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Chapter 29: Psychopharmacological Treatment
Laboratory Interferences
Circulating levels of thyroxine and triiodothyronine are asso-
ciated with a decrease in thyroid-stimulating hormone and
may be associated with treatment. Carbamazepine is also
associated with an increase in total serum cholesterol, pri-
marily by increasing high-density lipoproteins. The thyroid
and cholesterol effects are not clinically significant. Carba-
mazepine may interfere with the dexamethasone (Decadron)
suppression test and may also cause false-positive pregnancy
test results.
Dosing and Administration
The target dose for antimanic activity is 1,200 mg a day,
although this varies considerably. Immediate-release carbam-
azepine needs to be taken three or four times a day, which leads
to lapses in compliance. Extended-release formulations are thus
preferred because they can be taken once or twice a day. One
form of extended-release carbamazepine, Carbatrol, comes as
100-, 200-, and 300-mg capsules. Another form, Equetro, is
identical to Carbatrol and is marketed as a treatment for bipolar
disorder. These capsules contain tiny beads with three different
types of coatings so they dissolve at different times. Capsules
should not be crushed or chewed. The contents can be sprin-
kled over food, however, without affecting the extended-release
qualities. This formulation can be taken either with or without
meals. The entire daily dose can be given at bedtime. The rate
of absorption is faster when it is given with a high-fat meal.
Another extended-release form of carbamazepine, Tegretol XR,
uses a different drug-delivery system than Carbatrol. It is avail-
able in 100-, 200-, and 300-mg tablets.
Preexisting hematologic, hepatic, and cardiac diseases can
be relative contraindications for carbamazepine treatment. Per-
sons with hepatic disease require only one third to one half the
usual dosage; the clinician should be cautious about raising
the dosage in such persons and should do so only slowly and
gradually. The laboratory examination should include a com-
plete blood count with platelet count, liver function tests, serum
electrolytes, and an electrocardiogram in persons older than 40
years of age or with a preexisting cardiac disease. An electro-
encephalogram is not necessary before the initiation of treat-
ment, but it may be helpful in some cases for the documentation
of objective changes correlated with clinical improvement.
Table 29.13-3 presents a brief user’s guide to carbamazepine in
bipolar disorder.
Routine Laboratory Monitoring
Serum levels for antimanic efficacy have not been established.
The anticonvulsant blood concentration range for carbamaze-
pine is 4 to 12
m
g/mL, and this range should be reached before
determining that carbamazepine is not effective in the treatment
of a mood disorder. A clinically insignificant suppression of
the WBC count commonly occurs during carbamazepine treat-
ment. This benign decrease can be reversed by adding lithium,
which enhances colony-stimulating factor. Potential serious
hematologic effects of carbamazepine, such as pancytope-
nia, agranulocytosis, and aplastic anemia, occur in about 1 in
125,000 patients. Complete laboratory blood assessments may
be performed every 2 weeks for the first 2 months of treatment
and quarterly thereafter, but the FDA has revised the package
insert for carbamazepine to suggest that blood monitoring be
performed at the discretion of the physician. Patients should
be informed that fever, sore throat, rash, petechiae, bruising,
or unusual bleeding may indicate a hematologic problem and
should prompt immediate notification of a physician. This
approach is probably more effective than is frequent blood
monitoring during long-term treatment. It has also been sug-
gested that liver and renal function tests be conducted quarterly,
although the benefit of conducting tests this frequently has been
questioned. It seems reasonable, however, to assess hematologic
status, along with liver and renal functions whenever a routine
examination of the person is being conducted. A monitoring
protocol is listed in Table 29.13-4.
Carbamazepine treatment should be discontinued and a con-
sult with a hematologist should be obtained if the following lab-
oratory values are found: total WBC count below 3,000/mm
3
,
erythrocytes below4.0
×
10
6
/mm
3
, neutrophils below1,500/mm
3
,
hematocrit less than 32 percent, hemoglobin less than 11 g/
100 mL, platelet count below 100,000/mm
3
, reticulocyte count
below 0.3 percent, and a serum iron concentration below
150 mg/100 mL.
Table 29.13-3
Carbamazepine in Bipolar Illness:
A Brief User’s Guide
1. Start with low (200 mg) bedtime dose in depression or
euthymia; higher doses (600–800 mg/day in divided doses) in
manic inpatients.
2. All bedtime dosing is reasonable with carbamazepine
extended-release preparation.
3. Titrate slowly to the individual’s response or side effects
threshold.
4. Hepatic enzyme CYP450 (3A4) induction and autoinduction
occur in 2 to 3 weeks; slightly higher doses may be needed or
tolerated at that time.
5. Warn regarding benign rash, which occurs in 5%–10% of
those taking the drug; progression to rare, severe rash is
unpredictable, so the drug should be discontinued if any rash
develops.
6. Benign white blood cell count decreases occur regularly
(usually inconsequential).
7. Rarely, agranulocytosis and aplastic anemia may develop
(several per million new exposures); warn regarding
appearance of fever, sore throat, petechiae, and bleeding
gums and to check with physician to obtain an immediate
complete blood cell count.
8. Use adequate birth control methods, including higher dosage
forms of estrogen (as carbamazepine lowers estrogen levels).
9. Avoid carbamazepine in pregnancy (spina bifida occurs in
0.5%; other severe adverse outcomes occur in about 8%).
10. Some people will respond well to carbamazepine and not
other mood stabilizers (lithium) or anticonvulsants (valproic
acid).
11. Combination treatment often required to maintain remission
and prevent loss of effect via tolerance.
12. Major drug interactions associated with increases in
carbamazepine and potential toxicity from 3A4 enzyme
inhibition include calcium channel blockers (isradipine and
verapamil); erythromycin and related macrolide antibiotics;
and valproate.
