Amitriptyline and Imipramine Review


In this article, we are going to do two Tricyclic Antidepressants reviews. We will start with a general description of antidepressants, then hone in on the subset that is Tricyclic Antidepressants (TCAs). We will then end up by comparing the profiles of two TCAs, namely Amitriptyline and Imipramine.


Antidepressants are medications whose primary role is the treatment of Depression (Major Depressive Disorder). They take their efficacy from the fact that they are able to normalise the biochemical abnormalities in the nervous system of depressed patients.

Increasingly, it is being realised that the physical, psychological and social adversities that cause people to become depressed, all lead to decreased levels of chemicals. These chemical are in the brain, nerves and nerve junctions or connections. The most important of these chemicals are the NEUROTRANSMITTERS.

Abnormal nervous system chemistry, is the cause of the symptoms of depression. These symptoms include depressed mood, low energy levels, lack of enjoyment, decreased concentration, poor appetite and decreased libido.

By normalising the chemistry of the brain and its connections, antidepressants abolish the symptoms of depression. And they bring patients back to optimal functioning.

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These are among the earliest groups of antidepressants ever designed and used. They have been used globally for over half-a-century, and there is a wealth of experience about their clinical use. Their efficacy, side effects and adverse events are well documented.

TCAs are named after their chemical structure at the molecular level. They share a basic structure, which differs from agent to agent either naturally or due to human modification in the case of the synthetic members of the group.

The scientific or generic names of all members of this group of antidepressants end with -ine e.g. amitriptyline, imipramine, desipramine.


TCAs are mostly manufactured in tablet form. For the TCAs under discussion here, being amitriptyline and imipramine, there are tablets of 10mg and of 25mg.



For the treatment of Depression, the adult dose of the two agents is similar.

Unfortunately, a lot of patients do not get an adequate dose, and end up on 10mg, 25mg or 50mg as initial dosing. These doses are inadequate for normal adults below the age of 70, and many people end up not feeling better, not because the antidepressant is not working, but because of under-treatment.

The recommended therapeutic dose of both Amitriptyline and Imipramine is 75 – 150mg, preferably taken as a single dose at night (nocté). This is usually dispensed as 3 to 6 tablets of 25mg.


Patients are advised that sufficient improvement in their depressive symptoms will be felt after at least 10 to 14 days of therapy, although people around them may notice a change earlier.

TCA side effects, on the other hand, usually begin almost immediately on initiating treatment, but usually diminish as treatment is continued, as the body develops tolerance to the side effects. To help the body to tolerate the medication, an often omitted good practice is to initiate the treatment in this stepwise fashion (for both Amitriptyline and Imipramine):

  • 25mg nightly for 2 nights,
  • then 50mg nightly for 2 nights,
  • then 75mg nightly.

The dose can then be increased as necessary by the treating Health Practitioner.

Because of the harm that can occur (including possible death) if patients take an overdose of TCA (and the greatest risk is in the first few days of treatment initiation), patients should initially be given only a 10 days’ supply of Amitriptyline or Imipramine. At review after ten days, more tablets can then be dispensed, and the dose can be reviewed.

Correction of the biochemical abnormalities mentioned above, for ALL antidepressants, takes at least 6 weeks or 2 months. Treatment should never be shorter than two months. Ideally it should be for at least 6 months. Some patients may require a maintenance dose FOR LIFE. This maintenance dose is usually 50mg, for both Amitriptyline and Imipramine.

When patients are to stop treatment, patients should be gradually weaned off the medication, to cut the chance of disease relapse to 10%. This is done in a stepwise fashion similar to when initiating the drugs:

  • From 75mg to 50mg for a week or so,
  • then 50mg to 25mg for a week or so,
  • then 25mg on alternate nights and STOP.


There do exist, other registered uses of almost all antidepressants.

