13.4: Anxiolytics and Sedative-Hypnotics

Learning Objectives

By the end of this section, you should be able to:

• 13.4.1 Identify the characteristics of drugs used to treat anxiety and sleep disorders.
• 13.4.2 Explain the indications, actions, adverse reactions, contraindications, and interactions of drugs used to treat anxiety and sleep disorders.
• 13.4.3 Describe nursing implications for drugs used to treat anxiety and sleep disorders.
• 13.4.4 Explain the client education related to drugs used to treat anxiety and sleep disorders.

Anxiety can be described as a feeling of nervousness, apprehension, and/or worry about a future threat. Anxiety disorders involve excessive fear and anxiety and corresponding behaviors (American Psychiatric Association, 2022). Generalized anxiety disorder (GAD), panic disorder, obsessive-compulsive disorder (OCD), social anxiety disorder, and post-traumatic stress disorder (PTSD) are examples of anxiety disorders. Anxiety is considered pathological if it is (1) disproportionate to events, (2) sustained over a significant time period, (3) significantly impairing function during usual activities of daily living, and (4) apparently unrelated to any identifiable event or situation. Pathological levels of anxiety require treatment and usually will not fully resolve without therapeutic intervention. Clinical manifestations of anxiety are related to the activation of the sympathetic nervous system response. These include muscle tension, restless feeling, trembling, difficulty concentrating, irritability, tachycardia, palpitations, diaphoresis, dry mouth, dyspnea, and dizziness. Untreated high levels of anxiety predispose people to other comorbidities, such as hypertension, substance use, or depression. These high levels can impair memory, perception, judgment, and motor responses.

A simplistic explanation related to the pathophysiology of anxiety involves an excess of excitatory neurotransmitters (norepinephrine) or a deficiency of inhibitory neurotransmitters (GABA). Most of the medications known to improve symptoms of anxiety act directly or indirectly on the GABA system. Benzodiazepines are widely used for short-term treatment until the prescribed antidepressant reaches therapeutic levels. (Antidepressants were discussed earlier in the chapter.)

Sleep is essential for body restoration. During sleep, tissue repair, synthesis of skeletal muscle protein, and secretion of growth hormone occur. Insomnia is the inability to obtain an adequate amount of sleep needed to function efficiently during the day. Insomnia may be situational, lasting a few days to a few weeks. Insomnia disorder, however, is defined as a significant inability to initiate sleep (sleep latency) or maintain sleep, or early morning awakening with the inability to return to sleep (American Psychiatric Association, 2022). The occurrence is at least 3 nights/week and is present for at least 1 month and may persist for longer than 3 months. Insomnia disorder leads to increased morbidity (such as psychosis) and mortality. Many clients with insomnia have high rates of depression and anxiety.

Drug therapy includes benzodiazepines and the nonbenzodiazepine sedatives. Anxiolytics (antianxiety drugs) and sedative-hypnotics (drugs to invoke relaxation and produce sleep) are CNS depressants that have similar effects. The difference between the effects depends largely on the dose. Large doses of antianxiety and sedative-hypnotic agents produce sleep, and small doses of sedative-hypnotics have anxiolytic or sedative effects.

Benzodiazepines

Benzodiazepines are usually prescribed on a short-term basis for disabling anxiety and are considered second-line therapy due to the risk of dependence. They quickly reduce or prevent anxiety without causing extreme sedation. Benzodiazepines are classified as a Schedule IV controlled substance due to their potential for misuse and physical dependency. Benzodiazepines work in the limbic system and the reticular activating system (RAS) to make GABA more effective. GABA stabilizes the postsynaptic cells, which results in the interference of neuron firing.

When treating anxiety, a lower dose is necessary compared to when using it for sedative purposes. In addition to anxiety, these medications can be used for alcohol withdrawal, agitation, and seizure disorders. These drugs must be tapered slowly when discontinuing them or the client will experience withdrawal symptoms.

