THERAPEUTICS

Brands

• Elavil, Amitid, Amitril, Endep, Elatrol, Laroxyl, Saroten, Redomex, Triptafen, Tryptanol, Tryptizol, Trepiline, Triptyl

Generic?

• Yes

Class

• Tricyclic antidepressant (TCA)

Commonly Prescribed for

(FDA approved in bold)

• Depression

• Migraine prophylaxis

• Tension-type headache prophylaxis

• Fibromyalgia

• Neuropathic pain

• Post-herpetic neuralgia

• Bulimia nervosa

• Insomnia

• Anxiety

• Nocturnal enuresis

• Pseudobulbar affect

• Arthritic pain

How the Drug Works

• The mechanism of action of amitriptyline and its active metabolite (nortriptyline) is probably related to reuptake inhibition of serotonin and norepinephrine at the synaptic clefts of brain and spinal cord

• It also exhibits antagonism on 5-HT2A, 5-HT2C, 5-HT6, 5-HT7, α1-adrenergic, muscarinic, H1, and NMDA receptors, and agonism on opioid (σ1, σ2) receptors

• Antinociceptive and antidepressive effects are more likely related to adaptive changes in serotonin and norepinephrine receptor systems over time

How Long Until It Works

• Migraines: effective in as little as 2 weeks, but can take up to 3 months on a stable dose to see full effect

• Neuropathic pain: usually some effect within 4 weeks

• Insomnia, anxiety, depression: may be effective immediately, but full effects often delayed 2–4 weeks

If It Works

• Migraine: goal is a 50% or greater reduction in migraine frequency or severity. Consider tapering or stopping if headaches remit for more than 6 months or if considering pregnancy

• Neuropathic pain: the goal is to reduce pain intensity and symptoms, but usually does not produce remission

• Insomnia: continue to use if tolerated and encourage good sleep hygiene

If It Doesn't Work

• Increase to highest tolerated dose

• Migraine: address other issues, such as medication overuse, other coexisting medical disorders, such as anxiety, and consider changing to another agent or adding a second agent

• Neuropathic pain: either change to another agent or add a second agent

• Insomnia: if no sedation occurs despite adequate dosing, stop and change to another agent