Magnesium + Vitamin B6 for Bipolar Disorder

Overseen By Kyle Cuklanz, B.S.

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Mclean Hospital

Must not be taking: Levodopa, Quinidine, Proton-pump inhibitors, others

Disqualifiers: Substance use, Schizophrenia, Seizure disorder, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a mix of magnesium and vitamin B6 supplements for patients who have recently experienced their first episode of bipolar I disorder. The treatment aims to improve mood and reduce anxiety by supporting brain energy production and function.

Will I have to stop taking my current medications?

The trial requires that your psychiatric medications remain stable, meaning no changes in your current psychiatric medications for at least 2 weeks before the trial and no new psychiatric medications during the 4-week study period.

Is Magnesium + Vitamin B6 safe for humans?

Magnesium and vitamin B6 have been studied in various contexts and are generally considered safe for human use. However, very high doses of vitamin B6 can lead to reversible neurological issues, so it's important to use them within recommended limits. ^{1 2 3 4 5}

How does the drug Magnesium Vitamin B6 differ from other treatments for bipolar disorder?

Magnesium Vitamin B6 is unique because it combines magnesium and vitamin B6, which have shown benefits in reducing stress and improving mental health in other conditions. This combination may offer a novel approach by potentially enhancing mood and quality of life through mechanisms like stress reduction and magnesium restoration, which are not typically targeted by standard bipolar disorder treatments. ^{2 6 7 8 9}

Is the treatment Magnesium + Vitamin B6 effective for improving mental health in individuals with bipolar disorder?

Research suggests that magnesium combined with vitamin B6 can improve mental health and quality of life in stressed individuals, showing potential benefits for mood and anxiety. Additionally, vitamin B6 has been studied as an adjunctive therapy in bipolar disorder, indicating possible roles in mood regulation. ^{2 7 8 10 11}

Who Is on the Research Team?

Virginie-Anne Chouinard, MD

Principal Investigator

Mclean Hospital

Are You a Good Fit for This Trial?

This trial is for adults aged 18-45 with a recent diagnosis of bipolar I disorder, experiencing certain symptoms like depressed mood and anxiety. They should have moderate to severe stress but not be in a manic state, as shown by specific rating scales. Participants must be stable on their current psychiatric meds with no changes expected during the study.

Inclusion Criteria

You have been diagnosed with bipolar I disorder within the last 7 years according to the DSM V.

I have at least two symptoms of depression but my overall depression is mild.

I am experiencing high levels of stress.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Magnesium vitamin B6 or placebo three times daily for four weeks

4 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Magnesium Vitamin B6
• Placebo

Trial Overview The trial is testing if adding Magnesium vitamin B6 to usual treatment helps reduce depression, stress, and anxiety in those having their first episode of bipolar I disorder. It's a randomized test where patients won't know if they're getting the actual supplement or a placebo.

How Is the Trial Designed?

Group I: Magnesium vitamin B6 Experimental Treatment 1 Intervention

Magnesium vitamin B6 (MagnéVie B6®) composed of Magnesium citrate (100mg) and Pyridoxine hydrochloride (10mg) in tablet form, taken three times daily for four weeks.

Group II: Placebo Placebo Group 1 Intervention

Placebo tablet will be taken three times daily for four weeks.

Who Is Running the Clinical Trial?

Mclean Hospital

Lead Sponsor

Trials

221

Recruited

22,500+

Published Research Related to This Trial

In a 12-week double-blind trial involving 33 participants with bipolar depression and Vitamin D deficiency, Vitamin D3 supplementation did not lead to a significant difference in mood improvement compared to placebo, despite increasing Vitamin D levels in the treatment group.

Both the Vitamin D and placebo groups showed similar reductions in depression and anxiety symptoms, indicating that Vitamin D3 supplementation may not be effective as an adjunct treatment for bipolar depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin D supplementation in bipolar depression: A double blind placebo controlled trial. Marsh, WK., Penny, JL., Rothschild, AJ.[2019]

In an 8-week study involving individuals with low magnesium levels and high stress, combining magnesium with vitamin B6 led to greater reductions in anxiety and depression compared to magnesium alone.

Both treatments improved quality of life, but those taking the magnesium and vitamin B6 combination reported a greater perceived ability to engage in physical activities by week 4, highlighting the potential benefits of this combination for mental health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial. Noah, L., Dye, L., Bois De Fer, B., et al.[2022]

In a double-blind clinical trial involving 50 patients with bipolar disorder experiencing manic episodes, an 80 mg daily dose of vitamin B6 did not show significant improvement in mood status compared to a placebo group, as measured by the Young Mania Questionnaire.

Interestingly, the placebo group demonstrated a significant improvement in cognitive status compared to the vitamin B6 group, suggesting that vitamin B6 may not be beneficial in this context and highlighting the need for further research with larger sample sizes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of vitamin B6 as an adjunctive therapy to lithium in improving the symptoms of acute mania in patients with bipolar disorder, type 1; a double-blind, randomized, placebo-controlled, clinical trial. Badrfam, R., Mostafavi, SA., Khaleghi, A., et al.[2021]

In a study of 66 hospitalized patients with bipolar disorder, vitamin B6 significantly improved mood symptoms and sleep quality compared to a placebo when used alongside standard lithium treatment.

