Lithium therapeutic drug monitoring

Another use of the laboratory is for therapeutic drug monitoring (TDM) of psychotropics with defined optimal ranges, narrow therapeutic indices, or both. Although TDM is not essential for many psychotropics, it is for others, including lithium, several TCAs, valproate, and carbamazepine. It may also be helpful to optimize the use of certain antipsychotics (e.g., haloperidol, clozapine) ( 7). 

Saliva is not an important route of excretion since most of the chemicals present in saliva will eventually reach the gastrointestinal tract to be reabsorbed or eliminated in the feces. The unbound fraction of several therapeutic drugs may diffuse passively from plasma into saliva. This provides a noninvasive means of indirectly monitoring plasma concentrations of drugs like lithium, phenytoin, and theophylline. Metals like lead, cadmium, and mercury are also present in saliva. 

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. 

Lithium is used in the prophylaxis and treatment of mania and in the prophylaxis of bipolar disorders and recurrent depression. Lithium should be stopped 24 hours before major surgery but the normal dose can be continued for minor surgery, with careful monitoring of fluids and electrolytes. After major surgery, renal function is reduced and this may compromise clearance of lithium. Lithium is a drug with a narrow therapeutic index and it should be avoided if possible in patients with renal impairment. Renal function should be tested before initiating treatment. If lithium is given to patients with renal impairment, a reduced dose should be used and serum lithium concentrations should be monitored closely. 

The clinical value of monitoring drug therapy by measuring plasma levels is probably best exemplified by reference to lithium (F6). It is a useful drug, which has a narrow therapeutic index, and treatment without reference to plasma levels is probably not ethically justified. Toxic side effects are predictable and severe. It has an acceptably long plasma half-life, and its measurement both in blood and urine is comparatively simple. Moreover, there is no problem of interference from either active or inactive metabolites. 

Indications and Dosages Alert During acute phase, a therapeutic serum lithium concentration of 1-1.4 mEq/L is required. For long-term control, the desired level is 0.5-1.3 mEq/L. Monitor serum drug concentration and clinical response to determine proper dosage. 

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. 

During pregnancy, serum lithium levels need to be carefully monitored. The 50% to 100% increase in glomerular filtration rate (GFR) that normally occurs in the third trimester will proportionally lower lithium levels due to its increased clearance. Thus, dosage may need to be increased to maintain a therapeutic range ( 341). Because the GFR and lithium clearance quickly return to normal after delivery, it may be wise to stop the drug shortly before delivery and restart a few days after delivery at a lower dose. In summary ... 

The Depakote form of valproic acid is approved for the acute phase of bipolar disorder. It is also commonly used on a long-term basis, although its prophylactic effects have not been as well established. Valproic acid is now frequently used as a first-line treatment for bipolar disorders, as well as in combination with lithium for patients refractory to lithium monotherapy and especially for patients with rapid cycling and mixed episodes. Oral loading can lead to rapid stabilization, and plasma levels must be monitored to keep drug levels within the therapeutic range. 

Q5 Lithium (lithium carbonate or citrate) is administered in doses of between 0.2 and 1.5 g daily. The dose is monitored to provide a therapeutic plasma level of 0. 4-1.0 mmol l-1 12 hours after the most recent dose taken on days 4-7 of treatment. The plasma concentration is then measured every week until the dosage has been stabilized and the required concentration has remained constant for four weeks. Lithium can take several days to become effective. If a patient is suffering an acute attack of mania and is excessively disturbed, treatment with an antipsychotic drug may also be required. The antipsychotic... 

Close therapeutic monitoring of plasma drug levels is required during lithium treatment lithium is the first psychiatric drug that required blood level monitoring... 

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