Sideeffects Lithium

Since lithium has been in use for much of the latter half of the twentieth century, its side-effect profile has been well described. Tremor and gastrointestinal distress, particularly diarrhoea, are generally dose-related but some patients can have idiosyncratic sensitivity to these side-effects, even at relatively low doses. Lithium-induced tremor can be countered with the b-blocker propranolol in doses of 10 mg four times a day.

Side-effects most likely to be associated with non-compliance or discontinuation of the drug include a sense of psychomotor slowing, cognitive dulling, acne or psoriasis, and weight gain. There is preliminary evidence that the anticonvulsant topiramate may help to reverse or stabilize the lithium-related weight gain. Isolated case report data suggest that donepezil (AriceptĀ®) might be of some assistance in reversing lithium-induced cognitive impairment, although this clearly requires further systematic study.

Lithium interferes with the actions of ADH (i.e. vasopressin) because of its ability to block vasopressin-induced adenylate cyclase. A syndrome of reversible diabetes insipidus is thus induced which, in most patients, is not problematic, although in a small percentage of patients excretion of large volumes of urine can be extreme, inconvenient, and disruptive of normal social routines and sleep. This can be countered with ameloride or the thiazide diuretics (however, the latter also increase lithium levels!).

Lithium is clearly able to induce thyroid dysfunction with increases in thyroid-stimulating hormone, sometimes proceeding to more full-blown evidence of chemical hypothyroidism. The threshold for treating lithium-related increases in thyroid-stimulating hormone has not been definitively identified, but with some evidence of lower levels of free thyroxine being associated with increased levels of depression and other low thyroid indices being associated with increased cognitive dysfunction, replacement of thyroid hormone would appear indicated as thyroid-stimulating hormone begins to exceed normal levels. Whether thyroid supplementation can reverse or prevent these lithium-related abnormalities remains to be directly assessed in prospective studies.

Some investigators suggest that long-term lithium may be associated with slowly increasing creatinine levels and a decrease in creatinine clearance. (40) The incidence of these glomerular filtration abnormalities in lithium-treated patients compared with age- and gender-matched controls remains controversial, as does the mode of treatment in the face of progressive changes in these indices. Given the availability of other potential mood-stabilizing agents, a reduction in lithium levels and supplementation or switching to other agents would appear to be a conservative measure.

Severe episodes of lithium intoxication are to be avoided since they can be associated with a syndrome of irreversible cerebellar dysfunction. (4 ,42) The use of lithium with very high dose neuroleptic treatment is also to be avoided, since occasional idiosyncratic and irreversible organic brain syndromes have resulted on rare occasions/43,44 Marked EEG changes and tonic-clonic seizures were also observed with the combination of lithium and clozapine. (4 46) On the basis of its inhibition of adenylate cyclase, lithium can be associated with alterations in calcium homeostasis at the level of alterations in parathyroid hormone. (4Z> As mentioned above, lithium can increase white cells and platelets via its action on granulocyte-macrophage colony stimulating factor. (25

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