Amitriptyline is approved for treating depression but is utilized Off-label for any range of conditions, including insomnia, pain, and irritable bowel syndrome (IBS). However, in addition, it causes many side effects that turn away people, such as sleepiness, weight reduction, and impaired sexual and immune function. Learn about the possible uses of the drug and the side effects.
What Is Amitriptyline?
Amitriptyline is a tricyclic antidepressant. It is otherwise known as Elavil or Endep.
The tricyclic simply suggests that it contains three rings in its chemical structure.
This medication was at one point the most commonly used antidepressant. In England, it had been prescribed over 11 million times in 2013.
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While amitriptyline is only FDA-approved for the treatment of Depression, it is occasionally used off-label for many other conditions, such as migraines, fibromyalgia, and irritable bowel syndrome.
Amitriptyline Is converted to nortriptyline from the entire body, which will be its active form. This drug works via many mechanisms hence the many benefits and side effects.
Mechanism of Action
- It blocks the reuptake of both serotonin and noradrenaline. Therefore, both serotonin and noradrenaline stay in your system more, which prolongs their effects.
- It blocks the activity of histamine from the brain, which leads to nausea.
- It blocks NMDA receptors and activates adenosine A1 and opioid receptors. Each one of these can lead to pain relief.
Uses of Amitriptyline
FDA-Approved Software
1) Depression
Amitriptyline is just FDA-approved for treating depression.
According To a number of clinical trials, amitriptyline might be more effective at enhancing depression symptoms in contrast to many other antidepressants. On the other hand, the frequency of side effects often limits its usage.
Two Massive meta-analyses of 186 and 194 studies compared amitriptyline against other tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Both discovered that amitriptyline helped more people. But, it also generated more side effects compared to other medications.
More people who were taking amitriptyline dropped out of the studies due to side effects compared to individuals taking different medications.
With this drug, the antidepressant effects require a long time to choose effect. Often, patients see improvements in other regions like in pain or insomnia before noticing any antidepressant effects.
Off-Label Uses
Amitriptyline Is utilized for several off-label conditions, which we will discuss in the subsequent sections. If you’re prescribed amitriptyline, always take the medicine as instructed by your health care provider.
2) Migraines
A meta-analysis (12 studies, 1,006 participants) discovered that amitriptyline helped with migraines much better than placebo. The outcomes were better for those that took the drug for longer periods of time.
But, it causes more side effects than other medications used to treat migraines, such as selective serotonin reuptake inhibitors (SSRIs), particular norepinephrine reuptake inhibitors (SNRIs), or nortriptyline.
Additionally, research indicates that amitriptyline may not help children with migraines.
3) Neuropathic Pain
Amitriptyline is sometimes used for neuropathic pain, which is brought on by damage to nerve tissue.
According to a meta-analysis (17 studies, 1,342 participants), amitriptyline may enhance chronic neuropathic pain, but it was only effective in about 25% of people. It may help people with pain due to gingivitis, diabetes, spinal cord injury, or stroke.
But, Much research concluded that this medication wasn’t any better for pain than other pain relievers/antidepressants like nortriptyline, maprotiline, desipramine, pregabalin, or fluoxetine.
4) Irritable Bowel Syndrome (IBS)
There are 3 types of IBS: IBS with diarrhea (IBS-D), IBS with constipation, and mixed-stool pattern IBS. Tricyclic antidepressants work well against IBS-D.
Tricyclic Antidepressants like amitriptyline increase the time that food stays in the intestine, which allows for more solid defecations.
In 101 IBS patients given this medication, IBS increased in 66% of cases. The treatment decreased abdominal pain, stomach distress, and stool frequency and also enhanced the quality of life. However, the side effects were frequent.
A study (double-blind randomized controlled trial) of 54 patients, amitriptyline elevated rates of full recovery (no more symptoms).
Another study (double-blind randomized controlled trial) of 32 adolescents (12-18 years) revealed similar results.
A meta-analysis along with other research all showed that this drug improved IBS.
5) Fibromyalgia
Fibromyalgia is a constant annoyance in”tender points” lasting over three months. It can result in sleep reduction, fatigue, and melancholy.
A meta-analysis (9 studies, 649 patients) showed that amitriptyline was effective for fibromyalgia at 36% of individuals.
Two studies (double-blind randomized controlled trial) with 22 and 62 fibromyalgia patients, this medication improved sleep and diminished fatigue.
However, One research (double-blind randomized controlled trial) found that it really worsened fibromyalgia in 4 of the 19 patients.
