Amitriptyline (Elavil)
One thing about chemists is that they are molecule manipulators and they can produce an awful lot for you but as you know you've got to screen a whole lot before you get one that looks like its worth doing work beyond an animal stage. So the end result was we got a lot of tricylics, got a lot of phenothiazines, a lot of thioxanthenes and so on - Frank Ayd MD
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Classics in Chemical Neuroscience: Amitriptyline
Amitriptyline was the second tricyclic antidepressant to appear on the market for major depressive disorder under the brand name Elavil in 1961. Since its emergence, amitriptyline has been an effective therapeutic in various disease states and disorders but has also been a concerning source of cardiotoxicity. Amitriptyline inhibits serotonin and norepinephrine reuptake as well as produces off-target activity at histaminergic, muscarinic, and various other receptors. Its role as a modulator of monoamines helped further establish the monoamine theory to understand various mood disorders, paving the way for the now more common selective serotonin/norepinephrine reuptake inhibitors.
Articles of Interest
Amitriptyline for Anxiety: Is It Effective?
Overall, while there’s some evidence that amitriptyline can help with anxiety in certain situations, there isn’t a large, high quality body of research on its effectiveness as an anxiety treatment like there is for other anxiety medications.
Amitriptyline for neuropathic pain in adults
Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.
Amitriptyline v. the rest: still the leading antidepressant after 40 years of randomised controlled trials
We reviewed 186 RCTs. Amitriptyline is less well tolerated than tricyclics/heterocyclics and SSRIs, but slightly more patients treated on it recover than on alternative antidepressants.
Antidepressants and sexual dysfunction: a history
The effect of antidepressants on sex was first noted in 1960 by Frank Ayd, a psychiatrist and the discoverer of amitriptyline, who linked amitriptyline treatment to a sexual dysfunction distinct from the loss of libido that the melancholic states it was being used to treat can cause.
The Discovery of Antidepressants; Frank Ayd
Let me move on and ask you, you were also involved, as is often the case, the first drug in the field helps to make the field but the second drug becomes the best selling one, and you were involved with amitriptyline, do you want to tell me about that? Well amitriptyline's animal’s data suggested it too had phenothiazine-like effects. Merck approached me, along with Doug Goldman and Fritz Freyhan and Nate Kline, and asked us to look at this. It could have been 57/58,
‘Little evidence’ whether or not most antidepressants work for chronic pain
The review, conducted by Pincus and colleagues, looked at 176 randomised control trials involving nearly 30,000 patients. Among other drugs the trials included amitriptyline, a tricyclic antidepressant, selective serotonin reuptake inhibitors such as fluoxetine and citalopram, and duloxetine – a serotonin-noradrenaline reuptake inhibitor. Patients experiencing mental health conditions, such as depression, were excluded from most trials.
Resources
National Headache Foundation
Amitriptyline is included in a group of medications classified as tricyclic antidepressants. Amitriptyline is one of the first successful medications in this class to be developed. It was discovered in the late 1930s before scientists had today’s understanding of the chemistry of the brain. This drug was developed as a way to reduce anxiety. Frequently, people with depression are often very anxious. When amitriptyline was given to patients with anxiety, it also improved the depression. This result prompted further research and the development of newer agents to treat depression.
StatPearls
If QRS exceeds 100 msec, intravenous sodium bicarbonate is the appropriate intervention. Sodium bicarbonate is cardioprotective (it increases extracellular sodium concentration) and diminishes the effect of amitriptyline on the cardiac membrane, resulting in less sodium channel blockage. Alkalization favors the neutral form of amitriptyline and decreases the amount of active cyclic antidepressants.
