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Amitriptyline is an antidepressant that can also help with insomnia, pain, irritable bowel syndrome (IBS), and many other disorders and diseases. However, it also causes many side effects that turn people away. These include sleepiness, weight gain, and impaired immune and sexual function. Read on to see whether or not this drug is right for you.

Note: By writing this post, we are not recommending this drug.  Some of our readers who were already taking the drug requested that we commission a post on it and we are simply providing information that is available in the scientific literature. Please discuss your medications with your doctor.

Contents

What Is Amitriptyline?

Amitriptyline is a tricyclic antidepressant. It is otherwise known as Elavil or Endep [R, R].

The tricyclic simply means that it contains three rings in its chemical structure [R].

This drug was at one point the most widely used antidepressant. In England, it was prescribed over 11 million times in 2013 [R, R].

It is also among the most commonly used drugs against migraines [R].

Amitriptyline is converted to nortriptyline in the body, which is its active form. This drug works via many mechanisms hence the many benefits and side effects [R, R].

Mechanism of Action

  • It blocks the reuptake of both serotonin and noradrenaline. Therefore, both serotonin and noradrenaline stay in your system longer, which prolongs their effects [R].
  • It blocks the action of histamine in the brain, which results in drowsiness [R].
  • It blocks NMDA receptors and activates adenosine A1 and opioid receptors. All of these lead to pain relief [R, R].

Amitriptyline Uses

1) Amitriptyline Treats Depression

Two large meta-analyses of 186 and 194 studies (RCT) compared amitriptyline against other tricyclic antidepressants and selective serotonin reuptake inhibitors (SSRIs). Both found that amitriptyline helped the most people. However, it also produced more side effects than the other drugs [R, R].

More people dropped out from the studies due to side effects compared to people taking other drugs [R].

With this drug, the antidepressant effects take a long time to take effect. Often, patients see improvements in other areas such as in insomnia or pain before noticing any antidepressant effects [R, R].

2) Amitriptyline Helps with Migraines

A meta-analysis (12 studies, 1,006 participants) found that amitriptyline helped with migraines much better than placebo. The effects were better for those that took the drug for longer periods of time [R].

However, it causes more side effects than other drugs used to treat migraines, such as selective serotonin reuptake inhibitors (SSRIs), selective norepinephrine reuptake inhibitors (SNRIs), or nortriptyline [R, R].

Also, it doesn’t seem to help children with migraines [R, R].

3) Amitriptyline Helps Relieve Pain

Amitriptyline is mainly used to fight neuropathic pain, which is caused by damage to nerve tissue.

According to a meta-analysis (17 studies, 1342 participants), this drug is beneficial for chronic neuropathic pain but only works in about 25% of people. It may help people with pain due to diabetes, shingles, spinal cord injury, or stroke [R].

However, many studies concluded that this drug was not any better than other pain relievers/antidepressants such as nortriptyline, maprotiline, desipramine, pregabalin, or fluoxetine [R, R, R, R, R].

It is difficult to say if this drug will help as a pain reliever in a particular case because pain is caused by a variety of factors.

A good example is a study comparing amitriptyline to nortriptyline for pain caused by shingles. In the study (DB-RCT), 5 out of the 31 patients felt pain relief from amitriptyline, but not from nortriptyline. Four people felt pain relief from nortriptyline, but no effect from amitriptyline [R].

Amitriptyline applied to the skin can also relieve pain. Overall, 5% topical amitriptyline tends to have more local effects while 10% amitriptyline provides pain relief throughout the body [R].

In rats, this drug, unlike other pain relievers, was effective even when the nerves were damaged [R].

4) Amitriptyline Helps with Fibromyalgia

Fibromyalgia is a continuous pain in “tender points” lasting over three months. It can lead to sleep loss, fatigue, and depression [R].

A meta-analysis (9 studies, 649 patients) showed that amitriptyline cured fibromyalgia in 36% of patients [R].

In two studies (DB-RCT) with 22 and 62 fibromyalgia patients, this drug improved sleep and decreased fatigue [R, R].

However, one study (DB-RCT) found that it actually worsened fibromyalgia in 4 of the 19 patients [R].

5) Amitriptyline Improves Sleep

In a study (DB-RCT) of 27 opiate withdrawal patients suffering from insomnia, amitriptyline induced sleep equally well as another hypnotic drug, lorazepam. However, amitriptyline caused less drowsiness after waking. This allowed patients to go about their mornings without feeling sluggish [R].

Amitriptyline increased total sleep by 15 minutes in a study (DB-RCT) of 14 patients. They also fell asleep faster. The study noted increases in slow-wave sleep, or deep sleep, which is when muscles recover and you re-energize. A week after going off of the drug, it was already harder to fall asleep, and the sleep was more restless [R].

This drug reduced rapid eye movement (REM) sleep in 30 patients (DB-RCT). REM sleep is abnormally long in patients with depression [R, R, R].

6) Amitriptyline Reduces Anxiety

Amitriptyline decreased anxiety in a study (DB-RCT) of 55 patients awaiting surgery [R].

In a pilot study of 32 patients with anxiety and depression, this drug was effective in reducing anxiety [R].

Similarly, in two other studies, both of 30 patients, it reduced anxiety in insomnia patients [R, R].

Anxiety is also common in people with migraines. Reducing migraines with amitriptyline can help rid people of their anxiety [R, R].

This drug decreased anxiety in rats with migraines and under chronic stress [R, R, R].

Although useful for anxiety, it has a high dropout rate (30 to 50%) due to side effects. Patients tend to prefer selective serotonin reuptake inhibitors (SSRIs) and only move to tricyclic antidepressants when SSRIs fail [R].

