Evidence-Based Reviews

Nontraditional therapies for treatment-resistant depression: Part 2

Current Psychiatry. 2021 October;20(10):32-38 | doi: 10.12788/cp.0179

References

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Statins

In a meta-analysis of 3 randomized, double-blind trials, 3 statins (lovastatin, atorvastatin, and simvastatin) significantly improved depression scores when used as an adjunctive therapy to fluoxetine and citalopram, compared with adjunctive placebo (N = 165, P < .001).¹⁵

Specific adverse effects of statins include headaches, muscle pain (rarely rhabdomyolysis), dizziness, rash, and liver damage. Statins also have the potential for adverse interactions with other medications. Given the limited efficacy literature on statins for depression and the potential for serious adverse effects, these agents probably should be limited to patients with treatment-resistant depression for whom a statin is indicated for a comorbid medical disorder, such as hypercholesteremia.

Neurosteroids

Brexanolone is FDA-approved for the treatment of postpartum depression. It is an IV formulation of the neuroactive steroid hormone allopregnanolone (a metabolite of progesterone), which acts as a positive allosteric modulator of the GABA-A receptor. Unfortunately, the infusion needs to occur over a 60-hour period.

Ganaxolone is an oral analog formulation of allopregnanolone. In an uncontrolled, open-label pilot study, this medication was administered for 8 weeks as an adjunct to an adequately dosed antidepressant to 10 postmenopausal women with persistent MDD.¹⁶ Of the 9 women who completed the study, 4 (44%) improved significantly (P < .019) and the benefit was sustained for 2 additional weeks.¹⁶ Adverse effects of ganaxolone included dizziness in 60% of participants, and sleepiness and fatigue in all of them with twice-daily dosing. If the FDA approves ganaxolone, it would become an easier-to-administer option to brexanolone.

Zuranolone is an investigational agent being studied as a treatment for postpartum depression. In a double-blind RCT that evaluated 151 women with postpartum depression, those who took oral zuranolone, 30 mg daily at bedtime for 2 weeks, experienced significant reductions in Hamilton Depression Rating Scale-17 (HDRS-17) scores compared with placebo (P < .003).¹⁷ Improvement in core depression symptom ratings was seen as early as Day 3 and persisted through Day 45.

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