How does Temazepam (benzodiazepine) work and what are its side effects?

Temazepam: Mechanism of Action and Side Effects

How Temazepam Works

Temazepam is a benzodiazepine that enhances GABA (gamma-aminobutyric acid) neurotransmission in the central nervous system, producing sedative-hypnotic effects that improve sleep onset and maintenance. 1

Pharmacological Mechanism

• Temazepam binds to benzodiazepine receptors at the GABA-A receptor complex, potentiating the inhibitory effects of GABA and resulting in CNS depression that facilitates sleep 2, 3
• The drug acts as a minor metabolite of diazepam with specific hypnotic properties 3

Pharmacokinetic Profile

• Peak plasma concentrations occur approximately 3 hours after oral administration, which explains why temazepam is more effective for sleep maintenance than sleep onset 2, 4
• Mean elimination half-life is 10-15 hours (range 5-11 hours, longer in elderly patients), classifying it as an intermediate-acting benzodiazepine 2, 3, 4
• No clinically significant active metabolites are produced, reducing the risk of prolonged sedation compared to longer-acting benzodiazepines like flurazepam 3, 4

Clinical Effects on Sleep Architecture

• Temazepam 15 mg reduces subjective sleep latency by approximately 20 minutes and increases total sleep time significantly 5
• Temazepam 30 mg reduces sleep latency by 40-45 minutes and increases total sleep time by 53-55 minutes compared to placebo 5, 6
• Wake after sleep onset (WASO) is significantly reduced, making it effective for middle-of-night awakenings 5, 7
• Sleep efficiency improves with both subjective and objective measurements 5

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Side Effects of Temazepam

Common Side Effects (Most Frequent)

The FDA-approved labeling identifies these as the most common adverse effects: 1

• Drowsiness - most frequently reported
• Headache
• Tiredness/fatigue
• Nervousness
• Dizziness
• Nausea
• Next-day residual drowsiness - patients may not feel fully awake the morning after use 1

Serious Side Effects Requiring Immediate Medical Attention

Complex Sleep Behaviors (FDA Black Box Warning): 1

• Sleep-driving, sleep-eating, sleep-walking, and engaging in activities while not fully awake with no memory of the events
• Risk increases when combined with alcohol or other CNS depressants 1

Respiratory Depression and CNS Depression: 1

• Severe drowsiness, slowed or stopped breathing, coma, and death can occur, especially when combined with opioids, alcohol, or other CNS depressants 1
• This represents a critical drug interaction requiring emergency intervention 1

Psychiatric and Behavioral Effects: 1

• Abnormal thoughts and behavior including increased aggression, confusion, agitation, hallucinations 1
• Worsening of depression and suicidal thoughts or actions 1
• Delirium, paranoia, and loss of touch with reality in cases of abuse or misuse 1

Severe Allergic Reactions: 1

• Swelling of tongue or throat, difficulty breathing, nausea and vomiting requiring emergency treatment 1

Abuse, Dependence, and Withdrawal Risks

Temazepam is a Schedule IV controlled substance with significant potential for abuse, misuse, and addiction: 1

• Physical dependence develops even with prescribed use, and abrupt discontinuation causes serious withdrawal symptoms 1
• Withdrawal symptoms include seizures, severe mental status changes, hallucinations, extreme agitation, suicidal thoughts, and potentially life-threatening reactions 1
• Some withdrawal symptoms can persist for weeks to over 12 months, including anxiety, memory problems, depression, insomnia, paresthesias, weakness, tremor, and tinnitus 1
• Gradual tapering is mandatory - never stop temazepam suddenly 1

Cognitive and Psychomotor Impairment

• Daytime sedation and impaired psychomotor function can occur, particularly at doses of 30 mg or higher 3
• Memory impairment has been documented in systematic assessments 5
• Patients must not drive or operate heavy machinery until they know how temazepam affects them 1

Age-Related Considerations

In elderly patients (≥70 years): 5

• Longer elimination half-life increases risk of accumulation 3
• Dose reduction to 7.5-15 mg is recommended for geriatric or debilitated patients 1, 4
• Lower incidence of adverse effects at 7.5 mg dose with maintained efficacy in elderly insomniacs 8

Incidence and Severity Profile

The overall incidence of adverse effects is relatively low: 9

• Only 7.8% of patients reported adverse effects in controlled trials of older adults over 8 weeks 9
• Adverse effects are typically mild in severity and decrease over the treatment course 9
• Behavioral tolerance to adverse effects develops over time 9

Special Warnings and Contraindications

Temazepam is contraindicated in: 1

• Patients with known hypersensitivity to temazepam or benzodiazepines 1

Use with extreme caution in: 1

• Pregnancy - may cause birth defects or harm to the unborn baby 1
• Breastfeeding - passes into breast milk and may harm the infant 1
• History of depression, mental illness, or suicidal ideation 1
• History of substance abuse or addiction 1, 7
• Lung disease or breathing problems - risk of respiratory depression 1

Duration of Safe Use

Temazepam is approved only for short-term use: 1

• Safety and efficacy established for 7-10 days of treatment 1
• Safety beyond 2 weeks is not established 1
• The American Academy of Sleep Medicine recommends concurrent cognitive behavioral therapy for insomnia (CBT-I) to provide sustainable benefits beyond medication discontinuation 7

Critical Drug Interactions

Never combine temazepam with: 1

• Opioid medications - causes severe respiratory depression, coma, and death 1
• Alcohol - dramatically increases sedation and risk of complex sleep behaviors 1
• Other CNS depressants unless specifically directed by a healthcare provider 1

Common Pitfalls to Avoid

• Taking temazepam without allowing 7-8 hours for sleep increases risk of next-day impairment 1
• Using temazepam as monotherapy without CBT-I results in loss of therapeutic gains upon discontinuation 7
• Abrupt discontinuation rather than gradual tapering causes severe withdrawal 1
• Combining with alcohol or other sedatives exponentially increases risk of serious adverse events 1