7) Amitriptyline Reduces Inflammation

Mast cells release inflammatory molecules, which can worsen disorders such as chronic fatigue syndrome. Amitriptyline decreased the release of inflammatory agents from mast cells by up to 98% [R, R].

In rats, this drug also decreased levels of nitric oxide, IL1-beta, and TNF-alpha, which all increase inflammation [R, R].

Amitriptyline decreased gut and kidney inflammation in rats [R, R].

8) Amitriptyline May Decrease Histamine Levels

This drug caused mast cells to release less histamine, a potent allergy-inducing molecule [R].

It also enhanced histamine-N-methyltransferase (HNMT) and diamine oxidase (DAO) activity in guinea pigs. Both of these enzymes degrade histamine [R].

9) Amitriptyline Helps Improve Gut Function

Functional dyspepsia is a disorder that causes pain in the upper stomach, discomfort, and fullness after meals. Fifty-one of the 96 patients with functional dyspepsia improved when given amitriptyline (DB-RCT) [R].

In a study (DB-RCT) of 28 volunteers, this drug increased gut transit time. This is important for gut function and better digestion. Amitriptyline also made it easier to drink large volumes of water without problems, which can be important for people suffering from diarrhea [R].

10) Amitriptyline Improves Irritable Bowel Syndrome (IBS)

There are three types of IBS: IBS with diarrhea (IBS-D), IBS with constipation, and mixed-stool pattern IBS. Tricyclic antidepressants work best against IBS-D [R].

Tricyclic antidepressants like amitriptyline increase the time that food stays in the gut, which allows for more solid defecations [R].

In 101 IBS patients giventhis drug, IBS improved in 66% of cases. The treatment decreased stomach pain, stomach discomfort, and stool frequency and improved the quality of life. However, side effects were frequent [R].

In a study (DB-RCT) of 54 patients, amitriptyline increased rates of full recovery (no more symptoms) [R].

A different study (DB-RCT) of 32 adolescents (12-18 years) showed similar results [R].

A meta-analysis and other studies all showed that this drug improved IBS [R, R, R].

11) Amitriptyline May Help Combat Cancer

Amitriptyline caused cancer cell death in rats with multiple myeloma tumors. Tumor growth decreased and the rats survived longer [R].

In cell studies, amitriptyline killed uterine leiomyosarcoma cancer cells [R].

It also damaged lung, cervical, and hepatoma cancer cells. The drug increased levels of reactive oxygen species (ROS), which caused damage to the cancer cells [R].

Cancer cells resist chemotherapeutic drugs using enzymes glutathione S-transferases pi (GST-π) and glutathione S-transferases alpha (GST-α). In cell studies, amitriptyline inhibited the effects of both GST-π and GST-α [R].

12) Amitriptyline May Help with Stomach Ulcers

In rats, amitriptyline reduced stomach ulcers caused by [R]:

The drug reduced the acidity of the stomach [R].

Another rat study found that this drug also decreased gut bleeding [R].

13) Amitriptyline Promotes Brain Health and Repair

In cell studies, amitriptyline increased the production of brain-derived neurotrophic factor (BDNF) in brain cells (astrocytes and microglia). BDNF protects neurons and stimulates their growth. Increased BDNF is a potential mechanism by which amitriptyline produces antidepressant effects [R].

The drug increased BDNF in rats with Alzheimer’s disease, which increased both their short and long-term memory [R].

Similarly, amitriptyline increased GDNF levels in brain cells. Increasing GDNF can improve neuron survival and protect neurons against stress [R, R].

14) Amitriptyline May Improve Cognitive Function

Amitriptyline improved cognitive function and decreased stress (HPA axis activity) in aged rats [R].

It slightly improved cognitive function in depressed rats [R].

The drug also improved cognitive function in rats with Alzheimer’s disease and in stressed baby rats [R, R].

15) Amitriptyline May Help with Stress

In rats, amitriptyline decreased the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, which reacts to stress by releasing adrenocorticotropic (ACTH) hormone. Amitriptyline decreased stress-induced ACTH levels by 38% [R].

The HPA system also increases levels of corticosterone in response to stress. Rats stressed by separating them from their mothers saw no such increase when given amitriptyline [R].

16) Amitriptyline Improves Cystic Fibrosis Symptoms

Amitriptyline improved cystic fibrosis symptoms in a study (DB-RCT) of 19 patients. It also decreased levels of ceramides that tend to accumulate in the lungs of cystic fibrosis patients [R].

Another study (DB-RCT) of 19 patients showed similar results [R].

17) Amitriptyline May Be Beneficial in Autism

In 50 children with autism, amitriptyline improved symptoms of [R]:

  • Excessive activity
  • Impulsivity
  • Aggression
  • Self-injury

Another study noted that amitriptyline could also help with irritability, gut problems, and insomnia possibly by increasing levels of BDNF, an important molecule for brain health [R].

18) Amitriptyline May be Beneficial for Parkinson’s Disease

In rat models of Parkinson’s disease, amitriptyline decreased the loss of dopamine-sensitive neurons. It also protected neurons with tyrosine hydroxylase activity, which are decreased in patients with Parkinson’s disease [R, R].

The drug also increased dopamine levels and improved movement in rats with Parkinson’s-like disease [R].

19) Amitriptyline Helps with Chronic Cough

Amitriptyline was more effective in suppressing chronic cough than the cough-suppressant drug codeine/guaifenesin. In total, 14 of the 15 patients on amitriptyline saw some improvement. In fact, 11 of the 15 patients improved by 75 to 100% [R].

20) Amitriptyline Helps with Vocal Cord Dysfunction

In a study of 62 patients with vocal cord dysfunction, amitriptyline improved symptoms in 90% of cases. People that have had the condition for less than 12 months showed greater and quicker results [R].

