What is the sedative effect of doxepin (Sinequan)?

From the Guidelines

Doxepin is a highly sedating medication, particularly at lower doses (3-6 mg), with a significant impact on sleep quality and duration, as evidenced by studies such as 1 and 1. The sedating effects of doxepin are primarily due to its ability to block histamine H1 receptors in the brain, producing strong sedative effects similar to antihistamines but with more sustained action throughout the night. At higher doses (25-300 mg) used for depression or anxiety, the sedating effects remain significant but additional neurotransmitter effects become more prominent. Some key points to consider when prescribing doxepin include:

• The sedation typically begins within 30 minutes to an hour after taking the medication and can cause drowsiness that persists into the following day, especially when first starting treatment, as noted in studies like 1.
• This sedation tends to diminish somewhat over time as tolerance develops, but many patients continue to experience some degree of drowsiness throughout treatment.
• Due to its sedating properties, doxepin should be taken at bedtime, and patients should avoid driving or operating machinery until they understand how the medication affects them, as advised in guidelines such as 1.
• The sedating effect makes doxepin particularly useful for patients with depression or anxiety who also struggle with insomnia, but potentially problematic for those who need to maintain alertness during the day. It's also important to consider the potential risks and benefits of doxepin, as discussed in studies like 1, which found that the benefits of doxepin for insomnia outweigh the potential harms. Overall, doxepin's sedating effects make it a valuable treatment option for patients with insomnia, but its use should be carefully considered and monitored to minimize potential risks and maximize benefits, as supported by the most recent and highest quality study, 1.

From the FDA Drug Label

Drowsiness: Since drowsiness may occur with the use of this drug, patients should be warned of the possibility and cautioned against driving a car or operating dangerous machinery while taking the drug. Central Nervous System Effects: Drowsiness is the most commonly noticed side effect. This tends to disappear as therapy is continued Sedating drugs may cause confusion and over sedation in the elderly; elderly patients generally should be started on low doses of Doxepin and observed closely.

Doxepin is sedating. The sedating effects of doxepin are a common side effect, with drowsiness being the most commonly noticed side effect. However, this tends to disappear as therapy is continued. Elderly patients are at higher risk of confusion and over sedation due to doxepin's sedating effects, and should be started on low doses and observed closely 2.

From the Research

Sedating Effects of Doxepin

• Doxepin is a sedating tricyclic drug, with a sedative effect that makes it useful in treating insomnia and depression associated with anxiety 3, 4.
• The sedating properties of doxepin are due to its high specificity and affinity to the histamine H(1) receptor, which promotes the initiation and maintenance of sleep 5.
• Low-dose doxepin (3-6 mg) has been shown to be effective in improving sleep maintenance and sleep duration, with minimal next-day residual effects 3, 5.

Comparison to Other Sedating Agents

• Doxepin is recommended as a first-line agent for insomnia in older adults, along with controlled-release melatonin, due to its safety and efficacy profile 6.
• The z-drugs (zolpidem, eszopiclone, and zaleplon) are also effective for insomnia, but may have a higher risk of abuse and dependence compared to doxepin 6.
• Benzodiazepines are not recommended for insomnia due to their high abuse potential, and sedating antihistamines, antiepileptics, and atypical antipsychotics are not recommended unless used to treat another condition 6.

Side Effects and Tolerability

• Common side effects of doxepin include headache, somnolence, dry mouth, drowsiness, and constipation 3, 4, 5.
• Doxepin is generally well-tolerated, especially in elderly patients and those with cardiovascular disease, with fewer cardiovascular side effects compared to other tricyclic antidepressants 4, 5.