Adverse Effects

The frequency and severity of adverse reactions associated with Li+ therapy are directly related to serum lev els. Since Li+ has a low therapeutic index (approximately 3) and a narrow therapeutic window (0.5-1.5 mEq/L), the frequent measurement of serum steady-state concentrations is standard practice in the treatment of bipolar patients.

Adverse reactions occurring at serum trough levels (12 hours after the last dose) below 1.5 mEq/L are generally mild, whereas those seen above 2.5 mEq/L are usually quite severe. Mild toxicity is usually expressed as nausea, vomiting, abdominal pain, diarrhea, polyuria, sedation, and fine tremor. If the serum concentration of Li+ progressively rises above 2 mEq/L, frank neurological toxicity appears, beginning with mental confusion and progressing to hyperreflexia, gross tremor, dysarthria, focal neurological signs, seizures, progressive coma, and even death.

Adverse effects sometimes seen during chronic maintenance of bipolar patients with Li+ include hy-pothyroidism (approximately 5%) and nephrogenic dia betes insipidus. Both conditions are readily reversible by discontinuation of Li+. Routine laboratory monitoring includes TSH (thyroid-stimulating hormone) and serum creatinine measurements to detect hypothyroidism and any change in renal capacity to clear the drug.

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