21) Amitriptyline May Treat Polycystic Ovary Syndrome (PCOS)

Amitriptyline improved the function of ovaries, increased the production of sex hormones (estradiol, testosterone, and progesterone), and restored the reproductive cycle of rats with polycystic ovaries [R].

22) Amitriptyline Treats Cyclic Vomiting Syndrome

Cyclic vomiting syndrome is a disorder leading to constant nausea and vomiting. In a study (DB-RCT) of 64 children, 66% of patients given amitriptyline saw temporary recovery [R].

Safety and Side Effects

Many users experience amitriptyline-related side effects. In one study (DB-RCT), 95% of patients receiving amitriptyline noted some adverse event [R].

Common side effects are [R]:

  • Dry mouth
  • Drowsiness
  • Weight gain
  • Anticholinergic effects

Other side effects include:

  • Increased agitation [R, R]
  • Stomach pain [R]
  • Constipation [R]
  • Rashes [R]
  • Nightmares [R]
  • Hyperpigmentation [R]
  • Confusion [R]
  • Delirium [R]
  • Seizures [R]
  • Irregular heartbeats [R]

1) Amitriptyline Can Increase Weight Gain

Weight gain is especially common during early stages of amitriptyline use. It can be seen as either an improvement for depressed patients who under-eat or as a symptom in people that eat when depressed [R].

Weight gain after discontinuing amitriptyline can occur as a side effect of the treatment [R].

2) Amitriptyline Is Addictive

Antidepressants with sedative effects such as amitriptyline are vulnerable to abuse [R].

A meta-analysis of 14 case reports found that amitriptyline was the most abused among antidepressants. Abusers noted that taking this drug in large amounts produced a “high” feeling of euphoria and pleasantness [R].

This high can be especially addictive to narcotic users [R, R].

A survey of 346 individuals in a methadone maintenance program found that 25% of the people were taking amitriptyline for the feelings of euphoria. Of those surveyed, 34% of the individuals had traces of it in their urine [R].

Even doses of 100 to 200 mg a day, which is not substantially high, can induce drug dependence [R].

Abusers may take amitriptyline because it can escape urine tests looking for narcotics [R].

Withdrawal symptoms can occur within days of discontinuing drug use. Withdrawing from amitriptyline can cause [R]:

  • Gut distress
  • Pain
  • Fatigue
  • Sleep disturbances
  • Mood changes
  • Movement disorders

Other side effects can include nightmares and worsening of conditions such as [R]:

  • Irregular heartbeat and chest pain
  • Peptic ulcers

If withdrawal symptoms occur, it is advised to restart amitriptyline and wane off of the drug [R].

3) Amitriptyline May Worsen Fibromyalgia

One study (DB-RCT) found that amitriptyline worsened fibromyalgia in 4 of the 19 patients [R].

4) Amitriptyline Increases Sleepiness

A study (DB-RCT) of 14 male patients found that taking this drug produced drowsiness and sluggishness in the mornings [R].

Another study (DB-RCT) of 14 volunteers found that amitriptyline decreased next-day alertness and increased daytime sleepiness [R].

5) Amitriptyline May Cause Coenzyme-Q Deficiency

Amitriptyline induced coenzyme-Q deficiency, oxidative stress, and damage to mitochondria (the energy-producing organelle in cells) in 40 depressed patients [R].

It strongly decreased coenzyme-Q levels in the lungs and liver of rats [R].

6) Amitriptyline May Trigger Parkinson’s Disease

Studies report that a history of antidepressant use is strongly correlated with the occurrence of Parkinson’s disease [R].

In rats, amitriptyline increased neuron damage in the brain (substantia nigra). The drug caused movement dysfunction in the rats, a common symptom of Parkinson’s disease [R].

7) Amitriptyline May Suppress the Immune System

This drug decreased levels of white blood cells in burned rats by 40%. White blood cells protect the body against foreign invaders [R].

8) Amitriptyline May Impair Sexual Function and Decrease Libido

erectile dysfunction

In 8 studies (RCT), the average frequency of sexual dysfunction due to amitriptyline in men was 11.9% and 1.7% in women. Depressed patients were more likely to experience sexual dysfunction [R].

The drug impaired libido (sex drive), in both men and women, but the effect was more pronounced in women [R].

9) Amitriptyline May Impair Driving

In a study (DB) of 17 volunteers, this drug decreased concentration while driving [R].

Dosage

The drug is available in tablets (10, 25, and 50 mg) or as an oral solution [R].

The stronger tablets will have stronger effects but are also more likely to cause side effects. It is recommended to start off small and slowly increase the dosage until side effects start to occur.

Because it can cause drowsiness, the drug is often taken at night [R].

Overdose

Overtaking this drug can lead to confusion, delirium, and seizures. Overdosing can produce irregular heartbeats (heart arrhythmia) and can be fatal [R].

Deaths due to amitriptyline are fairly common. Most of these overdose deaths are suicidal, although in some cases it can be due to addiction [R].

Contraindications

Amitriptyline should be taken with caution in pregnancy. Amitriptyline and nortriptyline can both cross the placenta and be toxic to the fetus [R, R].

Newborns that have been exposed to tricyclic antidepressants may display withdrawal symptoms [R].

Complications such as pre-term delivery and increased blood pressure can also occur following tricyclic antidepressant use [R].

This drug can also be transferred via breast milk. A case study showed that breastfeeding while on amitriptyline can cause poor feeding and extreme sedation in the child [R].

Drug Interactions

Amitriptyline inhibits cytochrome P450 enzymes (CYP1A2, CYP2D6, and CYP2C9) at higher rates than other TCAs such as desipramine and nortriptyline. This causes more side effects and worse drug interactions [R].

