116 HANDBOOK OF PSYCHIATRIC DRUGS
116 HANDBOOK OF PSYCHIATRIC DRUGS
turn may lead to osteopenia, osteoporosis, bone resorption, and hypermagnesemia.
• Weight gain is another common adverse effect troublesome in long-term lithium treatment. Its mechanism is unknown. Patients should avoid caloric beverages, restrict food calories, and increase physical activity. Unlike the weight gain asso- ciated with medications such as olanzapine, lithium induced weight gain is dose-related. Therefore, reduction of the dose should be considered if the clinical situation allows it.
• Other occasional side effects of lithium are edema and a metallic taste in the mouth.
ANTICONVULSANTS Adverse effects that appear early in the course of valproate therapy are usually mild and transient, and tend to resolve in time. Gastrointestinal upset is probably the most common complaint in patients taking valproate and tends to be less of
a problem with the enteric-coated divalproex sodium prepa- ration. The administration of a histamine H2 antagonist such as famotidine (Pepcid) may alleviate persistent gastroin- testinal problems (the metabolism of valproate is inhibited by cimetidine).
• Other common complaints include tremor, sedation, increased appetite and weight, and alopecia. • Weight gain is even more of a problem when other drugs are administered that also promote weight gain, such as lithium, antipsychotics, and other anticonvulsants.
• Less common are ataxia, rashes, and hematological dysfunc-
tion, such as thrombocytopenia and platelet dysfunction. • Platelet count usually recovers with a dosage decrease, but the occurrence of thrombocytopenia or leukopenia may necessitate the discontinuation of valproate.
Serum hepatic transaminase elevations are common, dose related, and usually self-limiting and benign. Fatal hepatotox- icity is extremely rare, is usually restricted to young children, and usually develops within the first six months of valproate therapy. Hepatic function should be monitored periodically during treatment as previously described.
117 Other serious problems include pancreatitis and teratoge-
MOOD STABILIZERS
nesis. There is also a concern that polycystic ovary syndrome, possibly associated with weight gain, may be a risk for young women who take valproate. If at any point during adminis- tration the side effects of valproate become intolerable, the psychiatrist may need to discontinue it and try one of the other treatments described in this section as an alternative. If valproate is tolerated but not totally effective, the psychiatrist might use one of the other treatments as an adjunct.
Adverse reactions to carbamazepine (Table 3-12) are more likely if the dose of carbamazepine is built up rapidly:
• The most common effects in the first couple of weeks are drowsiness, dizziness, ataxia, diplopia, nausea, blurred vision, and fatigue.
• These tend to diminish in time or to respond to a temporary reduction in dose. • Less common reactions include gastrointestinal upset, hyponatremia, and a variety of skin reactions, some of which are severe enough to require discontinuation of carba- mazepine.
• Carbamazepine can be teratogenic and should be avoided during pregnancy. • About 10% of patients experience transient leukopenia, but unless infection develops, carbamazepine may be continued. • More serious hematopoietic reactions, including aplastic anemia and agranulocytosis, are rare.
Frequent blood monitoring, previously recommended, is generally considered unnecessary after the first few months of therapy. Instead, patients and their families should be instructed to contact the psychiatrist immediately if petechiae, pallor, weakness, fever, or infection occurs.
Carbamazepine has an antidiuretic hormone-like effect, which may help counteract the opposite effect (which produces polyuria) of lithium when the two drugs are used together. By itself, carbamazepine can cause hyponatremia. Gradual buildup of carbamazepine levels and smaller, more frequent dosing can help to minimize side effects, particularly in patients concomitantly taking other drugs, such as lithium.