For the TCAs, the commonest alternative uses are:

* treatment of pain, especially chronic pain, pain that is hard to manage e.g. post-herpetic neuralgia, or pain that has a (strong) psychological overlay

  • treatment of anxiety
  • prevention of migraine
  • treatment of nerve disorders
  • treatment of panic
  • management of insomnia (poor sleep)
  • treatment of Irritable Bowel Syndrome (IBS)
  • management of poor appetite
  • treatment of bed-wetting (nocturnal enuresis) in children
  • management of significant low weight or weight loss as occurs in AIDS or Cancer

Amitriptyline and Imipramine differ in their efficacy in these additional uses, and these differences are among those that will be summarised below.


  • Excessive appetite
  • Weight gain that may occur even in the absence of increased appetite

  • “Anticholinergic side effects”, namely drowsiness, dry mouth and other mucous membranes, dry eyes and blurred vision, decrease in blood pressure on standing (orthostatic hypotension), delay in initiating a urine stream (prostatism) and retention of urine, decreased bowel motility and constipation, and increase in the pressure of the fluid in the eyes (glaucoma).
  • disturbed sexual function
  • headache

Again, Amitriptyline and Imipramine differ in their ability to cause these side effects, and the differences are going to be tabulated below.

Effect – Antidepressant
Amitriptyline: Yes. Gold standard
Imipramine: Yes

Effect – Panic treatment
Amitriptyline: No
Imipramine: Yes

Effect – Pain management
Amitriptyline: Yes
Imipramine: Yes, better

Effect – Migraine management
Amitriptyline: Yes
Imipramine: Yes, better

Effect – Anticholinergic SEs
Amitriptyline: More
Imipramine: Less

Effect – Weight gain
Amitriptyline: More
Imipramine: Less

Effect – Treatment of IBS, Insomnia
Amitriptyline: Yes, better
Imipramine: Less effective

Effect – Toxicity in overdose
Amitriptyline: High
Imipramine: High

Aspect – Price
Amitriptyline: Affordable
Imipramine: A bit more expensive


In addition to medication, it is important to:

– address the precipitating and perpetuating issues. The patient has to adjust the environment to be a healthy one. If this is not possible, a change of environment, if possible, is advised (even a temporary change of environment sometimes helps)

– have Counseling or Psychotherapy

– eat healthy. Nutritional supplements may be added. Please visit for

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– exercise regularly.

If after consultation with a Healthcare Practitioner, the patient chooses to try a natural substance treat the Depression (especially if the symptoms are mild),

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Amitryptiline, developed in 1960, is a very effective antidepressant with a long history of use globally. It is considered a Gold Standard antidepressant. But, because of toxicity in overdose, especially cardiac toxicity which is potentially lethal, it is not used as a first line treatment, with the”SSRIs” being preferred.

Imipramine, which also carries the same toxicity risk, is a less efficacious antidepressant. However, imipramine tends to have fewer of the SEs that make some patients unable to tolerate amitriptyline, and it has other actions for which amitriptyline cannot be used.


FOR FURTHER READING, has the following discounted books:

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5 Replies to “Amitriptyline and Imipramine Review”

  1. I have tried a lot of antidepressants before but the truth is that they may not be very good to our health and we should learn to understand that. The way you have really explained all to know about it here is very good. This two ones you mentioned here should make a good try for me. Thanks.

  2. Hello there, thanks a lot for sharing this wonderful piece of information here with us. I must say i really did enjoyed going through your article as it contains detailed information’s one can hold on to in times like this. These are great antidepressant drugs but these side effects are really discouraging for me. Thanks for sharing this

    1. Hi,

      Thanks for your input.

      The side effects are manageable. Patients and Healthcare Workers should cooperate with each other.

  3. Thank you sharing your article about antidepressants. I knew there would be some side affects to these drugs but the list of them was rather large! However the good outweighs the bad and if we have an issue it needs to be treated. 

    I was also suprised to see these drugs are used to treat many other ailments. 

    I have a first-hand experience with some family members suffering from depression and by taking the recommended doses it has improved thier life! I am thankful!

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