With blood levels of lithium in the upper therapeutic range (therapeutic 0.6 to 1.2 mEq/L), it is not uncommon to observe a fast-frequency action tremor or asterixis, together with nausea, loose stools, fatigue, polydipsia, and polyuria. These symptoms usually subside with time. Above a level of 1.5 to 2 mEq/L, particularly in patients with impaired renal function or in those taking a thiazide diuretic, serious intoxication becomes manifest—clouding of consciousness, confusion, delirium, dizziness, nystagmus, ataxia, stammering, diffuse myoclonic twitching, and nephrogenic diabetes insipidus. Vertical (downbeating) nystagmus and opsoclonus (see Chap. 13) may also be prominent. A variety of skin problems is common including worsening of acne vulgaris. An uncommon toxic effect is the development of goiter but most patients remain euthyroid although the thyroid-stimulating hormone (TSH) levels may increase slightly. The goiter usually requires no treatment but it is possible to administer thyroid hormone so as to cause the thyroid enlargement to regress.
The myoclonic state, particularly when combined with confusion and sharp waves in the EEG, may mimic Creutzfeldt-Jakob disease (see Chap. 32) but there should be no problem in diagnosis if the setting of the illness and the administration of lithium are known. At blood lithium concentrations above 3.5 mEq/L, these symptoms are replaced by stupor and coma, sometimes with convulsions, and may prove fatal.
Discontinuing lithium in the intoxicated patient, which is the initial step in therapy, does not result in immediate disappearance of toxic symptoms. This may be delayed by a week or two, and the diabetes insipidus may persist even longer. Fluids, sodium chloride, aminophylline, and acetazolamide promote the excretion of lithium. Lithium coma may require hemodialysis, which has proved to be the most rapid means of reducing the blood lithium concentration.
Drugs that act primarily as CNS stimulants assume clinical importance for several reasons, mainly in their use for sleep disorders and attention deficit disorder. Some members of this group, the amphetamines, are much abused and others are not infrequent causes of poisoning. Their main mechanism of action is the release of endogenous catecholamine from vesicles in the presynaptic terminals.
The amphetamines (d-amphetamine, d,l-amphetamine, pemoline, methamphetamine, methylphenidate) are analeptics (CNS stimulants) and in addition have significant hypertensive, respiratory-stimulant, and appetite-depressant effects. They are effective in the management of narcolepsy but have been more widely and sometimes indiscriminately used for the control of obesity, the abolition of fatigue, and the treatment of hyperactivity in children (see Chap. 37 for full discussion). Undoubtedly, they are able to reverse fatigue, postpone the need for sleep, and elevate mood but these effects are not entirely predictable and the user must compensate for the period of wakefulness with even greater fatigue and often with depression that follows. The intravenous use of a high dose of amphetamine produces an immediate feeling of ecstasy.