84 Chlordiazepoxide
reduces chlordiazepoxide actions, andmorphineandmeperidineeach make
oral dosage of chlordiazepoxide less effective. The drug is suspected of af-
fecting blood clotting and is known to constrain the healing abilities of the
anticoagulant medicine warfarin.
Cancer.Chlordiazepoxide has produced DNA damage in experiments de-
signed to reveal potential for such defects. Under certain laboratory conditions
the drug can promote DNA damage in rats, which theoretically might en-
courage development of cancer, but that outcome has not been observed in
practice.
Pregnancy.“Nitrosatable” drugs, of which chlordiazepoxide is one, cause
birth defects in animal experiments. Some studies suggest that using chlor-
diazepoxide during pregnancy may cause human birth defects, but confir-
mation is elusive. For example, a study of 50,000 pregnancies published in
1975, including many women who used chlordiazepoxide, found no difference
in outcome regardless of whether women used the drug. In contrast, a study
of almost 20,000 pregnancies (published in 1974) compared women who took
chlordiazepoxide to those who took assorted other antianxiety drugs or none
at all in early pregnancy. In the chlordiazepoxide group birth defects were
more than two times as frequent compared to the “other drugs” group and
over four times as frequent compared to the “no drug” group. Some research-
ers believe chlordiazepoxide may cause infant skull deformities if a pregnant
woman uses the drug.
Combination products.Limbitrol is a combination product using chlordi-
azepoxide to reduce anxiety and amitriptyline as a tricyclic antidepressant.
Taking a tricyclic antidepressant along with an MAOI can be fatal. Tricyclics
are not recommended for persons with glaucoma or urinary difficulties. An
experiment with hamsters showed that the drug combination is more likely
to produce birth defects than either drug alone. Amitriptyline is Pregnancy
Category C and passes into a nursing mother’s milk supply.
Additional scientific information may be found in:Giri, A.K. and S. Banerjee. “Genetic Toxicology of Four Commonly Used Benzodiaze-
pines: A Review.”Mutation Research340 (1996): 93–108.
Harmatz, J.S., et al. “Differential Effects of Chlordiazepoxide and Oxazepam on Hos-
tility in a Small Group Setting.”American Journal of Psychiatry132 (1975):
861–63.
Palva, E.S., and M. Linnoila. “Effect of Active Metabolites of Chlordiazepoxide and
Diazepam, Alone or in Combination with Alcohol, on Psychomotor Skills Re-
lated to Driving.”European Journal of Clinical Pharmacology13 (1978): 345–50.
Salzman, C., et al. “Chlordiazepoxide-Induced Hostility in a Small Group Setting.”
Archives of General Psychiatry31 (1974): 401–5.
Sternbach, L.H. “The Discovery of Librium.”Agents and Actions43, nos. 3–4 (1994): 82–
85.