This is a randomized, double-blind, placebo-controlled proof-of-concept clinical trial to assess the efficacy and safety of Magnesium-vitamin B6in combination with treatment as usual for treating symptoms of depression, stress, and anxiety in patients with first episode bipolar I disorder.

After a first episode of bipolar disorder, subsequent depressive and anxiety symptoms can pose a major challenge to an individual's recovery early in the illness. Individuals often have depressive and anxiety symptoms for a significant proportion of their time. These mood and anxiety symptoms are associated with higher risk for relapse, chronicity and disability. Previous studies have shown that the combination of Magnesium-vitamin B6 has beneficial effects on stress, and depressive and anxiety symptoms. This randomized, double-blind, placebo-controlled trial will assess the benefits of Magnesium-vitamin B6 in combination with treatment as usual (standard of clinical care) on depressive and anxiety symptoms and stress in individuals with bipolar disorder in the early phase of illness. In addition, the investigators aim to assess the effects of Magnesium-vitamin B6 on brain free [Mg2+] and energy metabolism, observed to be altered in bipolar disorder, measured by in vivo 31P magnetic resonance spectroscopy (31P MRS). Magnesium is a promising targeted intervention for bipolar disorder given its significant effects on energy metabolism.

Inclusion Criteria:

• Persons between the ages of 18 and 50
• DSM V diagnosis of bipolar I disorder, onset of illness in the last 10 years
• Minimum of two of the following symptoms on the Hamilton Rating Scale of Depression HAM-D (HAM-D, 17 item): depressed mood, feelings of guilt, anxiety-psychic, anxiety-somatic, somatic symptoms-general, somatic symptoms-gastrointestinal.
• Young Mania Rating Scale (YMRS) scores of less than 15
• Ability to sign informed consent.
• Stable disorder and no change in psychiatric medications within 2 weeks of screening and expected to not require addition of any new psychiatric medications during the duration of the 4 weeks of the study.

Exclusion Criteria:

• Unable to sign informed consent.
• Persons weighing over 350lbs.
• Declines to participate.
• Bipolar NOS, Cyclothymia, or Schizoaffective Bipolar type.
• 2 or more manic symptoms that meet DSM-V criteria.
• Persons of childbearing potential who are not using a medically accepted means of contraception.
• Persons who are deemed a serious suicide or homicide risk.
• Unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease.
• The following DSM-V diagnoses: 1) substance use disorders, including alcohol, active within 2 months; 2) schizophrenia; 3) delusional disorder; 4) psychotic disorders not otherwise specified; 5) schizoaffective disorder; 6) acute bereavement; 7) severe borderline or antisocial personality disorder.
• Persons meeting criteria for bipolar mixed episode.
• Exposure to levodopa, quinidine, and proton-pump inhibitors within 3 months prior to screening.
• Severe hypomagnesemia (serum magnesium of 0.45 mmol/L).
• Persons who have taken an investigational psychotropic drug within the past 6 months unless the investigational drug was a one-time dose.
• Seizure disorder.
• Dietary supplements including SAMe, St. John's Wort, DHEA, Inositol, and Ginko biloba.
• Previous treatment with the following procedures: vagus nerve stimulation, or deep brain stimulation.
• Have a history of electroconvulsive therapy (ECT) or transcranial magnetic stimulation (TMS) within the last 3 months.
• Have any medical condition that would prevent blood draws.
• Have a history of significant head injury.
• Individuals with galactose intolerance, total lactase deficiency or glucose-galactose malabsorption syndrome (rare hereditary diseases)
• Individuals with allergies to magnesium citrate anhydrous, pyridoxine hydrochloride or any of the other components of Magne B6
• Patients taking psychostimulant medication