Safety Alert

Reversal Agent for Benzodiazepine Toxicity

Flumazenil is a specific benzodiazepine receptor antagonist and is beneficial in reversing the effects of benzodiazepine. It should be available for use as needed to reverse the effects of benzodiazepines administered for sedation. It is also used emergently to treat benzodiazepine overdose.

(Source: Shoar et al., 2023)

The most commonly used benzodiazepines are:

• Diazepam: Children are more sensitive to diazepam, especially related to mood and/or mental changes. They may experience paradoxical medication effects of CNS stimulation and excitation instead of getting a calming effect. Older adults are more sensitive to diazepam’s effects of drowsiness and poor coordination.
• Alprazolam: This drug is preferred over diazepam due to its rapid onset of action.
• Clonazepam: Monitor for suicidal ideations, liver function, and CBC.
• Lorazepam: This drug is most likely the benzodiazepine of first choice. It provides rapid tranquilization of agitated clients. When administered IV, it can induce procedural amnesia. When administered orally, it can help combat anxiety disorders and depression-associated anxiety along with stress-related insomnia.
• Midazolam: This drug is a short-acting medication. It is commonly used prior to surgery or procedures. It can be continuously administered via IV to maintain sedation. In addition, it is considered a valuable adjunct in pediatric anesthesia because it comes in an oral flavored syrup.
• Temazepam: This is the drug of choice for older adults and those with liver disease.
• Triazolam: This drug has a very rapid onset of action. It should be administered while the client is in bed. Cirrhosis of the liver and hepatic insufficiency are contraindications for this drug.

Table 13.19 lists common benzodiazepines and typical routes and dosing for adult and pediatric clients.

Table 13.19 Drug Emphasis Table: Benzodiazepines (source: https://dailymed.nlm.nih.gov/dailymed/)

Drug	Routes and Dosage Ranges
Diazepam (Valium)	Adults: 2–10 mg orally 2–4 times daily; 5–10 mg intramuscularly or intravenously or 0.2 mg/kg by rectum. Older or debilitated adults: 2–5 mg orally 1–2 times/day. Children ≥6 months: 0.12–0.8 mg/kg/day orally in divided doses every 6–8 hours.
Alprazolam (Xanax)	Anxiety: Adults: Immediate release: 0.25–0.5 mg orally 3 times daily. Average maintenance dose: 1–4 mg/day. Maximum dose: 4 mg/day in divided doses. Older or debilitated adults: 0.25 mg orally 2–3 times/day. Panic Disorder: Adults: Immediate release: Initial dose: 0.5 mg orally 3 times daily. Gradually increase to 4–10 mg/day. Extended release: Initial dose: 0.5–1 mg/day orally. Gradually increase as needed. Maximum dose: 3–6 mg/day. Children: Dosage has not been established for those under age 18.
Clonazepam (Klonopin)	Panic Disorder: Adults and children >10 years: Initial dose: 0.25 mg orally twice daily. May increase dose to 1 mg daily after 3 days. Maximum dose: 4 mg/day.
Lorazepam (Ativan)	Adults: 2–6 mg/day orally in 2–3 divided doses. Maximum dose: 10 mg/day. Children: Safety and effectiveness have not been established for those under age 12.
Temazepam (Restoril)	Adults: Average range: 7.5–30 mg/day before bedtime. Children: Safety and effectiveness have not been established for those under age 12.
Triazolam (Halcion)	Adults: Recommended dose: 0.25 mg once nightly before bedtime. Maximum dose: 0.5 mg once nightly. Children: Safety and effectiveness have not been established for those under age 12.