This drug should not be taken with:

  • Antipsychotics, such as quetiapine (Seroquel) and chlorpromazine (Largactil, Thorazine) [R, R]
  • Antifungals such as terbinafine (Lamisil) and fluconazole (Diflucan). They can increase levels of amitriptyline to toxic levels even 6 months after use [R, R, R]
  • Valproic acid (Depakote) [R]
  • Rifampicin (Rifadin, Rimactane), an antibiotic [R]
  • Phenprocoumon (Marcoumar), a drug that keeps blood from clumping [R]

Amitriptyline Compared to Other Medication

Amitriptyline vs. Nortriptyline

Both are equally effective in relieving pain, headaches, and migraines. However, amitriptyline had more side effects; thus, nortriptyline may be more useful [R, R, R, R].

Amitriptyline vs. Benzodiazepines

Amitriptyline produced better antidepressive effects than adinazolam (Deracyn), a benzodiazepine. However, it also caused more side effects [R].

Amitriptyline was also more effective than diazepam (Valium) [R].

Both amitriptyline and xanax (alprazolam) drugs were effective against depression in 80 patients (DB-RCT). Amitriptyline worked faster, but also caused more people to drop out of the study, even though the overall side effects were similar between the two drugs [R].

Another study (DB-RCT) of 130 patients found that Xanax was the quicker of the two and was better in curing anxiety [R].

Amitriptyline vs Selective Serotonin Reuptake Inhibitors (SSRIs)

In a study (DB-RCT) with 148 patients, paroxetine (Paxil, Pexeva) was better in relieving pain, improving quality of life, sleep, and emotional well-being [R].

Both drugs were effective in treating depression in a study (DB-RCT) of 40 patients. However, paroxetine produced a quicker response. Side effects were similar [R].

Amitriptyline vs. Opioids

A study (DB-RCT) of 45 patients found that tramadol (Ultram) and meperidine (Pethidine), stopped shivering quicker than amitriptyline. The response rate for amitriptyline was only 13% compared to 87% for tramadol and 93% for meperidine [R].

When used as an anesthetic, amitriptyline was more sedative than meperidine and produced fewer side effects [R].

Synergies with Other Drugs/Supplements

One study (DB-RCT) of 63 patients noted that amitriptyline with melatonin reduced pain better than amitriptyline alone [R].

Amitriptyline and fluoxetine (Prozac, Sarafem) work better when combined to improve pain, well-being, and sleep in fibromyalgia [R].

Combining amitriptyline with warfarin, increases and prolongs the effects of warfarin (blood thinning) [R].

Amitriptyline increases the blood levels and effectiveness of oxycodone [R].

Chlordiazepoxide (Librium) increases the antidepressant effects of amitriptyline [R].

Associated Genes

CYP2D6

CYP2D6 ultrarapid metabolizers should avoid the use of tricyclic antidepressants due to the potential lack of effectiveness (the drug gets degraded too quickly). They should consider an alternative drug not metabolized (broken down) by CYP2D6 [R].

For CYP2D6 intermediate metabolizers, a 25% reduction of the starting dose is recommended [R].

CYP2D6 poor metabolizers have higher than expected blood concentrations of tricyclic antidepressants when given usual doses. They should avoid the use of this drug because of the potential for side effects. If the use of amitriptyline is warranted, it is recommended to take 50% of the starting dose to avoid side effects [R].

In a pilot study of 31 patients, patients with normal or ultrarapid metabolism of amitriptyline (CYP2D6) displayed fewer side effects [R].

However, a study of 100 patients with major depressive order found that those with CYP2D6 ultrarapid metabolism were more likely to drop out from the study when drug doses were low. This was most likely due to lack of effect [R].

CYP2C19

CYP2C19 ultrarapid metabolizers should avoid the use of this drug due to reduced effectiveness. They should consider an alternative drug not metabolized by CYP2C19, such as nortriptyline or desipramine [R].

CYP2C19 poor metabolizers, should avoid the drug or consider a 50% reduction of the starting dose while monitoring drug blood levels to avoid side effects [R].

User Reviews

Many people say that this drug helped their IBS instantly and that not taking the drug brought back their symptoms.

A lot of the people that found no effect with SSRIs and other antidepressants saw improvements with amitriptyline.

Many people saw beneficial effects in migraine prevention. However, there were some that complained that the migraines reappeared months into the therapy.

There were more people that said this drug helped decrease pain than not, but many complained of side effects.

Regarding insomnia and fibromyalgia, there were many mixed reviews, but more people favored the drug.

Amitriptyline for Dogs and Cats

Interestingly, amitriptyline is prescribed for dogs with chronic or nerve pain after other painkillers fail [R, R].

Injecting the drug straight into the bloodstream can induce side effects such as [R]:

  • Sedation
  • Lack of muscle coordination (ataxia)
  • Rapid heart rate (transient tachycardia)
  • Excessive hunger (polyphagia)
  • Vomiting

Oral dosing can cause vomiting if the dogs are fasted [R].

A recommended dose for dogs is 1-4 mg/kg [R].

In cats, this drug given orally is more effective than over the skin [R].

The drug cured inflammation of the bladder in 9 of 15 cats. However, some side effects included [R]:

FDA Compliance

The information on this website has not been evaluated by the Food & Drug Administration or any other medical body. We do not aim to diagnose, treat, cure or prevent any illness or disease. Information is shared for educational purposes only. You must consult your doctor before acting on any content on this website, especially if you are pregnant, nursing, taking medication, or have a medical condition.

