BOTTOM LINE:
Vitamin D supplementation may be beneficial in depression, but the evidence is strongest for those with low vitamin D levels. Make sure patients take adequate doses, in the range of 1000–5000 IU daily.

FDA INDICATIONS:
None.

OFF-LABEL USE:
Depression.

DOSAGE FORMS:
Supplied over the counter as vitamin D2 and D3, as tablets, capsules, and softgels in “international units” (IU) dosing. We recommend D3: 1000 IU, 2000 IU, 5000 IU, 10,000 IU.

DOSAGE GUIDANCE:
For depression, use 1000–5000 IU per day.

MONITORING: Periodic vitamin D [25(OH)D] levels.   COST: $

SIDE EFFECTS:

• Most common: Well tolerated.
• Serious but rare: Vitamin D toxicity—characterized by hypercalcemia—can occur with excessive dosing.
• Pregnancy/breastfeeding: Considered safe.

MECHANISM, PHARMACOKINETICS, AND DRUG INTERACTIONS:

• May affect brain plasticity, inflammation, and immune regulation.
• Metabolized in liver to 25(OH)D, then in kidneys to active form (1,25-dihydroxyvitamin D); half-life: 12–50 days, depending on source and individual factors.
• No known significant interactions.

CLINICAL PEARLS:

• Vitamin D is synthesized in the skin via ultraviolet B exposure and obtained from diet and supplements. D3 (cholecalciferol, from animal sources) is preferred over D2 (ergocalciferol, from plants) because it is about three times more potent and has a longer duration of action.
• Most vitamin D comes from sun exposure, with conversion of 7-dehydrocholesterol in the skin to vitamin D3. Dietary sources (eg, oily fish, fortified foods, mushrooms) are often insufficient to meet needs without supplementation.
• There is no universal agreement on optimal 25(OH)D levels (which is the active form after metabolism). Many labs consider 30–60 ng/mL normal, 21–29 ng/mL insufficient, and 20 ng/mL or lower deficient.
• Several meta-analyses found no overall benefit of vitamin D supplementation in depression. However, subgroup analyses show significant improvements in patients who were vitamin D deficient at baseline and received adequate doses (greater than 800 IU/day).
• Studies in anxiety, psychosis, and dementia have not shown clear benefit from supplementation.

FUN FACT:
A number of things affect your vitamin D status, including how far away you live from the equator, the air quality in your community, your skin color, and your use of sunscreen.