Vitamin B1 did not show a significant effect on mood improvement, but both vitamins B1 and B6 were effective in enhancing sleep quality compared to placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of vitamins B1 and B6 as an adjunctive therapy to lithium in bipolar-I disorder: A double-blind, randomized, placebo-controlled, clinical trial. Zandifar, A., Mousavi, S., Schmidt, NB., et al.[2023]

Omega-3 fatty acids (O3FAs) show the strongest evidence for efficacy in treating bipolar depression, although some studies have not found positive effects, indicating mixed results.

Overall, the review concludes that there is insufficient evidence to support the routine use of nutritional supplements for bipolar depression, highlighting the need for more rigorous studies to draw definitive conclusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review of nutritional supplements for the treatment of bipolar depression. Rakofsky, JJ., Dunlop, BW.[2014]

Vitamin B6 plays a crucial role in drug interactions and can significantly affect the therapeutic efficacy of medications, such as reducing the effectiveness of levodopa in Parkinson's treatment when improperly supplemented.

Deficiencies in vitamin B6 can lead to adverse drug effects, such as peripheral neuropathy from isoniazid, which can be prevented by pyridoxine supplementation, highlighting the importance of maintaining adequate vitamin levels for optimal drug action.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-pyridoxal phosphate interactions. Ebadi, M., Gessert, CF., Al-Sayegh, A.[2019]

In a study of 44 autistic children, high doses of vitamin B6 combined with magnesium led to moderate clinical improvements in 15 participants, suggesting potential efficacy for some individuals with autism.

Biochemical analysis showed that treatment resulted in decreased levels of urinary homovanillic acid (HVA) and increased amplitude in middle latency evoked potentials, indicating possible mechanisms of action related to neurotransmitter regulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children. Lelord, G., Callaway, E., Muh, JP.[2015]

High doses of vitamin B6 (1.5 g/day) for 2-7 weeks significantly increased erythrocyte magnesium levels, while lower doses (1 g or less) did not affect magnesium absorption in the intestines.

Despite the potential benefits of high-dose vitamin B6, doses of 2 g/day have been associated with reversible neurological complications, suggesting that such high doses should be avoided for safety reasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Vitamin B6 and magnesium. Eisinger, J., Dagorn, J.[2015]

In a randomized trial involving 264 healthy adults with low magnesium levels, both magnesium alone and magnesium combined with vitamin B6 significantly reduced perceived stress, with no significant difference between the two treatments overall.

However, for individuals experiencing severe stress, those taking the magnesium and vitamin B6 combination showed a 24% greater improvement in stress levels compared to those taking magnesium alone, indicating a potential benefit of the combination in more stressed populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. Pouteau, E., Kabir-Ahmadi, M., Noah, L., et al.[2023]

The study found that a combination of magnesium supplementation with mineral bishofit solution and vitamin B6 (pyridoxine hydrochloride) effectively restored magnesium levels in magnesium-deficient alcoholic rats.

This supplementation also helped correct some behavioral disturbances caused by chronic alcohol consumption, suggesting potential therapeutic benefits for magnesium deficiency in similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of magnesium supplementation containing mineral bishofit (MgCl2 x 6H2O) solution and pyridoxine hydrochloride on erythrocyte magnesium depletion and behaviour of rats after three-month alcoholization. Iezhitsa, IN., Onishchenko, NV., Churbakova, NV., et al.[2016]

Chronic alcohol consumption in rats led to a significant decrease in magnesium levels and induced depressive-like behaviors, as shown by reduced locomotor activity and increased immobilization time in tests.

Treatment with a magnesium-containing preparation improved these depressive symptoms and restored magnesium levels in the blood, suggesting its potential as an antidepressant in the context of alcohol-related disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Study of pharmacological activity of complex magnesium-containing preparation based on mineral bishofit and pyridoxine hydrochloride in a rat model of chronic alcoholic intoxication]. Spasov, AA., Petrov, VI., Iezhitsa, IN., et al.[2015]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Vitamin D supplementation in bipolar depression: A double blind placebo controlled trial. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Effect of magnesium and vitamin B6 supplementation on mental health and quality of life in stressed healthy adults: Post-hoc analysis of a randomised controlled trial. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

The efficacy of vitamin B6 as an adjunctive therapy to lithium in improving the symptoms of acute mania in patients with bipolar disorder, type 1; a double-blind, randomized, placebo-controlled, clinical trial. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of vitamins B1 and B6 as an adjunctive therapy to lithium in bipolar-I disorder: A double-blind, randomized, placebo-controlled, clinical trial. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Review of nutritional supplements for the treatment of bipolar depression. [2014]

6. England pubmed.ncbi.nlm.nih.gov

Drug-pyridoxal phosphate interactions. [2019]

7. Italy pubmed.ncbi.nlm.nih.gov

Clinical and biological effects of high doses of vitamin B6 and magnesium on autistic children. [2015]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Vitamin B6 and magnesium. [2015]

9. United States pubmed.ncbi.nlm.nih.gov

Superiority of magnesium and vitamin B6 over magnesium alone on severe stress in healthy adults with low magnesemia: A randomized, single-blind clinical trial. [2023]

10. England pubmed.ncbi.nlm.nih.gov

Effect of magnesium supplementation containing mineral bishofit (MgCl2 x 6H2O) solution and pyridoxine hydrochloride on erythrocyte magnesium depletion and behaviour of rats after three-month alcoholization. [2016]

11. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Study of pharmacological activity of complex magnesium-containing preparation based on mineral bishofit and pyridoxine hydrochloride in a rat model of chronic alcoholic intoxication]. [2015]