Lithium contraindications

Volf N, Crismon ML. Leukemia in bipolar mood disorder is lithium contraindicated DICP 1991 25(9) 948-51. 

Lithium is a drug with a narrow therapeutic index and therefore plasma concentrations are regularly monitored. Lithium is used in the prophylaxis and treatment of mania. Concurrent administration of lithium and diuretics, particularly the thiazides, is contraindicated as lithium excretion is reduced, resulting in increased plasma-lithium concentration and hence toxicity. 

Contraindications Intestinal obstruction, GI tract not anatomically intact patients at risk of hemorrhage or GI perforation, if use would increase risk and severity of aspiration not effective for cyanide, mineral acids, caustic alkalis, organic solvents, iron, ethanol, methanol poisoning, lithium do not use charcoal with sorbitol in patients with fructose intolerance, hypersensitivity to charcoal or any component of the formulation... 

Contraindications to lithium are primarily based on the presence of medical disorders involving electrolyte balance and the cardiovascular and the renal... 

As noted earlier, lithium is contraindicated in patients with unstable congestive heart failure or the sick sinus node syndrome ( 307, 328). In older patients or those with prior cardiac histories, a pretreatment ECG should be obtained. Except for the potential adverse interactions with diuretics, the concomitant use of other cardiac drugs is generally safe. Because verapamil may lower serum levels of lithium, however, more careful monitoring may be required to assure continued therapeutic effects (329). Some data also indicate that verapamil may predispose to lithium neurotoxicity. Conversely, increased lithium levels leading to toxicity has occurred with methyidopa and enalapril. When antihypertensive therapy is necessary, b-blockers are a reasonable choice when lithium is coadministered. 

There is no final consensus on whether normal use of lithium, without any episode of toxicity (the vast majority of patients), may result in permanent renal impairment. Polyuria occurs in 20-40% and is due to inhibition of antidiuretic hormone (ADH) by lithium. It usually resolves on cessation of lithium as do any effects on glomerular function. Interference with thyroid function is due to inhibition of the action of thyroid stimulating hormone (TSH) and is easily managed by administration of thyroxine. Lithium is contraindicated during pregnancy (major vessel anomalies in fetus) and breastfeeding. 

The bradycardia-tachycardia ("sick sinus") syndrome is a definite contraindication to the use of lithium because the ion further depresses the sinus node. T-wave flattening is often observed on the ECG but is of questionable significance. 

Because lithium is not bound to any plasma or tissue proteins, it is widely distributed throughout the body. Lithium ions are eliminated mainly by the kidneys. There is a direct relationship between the amount of sodium chloride ingested and the fraction of filtered lithium resorbed, in that, the lower the sodium intake, the greater is the lithium retention. The contraindications are significant cardiovascular or renal diseases that would compromise its excretion. 

Mania can occur in any age group. Acute manic episodes in the elderly may best be managed with high potency neuroleptics. The use of lithium is not contraindicated in the elderly provided renal clearance is reasonably normal. The dose administered should be carefully monitored, as the half-life of the drug is increased in the elderly to 36-48 hours in comparison to about 24 hours in the young adult. The serum lithium concentration in the elderly should be maintained at about 0.5 mEq/litre. It is essential to ensure that the elderly patient is not on a salt-restricted diet before starting lithium therapy. The side effects and toxicity of lithium have been discussed in detail elsewhere (see p. 198 et seq.), and, apart from an increase in the frequency of confusional states in the elderly patient, the same adverse effects can be expected as in the younger patient. 

Q8 Why was Mr Watson advised not to take non-steroidal anti-inflammatory drugs in combination with lithium Are any other medications contraindicated for patients taking lithium ... 

Cardiovascular disease is not a contraindication to lithium, but the risks may be greater, in view of factors such as fluid and electrolyte imbalance and the use of concomitant medications. Close clinical and laboratory monitoring is necessary, and an alternative mood stabilizer may be preferred. While long-term tricyclic antidepressant therapy may be more cardiotoxic than lithium, the newer antidepressants (SSRIs and others) seem to be safe. 

Breast-milk lithium concentrations were measured in 11 women taking lithium carbonate 600-1,500 mg/day (506). Maternal serum concentrations were available in only three and infant concentrations in two. No infants had adverse effects that could be attributed to lithium, and the authors calculated that infant lithium exposure was low, leading them to challenge the general contraindication to breastfeeding under such circumstances. 

While there are no absolute contraindications to lithium, patients with advanced kidney disease or unstable fluid/ electrolyte balance may be more safely treated with an alternative mood stabilizer, such as carbamazepine, valproate, lamotrigine, or olanzapine. 

The 1996 Canadian Product Monograph for sumatriptan (but not the 1998 US package insert) listed the combination of sumatriptan and lithium as contraindicated. However, in a review, there was little evidence of a severe interaction of sumatriptan with lithium (692). 

Lithium and Diuretics. Sodium depletion is known to increase lithium toxicity, and it is generally recommended that lithium not be used in patients on diuretic therapy or on a sodium-restricted diet. Even protracted sweating or diarrhea can cause sufficient depletion of sodium to result in decreased lithium tolerance. The sodium depletion caused by diuretics reduces the renal clearance and increases the activity of lithium. However, if preferable therapeutic alternatives are not available, concurrent therapy need not be contraindicated as long as the interaction is recognized and appropriate steps are taken to monitor therapy and adjust the dosage. 

Lithium is contraindicated during pregnancy, especially the first trimester, due to congenital abnormalities, most notably of the heart. In rare situations, it may be necessary to continue lithium treatment in the pregnant patient, with dosage adjustments as necessitated by pregnancy-induced changes in kidney function. 

Two anticonvulsants, carbamazepine (Tegretol) and valproic acid, also referred to as valproate (Depakote, Depakene), have proven mood-stabilizing properties (see figure 15-E). These agents are most useful when lithium is contraindicated or when a patient does not respond to or cannot tolerate lithium. Rapid cyclers, who often are poorly controlled with lithium, are good candidates for one of these alternative agents. Valproic acid appears to be indicated more for manic or mixed states of bipolar disorder, and is probably not as effective in depressed states. The anticonvulsants are often employed in conjunction with lithium. 

Also note that the potential for an interaction between drugs does not preclude their concurrent use. Certain combinations are routinely prescribed without problems in many patients (as with lithium and antipsychotics), whereas others are contraindicated due to the severity of the interaction (for example, MAOIs and SSRIs). However, whenever psychiatric medications are coadministered, the additive potential of central nervous system depression and anticholinergic effects must be considered. 

ACE inhibitors are absolutely contraindicated in pregnancy (see Pregnancy section under Special Populations ) and in patients with a history of angioedema. Similar to diuretics, ACE inhibitors can increase lithium serum concentrations in patients on lithium therapy. Concurrent use of an ACE inhibitor with a potassium-sparing diuretic (including aldosterone antagonists), potassium supplements, or an ARB may result in excessive increases in potassium. 

This acts presynaptically, via activation of ATP-sensitive potassium channels, to inhibit neuromuscular transmission and acts at the muscle membrane to inhibit muscle contraction. Prolongation of neuromuscular block has been reported in patients receiving lithium and depolarizing and non-depolarizing neuromuscular blockers. Hence, the combination of litbium and ECT is relatively contraindicated. 

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