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8 COMMENTS

  • carol close

    Get to the cause of the problem. Don’t treat the symptoms. What is better than amitriptyline is checking hormone levels and getting hormones restored to normal levels. Bioidentical progesterone cream helps with depression, migraines, fibromyalgia, sleep, anxiety, inflammation, histamine, gut function, IBS, cancer, stomach ulcers, brain and health repair, improves cognitive function, PCOS and Parkinsons, even for men- as men’s levels should be equal to women’s levels in the follicular phase. Progesterone starts to decline in the mid 30s. Cannibis and alcohol lower progesterone levels at a much earlier age. Menopausal women produce 0 progesterone. https://en.wikipedia.org/wiki/Progesterone

    https://www.ncbi.nlm.nih.gov/pubmed/26408166 Endocannabinoids and the Endocrine System in Health and Disease.

    https://www.ncbi.nlm.nih.gov/pubmed/10397281 Acute effect of alcohol on estradiol, estrone, progesterone, prolactin, cortisol and luteinizing hormone in premenopausal women.

    Bioidentical hormones are needed to restore hormone levels- not synthetic progesterone like medroxyprogesterone because synthetic progesterones are foreign to our bodies and do not match exactly to our hormone receptors and do not activate the dopanergic and serotonergic pathways to prevent neurodegeneration or activate the p53 tumor suppressor or inhibit mTOR to put the brakes on cancer.

    https://www.ncbi.nlm.nih.gov/pubmed/17217322 A comprehensive review of the safety and efficacy of bioidentical hormones for the management of menopause and related health risks. Bioidentical hormones match the structure and function of hormones produced in our bodies. Although synthetic progesterones are known to be different with respect to molecular structure, receptor affinity, metabolism, and other physiological traits, most have been treated as if they were clinically identical to bioidentical hormones, but they are not identical with different clinical outcomes in the breast, endometrium, bone, cardiovascular system, and brain. The studies reviewed suggest bioidentical progesterone does not have a negative effect on blood lipids or vasculature as do many synthetic progestins, and may carry less risk with respect to breast cancer incidence. Studies of both bioidentical estrogens and progesterone suggest a reduced risk of blood clots compared to non-bioidentical preparations. (In other words, our health is improved with real normalized hormone levels. Synthetic hormones are bad or you! Synthetic hormones were made so pharmaceutical companies could get a patent and make more money. Recently the way pharmaceutical companies have been able to get patents on real hormones is by making estradiol in a patch and by micronizing progesterone. So that’s how they are making big money.)

    Amitriptyline is an anticholinergic which its side effect is dementia. https://www.medscape.com/viewarticle/838788 ‘Strongest Evidence Yet’ Links Anticholinergic Drugs, Dementia

    Amitriptyline over time disrupts Delta wave sleep.Delta sleep is important in Parkinson’s, Schizophrenia, diabetes and insulin resistance, fibromyalgia, narcolepsy, depression, anxiety, obsessive compulsive disorder, attention deficit hyperactive disorder, juvenile chronic arthritis. https://en.wikipedia.org/wiki/Delta_wave (Progesterone, GABA with HTP, tryptophan, rosemary, and Ashwagandha enhance Delta sleep.)

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3076958/ Antidepressant and Antipsychotic Drugs The antidepressant and antipsychotic drugs are a set of agents with a wide range of different pharmacologic effects. Many of these pharmacologic effects impact sleep-wake function. This can involve promoting sleep, promoting wakefulness, altering the amount or timing of sleep stages across the night and increasing the likelihood of restless legs syndrome and/or periodic movements of sleep which can disturb sleep.

    Depression-
    Low levels of progesterone decrease serotonin, which can cause poor sleep and depression. Also, diminished amounts of progesterone prevent the balancing of the stimulating effects of estrogen and can lead to anxiety. … Cortisol: Depression has been associated with both elevated and low levels of cortisol. https://socalbhrt.com/depression-and-irritability/
    Also, in particular, certain 3α-reduced metabolites of progesterone such as 3α,5α-tetrahydroprogesterone (allopregnanolone) and 3α,5β-tetrahydroprogesterone (pregnanolone) are potent positive allosteric modulators of the GABA(A) receptor complex. During the last years, the downregulation of neurosteroid biosynthesis has been intensively discussed to be a possible contributor to the development of anxiety and depressive disorder. Reduced levels of allopregnanolone in the peripheral blood or cerebrospinal fluid were found to be associated with major depression, anxiety disorders, premenstrual dysphoric disorder, negative symptoms in schizophrenia, or impulsive aggression. The importance of allopregnanolone for the regulation of emotion and its therapeutical use in depression and anxiety may not only involve GABAergic mechanisms, but probably also includes enhancement of neurogenesis, myelination, neuroprotection, and regulatory effects on HPA axis function. https://www.ncbi.nlm.nih.gov/pubmed/24215796 “The role of allopregnanolone in axiety and depression.”

    Migraines-
    2% natural progesterone cream: The estrogen dominance that is so common during perimenopause can trigger a migraine, due to estrogen’s excitory nature. Often, 2% bioidentical progesterone cream is all you need to relieve premenstrual or menopausal migraines https://www.drnorthrup.com/migraines/
    Click here for scientific research curing all patients of migraines http://www.ncbi.nlm.nih.gov/pubmed/26707041 “Is migraine a consequence of neurohormonal and metabolic integrity?”
    Also- http://www.lifeextension.com/magazine/2006/12/cover_migraine/page-01

    Fibromalgia –
    Sleep disturbances are common in fibromyalgia, and progesterone enhances slow wave deep Delta sleep phase, the hormone restorative phase.
    https://www.ncbi.nlm.nih.gov/pubmed/28545798 “Sleep disturbances in fibromyalgia: A meta-analysis of case-control studies.” https://en.wikipedia.org/wiki/Delta_wave

