurogenesis, all potential pathophysiological processes that may contribute to depression.16
Continue to: A systematic review...
