A Common Antioxidant Shows Promise in Bipolar Depression

RESEARCH UPDATE

The antioxidant coenzyme Q10 (CoQ₁₀) was found to be effective for the treatment of bipolar depression.¹ The effect size was large (0.87), athough it took eight weeks to separate fully from placebo.

The finding builds on two open label studies of CoQ₁₀ in geriatric bipolar depression, which saw improvement with 800 mg to 1200 mg daily in 29 patients.^2,3 The current study used a lower dose (200 mg/d) and the authors speculated that higher doses might yield a greater response.¹ CoQ₁₀ has also been studied in depression with multiple sclerosis, where a randomized-controlled trial found significant effects at 500 mg daily.⁴ The nutrient has improved well-being, vitality, and energy in small controlled trials of specific populations such as patients with breast cancer, the elderly, and Gulf War veterans.^5-7

Details of the study

Mehrpooya and colleagues¹ randomized 89 patients with moderate bipolar depression to receive CoQ₁₀ or placebo as an add-on to their usual regimen. Other medications, which included mood stabilizers and some antidepressants, were kept stable for two months prior to the study and during the study. The study participants were Iranian; with a mean age of 38; and an even ratio of men and women.

Assessments were double-blind and used the Persian version of the Montgomery-Asberg Depression Rating Scale (MADRS). Both groups improved to a similar degree in the first four weeks, but after eight weeks, the CoQ₁₀ group had marked improvement over placebo. Only three patients achieved full remission (all were in the treatment group), and the response rate was significantly higher with CoQ₁₀ than placebo (72% vs 12%).

A limitation of the study was the small sample size: 69 patients were analyzed after 20 dropped out. Although the discontinuations were evenly distributed among the two groups, they were not accounted for in the final data, which may inflate the results.

Mechanisms

CoQ₁₀ occurs naturally in the human body, but levels decline with age, depression, and medical illness. The coenzyme plays a role in several processes that are impaired in bipolar disorder: mitochondrial function, inflammation, and oxidative stress. CoQ₁₀ is also neuroprotective, and prevents neurodegeneration in Alzheimer, Parkinson, and Huntington diseases. It raises brain-derived neurotrophic factor and protects hippocampal cells against injury. Serotonin is another possible avenue for its antidepressant effects.

Risks and benefits »

Risks and benefits

CoQ₁₀ has few risks and caused no adverse effects in the depression studies. Possible adverse effects may include gastrointestinal discomfort, which is improved by spreading the dose throughout the day and taking with food, and insomnia, which improves with morning dosing. In patients with diabetes, CoQ₁₀ improves glycemic control but can also cause low blood sugar.⁸ CoQ₁₀ may also be of potential medical benefit to cardiac disease, hypertension, cancer, migraines, dementia, Huntington disease, Parkinson disease, and fibromyalgia. The major risk is an interaction with warfarin, whose anticoagulant effects may be impeded by CoQ₁₀.

How to use it

CoQ₁₀ can be started at 200 mg daily and titrated if no response is seen after two months. Dosages seen in studies on depression have been as high as 1200 mg daily without adverse effects, although it is not known whether there is a dose-dependent response. Most studies used regular CoQ₁₀, but absorption can be an issue and some products are formulated to enhance absorption (eg, with polysorbate 80, black pepper extract, Nano, and Q-Gel). Consumer Labs tests supplements for safety and quality, and I have listed a few of their cost-effective options in a patient brochure (as low as 16 cents a day).⁹

The bottom line

This is the first controlled study of CoQ₁₀ in bipolar depression. What’s missing is replication, an important step given the drop-out rate and small sample size. On the other hand, CoQ₁₀ has a well-established safety record. It lacks the medical risks that accompany most mood stabilizers, and it can prevent some of the medical problems that tend to accompany bipolar disorder. If patients have not recovered with standard therapeutics, it is worth a try. 

Dr Aiken is Instructor in Clinical Psychiatry at the Wake Forest University School of Medicine and the Director of the Mood Treatment Center in Winston-Salem, NC. He is Editor in Chief of The Carlat Psychiatry Report.

This article was originally posted on 10/31/18 and has since been updated.

Disclosures:

Dr Aiken does not accept honoraria from pharmaceutical companies but receives royalties from W.W. Norton & Co. for a book he co-authored with James Phelps, MD, Bipolar, Not So Much.

References:

1. Mehrpooya M, Yasrebifar F, Haghighi M, et al. Evaluating the effect of Coenzyme Q10 augmentation on treatment of bipolar depression: A double-blind controlled clinical trial.J Clin Psychopharmacol. 2018;38:460-466.

2. Forester BP, Zuo CS, Ravichandran C, et al. Coenzyme Q10 Effects on Creatine Kinase Activity and Mood in Geriatric Bipolar Depression. J Geriatr Psychiatry Neurol. 2012;25:43-50.

3. Forester BP, Harper DG, Georgakas J, et al. Antidepressant effects of open label treatment with Coenzyme Q10 in geriatric bipolar depression.J Clin Psychopharmacol. 2015;35:338-340.

4. Sanoobar M, Dehghan P, Khalili M, et al. Coenzyme Q10 as a treatment for fatigue and depression in multiple sclerosis patients: A double blind randomized clinical trial. Nutr Neurosci. 2016;19:138-43.

5. Golomb BA, Allison M, Koperski S, et al. Coenzyme Q10 benefits symptoms in Gulf War veterans: results of a randomized double-blind study. Neural Comput. 2014;26:2594-2651.

6. Johansson P, Dahlström Ö, Dahlström U, Alehagen U. Improved Health-Related Quality of Life, and More Days out of Hospital with Supplementation with Selenium and Coenzyme Q10 Combined. Results from a Double Blind, Placebo-Controlled Prospective Study. J Nutr Health Aging. 2015;19:870-877.

7. Iwase S, Kawaguchi T, Yotsumoto D, et al. Efficacy and safety of an amino acid jelly containing coenzyme Q10 and L-carnitine in controlling fatigue in breast cancer patients receiving chemotherapy: a multi-institutional, randomized, exploratory trial (JORTC-CAM01).Support Care Cancer. 2016;24:637-646.

8. Zhang SY, Yang KL, Zeng LT, et al. Effectiveness of coenzyme Q10 supplementation for type 2 diabetes mellitus: a systematic review and meta-analysis. Int J Endocrinol. 2018;2018:6484839.

9. Mood Treatment Center. Coenzyme Q10. http://www.moodtreatmentcenter.com/CoQ10.pdf. Accessed November 12, 2018.