118 HANDBOOK OF PSYCHIATRIC DRUGS

118 HANDBOOK OF PSYCHIATRIC DRUGS

Recently oxcarbazepine, the 10-keto analog of carba- mazepine, has become available as an alternative to carba- mazepine for the treatment of seizure disorders. Oxcarbazepine has less protein binding at 40%, and therefore less possibility for drug–drug interactions with highly protein bound drugs.

The only contraindication to lamotrigine use is hypersensi- tivity to the drug, though there is a box warning about derma- tologic events, particularly rashes.

• These rashes generally occur in approximately 10% of patients after two to eight weeks and are usually macular, papular, or erythematous in nature.

• Of those who develop a rash, one in 1,000 adults can proceed to a Stephens–Johnson type syndrome. • Because it is impossible to distinguish which rashes will develop into this serious condition, it is advisable to discon- tinue treatment at any sign of drug-induced rash.

Otherwise the most frequently encountered side effects include dizziness, ataxia, somnolence, headache, blurred vision, nausea, vomiting, and diplopia. To reduce the risk of rash and other side effects lamotrigine must be started at a low dose and titrated slowly, especially if combined with valproate therapy.

ANTIPSYCHOTICS Although clozapine is free from most of the extrapyramidal side effects (EPS) associated with typical antipsychotics and may not cause tardive movement disorders, it does carry the risk of serious adverse reactions, including agranulocytosis, seizures, and cardiorespiratory complications. It should be used for bipolar patients only after other options have failed. Many experienced clinicians believe clozapine is superior to tradi- tional antipsychotics in the treatment of bipolar disorder, but definitive, controlled data are lacking.

Olanzapine has structural and pharmacologic similarities to clozapine but is generally less toxic. It shares with clozapine a low incidence of EPS and of hyperprolactinemia, as compared to typical agents.

• Adverse effects during the short-term use of olanza- pine include constipation, weight gain, akathisia, dry

mouth, tremor, increased appetite, orthostatic hypotension,

119 • The most common side effect is somnolence, which is why

MOOD STABILIZERS

olanzapine is usually given in one q.h.s. dose. • In clinical trials, there was a 0.9% incidence of seizures, and although there were confounding factors, olanzapine should

be used cautiously in patients with known seizure disorders or lowered seizure thresholds. • Because of alanine aminotransferase elevations in some patients, it is also advised to use olanzapine cautiously in patients with known or suspected hepatic impairment.

As mentioned earlier, maintenance therapy with atypical antipsychotics requires that careful attention must be paid to patient weight and blood lipid and glucose levels. This is partic- ularly true for clozapine and olanzapine but may also be true to a lesser degree for the other atypical agents.

• Weight gain on olanzapine may be as great as 5–7 kg though this plateaus in under a year. More modest weight gain occurs less frequently with quetiapine and risperi- done. Severe weight gain occurs in a minority of patients and, unfortunately, there are currently no means to predict whether a specific patient will experience significant weight gain. However, weight gain with atypical antipsychotics may be more clearly associated with a dramatic incrase in appetite, in food consumption, and in carbohydrate craving. It may be possible to evaluate patients for these features and be prepared to see alternative treatments if they occur.

• Atypical antipsychotics are also associated with hyperlipi- demia and with development of abnormalities in glycemic

control (ranging from relative insulin resistence to dramatic and life-threatening new onset diabetes). Recommendations for monitoring metabolic parameters were discussed earlier.

• Some pharmacologic interventions which may reduce antipsychotic induced weight gain include addition of topi- ramate or of histamine-2 receptor blockers.