Lithium 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). 

Gram LF, Hansen MG], Sindrup SH et al. Citalopram interaction studies with levomepromazine, imipramine and lithium. Therap Drug Monitor 1993 15 18-24. 

LITHIUM The dosage of lithium is individualized according to serum levels and clinical response to the drug. The desirable serum lithium levels are 0.6 to 1.2 mEq/L Blood samples are drawn immediately before die next dose of lithium (8-12 hours after the last dose) when lithium levels are relatively stable During die acute phase die nurse monitors serum lithium levels twice weekly or until die patient s manic phase is under control. During maintenance therapy, the serum lidiium levels are monitored every 2 to 4 months. 

Lithium and other mood-stabilizing drugs require baseline and routine laboratory monitoring to help determine medical appropriateness for initiation of therapy and monitoring of potential adverse effects. Guidelines for such monitoring are outlined in Table 36-6. 

The development of lithium-specific electrodes has assisted greatly in monitoring patient compliance. The toxicity profile of lithium carbonate is now well established and the drug is safely administered and well tolerated. It is of limited use in other psychiatric disorders such as pathological aggression, although additional benefit may also include a reduction in actual or attempted suicide. 

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. 

Oxcarbazepine is a keto derivative of carbamazepine but offers several advantages over carbamazepine. Oxcarbazepine does not require blood cell count, hepatic, or serum drug level monitoring. It causes less cytochrome P450 enzyme induction than does carbamazepine (but may decrease effectiveness of oral contraceptives containing ethinyl estradiol and levonorgestrel). As opposed to carbamazepine, oxcarbazepine does not induce its own metabolism. These properties, combined with its similarity to carbamazepine, led many clinicians to use this medication for the treatment of bipolar disorder. Randomized controlled trials suggested efficacy in the treatment of acute mania compared with lithium and haloperidol, but these trials were quite small and did not include a placebo control (Emrich 1990). 

The pharmacokinetics of a drug can also determine the frequency of monitoring. Many believe that TDM requires frequent blood drawings, primarily based on the experience with lithium. However, this drug is relatively unique in that its levels are determined by multiple independent factors. Thus, the plasma level of lithium is not solely a function of the dose and of renal status, but also of fluid and salt intake and output, which can vary independent of dose. 

The use of drug plasma levels to effect optimal clinical response and to minimize adverse or toxic effects is standard practice in general medicine (e.g., phenytoin, digoxin), as well as in psychiatry (e.g., lithium, tricyclic antidepressants, valproate see Chapter 3). The theoretical basis for plasma level monitoring rests on several factors, including ... 

Finally, Stroberetal. (183) conducted an 18-month, prospective, naturalistic follow-up study of 37 bipolar-l adolescents (i.e., 13 to 17 years old) stabilized on lithium and found a relapse rate almost three times higher in those who discontinued prophylactic lithium (92%), as compared with those who complied (38%). Further, they noted that earlier relapse in these patients predicted a greater risk of subsequent relapse and that an early onset may be associated with a more virulent course, resistance to lithium, and the need to consider alternative mood stabilizers. Methodological problems with this study included a small sample size lack of assessment for personality disturbances and intrafamilial environment only a 4-week initial drug stabilization period and lack of precision in monitoring compliance to treatment. 

Doses of verapamil reported to have antimanic effects have ranged from 80 mg b.i.d. to 160 mg t.i.d. Typically, the initial dose is 80 mg two or three times daily, with rapid escalation up to, but not exceeding, 480 mg/day. (Personal communication with Dubovsky and Giannini indicates some patients may require and safely tolerate doses up to 640 mg/day.) The drug is usually well tolerated, and no specific laboratory monitoring is required. Further, its lack of teratogenic potential makes this (and perhaps other CCAs) attractive alternatives to agents such as lithium, VPA, and CBZ. 

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. 

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