942
Chapter 29: Psychopharmacological Treatment
Precautions and Adverse Reactions
The most common adverse reactions reported with phenytoin
therapy are usually dose related and include nystagmus, ataxia,
slurred speech, decreased coordination, and mental confusion.
Other side effects include dizziness, insomnia, transient ner-
vousness, motor twitching, and headaches. There have been
rare reports of phenytoin-induced dyskinesias, similar to those
induced by phenothiazine and other neuroleptic drugs. More
serious side effects include thrombocytopenia, leukopenia,
agranulocytosis, and pancytopenia, with or without bone mar-
row suppression.
A number of reports have suggested the development of
lymphadenopathy (local or generalized), including benign
lymph node hyperplasia, pseudolymphoma, lymphoma, and
Hodgkin’s disease. Prenatal exposure to phenytoin may increase
the risks for congenital malformations, and a potentially life-
threatening bleeding disorder related to decreased levels of
vitamin K–dependent clotting factors may occur in new-
borns exposed to phenytoin in utero. Hyperglycemia has been
reported with phenytoin use; in addition, the agent may increase
the serum glucose level in patients with diabetes.
Drug Interactions
Acute alcohol intake, amiodarone, chlordiazepoxide, cimetidine,
diazepam, disulfiram, estrogens, fluoxetine, H
2
-antagonists, iso-
niazid, methylphenidate, phenothiazines, salicylates, and tra-
zodone may increase phenytoin serum levels. Drugs that may
lower phenytoin levels include carbamazepine, chronic alcohol
abuse, and reserpine.
Laboratory Interferences
Phenytoin may decrease serum concentrations of thyroxine. It
may cause increased serum levels of glucose, alkaline phospha-
tase, and
g
-glutamyl transpeptidase.
Dosage and Clinical Guidelines
Patients may be started on one 100 mg extended oral capsule
three times daily, and the dosage then adjusted to suit individ-
ual requirements. Patients may then be switched to once-a-day
dosing, which is more convenient. In this case, extended-
release capsules may be used. Serial monitoring of phenytoin
levels is recommended, and the normal range is usually 10 to
20
m
g/mL.
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▲▲
29.7 Antihistamines
Antihistamines are frequently used in the treatment of a vari-
ety of psychiatric disorders because of their sedative and anti-
cholinergic activities. Certain antihistamines (antagonists of
histamine H
1
receptors) are used to treat neuroleptic-induced
parkinsonism and neuroleptic-induced acute dystonia and as
hypnotics and anxiolytics. Diphenhydramine (Benadryl) is
used to treat neuroleptic-induced parkinsonism and neuro-
leptic-induced acute dystonia and sometimes as a hypnotic.
Hydroxyzine hydrochloride (Atarax) and hydroxyzine pamoate
(Vistaril) are used as anxiolytics. Promethazine (Phenergan)
is used for its sedative and anxiolytic effects. Cyproheptadine
(Periactin) has been used for the treatment of anorexia nervosa
and inhibited male and female orgasms caused by serotonergic
agents. The antihistamines most commonly used in psychia-
try are listed in Table 29.7-1. Second-generation, “nonsedat-
ing” H
1
blockers, such as fexofenadine (Allegra), loratadine
(Claritin), and cetirizine (Zyrtec) are less commonly used in
psychiatric practice. The newer H
2
-receptor antagonists, such
Table 29.7-1
Histamine Antagonists Commonly Used in
Psychiatry
Generic Name
Trade Name
Duration of Action (hr)
Diphenhydramine Benadryl
4–6
Hydroxyzine
Atarax, Vistaril
6–24
Promethazine
Phenergan
4–6
Cyproheptadine
Periactin
4–6
