Carbamazepine

Carbamazepine is an anticonvulsant drug structurally related to the TCAs. Like TCAs, its absorption and metabolism is variable. It is rapidly absorbed, with peak plasma levels occurring within 4 to 6 hr. Eighty percent of plasma carbamazepine is protein bound and the half-life ranges from 13 to 17 hr. Carbamazepine is metabolized by the hepatic P450IID6 system. It induces the P450 enzymes, causing an increase in the rate of its own metabolism over time as well as that of other drugs metabolized by the P450 system. This often results in having to raise the dose within 2 to 4 months of treatment initiation.

Concomitant administration of carbamazepine with oral contraceptives, warfarin, theophylline, doxycycline, haloperidol, TCAs, or valproic acid leads to decreased plasma levels of these other drugs. Concomitant administration of drugs that inhibit the P450 system will increase plasma levels of carbamazepine. This includes fluoxetine, cimetidine, erythromycin, isoniazid, calcium channel blockers, and propoxyphene. Concomitant administration of phenobarbitol, phenytoin, and primidone causes a decrease in carbamazepine levels through induction of the P450 enzymes.

Since 1978 more than 19 studies (almost all small case series or open trials) have been published evaluating the effectiveness of carbamazepine in the treatment of mania. The majority of these trials have shown carbamazepine to be equal in efficacy to lithium and neuroleptics and more effective than placebo. However, the number of patients in each study has been small, the diagnoses heterogeneous or unspecified, concomitant medications have been used, and study designs have been unclear. Usual therapeutic doses of carbamazepine range from 400 to 1200 mg/day and therapeutic plasma levels range from 4 to 12 ^g/mL.

Carbamazepine frequently causes lethargy, sedation, nausea, tremor, ataxia, and visual disturbances during the acute treatment phase (Zajecka, 1993). Some patients can develop mild leukopenia or thrombocytopenia during this phase and usually do not progress. Carbamazepine has been reported to cause a severe form of aplastic anemia or agranulocytosis that is estimated to occur with an incidence of about 2 to 5/100,000. This is 11 times more likely than in the general population. While more than 80 percent of these reactions occur during the first 3 months of therapy, some cases have been reported as late as 5 years following initiation of therapy treatment. If white blood cell count drops below 3000 cells/mm3, the medication should be discontinued.

Carbamazepine has also been associated with fetal anomalies including a risk of spina bifida (1 percent), low birth weight, or small head circumference. It has also been shown to have effects on cardiac conduction, slowing AV conduction. Other reported side effects include inappropriate secretion of antidiuretic hormone (SIADH) with concomitant hyponatremia, decreased thyroid hormone levels without change in thyroid-stimulating hormone, severe dermatologic reactions such as the StevensJohnson syndrome, and hepatitis.

Carbamazepine is associated with more side effects and potential toxicity than most other mood stabilizers. Because of the cardiac, hematological, endocrine, and renal side effects associated with carbamazepine, patients should have had a recent physical examination, complete blood count (CBC) with platelet count, liver function, thyroid function, and renal indices prior to initiation of treatment. The CBC and liver function should be monitored every 4 to 8 weeks during the initial 3 to 4 months of treatment, and all baseline tests should be repeated at a minimum of yearly intervals thereafter. Any change in the above tests should warrant closer evaluation and follow-up. Carbamazepine shares with the TCAs the risk of hypertensive crisis when coadministered with MAOIs, and so this combination should not be routinely used. If it has a role, it is more likely as an adjunct in rapid cyclers and dysphoric mania and mixed states.

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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