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Doxepin for sleep – Precautions & side effects

by egpat         22 May 2024

Doxepin is classified as an anti-depressant. It is one of the tricyclic anti-depressants commonly known as TCA. This drug is used for the treatment of depression, but because of its sedative properties, doxepin can also be used in the management of anxiety and in the treatment of insomnia, where this drug can maintain sleep and reduce anxiety.

This medication mainly acts on the CNS. It can improve the transmission of two types of neurotransmitters: norepinephrine and serotonin (5-HT). By improving the transmission of these monoamines, doxepin can reduce depression, anxiety, and even induce sleep. But for the treatment of insomnia, doxepin is available as a tablet at low strength. So it is available as 3 mg and 6 mg tablets for the management of insomnia, whereas for the treatment of depression, it can be used at higher doses.

Among the tricyclic antidepressants, doxepin is one of the medications that is used in the management of insomnia. This drug is particularly a chemical derivative of dibenzoxepine. From this chemical name, we can identify the name doxepin. Since this is an anti-depressant, doxepin can also be used for the management of depression. It is available as a capsule at a strength starting from 25 mg to 75 mg.

At higher doses, doxepin can be used for the treatment of depression, but at lower doses, it is mainly used in the management of insomnia. Similarly, this drug can also be used for other conditions, and it is topically available as a cream. It can be used for the management of itching, dermatitis, or neuropathic pain, where it is applied topically to control pruritic conditions.

Mechanism of action

Doxepin acts through multiple mechanisms. It improves the transmission of monoamines like norepinephrine as well as another monoamine, serotonin. So transmission of norepinephrine as well as serotonin is increased within the CNS, and at the same time, doxepin can act in different ways by blocking the various types of receptors. Doxepin can mainly block the H1 histamine receptors, which may be responsible for inducing sleep. It can also block alpha-1 adrenergic receptors, even muscarinic receptors.

However, the main action of doxepin is attributed to improved transmission of monoamines like norepinephrine and 5-HT. So within the CNS, a few of the neurons can store mediators like norepinephrine. When this norepinephrine is released, it can act on the post-synaptic adrenergic receptors, which produce post-synaptic excitation. This results in adrenergic transmission within the CNS.

Similarly, another monoamine is 5-HT, or serotonin. The release of serotonin can stimulate 5-HT receptors. However, the release of norepinephrine and 5HT is controlled by a few of the transporters. One is the norepinephrine transporter (NET), which is present on presynaptic neurons; similarly, another is the SERT, or serotonin reuptake transporter, which is again located on presynaptic neurons. Now these transporters are targeted by doxepin.

In people with depression, generally, monoamine transmission is reduced. In such people, the released norepinephrine is going to be taken back into the nerve terminal by the norepinephrine transporter, just as serotonin is going to be taken by serotonin reuptake transporters. Now, doxepin can block this norepinephrine transporter as well as the serotonin reuptake transporter, thereby preventing the reuptake of both norepinephrine and serotonin. This increases the levels of norepinephrine and 5HT within the synaptic cleft, leading to an improvement in monoaminergic transmission. This relieves the symptoms of depression.

Apart from these actions, the action of doxepin on H1 receptors and adrenergic and muscarinic receptors may also play an important role. Particularly, the induction of sleep may be attributed to the antagonistic action of doxepin on H1 receptors. Even though the exact mechanism is not clear, all these may contribute to reducing the symptoms of depression as well as insomnia.


With the use of doxepin, people may observe some abnormal behavior due to its sedative effects. It can produce some sleep driving, where people can drive the vehicles with less consciousness and some sedation. It can also cause abnormal thinking, which may alter their daytime activities. Even though this effect is not observed in all people, any development of abnormal behavior with doxepin should be thoroughly monitored.

Doxepin can reduce the symptoms of insomnia within 7 to 10 days of the treatment. However, if you observe no improvement in the symptoms of insomnia even after treatment for 10 days, then doxepin may be ineffective.

Insomnia may be produced by many causes, like the development of psychosis, depression, or any other psychological disorder. All these cause disturbances in sleep, resulting in insomnia. So if you observe no improvement in the insomnia within 10 days of the treatment, then doxepin treatment should be stopped, and any other root causes for the development of insomnia should be thoroughly checked.

Another important precaution is that doxepin can act on the CNS and can produce CNS depression. So doxepin can produce some sedation, which may impair daytime activities. That's why, while taking doxepin, alcohol can improve the sedation. Anti-histamines used for the treatment of either allergies or colds can also increase sedation.

Before the use of doxepin, the patient should be thoroughly monitored for any signs of depression because, at low doses, doxepin can further worsen the depression, which may increase suicidal thoughts and suicidal risk.

Side effects

Since it acts on the CNS, it mainly produces central side effects, so doxepin causes sedation, somnolence, and sleepiness in people. Nasopharyngitis-like symptoms can be observed. Nausea, dizziness, and ataxia leading to loss of balance can be observed with doxepin.


Doxepin is available in different dosage forms, but for the treatment of insomnia, it is available as a tablet at a strength of 3 mg and 6 mg. The dose of this medication depends on age. In adults, the initial dose of this tablet is 6 mg, given once daily. However, in the elderly, the dose may be reduced to 3 mg given once daily. These tablets should be taken 30 minutes before bedtime because this drug is intended for the treatment of insomnia.

At the same time, this drug should not be taken within 3 hours of meal intake because it may be ineffective within 3 hours and it cannot produce sufficient sleep maintenance. That's why this medication should be taken 30 minutes before bedtime in order to induce sleep.


Doxepin is one of the tricyclic antidepressants that has sedative properties, so it can be used for the management of insomnia and the maintenance of sleep at a low dose, such as 6 mg. It can also be used for the management of depression at higher doses, starting from 25 mg to 75 mg, but for insomnia, it is used at a low dose.

Sedation, dizziness, and abnormal behavior are important precautions that should be considered with the use of doxepin. This medication should be given 30 minutes before bedtime in order to induce sleep, and it should not be given within 3 hours of food intake as it impairs the effectiveness of this treatment.