Adverse Effects and Contraindications

Due to the prolonged half-life, both therapeutic and adverse effects are more likely to occur after 3 days of therapy. A client with a history of psychosis should avoid taking benzodiazepines due to the potential exacerbation of symptoms. Acute narrow-angle glaucoma is also a contraindication because this drug class can increase the intraocular pressure. Acute alcohol intoxication or opioid use can intensify the CNS depressant effects. Anyone who is pregnant or breastfeeding should avoid these drugs because they can easily cross the placenta and mammary glands, causing significant sedation in the fetus or infant. Benzodiazepines may produce paradoxical excitement and aggression in adults older than age 50 who have a history of psychosis. Likewise, clients with impaired hepatic function should avoid taking these medications because they are metabolized by the liver. Clients with renal impairment should avoid this drug because the active metabolites may accumulate, resulting in excessive sedation and respiratory depression. Calcium channel blockers decrease the benzodiazepine’s drug metabolism, leading to increased adverse drug effects. Cimetidine is a hepatic enzyme inhibitor. If the dose of the sedative-hypnotic is not decreased, it will accumulate and become toxic. Taking disulfiram concurrently can potentiate the effects of benzodiazepines.

Safety Alert

Similarly Named Drugs Associated with Benzodiazepines

Do not confuse:

• Diazepam (benzodiazepine) with diltiazem (Calcium channel blocker)
• Alprazolam (benzodiazepine) with clonazepam or lorazepam (both benzodiazepines)
• Xanax (benzodiazepine) with Tenex (CNS nonstimulant)
• Clonazepam (benzodiazepine) with clozapine (antipsychotic)
• Klonopin (benzodiazepine) with clonidine (alpha-2 adrenergic agonist)
• Lorazepam (benzodiazepine) with Lovaza (omega-3 acid ethyl esters)

(Source: ISMP, 2023)

Special Considerations

Age

• Children: Great caution needs to be given when administering benzodiazepines or sedative-hypnotics to children because their response to the drug is very unpredictable. Of the benzodiazepines, only chlordiazepoxide, clonazepam, lorazepam, midazolam, and diazepam have established pediatric dosages. Children must be monitored for both CNS depression and excitability.
• Older adults: Older adults may be more susceptible to adverse drug reactions, especially the CNS effects of sedation, dizziness, and possible hallucinations. Reduced doses should be implemented, and safety precautions should be in place. Older adults should be screened for physical conditions, neurological deterioration, or depression, which could be contributing factors to insomnia or anxiety.

Table 13.20 is a drug prototype table for benzodiazepines featuring diazepam. It lists drug class, mechanism of action, adult and pediatric dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Table 13.20 Drug Prototype Table: Diazepam (source: https://dailymed.nlm.nih.gov/dailymed/)

Drug Class Benzodiazepine (Schedule IV controlled substance) Mechanism of Action Enhances the inhibitory effect of GABA	Drug Dosage Adults: 2–10 mg orally 2–4 times daily; 5–10 mg intramuscularly or intravenously or 0.2 mg/kg by rectum. Older or debilitated adults: 2–5 mg orally 1–2 times/day. Children ≥6 months: 0.12–0.8 mg/kg/day orally in divided doses every 6–8 hours.
Indications To relieve anxiety, tension, and nervousness Insomnia As a muscle relaxant Seizures Sleepwalking or night terrors in children Prevention of agitation and delirium tremens in alcohol withdrawal Therapeutic Effects Decreases neuronal excitability Enhances action of GABA	Drug Interactions CNS depressants Opioids Calcium channel blockers Cimetidine Disulfiram Food Interactions Alcohol
Adverse Effects Sedation/drowsiness Ataxia Memory disturbances Confusion Disinhibition Shallow breathing Sleep driving Headaches Depressed mood with/without suicidal ideations Dry mouth Constipation Elevated liver enzymes Urinary retention and hesitancy Blood disorders/anemia	Contraindications Hypersensitivity to drug or any of its ingredients Clients <6 months of age Myasthenia gravis Severe respiratory insufficiency Severe hepatic insufficiency Sleep apnea Acute narrow-angle glaucoma Caution: Depression/suicidal ideations

FDA Black Box Warning

Benzodiazepines

Concomitant use of benzodiazepines with opioids can result in profound sedation, respiratory depression, coma, or death.

Midazolam, when given intravenously, can cause significant respiratory depression that may lead to hypoxia, brain damage, or death.

