Amitriptyline vs Fluoxetine: side-by-side comparison
Amitriptyline (Tricyclic antidepressant (TCA)) and Fluoxetine (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 | Fluoxetine |
|---|---|---|
| Therapeutic class | Tricyclic antidepressant (TCA) | Selective serotonin reuptake inhibitor (SSRI) |
| CAS | 50-48-6 | 54910-89-3 |
| ATC | N06AA09 | N06AB03 |
| Molecular weight | 277.40 g/mol | 309.33 g/mol |
| Brands with this active ingredient | 1 | 1 |
What they share
Amitriptyline and Fluoxetine 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 Fluoxetine, 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. Fluoxetine: Fluoxetine selectively inhibits the serotonin reuptake transporter, increasing synaptic serotonin availability.
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… Fluoxetine: Fluoxetine is approved for major depressive disorder (adult and paediatric from age 8), obsessive-compulsive disorder, bulimia nervosa, panic disorder and premenstrual dysphoric disorder.
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. Fluoxetine: Common adverse effects include nausea, headache, sleep disturbance, sexual dysfunction and reduced appetite.
Frequently asked questions
Is Amitriptyline better than Fluoxetine? ▾
Amitriptyline and Fluoxetine are not "better or worse" — they treat different things. The sensible question is which fits your specific need.
Can Amitriptyline and Fluoxetine 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 Fluoxetine
The information on this website is provided for reference and educational purposes only. It does not replace consultation with a qualified healthcare professional.