Lithium trial , adverse effects

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. 

During 2004 a number of clinical trials were reported involving acute and maintenance studies of lithium, mostly either comparing new atypical antipsychotic drugs with lithium in bipolar disorder or in combined treatment studies. Of the relatively few studies of the adverse effects of lithium, most clustered in the areas of cardiovascular effects and issues regarding lithium toxicity. 

Table 1 Adverse effects of lithium and carbamazepine in a double-blind trial (in %)...

Patients with bipolar disorders may benefit from risperidone. This has been observed in an open trial of ten patients with rapid cycling bipolar disorder who were refractory to lithium carbonate, carbamazepine, and valproate eight improved after 6 months of treatment. One patient dropped out through non-adherence to therapy and one because of adverse effects (agitation, anxiety, insomnia, and headache) (5). There was a similar beneficial effect in eight adults with moderate to profound mental retardation (6). Risperidone was associated with a significant reduction in aggression and self-injurious behavior, whereas adverse effects were primarily those of sedation and restlessness. 

In a 6-week open study of risperidone (mean dosage 4.7 mg/day) in combination with mood-stabilizing treatments (usually lithium, carbamazepine, or valproate) for the treatment of schizoaffective disorder in 102 patients, 95 of whom completed the trial, at week 4 most patients had improved symptom severity and 9.3% were completely symptom-free (35). There were no statistically significant differences between baseline and week 4 in the severity of extrapyramidal symptoms, as measured by the UKU Side-Effect Rating Scale subscale for neurological adverse effects other adverse effects included depressive symptoms (n = 13), exacerbation of mania ( n = 5), drowsiness (n = 3), and impotence (n = 2). 

The recommended guidelines for baseline and routine laboratory testing for lithium are listed in Table 68-12. The 12-hour postdose lithium serum concentration may be 12% to 33% higher with extended-release preparations and lower with regular-release tablets with divided dosage schedules. The dose should be adjusted based on the steady-state serum concentration drawn 12 hours ( 30 minutes) after the last dose. A therapeutic trial (lithium serum concentrations of 0.6 to 1.2 mEq/L) should last a minimum of 4 to 6 weeks. Acutely manic patients may require serum concentrations of 1 to 1.2 mEq/L, and some need up to 1.5 mEq/L to achieve a therapeutic response. Although serum concentrations less than 0.6 mEq/L are associated with higher rates of relapse, some patients may do well at 0.4 to 0.7 mEq/L. For bipolar prophylaxis in elderly patients, serum concentrations of 0.4 to 0.6 mEq/L are recommended because of increased sensitivity to adverse effects. ... 

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