Lithium treatment monitoring

If any ACE inhibitor is added to established lithium treatment, monitor well for symptoms of lithium toxicity (see Lithium , (p. 1111)) and consider measuring lithium levels more frequently. Be alert for the need to reduce the lithium dosage (possibly by between one-third to one-half) The development of the interaction may be delayed, so monitoring lithium levels every week or every two weeks" for several weeks has been advised. 

Thyroid Hormone (Thyroxine, Synthroid). The most common use of thyroxine in bipolar patients is the treatment of lithium-induced hypothyroidism. Approximately 5% of patients receiving long-term lithium treatment ultimately develop hypothyroidism. When this occurs, the patient with bipolar disorder may present with symptoms of a depressive episode. Therefore, periodic thyroid axis monitoring, that is, a serum thyroid stimulating hormone (TSH) test, is required for all patients taking lithium and should always be performed when the bipolar patient experiences a depressive episode. 

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

Renal function should be closely monitored when patients on lithium treatment are given ACE-I. Doses of both drugs should be chosen with caution to avoid serious drug interaction [27]. 

The polyuria which often accompanies lithium treatment is normally compensated for by drinking water, but when consciousness is impaired severe hypernatremia may develop. When any acute illness (particularly if associated with gastrointestinal symptoms) occurs or when new medication is given, lithium blood levels should be closely monitored, and the lithium dose adjusted. 

Laboratory monitoring is necessary throughout lithium treatment to determine a safe and therapeutic dose and to limit side effects. The especially critical times to obtain a lithium level are during initiation, with dosage changes, with breakthrough... 

The advantages for the psychiatrist are that time is saved because only one interview is required. Doubtful or disputed results can be repeated immediately and patients who have defaulted on treatment can face this with confidence. Changes in medication may be more rapidly monitored and, in the initial stages of lithium treatment, the time taken to attain optimum plasma lithium can be reduced because the new dose can be instigated as soon as possible. The response from our collaborating clinicians has been very positive and we are developing the procedure for wider acceptance [86,87]. This analytical advance may prove to be one of the most important improvements to be made in the clinical use of lithium in the immediate future [60]. 

Treatment of Manic—Depressive Illness. Siace the 1960s, lithium carbonate [10377-37-4] and other lithium salts have represented the standard treatment of mild-to-moderate manic-depressive disorders (175). It is effective ia about 60—80% of all acute manic episodes within one to three weeks of adrninistration. Lithium ions can reduce the frequency of manic or depressive episodes ia bipolar patients providing a mood-stabilising effect. Patients ate maintained on low, stabilising doses of lithium salts indefinitely as a prophylaxis. However, the therapeutic iadex is low, thus requiring monitoring of semm concentration. Adverse effects iaclude tremor, diarrhea, problems with eyes (adaptation to darkness), hypothyroidism, and cardiac problems (bradycardia—tachycardia syndrome). 

MRI lithium measurements are playing an important role in the development and understanding of the role of lithium in treating and preventing ASR. The spatial resolution and speed make this measurement technique very attractive for monitoring the removal of lithium from the pore solution during ASR and also in investigating how well various surface treatments will slow ASR. 

Lithium is commonly used for bipolar affective disorders. Lithium however has a narrow therapeutic index and high risk for toxicity (Groleau 1994). The use of loop diuretics or ACE-inhibitors significantly increases the risk of hospitalisation for lithium toxicity in the elderly (Juurlink et al. 2004). Treatment of elderly patients with lithium should be thoroughly monitored. 

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. 

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). 

It has narrow therapeutic index and treatment requires facility for therapeutic monitoring of serum lithium levels. 

After resolution of the acute phase, maintenance levels of at least 0.8 mEq/L are necessary for optimal efficacy and should be checked once every 6 to 12 months, or more often if clinically indicated. Other follow-up tests include periodic thyroid function tests, blood urea nitrogen, serum creatinine, serum calcium (because lithium may cause hypoparathyroidism), and an EGG. Thyroid function tests and renal function should be monitored approximately every 6 to 12 months (see the section Maintenance/Prophylaxis Treatment in Chapter 10). 

In partially responsive or nonresponsive patients, the first issue is to determine whether an individual is truly treatment-resistant, because many receive nontherapeutic doses and the potential for improvement may not be adequately tested. Thus, in some situations, more aggressive treatment (dose increase, augmentation) may be appropriate, if not precluded by adverse effects. In selected cases, it may also be helpful to monitor plasma levels to ensure that they are in a reasonable range (see Pharmacokinetics/Plasma Levels earlier in this chapter). If a patient continues to demonstrate significant symptoms after a sufficient trial (2 to 3 weeks), alternatives to switching to another antipsychotic may include the addition of lithium, an anticonvulsant, or a second antipsychotic agent. An antidepressant or anxiolytic may also be helpful, especially if affective or anxiety symptoms are prominent. 

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. 

Because no antidote is available, treatment is supportive. A patient s condition should be monitored closely, including fluid intake and output, mental status, and serum levels of lithium, creatinine, and electrolytes. Patients with normal renal function should be able to clear lithium unassisted. If necessary, attempts should be made to remove excess lithium from the body by gastric lavage and emesis. 

The appearance of laboratory abnormalities does not require cessation of treatment however, if enzyme levels do not stabilize or return to normal, VPA should be discontinued and an alternate mood-stabilizing agent such as lithium used in its place. Liver function tests should be monitored more often during the first several weeks of therapy and every 6 to 12 months afterward. Routine liver function testing probably does not significantly prevent the occurrence of these unpredictable drug effects. Therefore, patients should be cautioned to immediately report symptoms of possible early hepatotoxicity such as easy bruising, decreased appetite, malaise, jaundice, and periorbital or dependent edema. In summary ... 

The first use of lithium for therapeutic purposes began in the mid-19th century to treat gout. Lithium had a relatively brief period of use as a substitute for sodium chloride in hypertensive patients in the 1940s, but it proved too toxic when available without monitoring and was banned. In 1949, Cade discovered that lithium was an effective treatment for bipolar disorder, engendering a series of controlled trials which confirmed its efficacy as monotherapy for the manic phase of bipolar disorder. 

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