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taken for polydipsia) and leukocytosis not due to infection are fairly common Other side effects include goiter (3%; often euthyroid), hypothyroidism (10%; concomitant administration of lithium and iodide or lithium and carbamazepine enhances the hypothyroid and goitrogenic effect of either drug), changes in the glucose tolerance test toward a diabetes-like curve, nephrogenic diabetes insipidus (usually resolving about 8 weeks after cessation of lithium therapy), nephrotic syndrome, edema, folate deficiency, and pseudotumor cerebri (ophthalmoscopy is indicated if there are complaints of headache or blurred vision) A metallic taste, hair loss, and Raynaud s phenomenon have been reported in a few cases Thyroid and kidney function should be checked at 3- to 4-month intervals Most of these side effects subside when lithium is discontinued; when residual side effects exist, they are usually not serious Most clinicians treat lithium-induced hypothyroidism (more common in women) with thyroid hormone while continuing lithium therapy Hypercalcemia and elevated parathyroid hormone levels occur in some patients Electrocardiographic abnormalities (principally T wave flattening or inversion) may occur during lithium administration but are not of major clinical significance Sinoatrial block may occur, particularly in the elderly Other drugs that prolong intraventricular conduction, such as TCAs, must be used cautiously in conjunction with lithium Lithium impairs ventilatory function in patients with airway obstruction Lithium alone does not have a significant effect on sexual function, but when combined with benzodiazepines (clonazepam in most symptomatic patients) it causes sexual dysfunction in about 50% of men Lithium may precipitate or exacerbate psoriasis in some patients Patients receiving long-term lithium therapy may have cogwheel rigidity and, occasionally, other extrapyramidal signs Lithium potentiates the parkinsonian effects of haloperidol Long-term lithium therapy has also been associated with a relative lowering of the level of memory and perceptual processing (affecting compliance in some cases) Some impairment of attention and emotional reactivity has also been noted Lithium-induced delirium with therapeutic lithium levels is an infrequent complication usually occurring in the elderly and may persist for several days after serum levels have become negligible Encephalopathy has occurred in patients receiving combined lithium and neuroleptic therapy and in those who have cerebrovascular disease, thus requiring careful evaluation of patients who develop neurotoxic signs at subtoxic blood levels Some reports have suggested that the long-term use of lithium may have adverse effects on renal function (with interstitial fibrosis or tubular atrophy) A rise in serum creatinine levels is an indication for in-depth evaluation of renal function and consideration of alternative treatments if the individual can tolerate a change Incontinence has been reported in women, apparently related to changes in bladder cholinergic-adrenergic balance Prospective studies suggest that the overall risk imposed by lithium in pregnancy may be overemphasized However, lithium exposure in early pregnancy does increase the frequency of congenital anomalies, especially Ebstein s and other major cardiovascular anomalies For women who take psychotropic medications who become pregnant, the decision to
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make a change in medication is complex and requires informed consent regarding the relative risks to the patient and fetus Indeed, the risk of untreated bipolar disorder carries its own risks for pregnancy Formula feeding should be considered in mothers taking lithium, since concentration in breast milk is one-third to half that in serum Frank toxicity usually occurs at blood lithium levels above 2 mEq/L Because sodium and lithium are reabsorbed at the same loci in the proximal renal tubules, any sodium loss (diarrhea, use of diuretics, or excessive perspiration) results in increased lithium levels Symptoms and signs include vomiting and diarrhea, the latter exacerbating the problem since more sodium is lost and more lithium is absorbed Other symptoms and signs, some of which may not be reversible, include tremors, marked muscle weakness, confusion, dysarthria, vertigo, choreoathetosis, ataxia, hyperreflexia, rigidity, lack of coordination, myoclonus, seizures, opisthotonos, and coma Toxicity is more severe in the elderly, who should be maintained on slightly lower serum levels Lithium overdosage may be accidental or intentional or may occur as a result of poor monitoring Patients with massive ingestions of lithium or blood lithium levels above 25 mEq/L should be treated with induced emesis and gastric lavage If renal function is normal, osmotic and saline diuresis increases renal lithium clearance Urinary alkalinization is also helpful, since sodium bicarbonate decreases lithium reabsorption in the proximal tubule, as does acetazolamide as well Aminophylline potentiates the diuretic effect by increasing the clearance of lithium Drugs affecting the distal loop have no effect on lithium reabsorption Blood lithium levels above 25 mEq/L (confirmed by cerebrospinal fluid lithium levels) should be considered an indication for hemodialysis Compliance with lithium therapy is adversely affected by the loss of some hypomanic experiences valued by the patient These include social extroversion and a sense of heightened enjoyment in many activities such as sex and business dealings, often with increased productivity in the latter 3 Drug interactions Patients receiving lithium should use diuretics with caution and only under close medical supervision The thiazide diuretics cause increased lithium reabsorption from the proximal renal tubules, resulting in increased serum lithium levels (Table 25 10), and adjustment of lithium intake must be made to compensate for this Reduce lithium dosage by 25 40% when the patient is receiving 50 mg of hydrochlorothiazide daily Potassium-sparing diuretics (spironolactone, amiloride, triamterene) may also increase serum lithium levels and require careful monitoring of lithium levels Loop diuretics (furosemide, ethacrynic acid, bumetanide) do not appear to alter serum lithium levels Concurrent use of lithium and angiotensin-converting enzyme inhibitors requires a 50 75% reduction in lithium intake to achieve therapeutic lithium levels
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