Protriptyline side effects: Protriptyline: MedlinePlus Drug Information
Protriptyline – StatPearls – NCBI Bookshelf
Continuing Education Activity
Protriptyline hydrochloride is a tricyclic antidepressant used to improve mood in people with depression. It is also useful in treating anxiety. It is a more potent antidepressant and has fewer sedative and tranquilizing effects than other TCAs. FDA-approved uses include mental depression, narcolepsy, attention deficit hyperactivity disorder, and headaches. It also has other non-FDA approved indications. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of protriptyline, so providers can direct patient therapy in treating conditions for which it is indicated, as part of the interprofessional team.
Objectives:
Identify the mechanism of action of protriptyline.
Review the approved and off-label indications for initiating protriptyline therapy.
Describe the adverse event profile and contraindications of protriptyline.
Summarize interprofessional team strategies for improving care coordination and communication to advance protriptyline and improve patient outcomes.
Access free multiple choice questions on this topic.
Indications
Protriptyline hydrochloride is a tricyclic antidepressant used to improve mood in people with depression. It is also used for anxiety. Protriptyline was first patented in 1962, and it is sold under many brand names. It is an amine with the empirical formula of CHN. It is a more potent antidepressant and has fewer sedative and tranquilizing effects than other TCAs.
FDA-Approved Uses
[1]
[2]
Results of one study of 25 women who were treated with 20 mg of protriptyline each morning for 12 weeks showed 86% fewer headaches each month, with an average dropping from 28.2 to 11.7 days[3]. More than two-thirds had a 50% reduction in the number of headaches per month. The study also showed an average of 1 pound (0/45 kg) per month of weight loss.
Non-FDA-Approved Uses
One study reported that protriptyline could be helpful in brain-injured adults with attention and behavioral difficulties.[4][1] Research has also shown it to improve the drowsiness, apneic episodes, snoring, and cataplexy related to narcolepsy.[5]
Mechanism of Action
When it comes to mood, the two important chemicals in the brain are serotonin and norepinephrine. These often decrease in people who are depressed and are the main targets of antidepressants. Protriptyline has the fastest onset of action among other tricyclic antidepressants, and thus clinical effects can occur within the first week of use. It is a secondary tricyclic amine and structurally similar to nortriptyline. It undergoes limited first-pass hepatic metabolism and can cross the blood-brain barrier. Protriptyline has a long half-life of 80 to 200 hours when used long-term, requiring up to a month to reach a steady state. The half-life of protriptyline is approximately 74 hours (greater than three days).
Increases norepinephrine neurotransmission by blocking norepinephrine reuptake pump.
In the frontal cortex, dopamine neurotransmission increases secondary to the norepinephrine reuptake inhibition.[4]
At high doses, protriptyline can increase serotonin neurotransmission.
Protriptyline also can cause calcium-independent cell death.[6]
Administration
Unlike other tricyclic or tetracyclic antidepressants, which have doses from 75 to 300 mg/day, protriptyline dosing uses much lower doses and then increased as necessary. Unlike other tricyclic and tetracyclic drugs, which often have once a day dosing, dosage for protriptyline is divided into 3 or 4 times a day. When stopping the medication is necessary, taper to avoid the effects of withdrawal.
Protriptyline is available in tablets of 5 or 10 mg.
Initiate at 15 to 40 mg a day, starting with the morning dose.
Divide dose into 3 or 4 doses, not to be taken all at one time.
The maximum dose is 60 mg a day, if necessary, beginning at a lower level and increasing gradually while looking for the patient’s response and any side effects as the dosage increase.
