THERAPEUTICS

Brands

• Eskalith
• Eskalith CR
• Lithobid slow-release tablets
• Lithostat tablets
• Lithium carbonate tablets
• Lithium citrate syrup
• see index for additional brand names

Generic?

• Yes

Class

• Mood stabilizer

Commonly Prescribed for

• (bold for FDA approved)
• Manic episodes of manic-depressive illness
• Maintenance treatment for manic-depressive patients with a history of mania
• Bipolar depression
• Major depressive disorder (adjunctive)
• Vascular headache
• Neutropenia

How the Drug Works

• Unknown and complex
• Alters sodium transport across cell membranes in nerve and muscle cells
• Alters metabolism of neurotransmitters including catecholamines and serotonin
• May alter intracellular signaling through actions on second messenger systems
• Specifically, inhibits inositol monophosphatase, possibly affecting neurotransmission via phosphatidyl inositol second messenger system
• Also reduces protein kinase C activity, possibly affecting genomic expression associated with neurotransmission
• Increases cytoprotective proteins, activates signaling cascade utilized by endogenous growth factors, and increases gray matter content, possibly by activating neurogenesis and enhancing trophic actions that maintain synapses

How Long Until It Works

• 1–3 weeks

If It Works

• The goal of treatment is complete remission of symptoms (i.e., mania and/or depression)
• Continue treatment until all symptoms are gone or until improvement is stable and then continue treating indefinitely as long as improvement persists
• Continue treatment indefinitely to avoid recurrence of mania or depression

If It Doesn’t Work

• Many patients have only a partial response where some symptoms are improved but others persist or continue to wax and wane without stabilization of mood
• Other patients may be nonresponders, sometimes called treatment-resistant or treatment-refractory
• Consider checking plasma drug level, increasing dose, switching to another agent or adding an appropriate augmenting agent
• Consider adding psychotherapy
• Consider the presence of noncompliance and counsel patient
• Switch to another mood stabilizer with fewer side effects
• Consider evaluation for another diagnosis or for a comorbid condition (e.g., medical illness, substance abuse, etc.)

Best Augmenting Combos for Partial Response or Treatment Resistance

• Valproate
• Atypical antipsychotics (especially risperidone, olanzapine, quetiapine, ziprasidone, and aripiprazole)
• Lamotrigine
• Antidepressants (with caution because antidepressants can destabilize mood in some patients, including induction of rapid cycling or suicidal ideation; in particular consider bupropion; also SSRIs, SNRIs, others; generally avoid TCAs, MAOIs)

Tests

• Before initiating treatment, kidney function tests (including creatinine and urine specific gravity) and thyroid function tests; electrocardiogram for patients over 50
• Repeat kidney function tests 1–2 times/year
• Frequent tests to monitor trough lithium plasma levels (should generally be between 1.0 and 1.5 mEq/L for acute treatment, 0.6 and 1.2 mEq/l for chronic treatment)
• Since lithium is frequently associated with weight gain, before starting treatment, weigh all patients and determine if the patient is already overweight (BMI 25.0–29.9) or obese (BMI ≥30)
• Before giving a drug that can cause weight gain to an overweight or obese patient, consider determining whether the patient already has pre-diabetes (fasting plasma glucose 100–25 mg/dL), diabetes (fasting plasma glucose >126 mg/dL), or dyslipidemia (increased total cholesterol, LDL cholesterol and triglycerides; decreased HDL cholesterol), and treat or refer such patients for treatment, including nutrition and weight management, physical activity counseling, smoking cessation, and medical management
• Monitor weight and BMI during treatment
• While giving a drug to a patient who has gained >5% of initial weight, consider evaluating for the presence of pre-diabetes, diabetes, or dyslipidemia, or consider switching to a different agent