Miscellaneous anxiolytics, sedatives and hypnotics

Miscellaneous anxiolytics, sedatives, and hypnotics are those anxiolytics, sedatives, and hypnotics that are unique in their action and not comparable to any other anxiolytics, sedatives and hypnotics currently on the market, although their side effects may be similar. They do not resemble benzodiazepines or barbiturates in their structure.

Anxiolytics, sedatives, and hypnotics are medicines that are used to relieve anxiety, calm, or induce sleep.

What are miscellaneous anxiolytics, sedatives, and hypnotics used for?

Miscellaneous anxiolytics, sedatives, and hypnotics act in the brain to treat anxiety and insomnia and to induce calm. Apart from the “Z” drugs (zolpidem, eszopiclone, and zaleplon), most are older drugs that have been largely superseded by newer, less toxic agents. Some may be considered for the treatment of the following conditions when other agents have been ineffective or are not tolerated:

• Alcohol withdrawal
• Anxiety
• Sleeplessness (insomnia)
• To help calm patients before surgery or diagnostic procedures
• To help control post-operative pain
• To help with the withdrawal of opiates or barbiturates.

What are the differences between miscellaneous anxiolytics, sedatives, and hypnotics?

Miscellaneous anxiolytics, sedatives, and hypnotics are a diverse group of medicines with no consistent structural relationship. Many are older drugs and most have an unknown mechanism of action but work on the central nervous system to treat anxiety and insomnia.

Although diphenhydramine and doxylamine are listed here under miscellaneous anxiolytics, sedatives, and hypnotics; they both are antihistamines. Because one of their side effects is sedation, they may be used short-term to aid sleep.

Zolpidem, zopiclone (not available in the U.S.), eszopiclone, and zaleplon are commonly referred to as “Z” drugs. These drugs are not benzodiazepines, but they act in a similar way to benzodiazepines and have a similar risk of dependence with long-term use. "Z" drugs are structurally unrelated to each other.

Please refer to individual drug monographs for each drug's mechanism of action, route of administration, and antibiotic spectrum.

Are miscellaneous anxiolytics, sedatives, and hypnotics safe?

The older agents can cause respiratory depression (slow and shallow breathing) and the risk of toxicity is increased if used in combination with alcohol and opiates and in people of an older age.

Severe allergic reactions have been reported with many sedative/hypnotics including angioedema, shortness of breath, nausea, and vomiting.

Tolerance is reported with many of the older agents, such as chloral hydrate. This is when chronic users can ingest large dosages without any ill effects; however, death may occur if a new user was to take a similar dose.

If sedative/hypnotics are taken during the middle of the night with less than 7 to 8 hours sleep remaining, or if higher than recommended dosages are taken, then there is a high risk of next-day impairment in the performance of tasks which may result in events such as falling asleep while driving.

Sedative/hypnotics have also been associated with bizarre behavior including sleep-related activities (such as driving while asleep, making phone calls while asleep), aggressiveness or extroversion that seem out of character. Amnesia may also occur.

Withdrawal effects have also been reported following a rapid dose decrease or abrupt discontinuation. If sedative/hypnotics have been administered for a long period of time then they should be discontinued slowly.

Many of the older agents are seldom used nowadays because of their high risk of toxicity. Examples of severe side effects associated with some miscellaneous anxiolytics, sedatives, and hypnotics include:

• Chloral hydrate: Toxic and potentially fatal in overdose, causes excessive sedation as well as cardiac arrhythmias. Genotoxic (destructive to a cell’s DNA) and carcinogenic in mice; effect on humans unknown
• Buspirone: Can cause serotonin syndrome if used in combination with other agents that also release serotonin (such as selective serotonin uptake inhibitors (SSRIs), monoamine oxidase inhibitors (MAOI) and possibly on its own)
• Diphenhydramine/doxylamine; overdosage has been fatal in pediatric patients. These agents should not be given to children under 12 years as a night-time sleep aid
• Meprobamate: Toxic and potentially fatal in overdose producing unconsciousness, profoundly low blood pressure, and respiratory failure
• Sodium oxybate: Can cause respiratory depression (slow and shallow breathing) and has the potential to be abused. Use is restricted (Xyrem REMS Program)
• Suvorexant: Exposure is increased in obese patients and in females. Risk of drug abuse.

Significant drug interactions may exist with some miscellaneous anxiolytics, sedatives, and hypnotics.

For a complete list of severe side effects, please refer to the individual drug monographs.

What are the side effects of miscellaneous anxiolytics, sedatives, and hypnotics?

Each one of these agents works in a different way, which means some of their side effects differ; however, they all tend to cause dizziness and drowsiness. Examples of side effects associated with some miscellaneous anxiolytics, sedatives, or hypnotics include:

• Buspirone: nausea, vomiting, dizziness, drowsiness, miosis, and gastric
• Chloral hydrate: ataxia, diarrhea, dizziness, nausea, vomiting
• Diphenhydramine/doxylamine: dry mouth, dizziness, drowsiness, low blood pressure, and a rapid heart-beat
• Eszopiclone: dry mouth, dizziness, headache, sedation, unpleasant taste
• Melatonin: a headache, short-term feelings of depression, daytime sleepiness, dizziness, stomach cramps, and irritability
• Meprobamate: blurred vision, diarrhea, dizziness, nausea, unsteadiness, vomiting
• Ramelteon: dizziness, fatigue, nausea
• Sodium oxybate: confusion, diarrhea, dizziness, nausea, urinary incontinence, vomiting
• Suvorexant: drowsiness, dizziness, dry mouth,
• Tasimelteon: a headache, abnormal dreams, urinary tract infection, abnormal liver function tests
• Tryptophan: dizziness, drowsiness, dry mouth, headache, loss of appetite, nausea
• Zaleplon: a headache, drowsiness, dizziness, dysmenorrhea, nausea
• Zolpidem: a headache, drowsiness, dizziness, diarrhea

For a complete list of side effects, please refer to the individual drug monographs.