    IBS-
    Recent clinical and experimental findings support the modulatory actions of sex hormones exerted at different levels of the brain-gut-microbiota axis in irritable bowel syndrome (IBS). Sex hormones may influence peripheral and central regulatory mechanisms contributing to the alterations in visceral sensitivity, motility, permeability, and immune activation of intestinal mucosa. A new concept of “microgenderome” is emerging based on the observations that the gender bias present in numerous diseases may be reinforced by the commensal microbiota of the host. Significant sex differences in epidemiology, symptomatology, and treatment outcome in IBS indicate the necessity for sex-tailored therapeutic approach in this disorder. Furthermore, a growing body of evidence indicates a protective role of androgens in pain modulation and anti-inflammatory properties of testosterone that may inhibit the development of visceral hyperalgesia.
    Sex steroid hormones such as progesterone, estradiol, and testosterone play a number of important physiological roles including reproduction, differentiation, development, cell proliferation, apoptosis, inflammation, metabolism, homeostasis, and brain function. They are mainly synthesized by gonads, the adrenal gland, and the placenta and are released into the blood stream to act both in peripheral target tissues and the central nervous system. Sex steroid hormones exert their function by binding to either specific intracellular receptors that act as ligand-dependent transcription factors (classical mechanism) or membrane receptors that stimulate several signal transduction pathways (nonclassical mechanism).
    Interestingly, sex steroid hormones also participate in the communication between microorganisms and mammal hosts. This type of communication is commonly referred to as “interkingdom signaling” and can be used by microbial pathogens to activate their virulence factors and control the course and outcome of infection. Notably, human and animal males, in general, are more susceptible to protozoan, fungal, bacterial, and viral infections than females. This susceptibility could be due to the lower immune responses presented in males than in females, since innate responses, antibody-mediated, and cellular responses are typically lower in males than in females.
    Numerous studies have reported the effects of sex steroid hormones on the dimorphic sex differences in the response to microbial and viral infections. In addition to affecting host immunity, sex hormones alter gene expression and behavior that influence susceptibility and resistance to infection. This paper mainly focuses on the participation of sex hormones in the interaction between pathogenic bacteria and their hosts, their involvement in the host mechanisms used to minimize and eradicate the infection, as well as in the pathways used by bacteria to evade the immune response. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3949254/ “Sex hormones in the modulation of irritable bowel syndrome”

    1. Biljana N

      Thank you for all the information.

      We are by no means promoting amitriptyline as a go-to solution for any of these problems. All of these health issues are complex, and there are a number of ways to approach them. Also what works for one person, may not necessarily work for the other.

      We do have many posts on natural substances that help with many of these issues. We also have a post about progesterone and its benefits.

      The information here is provided for people who cannot avoid using this drug, and for those who would like to know more about it and its effects.

  • carol close

    Brain health and repair. Improving cognitive function-
    Previous studies have shown that progesterone supports the normal development of neurons in the brain, and that the hormone has a protective effect on damaged brain tissue. It has been observed in animal models that females have reduced susceptibility to traumatic brain injury and this protective effect has been hypothesized to be caused by increased circulating levels of estrogen and progesterone in females. The mechanism of progesterone protective effects may be the reduction of inflammation that follows brain trauma and hemorrhage. Damage incurred by traumatic brain injury is believed to be caused in part by mass depolarization leading to excitotoxicity. One way in which progesterone helps to alleviate some of this excitotoxicity is by blocking the voltage-dependent calcium channels that trigger neurotransmitter release. It does so by manipulating the signaling pathways of transcription factors involved in this release. Another method for reducing the excitotoxicity is by up-regulating the GABA, a widespread inhibitory neurotransmitter receptor.
    Progesterone has also been shown to prevent apoptosis in neurons, a common consequence of brain injury. It does so by inhibiting enzymes involved in the apoptosis pathway specifically concerning the mitochondria, such as activated caspase 3 and cytochrome c. Not only does progesterone help prevent further damage, it has also been shown to aid in neuroregeneration. One of the serious effects of traumatic brain injury includes edema. Animal studies show that progesterone treatment leads to a decrease in edema levels by increasing the concentration of macrophages and microglia sent to the injured tissue. This was observed in the form of reduced leakage from the blood brain barrier in secondary recovery in progesterone treated rats. In addition, progesterone was observed to have antioxidant properties, reducing the concentration of oxygen free radicals faster than without. There is also evidence that the addition of progesterone can also help remyelinate damaged axons due to trauma, restoring some lost neural signal conduction. Another way progesterone aids in regeneration includes increasing the circulation of endothelial progenitor cells in the brain. This helps new vasculature to grow around scar tissue which helps repair the area of insult. https://en.wikipedia.org/wiki/Progesterone

    Inflammation-
    Progesterone acts as an antiinflammatory agent and regulates the immune response. https://en.wikipedia.org/wiki/Progesterone
    Real progesterone increases T cells synergistically with Vitamin D. Real progesterone with vitamin D promotes generation of induced regulatory T cells with increased stability. Real progesterone is responsible for immune function in cooperation with vitamin D which fail with lowered progesterone and lowered vitamin D both causing autoimmune disorders and other diseases. Vitamin D makes progesterone effective. Progesterone works synergistically with Vitamin D in the central nervous system and in immune function increasing T cells.