5) Sleep Issues and Insomnia
In a study (double-blind randomized controlled trial) of 27 opiate withdrawal patients suffering from insomnia, amitriptyline Induced sleep equally well as another antipsychotic medication, lorazepam. But, amitriptyline caused less nausea after waking. This may allow individuals to go about their mornings without feeling lethargic.
Amitriptyline increased total sleep by 15 minutes In a research (double-blind randomized controlled trial) of 14 patients. Additionally, they fell asleep quicker. The study noted increases in slow-wave sleep or profound sleep, and this is when muscles recuperate and you re-energize. A week after going from the medication, patients reported it had been harder to drop asleep.
This Drug may also reduce rapid eye movement (REM) sleep, according to a double-blind placebo-controlled trial of 30 patients. REM sleep can be abnormally long in patients with depression.
6) Stress
Amitriptyline diminished anxiety at a research (double-blind randomized controlled trial) of 55 patients awaiting surgery.
In a pilot study of 32 patients with depression and anxiety, this drug was effective in reducing stress.
In the same way, in two different studies, the two with 30 patients, it decreased anxiety in insomnia patients.
Anxiety Is also common in people with migraines. Reducing the frequency of migraines using amitriptyline can help reduce anxiety as well.
Though useful for anxiety, it’s a high dropout rate (30 to 50 percent ) because of side effects. Patients have a tendency to prefer selective serotonin reuptake inhibitors (SSRIs) and just move to tricyclic antidepressants when SSRIs fail.
Research About Amitriptyline
Clinical Research
Clinical Research is also investigating using amitriptyline for several other states, which are explained below. However, this study is preliminary and investigational only. The effectiveness and safety of amitriptyline for these conditions is uncertain until more studies have been conducted.
Functional Dyspepsia
Functional Dyspepsia, more commonly called indigestion, is a disease that causes pain in the upper stomach, distress, and fullness after meals. Fifty-one of the 96 patients using functional dyspepsia improved when given amitriptyline in a double-blind randomized controlled trial.
In a different double-blind randomized controlled trial of 28 volunteers, amitriptyline increased gut transit time, Which may be significant for gut function and improved digestion. Amitriptyline can also make it easier to drink large volumes of water without difficulties, which might be significant for people experiencing diarrhea.
Cystic Fibrosis Symptoms
According To a double-blind placebo-controlled trial of 19 patients, amitriptyline may improve cystic fibrosis symptoms. It might also reduce levels of ceramides that typically accumulate in the lungs of cystic fibrosis sufferers.
Still another double-blind randomized controlled trial of 19 patients showed similar effects.
Autism
As per a study of 50 children with autism, amitriptyline can improve symptoms of:
- Excessive activity
- Impulsivity
- Aggression
- Self-injury
Chronic Cough
A randomized controlled study of 28 people found that amitriptyline may be more effective in curbing chronic cough compared to the cough-suppressant drug codeine/guaifenesin. In total, 14 of the 15 patients on amitriptyline saw some improvement. In reality, 11 of the 15 patients improved by 75 to 100 percent.
Vocal Cord Dysfunction
In A study of 62 patients with vocal cord disorder, amitriptyline improved symptoms in 90 percent of cases. People that have experienced the illness for less than 12 months revealed greater and quicker results.
Cyclic Vomiting Syndrome
Cyclic Vomiting Syndrome is a disease leading to persistent nausea and vomiting. In a double-blind randomized controlled trial of 64 children, 66% of individuals given amitriptyline saw temporary retrieval.
Animal And Cell Research
No Clinical evidence supports the use of amitriptyline for any of the conditions listed in this section. Below is a list of the present animal and cell-based research, which ought to guide additional investigational efforts. On the other hand, the studies listed below should not be interpreted as supportive of any health advantage.
Parkinson’s Disease
In rat models of Parkinson’s disease, amitriptyline diminished the loss of dopamine-sensitive nerves. It also protected neurons with tyrosine hydroxylase activity, which can be decreased in patients with Parkinson’s disease.
The drug also increased serotonin levels and improved movement in rats with Parkinson’s-such as illness.
Inflammation
In cell studies, amitriptyline decreased the release of inflammatory agents by mast cells by around 98%.
In rats, this drug also decreased levels of nitric oxide, IL1-beta, and TNF-alpha, which all increase inflammation.
Amitriptyline decreased gut and kidney inflammation in rats.
Brain Health and Repair
In rat studies, amitriptyline increased BDNF in rats using Alzheimer’s disease, which increased both their short and long term memory.
