Chapter 10

### INTRODUCTION

Lithium was discovered in 1818, and its psychiatric benefits were discovered in the 1940s. Until 1950, the popular beverage 7-Up contained lithium citrate and was positioned for people with hangovers. The number “7” in 7-Up is in reference to the atomic mass of lithium and the word “Up” is in reference to the uplifting effects of the lithium citrate.

Lithium is indicated for the management of bipolar disorders, the acute treatment of manic episodes or mixed episodes in patients with bipolar 1 or bipolar 2 disorder, and maintenance therapy in bipolar disorders to prevent or decrease the intensity of subsequent manic episodes.1, 2, 3, 4, and 5 Lithium is also indicated for refractory unipolar depression (60–80% efficacy).3 Lithium has also been used for the management of bulimia, tardive dyskinesia, alcoholism, cluster headaches, postpartum psychosis, corticosteroid psychosis, posttraumatic stress disorder, aggression, as an augmentation agent for patients with depression, disorders of impulse control, schizoaffective and schizophrenic disorders, neutropenia or anemia, and hyperthyroidism.3, 4, 5, and 6 Lithium has been used for the syndrome of inappropriate antidiuretic hormone, however, due to the perils of using lithium in patients with water imbalances and the availability of demeclocycline and the newer vaptans such as conivaptan, lithium should only be used as a refractory agent.

Lithium has several mechanisms of action that influence its clinical effects in psychiatry. Lithium reduces cation transport such as calcium, magnesium, sodium, and potassium into cell membranes in the nerves and muscles.2,3 These univalent and divalent cations are involved in the synthesis, storage, release, and reuptake of catecholamines. Lithium also reduces the reuptake of catecholamines and attenuates supersensitive receptors, resensitizing the receptor and reestablishing the effects of norepinephrine, epinephrine, serotonin, and dopamine.3 Both norepinephrine and dopamine may be involved in the pathogenesis of mania, and serotonin may be involved with depression. The effects of lithium may be noted within 7–14 days, and 14–21 days for a full effect.

### THERAPEUTIC AND TOXIC PLASMA CONCENTRATIONS

Lithium has a narrow therapeutic index but a well-defined plasma concentration range. The usual lithium target serum level for acute manic or mixed episodes in patients with bipolar 1 or bipolar 2 disorder is 0. 8–1.2 mEq/L; rarely levels of 1.2–1.5 mEq/L are needed.6 Once the patient's manic episode is stabilized, maintenance lithium serum levels are 0.6–1.0 mEq/L and rarely 1.0–1.2 mEq/L. In order to minimize lithium-adverse effects, the target ranges of lithium for the elderly are usually 0.2 mEq/L or less.7 The available target serum levels for lithium assume a multiple daily dose model; no target level has been established for once-daily dosing.

Two of the most common adverse effects associated with lithium are gastrointestinal and central nervous system (CNS) related, and generally resolve with continued treatment.2 Gastrointestinal side ...

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