    Parkinson’s-
    Sleep disturbances, as well as dementia are common features of Parkinson’s disease, and patients with this disease show disrupted brain wave activity. The drug Rotigotine, developed for the treatment of Parkinson’s disease, has been shown to increase delta power and slow-wave sleep. Delta-wave inducing peptide injected into the substantia nigra of the rat model has been shown to increase Parkinsonian symptoms. https://en.wikipedia.org/wiki/Delta_wave
    Progesterone enhances Delta wave sleep. https://books.google.com/books?id=D1fOTC6CP3kC&pg=PA49&lpg=PA49&dq=progesterone+enhances+delta+sleep&source=bl&ots=_8sBxqnnT7&sig=9gB-f4OHVd4QDL-aCnBRIn1xNGE&hl=en&sa=X&ved=0ahUKEwixvaK_zt_XAhXo44MKHQllD58Q6AEIQzAE#v=onepage&q=progesterone%20enhances%20delta%20sleep&f=false “Neurosteroids and the Nervous System”

    Delta sleep stimulates the release of human growth hormone and human growth hormone which growth hormone is linked to Klotho, the anti-aging hormone, which regulates calcium and phosphate homeostasis and vitamin D metabolism. Klotho Protein Fragment Improves Brain Function, Resilience in Mice; May Eventually Benefit Parkinson’s Patients. https://parkinsonsnewstoday.com/2017/08/14/klotho-protein-improves-brain-function-resilience-mice-may-potentially-benefits-parkinsons-alzheimers/

    Histamine-
    Progesterone is needed to upregulate DAO. Estrogen downregulates DAO. Estrogen triggers histamine release. Progesterone can also directly inhibit the release of histamine from mast cells, even during allergic reactions that trigger their degranulation.
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377947/ Role of sex hormones, estradiol and progesterone, in mast cell behavior. Frontiers in Immunology, 3(169).
    http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3537328/ Estrogen effects in allergy and asthma. Current Opinion in Allergy and Clinical Immunology, 13(1), 92-99.

    Stomach ulcers-
    The gastric acid secretion was determined in rats with gastric ulcers equipped with chronic gastric fistula. Treatment with progesterone significantly accelerated ulcer healing and increased the gastric and lingual blood flow at margin of these ulcers. https://www.ncbi.nlm.nih.gov/pubmed/15608364 The role of female and male sex hormones in the healing process of preexisting lingual and gastric ulcerations.

    PCOS-
    Combined Follicle Stimulating Hormone and progesterone treatments restored estradiol level and reduced cystic signs in the follicles, and attenuates PCOS characteristics. https://www.ncbi.nlm.nih.gov/pubmed/29062793 Ultra-low Doses of Follicle Stimulating Hormone and Progesterone Attenuate the Severity of Polycystic Ovary Syndrome Features in a Hyperandrogenized ….

    Cancer-
    With The Women’s Health Initiative, the estrogen plus progestin trial was stopped in July 2002, after investigators found that the associated health risks of the combination hormone therapy outweighed the benefits. Participants were followed for an average of 5.6 years. The study found that conjugated equine estrogen and synthetic progesterone that were once popular cause cancer by 30% or more. They are foreign to our bodies. However, real or micronized progesterone (not synthetic) both inhibits mTOR and activates the p53 tumor suppressor gene which together both p53 and mTOR kill and put the brakes on cancer. Now pharmaceutical companies have estradiol patches and micronized progesterone instead; however, at below normal levels to prevent spotting.
    The well-established body of literature demonstrating the harmful effects of non-bioidentical hormones might lead some women to fear taking bio-identical hormones as well. A review of the published scientific literature indicates those fears are misunderstood and unfounded. For example, thirteen studies document that non-bioidentical progestin significantly increases estrogen-stimulated breast cell replication and growth. In stark contrast; seven studies have shown that bioidentical progesterone does not induce estrogen-stimulated breast cell proliferation.

    Progesterone levels equal to the third trimester- (468 nmol/l) kill ovarian cancer. Progesterone is recommended in advanced stage ovarian cancer disease.
    https://www.ncbi.nlm.nih.gov/pubmed/21761364 “Expression of membrane progesterone receptors (mPR/PAQR) in ovarian cancer cells: Implications for progesterone-induced signaling events.” The high mortality rates associated with ovarian cancer are largely due to a lack of highly effective treatment options for advanced stage disease; a time when initial diagnosis most commonly occurs. Progesterone which possess anti-tumorigenic properties is recommended in advanced stage ovarian cancer.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4189458/ “Protective Effect of Progesterone during Pregnancy against Ovarian Cancer”
    https://www.ncbi.nlm.nih.gov/pubmed/9149021/ “Progesterone induces apoptosis and up-regulation of p53 expression in human ovarian carcinoma cell lines.”
    https://www.ncbi.nlm.nih.gov/pubmed/14534535/ “Progesterone-induced apoptosis in immortalized normal and malignant human ovarian surface epithelial cells involves enhanced expression of FasL.”
    .
    Progesterone kills brain cancer. http://www.oncologynurseadvisor.com/headlines/progesterone-could-be-added-to-brain-cancer-therapies/article/356841/ Progesterone could become part of therapy against the most aggressive form of brain cancer.

    Progesterone and estrogen double lung cancer survival. https://www.lungcancerfoundation.org/2014/03/lung-cancer-survival-rate-doubled-with-progesterone-and-oestrogen-therapy/ Progesterone and estrogen doubled lung cancer survival rate.

  • carol close

    Re: #2 Amitryptyline helps with migraines.

    Click here below for scientific research curing all patients of migraines http://www.ncbi.nlm.nih.gov/pubmed/26707041 “Is migraine a consequence of neurohormonal and metabolic integrity?”

    Also http://www.lifeextension.com/magazine/2006/12/cover_migraine/page-01

  • carol close

    Re: #2. Amitryptyline helps with migranes.

    Click here for scientific research curing all patients of migraines http://www.ncbi.nlm.nih.gov/pubmed/26707041 “Is migraine a consequence of neurohormonal and metabolic integrity?”

    Also http://www.lifeextension.com/magazine/2006/12/cover_migraine/page-01

  • carol close

    Re: #5 Amitryptyline Improves Sleep. Wrong: It does NOT improve sleep because with time, it reduces and delays Delta sleep.