Adverse Effects
Protriptyline, like all TCAs, has multiple adverse effects. Although as effective as SSRIs and SNRIs, TCAs, and MAOs are not first-line treatment due to their side effects. Among the TCAs, protriptyline is the most likely to cause tachycardia, hypotension, anxiety, and agitation, and for this reason, some European countries have discontinued protriptyline use.[7][8][2][9]
Adverse Effects (like all TCAs)
CNS depression
Convulsions
Cardiac toxicity
Weight gain
Coma
Most Common Adverse Effects
Anxiety
Agitation
Apathy
Anorexia
Nausea
Headache
Diarrhea
Constipation
Urinary retention
Dizziness
Restlessness
Insomnia (decrease of REM sleep)
Nightmares
Hypotension
Hyponatremia
Diaphoresis
Itching
Rash
Blurred vision
Dry mouth Impotence
Change of libido
Impotence
Difficulty having an orgasm
Suicidal thoughts and suicide attempts (black box warning) and risk, especially in that younger than 24 years old, is greater during the initial two months of starting the drug and during dosage adjustment.
Rare, More Serious Adverse Effects
Hepatic failure
Increased intraocular pressure
Induction of mania
Paralytic ileus
Extrapyramidal symptoms
QTc prolongation, arrhythmia, tachycardia, myocardial infarction
Stroke, seizures, coma
Sudden death
Contraindications
Tricyclic antidepressants have many side effects, some of which are life-threatening. Among the tricyclic antidepressants, protriptyline is the most potent and most likely to cause hypotension, agitation, and cardiac effects. For this reason, protriptyline has multiple contraindications, including people with the following [7][9][8][9]:
Heart problems such as prolonged QTC interval, uncompensated heart failure, arrhythmias, heart block, palpitations, hypotension, hypertension, and recent myocardial infarction.
Use of drugs that inhibit TCA metabolism, inhibit CYP450 2D6, or prolong QTc interval.
(Look for hypokalemia before starting protriptyline.)Use of tramadol (increase the risk of seizures with TCAs), and people with a seizure disorder require careful monitoring.
Use of anticholinergic drugs (risk of hyperthermia and paralytic ileus).
Use of SSRIs, SNRIs, and MAOIs to prevent serotonin syndrome, hypertensive crisis or hypotensive crisis, hyper-pyretic, and convulsions, a washout period of at least 14 days must take effect before starting one of these drugs.
Weight gain concerns and/or metabolic syndrome.
Psychosis due to TCAs aggravating psychotic symptoms
Possible pregnancy or women who are breastfeeding (due to potential adverse effects to the fetus such as fetal malformations, lethargy, and withdrawal symptoms. protriptyline is classified in pregnancy category C)
Age younger than 12 due to the increased risk of suicidal thoughts/suicidal attempts in children
History of hypersensitivity to protriptyline
Hyperthyroidism, urinary retention, and angle-closure glaucoma merit closer monitoring.
Renal or hepatic impairment may need to lower dose and may need to monitor closely.
Consumption of alcohol should also be avoided due to the additive CNS effects.
(Look for hypokalemia before starting protriptyline.)
Monitoring
Protriptyline’s initial dose is 15 mg per day divided into 3 or 4 doses per day, with a max dose of 60 mg per day. However, taking more than recommended or taking the daily dose at one time can have significant consequences which can manifest in cardiac arrhythmias or EKG changes, especially QRS-widening hypotension, confusion, visual hallucinations, delusions, ataxia, tremors, syndrome of inappropriate ADH, tinnitus, hyperactive reflexes, muscle rigidity stupor, convulsions, coma, and even death.[2][7]
ECG is a recommendation and close monitoring for patients over the age of 50, especially in those taking more than 20 mg per day, due to sensitivity to anticholinergic, cardiovascular, hypotensive, and sedative effects.
Like other antidepressants, protriptyline increases suicidal ideation and attempts in children, adolescents, and young adults.
It is not recommended in patients under the age of 12 or intended for those under the age of 6.
Toxicity
Tricyclic antidepressants, like all antidepressants, are used in a group of patients that are already at increased risk of attempted suicide. Thus, overdose with such drugs is something that needs to have a plan at hand. Furthermore, TCAs are often used in drug-resistant depression, which makes them even more of a risk than the first-line SSRIs and SNRIs. Thus protriptyline is a very potent TCA and a dangerous drug for overdose.
