Antihistamines
For a more detailed discussion of this topic, see Antihistamines, Sec. 31.8, p. 3033 in Comprehensive Textbook of Psychiatry, 9th Edition.
The sedative and anticholinergic activity of antihistamines provides the basis for their frequent use in a variety of psychiatric disorders. Certain antihistamines (antagonists of histamine H1 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 neuroleptic-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 orgasm caused by serotonergic agents. The antihistamines most commonly used in psychiatry are listed in Table 6-1. Fexofenadine (Allegra), loratadine (Claritin), and cetirizine (Zyrtec) are less commonly used in psychiatric practice.
Table 6-2 lists antihistaminic drugs not used in psychiatry but that may have psychiatric adverse effects or drug–drug interactions.
Pharmacologic Actions
The H1 antagonists used in psychiatry are well absorbed from the gastrointestinal (GI) tract. The antiparkinsonian effects of intramuscular (IM) diphenhydramine have their onset in 15 to 30 minutes, and the sedative effects of diphenhydramine peak in 1 to 3 hours. The sedative effects of hydroxyzine and promethazine begin after 20 to 60 minutes and last for 4 to 6 hours. Because all three drugs are metabolized in the liver, persons with hepatic disease, such as cirrhosis, may attain high plasma concentrations with long-term administration. Cyproheptadine is well absorbed after oral administration, and its metabolites are excreted in the urine.
Activation of H1 receptors stimulates wakefulness; therefore, receptor antagonism causes sedation. All four agents also possess some antimuscarinic cholinergic activity. Cyproheptadine is unique among the drugs because it has both potent antihistamine and serotonin 5-HT2 receptor antagonist properties.
Therapeutic Indications
Antihistamines are useful as a treatment for neuroleptic-induced parkinsonism, neuroleptic-induced acute dystonia, and neuroleptic-induced akathisia. They are
an alternative to anticholinergics and amantadine for these purposes. The antihistamines are relatively safe hypnotics, but they are not superior to the benzodiazepines, which have been much better studied in terms of efficacy and safety. The antihistamines have not been proven effective for long-term anxiolytic therapy; therefore, the benzodiazepines, buspirone (BuSpar), or selective serotonin reuptake inhibitors (SSRIs) are preferable for such treatment. Cyproheptadine is sometimes used to treat impaired orgasms, especially delayed orgasm resulting from treatment with serotonergic drugs.
an alternative to anticholinergics and amantadine for these purposes. The antihistamines are relatively safe hypnotics, but they are not superior to the benzodiazepines, which have been much better studied in terms of efficacy and safety. The antihistamines have not been proven effective for long-term anxiolytic therapy; therefore, the benzodiazepines, buspirone (BuSpar), or selective serotonin reuptake inhibitors (SSRIs) are preferable for such treatment. Cyproheptadine is sometimes used to treat impaired orgasms, especially delayed orgasm resulting from treatment with serotonergic drugs.
Table 6-1 Histamine Antagonists Commonly Used in Psychiatry | ||||
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