Nonbenzodiazepine Sedative-Hypnotics

This classification produces sleep. Clients may receive nonbenzodiazepine sedative-hypnotics prior to diagnostic or surgical procedures or take them for sleepless nights. These drugs should only be taken when insomnia is causing distress and nonpharmacologic measures have been ineffective. They should not be taken every night unless absolutely necessary. Intermittent administration can help maintain the drug’s effectiveness and also prevent dependence. Additionally, it reduces disturbances of normal sleep patterns.

The loss of awareness to and reaction of environmental stimuli is termed sedation. This may be a desirable characteristic for some clients who are restless, nervous, or overreactive to certain stimuli. A sedative is a drug that depresses the central nervous system (CNS). Although a sedative is used more as an anxiolytic, it frequently leads to drowsiness. A hypnotic causes extreme sedation and is used in individuals to promote sleep. These drugs act on the RAS and block the brain’s response to incoming stimuli:

• Eszopiclone (Schedule IV): Eszopiclone is one of two drugs used long-term (12 months or longer) for chronic insomnia. Studies have shown that clients did not experience tolerance to the hypnotic benefits over a 6-month period (DailyMed, Eszopiclone, 2022). Its mechanism of action is due to an interaction with GABA receptors close to or coupled with benzodiazepine receptors. Adverse effects associated with this drug include reduced inhibition, aggression or bizarre behavior, worsening depression and suicidal ideations, hallucinations, and anterograde amnesia (memory loss). Many clients report an unpleasant taste of the drug. Clients who take eszopiclone should allow for 8 hours of sleep because it increases total sleep time and reduces sleep latency. It has no effect on reducing nighttime awakenings. Clients should take the drug immediately prior to going to bed due to its rapid onset. The medication should not be taken immediately following a high-fat meal because it can delay the onset by 1 hour.

Safety Alert

Beers Criteria^®

Eszopiclone should be avoided in older adults.

(Source: American Geriatrics Society, 2023)

• Ramelteon (not a controlled substance): Ramelteon is a melatonin receptor agonist used long-term for chronic insomnia. This drug is beneficial for decreasing sleep latency. ADRs specific to this drug include hormonal effects due to increased levels of prolactin, reduced cortisol levels, and decreased testosterone. Other ADRs include headaches, dizziness, myalgia, arthralgia, abnormal thoughts and/or behaviors, impaired mental alertness, and alteration in taste. This drug should not be taken following a high-fat meal because it will delay the onset of action. Caution must be used in clients with depression and respiratory conditions, such as sleep apnea, because the drug can worsen these. This drug is contraindicated in clients with severe hepatic impairment.
• Zaleplon (Schedule IV): Zaleplon is used for short-term treatment (7–10 days) for insomnia. It can help people initiate sleep (decreases sleep latency). The drug does not increase total sleep time or decrease the number of awakenings due to its short half-life. Severe hepatic insufficiency is a contraindication. Clients with mild to moderate hepatic impairment can receive lower doses with frequent follow-up to assess worsening liver failure.
• Zolpidem (Schedule IV): Zolpidem is a CNS depressant used for short-term treatment of insomnia associated with difficulties with sleep initiation.
• Suvorexant (Schedule IV): Suvorexant belongs to a new class of drugs used to treat insomnia called orexin receptor antagonists. The orexin signaling system is thought to be a central promotor of wakefulness. Blocking these sites suppresses the drive to wake up. For safety purposes, the client should be in bed within 30 minutes of taking the drug. The client should anticipate being in bed for 7 hours.
• Lemborexant (Schedule IV): Lemborexant is an orexin receptor antagonist indicated for the treatment of adult clients with insomnia, characterized by difficulties with sleep onset and/or sleep maintenance. It can cause the same adverse effects as zolpidem. Sleep onset may be delayed if lemborexant is taken with or soon after a meal.
• Daridorexant (Schedule IV): Daridorexant is also an orexin receptor antagonist. It has the same mechanism of action and indications for use as lemborexant. Food also can delay the onset of its effect.

Table 13.21 lists common nonbenzodiazepine sedative-hypnotics and typical routes and dosing for adult clients. Nonbenzodiazepine sedative-hypnotics are either not recommended in children or the safety, efficacy, and dose have not been established.

