What is the interaction between amitriptyline and hydroxyzine?

From the Guidelines

Amitriptyline and hydroxyzine can be used together, but with caution due to potential increased sedation and anticholinergic effects, as noted in studies such as 1 and 1. When considering the use of amitriptyline and hydroxyzine together, it's essential to weigh the benefits against the potential risks. Amitriptyline is a tricyclic antidepressant often prescribed for depression, neuropathic pain, migraine prevention, and certain chronic pain conditions, typically starting at 10-25mg at bedtime and gradually increasing if needed. Hydroxyzine is an antihistamine used for anxiety, itching, and as a sleep aid, commonly dosed at 25-50mg up to four times daily. Some key points to consider when using these medications together include:

• Enhanced drowsiness, dry mouth, constipation, and blurred vision may occur due to the additive effects of both medications, as seen in the study 1.
• Patients should avoid alcohol and use caution when driving or operating machinery, as advised in 1.
• Both medications work on different neurotransmitter systems - amitriptyline primarily affects serotonin and norepinephrine, while hydroxyzine blocks histamine receptors, which can lead to complementary effects beneficial for certain patients, as mentioned in 1.
• The combination is sometimes intentionally prescribed for conditions like insomnia with anxiety or chronic pain with anxiety components. It's crucial to monitor patients closely for adverse effects, especially in older adults or those with comorbid conditions, and to adjust dosages accordingly, as recommended in 1. Some potential alternatives or considerations include:
• Using second-generation antihistamines, which have less sedative and anticholinergic effects, as suggested in 1.
• Adjusting the dosage or timing of either medication to minimize adverse effects, as seen in 1.
• Considering other treatment options, such as cognitive-behavioral therapy or alternative medications, as mentioned in 1.

From the Research

Amytryptiline and Hydroxyzine

• Amytryptiline is a tricyclic antidepressant, and hydroxyzine is an anti-histamine medication used to treat anxiety 2, 3.
• Hydroxyzine has been shown to be effective in treating generalized anxiety disorder (GAD), with some evidence suggesting it is more effective than placebo 2.
• In terms of side effects, hydroxyzine was associated with a higher rate of sleepiness/drowsiness than active comparators 2.
• The combination of anxiolytic drugs such as hydroxyzine with antidepressants, particularly with specific serotonin reuptake inhibitors, may be beneficial 3.
• Antidepressant treatment, including tricyclic antidepressants like amitriptyline, is effective in anxiety disorders, with broad efficacy of selective serotonin reuptake inhibitors suggesting the importance of enhanced serotonergic function 4, 5.
• The efficacy and tolerability of antidepressants, including amitriptyline, in individuals suffering from physical conditions and depressive disorders have been assessed, with results indicating that antidepressants are effective but tolerability is a concern 5.
• Combination sedative therapy, including the use of small doses of agents from different drug classes, may be advantageous in treating concomitant behavioral problems, but requires careful consideration of administration and weaning from pharmacologic effects 6.