    Delta sleep is important for producing growth hormone and for also producing Klotho, the anti aging hormone that regulates calcium and phosphorous homeostasis. Delta sleep is also when your core body temperature drops which is usually 1 hour after falling asleep, so then brain cells shrink 60% and the body’s glymphatic system, the nighttime brain housekeeping system, goes to work with cerebrospinal fluid washing out the brains toxins including Beta amyloid produced during the day by a hardworking brain and made soluble by progesterone allowing the Beta amyloid to be washed out. When progesterone declines with age starting in your late 30s, then luteinizing hormone rises which raises the night time core body temperature decreasing Delta sleep not allowing the body core temperature to drop like normal for quality Delta sleep. Without Delta sleep, you are in danger of developing dementia, Alzheimer’s, Parkinsons, ALS, and other neurodegenerative diseases. A 20 year old spends 20% of the night in Delta sleep, a 40 year old spends 5% of the night in Delta sleep, and an 80 year old spends 0% of the night in Delta sleep. 30% of people over 85 have dementia. Rosemary, Ashwagandha, GABA with 5HTP, vitamin D, tryptophan, and progesterone increase Delta sleep. Valerian reduces Delta sleep and so does Amitryptyline and other anticholinergics.

    Amitryptyline is an anticholinergic which anticholinergics are implicated in dementia and neurodegenerative diseases. Anticholinergics are a group that encompasses medications for colds and allergies, anxiety, depression, insomnia, high blood pressure, and incontinence…. Pretty much any medicine that makes you groggy and your mouth really dry. Taking an anticholinergic for the equivalent of 3 years or more was associated with a 54% higher dementia risk than taking the same dose for 3 months or less. “The Beer’s List published by the American Geriatrics Society has long recognized benzodiazepines, antihistamines, and tricyclic antidepressants, including Amitryptyline, as potentially inappropriate for older adults, given their side effects,” says Dr. Lauren J. Gleason, a physician in the Division of Aging at Harvard-affiliated Brigham and Women’s Hospital. Such drugs are on the list because they share troubling side effects—confusion, clouded thinking, and memory lapses—that can lead to falls, fractures, and auto accidents. https://www.health.harvard.edu/mind-and-mood/two-types-of-drugs-you-may-want-to-avoid-for-the-sake-of-your-brain

    Your first source in this article about the 14 people and Delta sleep increase is from 1973. Since then, they have found that Amitriptyline initially improves sleep symptom scores and patients have a meaningful response, however, by six months the response declines. Check here. CLINICAL SLEEP DISORDERS 2012 https://books.google.com/books?id=-ZTfjy2GLBYC&pg=PA463&lpg=PA463&dq=amitriptyline+delta+sleep&source=bl&ots=C9wuvwD6Tr&sig=EEIBDW4dNQBNphdmPlbCsSh-9Kg&hl=en&sa=X&ved=0ahUKEwiZ28nJ1NjXAhUFMd8KHazwDEkQ6AEIWjAH#v=onepage&q=amitriptyline%20delta%20sleep&f=false

    https://www.sleepsomatics.com/sleepsomatics-journal-blog-about-sleep/what-causes-deficient-restorative-sleep/2014/7/18 It must be stated here that you should never alter or adjust your prescription medication usage without direction from or supervision of the prescribing physician. Nor should a patient assume that because a medication is listed below that Stage N3 delta or Stage REM suppression or sleep disruption are guaranteed or confirmed effects.

    The list below is only a sample of medications within those categories or medication groups, and it is the groups that are commonly associated with sleep architecture changes. Psychiatric prescription medications that can potentially reduce, delay, or worsen physiologically-restorative and hormone-balancing Stage N3 delta slow-wave sleep and/or reduce cognitively-restorative Stage REM sleep include: :

    •Benzodiazepines ◦Alprazolam (Xanax)
    ◦Clonazepam (Klonopin)
    ◦Diazepam (Valium)
    ◦Lorazepam (Ativan)
    ◦Temazepam (Restoril)

    •MAOI (monoamine oxidase inhibitor) ◦Isocarboxazid (Marplan)
    ◦Phenelzine (Nardil)
    ◦Selegiline (Emsam)
    ◦Tranylcypromine (Parnate)

    •Selective SNRI (serotonin and norepinephrine reuptake inhibitor) ◦Desvenlafaxine (Pristiq)
    ◦Duloxetine (Cymbalta)
    ◦Venlafaxine (Effexor)

    •SSRI (selective serotonin reuptake inhibitors) ◦Citalopram (Celexa)
    ◦Escitalopram (Lexapro)
    ◦Fluoxetine (Prozac)
    ◦Paroxetine (Paxil)
    ◦Sertraline (Zoloft)

    •TCA (tricyclic antidepressants) ◦Amitriptyline (Elavil)

    Be aware that all anti-histamines including Benadryl, sleeping pills and sleep aids, including Seroquel, and over the counter cold pills also reduce, delay or worsen Delta slow wave deep sleeps. Below are sites listing dementia causing drugs and medicines.

    Are Your Drugs Raising Your Risk for Dementia? – The People’s …
    https://www.peoplespharmacy.com/2015/01/27/are-your-drugs-raising-your-risk-for-dementia/

    ‘Strongest Evidence Yet’ Links Anticholinergic Drugs, Dementia https://www.medscape.com/viewarticle/838788 Jan 27, 2015

  • Cindy Lindsey

    My neurologist recommended this drug for “nerve pain” when I told them that I’m having headaches they seem to be coming from the area of the incision I got when I had brain surgery almost two years ago. I’m VERY concerned about side effects from all drugs. Should I look for other ways to resolve the headaches (Tylenol, etc don’t seem to be enough), or try this and go from there?

    1. Nattha Wannissorn, PhD

      Please speak to your doctor.

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