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CARBAMAZEPINE
Carbamazepine (CBZ) is efficacious in acute mania, mixed state and secondary
bipolar disorder (Post, 1990). Although there is some evidence of its
prophylactic efficacy the data is not as impressive as with Lithium. It
is now suggested that it is not very effective in rapid cycling (Okuma,
1993). It has weak anti-depressant properties. It is commonly used when
there has been failure to respond to Lithium.
The therapeutic serum level for CBZ has not been established although
it is common practice to stay within the range of 4-15 mi.gm/ml. Onset
of action is between 7-14 days. Non-adherence to treatment occurs in 20-35%
of cases and is often associated with the side effects of the medication.
Side effects and drug interactions may persist even after discontinuation
of CBZ as its metabolite remains active long after the parent compound
becomes undetectable. (Denicoff et al, 1994). Neural tube defects have
been reported with CBZ use in the first trimester, and it probably has
a teratogenic risk higher than Lithium (Rosa, 1991).
References
Denicoff KD, Smith-Jackson E, Disney E et al. 1994. Outcome in Bipolar
Patients Randomized to Lithium or Carbamazepine Prophylaxis and crossed
over in year two. Abst. First Int Conf on Bipolar Disorder. Pittsburg,
PA.
Okuma T. 1993. Effects of Carbamazepine and Lithium on Affective Disorders.
Neuropsychobiology. 27. 138-145.
Post RM. 1990. Alternatives to Lithium for Bipolar Affective Illness.
In: Review of Psychiatry. Tasmana. Ed. American Psychiatric Press. 170-202.
Rosa FW. 1991. Spina Bifida in Infants of Women Treated with Carbamazepine
during Pregnancy. N Engl J Med. 324. 674-677.
Predictors of Response
to Carbamazepine
Acute mania, mixed states and secondary bipolar disorder are associated
with good response to Carbamazepine.
References
Okuma T. 1993. Effects of Carbamazepine and Lithium on Affective Disorders.
Neuropsychobiology. 27. 138-145.
Post RM. 1990. Alternatives to Lithium for Bipolar Affective Illness.
In: Review of Psychiatry. Tasmana. Ed. American Psychiatric Press. 170-202.
Predictors of Non-Response
to Carbamazepine
Carbamazepine is likely relatively ineffective in rapid cycling contrary
to previous opinion and has little efficacy in acute bipolar depression
and in recurrent or relapsing bipolar disorder with predominantly depressive
episodes (Okuma, 1993; Post, 1990).
References
Okuma T. 1993. Effects of Carbamazepine and Lithium on Affective Disorders.
Neuropsychobiology. 27. 138-145.
Post RM. 1990. Alternatives to Lithium for Bipolar Affective Illness.
In: Review of Psychiatry. Tasmana. Ed. American Psychiatric Press. 170-202.
Carbamazepine:
Adverse Effects and Interactions
Sedation, cognitive impairment, neurotoxicity, minor hemotopoetic suppression,
gastro-intestinal distress, dizziness, rash heralding significant dermatological
complications, elevations in liver enzymes, failure of concomitant oral
contraceptives, weight gain, and neural tube defects in the developing
fetus are all associated with Carbamazepine. (McElroy et al 1995; Denicoff
et al, 1994; Rosa, 1991)
Carbamazepine (CBZ) induces its own metabolism, has profound effects on
the liver including induction of the cytochrome enzyme system thus potentiating
many drug interactions. There is an increased hematological risk with
medications like Clozapine. Divalproex, cimetidine, erythromycin, isoniazid,
SSRIs and calcium channel blockers may increase CBZ serum levels. CBZ
may lower serum levels of TCAs, theophylline and warfarin, and increase
the metabolism of contraceptive hormones.
References
Denicoff KD, Smith-Jackson E, Disney E et al. 1994. Outcome in Bipolar
Patients Randomized to Lithium or Carbamazepine Prophylaxis and crossed
over in year two. Abst. First Int Conf on Bipolar Disorder. Pittsburg,
PA.
McElroy SL and Keck PE. 1995. Antiepileptic Drugs. Ch. 17, P6 351-375.
In Textbook of Psychopharmacology. Ed. Schatzberg and Nemeroff. APA Press.
Rosa FW. 1991. Spina Bifida in Infants of Women Treated with Carbamazepine
during Pregnancy. N Engl J Med. 324. 674-677.
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