Table 13.21 Drug Emphasis Table: Nonbenzodiazepine Sedative-Hypnotics (source: https://dailymed.nlm.nih.gov/dailymed/)

Drug	Routes and Dosage Ranges
Eszopiclone (Lunesta)	Adults: 1 mg orally at bedtime to promote sleep. May increase to 3 mg if needed. Older adults, debilitated clients, and those with hepatic impairment: 1 mg orally at bedtime. May increase to 2 mg if needed.
Zaleplon (Sonata)	Adults: 10 mg orally at bedtime. Maximum dose: 20 mg orally at bedtime. Low-weight older adults and those with mild to moderate hepatic impairment: 5 mg orally at bedtime.
Zolpidem (Ambien)	Immediate-release tablet: 5 mg for females and 5–10 mg for males orally at bedtime. Sublingual tablet: 1.75 mg for females and 3.5 mg for males orally once per night as needed if the client wakes during the night and has difficulty returning to sleep. Extended-release tablet: 6.25 mg for females and 6.25–12.5 mg for males orally at bedtime.
Ramelteon (Rozerem)	8 mg orally at bedtime. Must take within 30 minutes of going to bed.
Suvorexant (Belsomra)	10–20 mg orally within 30 minutes of bedtime with at least 7 hours remaining before planned awakening.
Lemborexant (Dayvigo)	5 mg orally once per night, immediately before going to bed, with at least 7 hours remaining before planned awakening. Maximum dose: 10 mg nightly.
Daridorexant (Quviviq)	25–50 mg once per night, taken orally within 30 minutes before going to bed, with at least 7 hours remaining prior to planned awakening.

Adverse Effects and Contraindications

Clients can experience angioedema if they are allergic to any of the components in the drug. These drugs are metabolized by the liver, so they should be avoided by anyone with severe hepatic failure. Lower doses should be administered for those with mild to moderate hepatic insufficiency and in the older adult. Glaucoma, psychosis, and acute alcohol intoxication can be exacerbated by the CNS depression of these drugs. Due to the potential for respiratory depression, clients with a history of COPD or sleep apnea should use caution. If taking a nonbenzodiazepine sedative-hypnotic for at least 1 week, gradual tapering is crucial when discontinuing. If stopped abruptly, withdrawal syndrome can occur including nausea, headache, vertigo, nightmares, and seizures. Rebound insomnia can potentially occur but only lasts a few days after the drug has been stopped. Essentially, it resolves on its own.

Lemborexant and daridorexant are both contraindicated for the use in narcolepsy. It has been advised that these two drugs should not be used in the presence of hepatic disease. The safety and effectiveness in those under age 18 has not been established.

Concurrently taking another CNS depressant or drinking alcohol with this medication can intensify CNS depression and cause excessive drowsiness along with respiratory depression. Both of these can increase the risk for injury.

If a client takes the medication directly after consuming a high-fat meal, it can significantly delay absorption of the drug. Herbal supplements should be avoided.

Safety Alert

Similarly Named Drugs Associated with Nonbenzodiazepine Sedative-Hypnotics

Do not confuse:

• Lunesta (nonbenzodiazepine sedative-hypnotic) with Neulasta (bone marrow stimulant)
• Rozerem (nonbenzodiazepine sedative-hypnotic) with Razadyne (acetylcholinesterase inhibitor for dementia)

(Source: ISMP, 2023)

Table 13.22 is a drug prototype table for nonbenzodiazepine sedative-hypnotics featuring zolpidem. It lists drug class, mechanism of action, adult dosage, indications, therapeutic effects, drug and food interactions, adverse effects, and contraindications.

