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 whether a combination of magnesium and vitamin B6 can reduce symptoms of depression, stress, and anxiety in individuals with bipolar I disorder who have experienced their first episode. Participants will take either this supplement or a placebo (a pill with no active ingredient) alongside their usual treatment for four weeks. The trial seeks individuals diagnosed with bipolar I disorder within the last 10 years who currently feel stable and have not recently changed their psychiatric medications. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

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 there any evidence suggesting that Magnesium Vitamin B6 is likely to be safe for humans?

Revised FAQ Answer:

Initial findings suggest that taking magnesium and vitamin B6 together is generally safe for most people. Research shows that this combination may help with stress, depression, and anxiety. In a study with 44 children with autism, high doses of vitamin B6 and magnesium led to moderate improvements in some participants. This suggests that many people can tolerate the treatment well.

It's important to know that this clinical trial is in an early stage. The treatment has been tested in smaller groups, and more research is needed to understand its safety in larger populations. If the FDA has approved the treatment for another condition, it indicates some level of safety, but it doesn't mean it's completely risk-free for all uses. Always consider consulting a healthcare professional about potential risks before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for bipolar disorder?

Researchers are excited about using Magnesium and Vitamin B6 for bipolar disorder because this combination offers a novel approach compared to traditional treatments like mood stabilizers and antipsychotics. Unlike these conventional drugs, Magnesium and Vitamin B6 focus on providing essential nutrients that may help regulate mood naturally. Additionally, this treatment is administered in an accessible tablet form that could potentially have fewer side effects. This nutrient-based intervention is promising as it might offer a more gentle alternative with a different mechanism of action, aiming to support mood stabilization without the harsher side effects associated with more typical medications.

What evidence suggests that Magnesium Vitamin B6 might be an effective treatment for bipolar disorder?

This trial will compare the effects of Magnesium Vitamin B6 with a placebo in individuals with bipolar disorder. Research has shown that taking magnesium and vitamin B6 together can help with stress, depression, and anxiety. Studies have found that magnesium can boost energy levels, which is important for people with bipolar disorder. Whether taken alone or with vitamin B6, magnesium may help reduce stress. Previous research also suggests that this combination can moderately improve related symptoms. Overall, the evidence is promising for using magnesium and vitamin B6 to support mental health in people with bipolar disorder. ^{1 2 5 6 7}

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 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 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]

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]

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]

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]

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]

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 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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05837104

Efficacy and Safety of Magnesium Vitamin B6 in First ... Previous studies have shown that the combination of Magnesium-vitamin B6 has beneficial effects on stress, and depressive and anxiety symptoms. This randomized, ...

2. trialx.com trialx.com/clinical-trials/listings/228794/efficacy-and-safety-of-magnesium-vitamin-b6-in-first-episode-bipolar-disorder/?&geo_lat=42.4829&geo_lng=-71.1574&radius=10&place=Woburn&user_country=United%20States

Efficacy and Safety of Magnesium Vitamin B6 in First ... Magnesium is a promising targeted intervention for bipolar disorder given its significant effects on energy metabolism. Eligibility. Inclusion ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9292249/

Effect of magnesium and vitamin B6 supplementation on ... Magnesium supplementation, with or without vitamin B6, could provide a meaningful clinical benefit in daily life for individuals with stress and low magnesemia.

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05837104/efficacy-and-safety-of-magnesium-vitamin-b6-in-first-episode-bipolar-disorder

Efficacy and Safety of Magnesium Vitamin B6 in First ... Previous studies have shown that the combination of Magnesium-vitamin B6 has beneficial effects on stress, and depressive and anxiety symptoms.

5. withpower.com withpower.com/trial/phase-2-disease-4-2023-5aecc

Magnesium + Vitamin B6 for Bipolar Disorder In a study of 44 autistic children, high doses of vitamin B6 combined with magnesium led to moderate clinical improvements in 15 participants, suggesting ...

6. trialx.com trialx.com/clinical-trials/listings/228794/efficacy-and-safety-of-magnesium-vitamin-b6-in-first-episode-bipolar-disorder/

Efficacy and Safety of Magnesium Vitamin B6 in First ... This is a randomized, double-blind, placebo-controlled proof-of-concept clinical trial to assess the efficacy and safety of Magnesium-vitamin ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3804335/

Nutritional and Safety Outcomes from an Open-Label ... This small open-label trial provides preliminary data suggesting that EMP+ may be safe in children ages 6–12 with BPSD not taking mood stabilizing medications.