Lithium - Adverse effects
Lithium has an indisputable efficacy for the prevention of bipolar disorders. it reduces the symptoms without inducing behavior disorders such as thoses observed with neuroleptics. It has adverse effects however, even when the plasma concentration recommended between 0.5 and 0.8 meq/L is respected, and more frequently when it is exceeded.
- Hand tremor which can be very troublesome, is frequently observed. This tremor can be attenuated by reducing the day doses and increasing the evening dose. i.e. by giving a higher dose the evening than the morning. Beta-blockers can also decrease tremor.
- Muscular weakness
- Increase in weight
- Polyuria inducing polydipsia, because lithium inhibits the response of the kidney to the antidiuretic hormone on aquaporins 2. This polyuria can decrease during treatment, but when it persists and induces a diabetes insipidus, the treatment should be stopped.
- Inhibition of secretion of thyroid hormones, which generally induces a compensatory goiter without true hypothyroidism
- Hyperleucocytosis with neutrophils reaching from 10 000 to 20 000 mm3 instead of 7 to 8 000 normally. This hyperleucocytosis is reversible with the discontinuation of the treatment.
- Neurological disorders which are observed primarily with overdoses and poisonings: ataxia, mental confusion, delusion, hallucinations, nystagmus and seizures. The symptoms announcing poisoning are muscular contractions, difficulties of writing, a difficult step, apathy and dysarthria.
- Teratogenic risk: it is advised to stop lithium before a pregnancy and not to prescribe it during pregnancy because, in experiments, it was teratogenic. However the majority of the women who have taken lithium during their pregnancy had normal children.
- It is advised to stop lithium at least a week before the onset of electroconvulsive therapy.
- Studies comparing the intellectual abilities of patients with bipolar disorder treated by lithium indicate that lithium could reduce their creativity and their memory, partly explaining the reluctance of certain patients to continue lithium in spite of its therapeutic efficacy.
- When lithium is effective in a patient, discontinuing temporally has been suspected to create a refractory state leading to decrease in its efficacy when it is taken again.
This enumeration of adverse effects of lithium is to be taken into account but does not rule out its use because, when it is prescribed advisedly, its beneficial effects overweigh largely its possible adverse effects.
Because of its adverse effects, the onset of treatment with lithium requires a renal control (urea nitrogen, creatinine, proteinuria,
sodium and potassium determination) a thyroid assessment, especially if there is suspicion of hypothyroidism, a blood count and possibly a pregnancy test.
During the treatment, the measurement of plasma lithium, frequent at the beginning of treatment, and during dosage adjustment, can then be spaced to one control every month or every three months for example. But it is necessary to control lithium level every time there is a suspicion of poisoning and inefficiency of the treatment, or when there is a concomitant prescription of drugs able to modify its elimination, such as NSAIDs.
The alternative mood-stabilisers able to be used in the place of lithium for the treatment of the manic-depressive disorder and the related disorders are carbamazepine, valproic acid and lamotrigine. According to studies carbamazepine and valproic acid have effects almost equivalent to those of lithium which remains the reference product. They could perhaps be combined in the resistant patients: lithium plus carbamazepine or lithium plus valproic acid, with possible reduction of the dosage of each one of them.
Note:
Lithium, in the form of gluconate, is used as a dermatological gel for the treatment of seborrheic dermatitis of the face in adults. Its mechanism of action is poorly understood: it could have an antifungal action on Malassezia furfur. (Other drugs, not related to lithium, used topically for the treatment of seborrheic dermatitis are ketoconazole and ciclopirox olamine).
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