Table 13.22 Drug Prototype Table: Zolpidem (source: https://dailymed.nlm.nih.gov/dailymed/)

Drug Class Nonbenzodiazepine sedative-hypnotics (Schedule IV controlled substance) Mechanism of Action Selectively binds to specific GABA receptors	Drug Dosage Immediate-release tablet: 5 mg for females and 5–10 mg for males orally at bedtime. Sublingual tablet: 1.75 mg for females and 3.5 mg for males orally once per night as needed if the client wakes during the night and has difficulty returning to sleep. Extended-release tablet: 6.25 mg for females and 6.25–12.5 mg for males orally at bedtime.
Indications Immediate-release form: Short-term treatment (7–10 days) for insomnia Extended-release form: Decreases sleep latency and increases total sleep time Therapeutic Effects Reduces sleep latency and increases sleep time	Drug Interactions CNS depressants (antihistamines, kava, valerian) Opioids Food Interactions Alcohol High-fat meals
Adverse Effects Daytime drowsiness Reduced inhibition Aggression Worsening depression and suicidal ideations Hallucinations Abnormal dreams Anterograde amnesia Headache/dizziness Sleep driving Unpleasant taste Withdrawal syndrome—rebound insomnia Respiratory depression Tolerance can occur after 2 weeks	Contraindications Hypersensitivity Severe hepatic impairment Caution: COPD Sleep apnea Pregnancy and lactation Depression Impaired hepatic function Impaired respiratory function

Safety Alert

Beers Criteria^®

Sedative-hypnotics should be avoided in older adults (age 65 or older) because of associated risks including memory problems, drowsiness, increased risk of falls, and increased risk of having a motor vehicle collision.

(Source: Lee & Green, 2019)

Nursing Implications

The nurse should do the following for clients who are taking anxiolytics or sedative-hypnotics:

• Help the client to identify triggers and develop coping mechanisms to help with reducing anxiety.
• Assess the client’s sleep patterns.
• Monitor heart rate, blood pressure, respiratory rate, temperature, and weight.
• Assess level of consciousness and orientation.
• Evaluate mood for anger, aggression, or hallucinations (paradoxical response).
• Assess for signs/symptoms of dependence, overdose, and withdrawal, such as psychomotor agitation, insomnia, headache, tremor, palpitations, psychosis, and seizures.
• Monitor renal and liver function tests and CBC.
• Modify the environment to promote sleep (dim lights, turn off television).
• Relieve symptoms that are interfering with sleep, such as analgesics for pain or antitussives for cough.
• Provide safety precautions when the client is ambulatory.
• Instruct the client that the immediate-release formulation is used to help them fall asleep and that the extended-release formulation is used to maintain sleep throughout the night.
• Use a large muscle when administering the intramuscular (IM) preparation. Inject it slowly and rotate sites.
• Monitor injection sites for local reactions and institute care immediately.
• Provide client teaching regarding the drug and when to call the health care provider. See below for client teaching guidelines.

Client Teaching Guidelines

The client taking drugs for anxiety and sleep disorders should:

• Understand the drug will reduce the symptoms but does not cure the underlying problem.
• Verbalize the importance of attending counseling to learn ways to manage their anxiety.
• Identify nondrug measures to manage stress and promote sleep, such as relaxation techniques and hobbies.
• Limit the daily consumption of caffeine and avoid caffeine close to bedtime.
• Establish a bedtime routine to consistently follow.
• Increase physical activity.
• Take the sedative-hypnotic just before going to bed so the client is lying down when the drug begins to work.
• Notify the provider if experiencing any hallucinations or thoughts of suicide.
• Avoid daytime naps.
• Place sublingual tablets under the tongue and allow them to dissolve.
• Only use as needed and for the shortest duration.

The client taking drugs for anxiety and sleep disorders should not:

• Stop any drug abruptly due to withdrawal syndrome and the risk of seizures in epileptic clients.
• Chew, crush, or break in half any extended-release tablets/capsules.
• Use these on a long-term basis.
• Take any stimulant drugs, such as cold remedies or appetite suppressants.
• Engage in activities that require alertness until the effects of the drug are known.
• Take nonbenzodiazepines with a high-fat meal due to delayed absorption.
• Consume any caffeinated beverages/foods or excess water during evening hours.
• Swallow the sublingual tablets or take with water.
• Consume any alcohol.