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Amitriptyline vs Paroxetine: side-by-side comparison

Amitriptyline (Tricyclic antidepressant (TCA)) and Paroxetine (Selective serotonin reuptake inhibitor (SSRI)) belong to different therapeutic classes and are rarely substitutes for each other. The comparison is useful when a single patient is weighing both options for adjacent or overlapping needs.

Property Amitriptyline Paroxetine
Therapeutic class Tricyclic antidepressant (TCA) Selective serotonin reuptake inhibitor (SSRI)
CAS 50-48-6 61869-08-7
ATC N06AA09 N06AB05
Molecular weight 277.40 g/mol 329.37 g/mol
Brands with this active ingredient 1 1

What they share

Amitriptyline and Paroxetine share the common regulatory framework for prescription active ingredients, bioequivalence standards for generics, and pharmacist oversight. Beyond that, points in common are limited.

Key differences

Amitriptyline acts by a different mechanism than Paroxetine, with indications that barely overlap. Comparing the two is useful when a clinician has mentioned both in the same context or the patient wants to understand why one was prescribed instead of the other.

Mechanisms compared

Amitriptyline: Amitriptyline inhibits the reuptake of serotonin and noradrenaline at central synapses, raising synaptic levels of both neurotransmitters. Paroxetine: Paroxetine selectively inhibits the serotonin reuptake transporter, increasing serotonin availability at the synapse.

Indications compared

Amitriptyline: Amitriptyline is approved for major depressive disorder, but contemporary use is dominated by low-dose off-label indications: neuropathic pain, fibromyalgia, chronic tension headache, migraine prevention, irritable bowel… Paroxetine: Paroxetine is approved for major depressive disorder, generalised anxiety disorder, social anxiety disorder, panic disorder, obsessive-compulsive disorder and post-traumatic stress disorder, with regional variation.

Safety profile

Amitriptyline: Common adverse effects reflect anticholinergic, antihistaminic and α1-blocking activity: dry mouth, constipation, urinary hesitancy, blurred vision, sedation, weight gain and orthostatic hypotension. Paroxetine: Common adverse effects include nausea, sexual dysfunction (more pronounced than with most SSRIs), weight gain, sleep disturbance, fatigue and anticholinergic symptoms.

Frequently asked questions

Is Amitriptyline better than Paroxetine?

Amitriptyline and Paroxetine are not "better or worse" — they treat different things. The sensible question is which fits your specific need.

Can Amitriptyline and Paroxetine be combined?

Whether they can be combined depends on the indications and the interaction profile of each. If both are in a single prescription, the prescriber has weighed it; in self-medication they should never be combined.

Do they have the same side-effect profile?

No — they belong to different classes and have distinct side-effect profiles. Each has its own prescribing information.

Products with Amitriptyline

Products with Paroxetine

The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.