Chapter 184: Nonbenzodiazepine Sedatives

INTRODUCTION

The term sedative-hypnotic refers to any drug designed to produce sedation and sleepiness. These drugs can be divided into the benzodiazepines (see chapter 183, Benzodiazepines) and nonbenzodiazepines (Table 184-1).

One is most likely to encounter toxicity from these sedative drugs as part of accidental or nonaccidental overdose, as well as after an assault or trauma. Many nonbenzodiazepines were developed and are marketed for the treatment of insomnia.¹ The sedative effect of other agents, including antihistamines (e.g., diphenhydramine, doxylamine), antidepressants (e.g., amitriptyline, trazodone, and mirtazapine), and antipsychotics (e.g., quetiapine), are also used to promote sleep.

Three sedative agents used in the past have been removed from the legal U.S. and Canadian markets: ethchlorvynol, glutethimide, and methaqualone. However, comments on the Internet suggest these drugs might be available to North American customers from locations in Eastern Europe, Africa, Asia, and South America.²

BUSPIRONE

Buspirone is approved by the U.S. Food and Drug Administration for treatment of anxiety disorders.³ Other off-label uses include treatment of depression and nicotine dependence. Buspirone is a partial agonist at the serotonin-1A receptor and an antagonist of the dopamine-2 receptor. The resultant effect on serotonin and dopamine neurotransmitter levels is complex, depending on the concentration of the drug and specific brain location, but overall effects are primarily suppression of CNS serotoninergic activity and enhancement of dopaminergic and, possibly, noradrenergic activity.

The typical starting dose for buspirone is 5 milligrams PO three times daily, and the maximum recommended total daily dose is 60 milligrams. Following ingestion, absorption is rapid and nearly complete, with significant first-pass metabolism in the liver, primarily via oxidation, resulting in a low bioavailability. Metabolism of buspirone, by cytochrome P3A4, produces several metabolites, including one active metabolite. Primary elimination is renal, with additional substantial fecal elimination.

Common adverse effects with buspirone use include sedation, GI discomfort, vomiting, and dizziness. In therapeutic dosing, buspirone does not appear to cause psychomotor depression and has not been associated with any potential for abuse or withdrawal.⁴

The effects observed with a buspirone overdose would likely be an exaggeration of adverse effects observed during therapeutic dosing. In general, the drug is well tolerated ...