Similarly, amitriptyline increased GDNF amounts in cells. Increasing GDNF may improve neuron survival and protect neurons from anxiety.
In cell studies, amitriptyline improved the production of brain-derived neurotrophic factor (BDNF) in brain cells (astrocytes and microglia). BDNF protects nerves and stimulates their development. Greater BDNF is a possible mechanism by which amitriptyline produces antidepressant effects.
Cognitive Function
Amitriptyline enhanced cognitive functioning and diminished stress (HPA axis action) in rats.
It marginally improved cognitive function in depressed rats.
The drug also improved cognitive function in rats with Alzheimer’s disease and in stressed baby rats.
Stress
In rats, amitriptyline decreased the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which response to stress by releasing adrenocorticotropic (ACTH) hormone. Amitriptyline decreased stress-induced ACTH levels by 38 percent.
The HPA system also increases levels of corticosterone in response to stress. Rats stressed by separating them by their mothers saw no such growth when given amitriptyline.
Stomach Ulcers
In rats, amitriptyline reduced stomach ulcers caused by:
- Alcohol
- Aspirin
- Indomethacin (an anti-inflammatory drug)
- Stress
The drug reduced the acidity of the stomach.
Another rat study found that this drug also diminished bowel bleeding.
Histamine Legislation
Amitriptyline improved histamine-N-methyltransferase (HNMT) and diamine oxidase (DAO) action in guinea pigs. Both these enzymes degrade histamine.
This drug also caused mast cells to discharge histamine, a powerful allergy-inducing molecule.
Polycystic Ovary Syndrome (PCOS)
Based on animal research, amitriptyline improved the use of ovaries, improved the production of sex hormones (estradiol, testosterone, and progesterone), also revived the reproductive cycle of rats with polycystic ovaries.
Security of Amitriptyline
Side Effects
Negative Effects could be common when taking amitriptyline. If any side effects persist or worsen, then let your doctor know. Additionally, this is not a comprehensive list of possible side effects. Tell your physician if you experience any serious side effects or notice any effects not listed here.
Some Frequent side effects are:
- Dry mouth
- Drowsiness
- Weight gain
- Dizziness
- Constipation
- Difficulty urinating
- Blurred vision
Some rare, but severe side effects include:
- Increased agitation
- Severe stomach pain
- Reduced sexual appetite
- Muscle spasms
- Rashes
- Nightmares
- Confusion
- Delirium
- Seizures
- Irregular heartbeats
- Bruising and bleeding
Precautions
1) Increased Risk of Suicide
Antidepressants Are associated with a greater risk of suicidal thinking and behavior, particularly in children and young adults. Those taking amitriptyline should be tracked and any changes in behavior ought to be reported to your doctor.
2) Withdrawal Symptoms
There Is a high risk of experiencing adverse events or withdrawal symptoms after abruptly discontinuing amitriptyline treatment, in as little as 12 hours. Speak with your doctor before stopping this medicine.
Withdrawing from amitriptyline can cause:
- Gut distress
- Pain
- Fatigue
- Sleep disturbances
- Disposition changes
- Movement disorders
3) Drowsiness
Taking Amitriptyline may cause drowsiness, dizziness, and blurred vision. Don’t operate a car or heavy machinery until you know how this medication may impact you.
4) Caution in Pregnancy and Breastfeeding
Some Research suggests that amitriptyline may be related to birth defects, although powerful clinical evidence is lacking. Amitriptyline should only be used during pregnancy if a doctor decides that the benefits outweigh risks.
Little Quantities of amitriptyline are excreted in breast milk. Again, a doctor will determine if amitriptyline may be used during breastfeeding.
If you are taking amitriptyline and are pregnant or intending to get pregnant, let your physician know.
5) Risk of Bleeding
Amitriptyline May increase the risk of bleeding. Tell your doctor that you’re taking amitriptyline before having any sort of surgery.
Contraindications
Hypersensitivity
People Who are sensitive or allergic to amitriptyline or some other excipients? (compounds which are present in the medication together with the medication ) should avoid using amitriptyline.
Concomitant Use with Monoamine Oxidase Inhibitors (MAOIs)
The Concomitant use of amitriptyline using monoamine oxidase inhibitors (another type of antidepressant) is contraindicated. The mixture of both medications may result in dangerously large blood pressure, convulsions, and even death.
MAOI treatment should not be started until after at least 7 days after discontinuing amitriptyline.
