From the Guidelines
Sedating antidepressants, specifically those with sedative effects, include mirtazapine, trazodone, amitriptyline, and doxepin, which can be valuable treatment options for patients with depression and insomnia, but should be used with caution, especially in elderly patients and those with cardiac conditions, as recommended by the most recent study 1.
Sedating Antidepressants
The most commonly prescribed sedating antidepressants include:
- Mirtazapine (15-45mg), typically taken at bedtime, with strong antihistamine effects at lower doses (15mg)
- Trazodone (50-150mg), often prescribed for insomnia at lower doses, and higher doses (150-300mg) for antidepressant effects
- Tricyclic antidepressants like amitriptyline (10-150mg) and doxepin (10-150mg), which provide significant sedation but carry more anticholinergic side effects and cardiac risks
Mechanism of Action
These medications work through various mechanisms, including blocking histamine, serotonin, and norepinephrine receptors, which explains their sedating properties.
Precautions and Side Effects
When prescribing these medications, start at low doses and gradually increase to minimize side effects. Morning drowsiness is common initially but often improves with continued use. Patients should avoid alcohol while taking these medications as it can dangerously increase sedation effects.
Recommendations
According to the most recent study 1, cognitive behavioral therapy for insomnia is recommended as first-line treatment before the initiation of sedating antidepressants. Hypnotics such as zolpidem and eszopiclone should be prescribed with caution due to potential cognitive impairment and increased fall risk.
From the FDA Drug Label
A sedative effect may be apparent before the antidepressant effect is noted Sedating drugs, including mirtazapine tablets, may cause confusion and over-sedation in the elderly
Sedating antidepressants with sedative effects (Sedative-Hypnotic) include:
- Amitriptyline: has a sedative effect that may be apparent before the antidepressant effect is noted 2
- Mirtazapine: is known to be a sedating drug that may cause confusion and over-sedation, particularly in the elderly 3
From the Research
Sedating Antidepressants
Sedating antidepressants, specifically those with sedative effects (Sedative-Hypnotic), are a class of medications used to treat depression, anxiety, and insomnia.
- Mirtazapine is a sedative antidepressant that exhibits both noradrenergic and serotonergic activity, making it effective in treating mild to severe depression, as well as anxiety and insomnia 4, 5, 6.
- It is known for its sedative effects, which can be beneficial for patients with depression and insomnia, but may also cause drowsiness and weight gain as adverse effects 6.
- Other sedating antidepressants include tricyclic antidepressants such as amitriptyline, clomipramine, and doxepin, which possess anticholinergic, alpha 1 anti-adrenergic, and H1 antihistaminic properties 7.
- The dosage equivalents of these sedating antidepressants have been studied, with mirtazapine being equivalent to 50.9mg/day compared to fluoxetine 40mg/day 7.
- New-generation antidepressants, such as noradrenergic and selective serotonergic antidepressants (NaSSAs), have been developed to provide alternative treatment options with different mechanisms of activity and tolerability profiles 8.
Mechanism of Action
The mechanism of action of sedating antidepressants varies, but many work by enhancing central noradrenergic and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission, such as mirtazapine 5.
- Mirtazapine's dual enhancement of central noradrenergic and serotonin 5-HT1 receptor-mediated serotonergic neurotransmission contributes to its antidepressant effect and sedative properties 5.
- Other sedating antidepressants, such as tricyclic antidepressants, work by inhibiting the reuptake of norepinephrine and serotonin, while also possessing anticholinergic and antihistaminic properties 7.
Clinical Use
Sedating antidepressants are used to treat a variety of conditions, including depression, anxiety, and insomnia.
- Mirtazapine is particularly useful in patients who experience sexual side effects from other antidepressants, as well as those with significant anxiety or insomnia 4, 5.
- Tricyclic antidepressants, such as amitriptyline and doxepin, are also used to treat depression, anxiety, and insomnia, but may have more anticholinergic and antihistaminic side effects 7.
- New-generation antidepressants, such as NaSSAs, offer alternative treatment options with different mechanisms of activity and tolerability profiles, which can be beneficial for patients who do not respond to traditional antidepressants 8.