Can B12 Boost Your Response to Psych Meds?

Vitamin B12 is a key component of several metabolic pathways in the brain.

Posted Aug 10, 2018

Originally published in the APA's Psychiatric News

Deficiency of this key vitamin has been linked with treatment resistance in psychiatric illness.

Vitamin B12 is a key building block for the brain, and evidence suggests that vitamin B12 deficiency is linked with treatment-resistant depression, anxiety, panic disorder, and even cognitive decline (1). Medications for treating these disorders cannot improve brain function if neurons do not have the building blocks needed to make neurotransmitters such as serotonin or make the proper fats for myelin.

How can a clinician know whether vitamin B12 deficiency is weakening a patient’s response to medication? Standard blood tests can offer one measurement of B12 levels, but a serum or plasma B12 level does not provide any indication of intracellular B12 levels (2). Conducting a dynamic B12 assessment that considers lab values and patient history can give you a better sense of whether your patient has B12 deficiency.

First, I do a CBC (complete blood count) to look at both total red blood cell count (RBC) and mean corpuscular volume (MCV), which tells you the average size of the red blood cells. Vitamin B12 deficiency reduces the ability to make red blood cells. Since red blood cells are being produced at a slower rate, the old blood cells hang around and grow, leading to a condition known as macrocytic anemia (low blood cell count, but large blood cells). If the blood test trends in this direction, this suggests your patient may have vitamin B12 deficiency. However, also check the patient’s iron levels. Iron deficiency leads to smaller red blood cells, so a patient with both low levels of iron and B12 will be anemic, but not have macrocytic anemia.

A second test I usually order to confirm the blood values is a homocysteine test. This metabolite is a component of the methionine cycle that becomes elevated in the blood of people with B12 deficiency. Importantly, homocysteine levels, which should be around 7.0, can be increased due to folic acid deficiency independent of B12 deficiency. This makes the homocysteine level a useful but non-specific test, which tells me how the methylation cycle is working. Some clinicians prefer to use a methylmalonic acid (MMA) test in place of a homocysteine test, but MMA is also a non-specific biomarker.

In addition to blood work, it’s important to get a good history to assess risk factors for B12 deficiency. Patient age is one consideration; gastric parietal cells, which make intrinsic factor (a stomach protein that enables the body to absorb B12), become less functional with age. Patients with a history of autoimmune problems also are more likely to have autoantibodies against intrinsic factor and have reduced B12 uptake. Vegans are also more likely to be B12 deficient.

Additionally, check to see if your patient is taking medications that can cause B12 deficiency; these include the anti-diabetic medication Glucophage, acid blockers such as Prilosec, tetracycline antibiotics, antiseizure medications, and valproic acid; the list is longer than this, but it can be easily found online.

If you suspect that your patient may have a B12 deficiency, the next step is to normalize his or her B12 levels. You can try and encourage dietary changes and/or B12 supplements, but because B12 is so important to the nervous system, I almost always provide B12 injections for three months to boost brain repair, followed by a sublingual maintenance formulation.

It’s important to point out that there are four forms of vitamin B12, which have their own properties: hydroxocobalamin, methylcobalamin, adenosylcobalamin, and cyanocobalamin. For the initial B12 injection, I typically administer a 25-mg mixture of B12 in a 10cc formulation, with an equal mix of hydroxocobalamin and methylcobalamin. After this initial injection, I recommend 0.5 cc injections of this B12 formulation three times a week for about three to four months, at which point I retest CBC and homocysteine.

If a medication or autoimmune problem is causing the deficiency, then the patient may need ongoing injections after that, but with some training most patients can administer the shots themselves. Eventually when the blood parameters are corrected, injections can be reduced to once weekly, or even twice monthly, if sublingual supplementation is not appropriate.

If a patient has a serious B12 deficiency but is resistant to B12 injections, it is important to educate the patient about the destructive effects of B12 deficiency on the brain and the ways this may worsen their symptoms.

In my clinical experience, some people can become agitated following a B12 injection, so it is best to administer in the morning and advise them of this risk. Regular monitoring of patient behavior following an injection is also important, as there can be a chance of overmethylation, which can lead to adverse symptoms including insomnia, hyperactivity, or hypomania. Some labs do offer comprehensive methylation panels that can confirm a suspicion of over- or under-methylation.
Once B12 levels are normalized, patients will likely begin to experience improvements. I have treated patients who have shown remarkable responses within a few days after starting B12 injections. 

Published December 2017 in American Psychiatric Association's Psychiatric News


1. Briani C, Dalla Torre C, Citton V, et al. Cobalamin Deficiency: Clinical Picture and Radiological Findings. Nutrients.2013;5(11):4521-4539. 2. Clarke R. B-vitamins and Prevention of Dementia. Proc Nutr Soc. 2008;67:75-81.