Amitriptyline treatment shouldn’t be started within 14 days of stopping therapy with MAOIs.
Drug Interactions
Amitriptyline inhibits cytochrome P450 enzymes (CYP1A2, CYP2D6, and CYP2C9) At higher prices than other TCAs like desipramine and nortriptyline. This causes more side effects and worse drug interactions.
Beneath Are a few reported drug interactions with amitriptyline. This is not a comprehensive list, always let your doctor know about all the medicines and supplements you are taking.
- MAO inhibitors, such as isocarboxazid, linezolid, phenelzine, selegiline
- Antipsychotics, such as quetiapine (Seroquel) and chlorpromazine (Largactil, Thorazine)
- Antifungals like terbinafine (Lamisil) and fluconazole (Diflucan)
- Valproic acid (Depakote)
- Rifampicin (Rifadin, Rimactane), an antibiotic
- Phenprocoumon (Marcoumar), a medication that keeps blood from clumping
- NSAIDs, such as ibuprofen
- Warfarin
- Cimetidine
- Amiodarone
- Quinidine
- Sotalol
Amitriptyline Dosing
Patients Will respond to antidepressants otherwise and it might take time to find the ideal dose for you. Antidepressants like amitriptyline may take time to operate and patients may not believe benefits for 1-3 weeks or more. Consistently take amitriptyline as directed by a doctor and do not stop the drug abruptly.
Amitriptyline is available in a variety of forms and dosages. Amitriptyline is most frequently regarded as an oral pill.
When beginning this medication, dosages are usually started low and gradually improved.
For depression in adults, the first dose of amitriptyline is usually 75 mg daily which might be taken in divided doses.
The maintenance dose usually ranges from 40 to 100 milligrams every day. The maximum dose is 150 mg per day.
Amitriptyline is not approved for patients under 12 years of age.
Amitriptyline Compared to Other Medications
Nortriptyline
Research suggests that both are equally effective in relieving pain, headaches, and migraines. However, amitriptyline may have more side effects.
Benzodiazepines
Studies suggest that amitriptyline might have better anti-depressive effects than adinazolam (Deracyn), a benzodiazepine. However, it also caused more side effects.
Amitriptyline may even be more successful than diazepam (Valium).
Both amitriptyline and Xanax (alprazolam) drugs were effective against depression in 80 patients in A double-blind controlled trial. Amitriptyline worked quicker, but also caused more people to fall out of the study, though the overall side effects were comparable between both drugs.
Another Research (double-blind randomized controlled trial) of 130 patients discovered that Xanax was the quicker of both and could be better for anxiety.
Selective Serotonin Reuptake Inhibitors (SSRIs)
In a research (double-blind randomized controlled trial) with 148 patients, paroxetine (Paxil, Pexeva) was better at relieving pain, enhancing the quality of life, sleep, and emotional well-being.
Both drugs were effective in treating depression in a study (double-blind randomized controlled trial) of 40 patients. However, paroxetine made a quicker response. Side effects were similar.
Opioids
A Research (double-blind randomized controlled trial) of 45 patients discovered that tramadol (Ultram) and meperidine (Pethidine), stopped shivering faster than amitriptyline. The response rate for amitriptyline was only 13% compared to 87 percent for tramadol and 93 percent for meperidine.
When used as an anesthetic, amitriptyline was more sedative than meperidine and produced fewer side effects.
Genetics
CYP2D6
CYP2D6 ultrarapid metabolizers may have to avoid the use of tricyclic antidepressants because of the possible lack of efficacy (the drug gets degraded too quickly).
For CYP2D6 intermediate metabolizers, a 25% reduction of the starting dose is recommended.
CYP2D6 poor metabolizers Have higher than expected blood concentrations of tricyclic antidepressants when given usual doses. In the event the usage of amitriptyline is warranted, it’s advisable to take 50 percent of the starting dose to prevent side effects.
A pilot study of 31 patients, patients with normal or ultrarapid metabolism of amitriptyline (CYP2D6) shown fewer unwanted side effects.
But, A study of 100 patients with major depressive order discovered that people who have CYP2D6 ultrarapid metabolism were more likely to drop out of the study when drug doses were low. This was most likely because of a lack of effect.
CYP2C19
CYP2C19 ultrarapid metabolizers may need to avoid the usage of this drug because of reduced effectiveness.
CYP2C19 poor metabolizers, should avoid the drug or consider a 50% decrease of The starting dose whilst tracking medication blood levels to prevent unwanted Consequences.