Other Warnings/Precautions

• Folic acid may mask symptoms of B12 deficiency (e.g., pernicious anemia), although this may be less likely with l-methylfolate

• Use with caution in patients with bipolar disorder unless treated with concomitant mood-stabilizing agent

• Monitor patients for activation of suicidal ideation, especially children and adolescents

• Folic acid, when administered in doses above 800 mcg, may increase the amount of unmetabolized folic acid, which has been linked to accelerated growth of existing neoplasms in the colon; l-methylfolate may be less likely than folic acid to accelerate the growth of existing neoplasms

Do Not Use

• If there is a proven allergy to folate or folic acid

METHYLFOLATE (L): SPECIAL POPULATIONS

Renal Impairment

• Dose adjustment not necessary

Hepatic Impairment

• Dose adjustment not necessary

Cardiac Impairment

• Dose adjustment not necessary

Elderly

• Dose adjustment not necessary

Children and Adolescents

• Use with caution, observing for activation of known or unknown bipolar disorder and/or suicidal ideation, and inform parents or guardians of this risk so they can help observe child or adolescent patients

• Safety and efficacy have not been established

Pregnancy

• L-methylfolate has not been formally assigned a pregnancy risk category; there are no controlled studies in humans or animals

• At recommended doses, folic acid is pregnancy risk category A [adequate, well-controlled studies in pregnant women have failed to demonstrate risk to the fetus]

• At high doses, folic acid is pregnancy risk category C [no controlled studies in humans]

• Because pregnant women are advised to take folic acid or prenatal vitamins that contain folic acid, it is important to ask the patient about any supplements or vitamins she may be taking and consider this when deciding whether to prescribe l-methylfolate

Breast Feeding

• Some drug is found in mother’s breast milk

METHYLFOLATE (L): THE ART OF PSYCHOPHARMACOLOGY

Potential Advantages

• Patients who need efficacy greater than an antidepressant alone at the initiation of treatment

• Patients with partial or inadequate response to antidepressants

• Patients who cannot tolerate other antidepressants

Potential Disadvantages

• Patients with adequate folate levels

Primary Target Symptoms

• Depressed mood

• Cognitive symptoms

Pearls

• Numerous studies suggest that low plasma, red blood cell, and/or cerebrospinal fluid levels of folate may be associated with depression in some patients

• Treatment with l-methylfolate seems to be safe, has few if any side effects, and is generally less expensive than augmenting with a second branded antidepressant or atypical antipsychotic

• L-methylfolate is able to cross the blood-brain barrier and support the synthesis of monoamines

• Early studies suggest that those with obesity may be better responders

• Early studies suggest that those with genetic polymorphisms reducing the formation of l-methylfolate may be better responders

Suggested Reading

Bottiglieri T. Homocysteine and folate metabolism in depression. Prog Neuropsychopharmacology Biol Psychiatry 2005;29:1103–12.

Fava M, Mischoulon D. Folate in depression: efficacy, safety, differences in formulations, and clinical issues. J Clin Psychiatry 2009;70 (Suppl 5):S12–17.

Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev 2008;13(3):216–26.

Stahl SM. L-methylfolate: A vitamin for your monoamines. J Clin Psychiatry 2008;69(9):1352–3.

METHYLPHENIDATE (D)

METHYLPHENIDATE (D): THERAPEUTICS

Brands

• Focalin

• Focalin XR

see index for additional brand names

Generic?

Yes

Class

• Stimulant

Commonly Prescribed for

(bold for FDA approved)

• Attention deficit hyperactivity disorder (ADHD) in children ages 6–17 (Focalin, Focalin XR) and in adults (Focalin XR)

• Narcolepsy

• Treatment-resistant depression

How the Drug Works

✽ Increases norepinephrine and especially dopamine actions by blocking their reuptake

• Enhancement of dopamine and norepinephrine actions in certain brain regions (e.g., dorsolateral prefrontal cortex) may improve attention, concentration, executive function, and wakefulness

• Enhancement of dopamine actions in other brain regions (e.g., basal ganglia) may improve hyperactivity

• Enhancement of dopamine and norepinephrine in yet other brain regions (e.g., medial prefrontal cortex, hypothalamus) may improve depression, fatigue, and sleepiness