Treatment of protriptyline toxicity includes gastrointestinal decontamination with gastric lavage and activated charcoal l and treating the symptoms that arise due to the overdose as necessary; for example, norepinephrine and IV fluids for hypotension, IV sodium bicarbonate for prolonged QRS duration, and benzodiazepines for anxiety, agitation, or seizures.
Enhancing Healthcare Team Outcomes
Protriptyline is an older tricyclic antidepressant which has little use today.
Healthcare workers, including the pharmacist and prescribing nurse, should be familiar with newer antidepressants, which are much safer. Patients already on protriptyline should be gradually weaned off and started on the newer antidepressants if there are no contraindications.
Review Questions
Access free multiple choice questions on this topic.
Comment on this article.
References
- 1.
Wilens TE, Biederman J, Abrantes AM, Spencer TJ. A naturalistic assessment of protriptyline for attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1996 Nov;35(11):1485-90. [PubMed: 8936915]
- 2.
Furukawa TA, McGuire H, Barbui C. Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review. BMJ. 2002 Nov 02;325(7371):991. [PMC free article: PMC131022] [PubMed: 12411354]
- 3.
Cohen GL. Protriptyline, chronic tension-type headaches, and weight loss in women.
Headache. 1997 Jul-Aug;37(7):433-6. [PubMed: 9277026]- 4.
Bansode SB, Jana AK, Batkulwar KB, Warkad SD, Joshi RS, Sengupta N, Kulkarni MJ. Molecular investigations of protriptyline as a multi-target directed ligand in Alzheimer’s disease. PLoS One. 2014;9(8):e105196. [PMC free article: PMC4139341] [PubMed: 25141174]
- 5.
Smith IE, Quinnell TG. Pharmacotherapies for obstructive sleep apnoea: where are we now? Drugs. 2004;64(13):1385-99. [PubMed: 15212557]
- 6.
Cheng HH, Chou CT, Liang WZ, Kuo CC, Shieh P, Wang JL, Jan CR. Effect of Protriptyline on [Ca²⁺]i and Viability in MDCK Renal Tubular Cells. Chin J Physiol. 2017 Apr 30;60(2):114-123. [PubMed: 28468029]
- 7.
Elonen E, Mattila MJ, Saarnivaara L. Cardiovascular effects of amitriptyline, nortriptyline, protriptyline and doxepin in conscious rabbits. Eur J Pharmacol. 1974 Sep;28(1):178-88. [PubMed: 4430320]
- 8.
Anderson IM. Meta-analytical studies on new antidepressants.
Br Med Bull. 2001;57:161-78. [PubMed: 11719915]- 9.
Elonen E, Mattila MJ. Cardiovascular effects of amitriptyline, nortriptyline, protriptyline, and doxepin in conscious rabbits after subacute pretreatment with protriptyline. Med Biol. 1975 Aug;53(4):238-44. [PubMed: 1186320]
Headache. 1997 Jul-Aug;37(7):433-6. [PubMed: 9277026]
Br Med Bull. 2001;57:161-78. [PubMed: 11719915]Disclosure: Moadh Saef declares no relevant financial relationships with ineligible companies.
Disclosure: Musa Yilanli declares no relevant financial relationships with ineligible companies.
Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.
Protriptyline – StatPearls – NCBI Bookshelf
Continuing Education Activity
Protriptyline hydrochloride is a tricyclic antidepressant used to improve mood in people with depression. It is also useful in treating anxiety. It is a more potent antidepressant and has fewer sedative and tranquilizing effects than other TCAs.
FDA-approved uses include mental depression, narcolepsy, attention deficit hyperactivity disorder, and headaches. It also has other non-FDA approved indications. This activity outlines the indications, mechanism of action, methods of administration, important adverse effects, contraindications, monitoring, and toxicity of protriptyline, so providers can direct patient therapy in treating conditions for which it is indicated, as part of the interprofessional team.
Objectives:
Identify the mechanism of action of protriptyline.
Review the approved and off-label indications for initiating protriptyline therapy.
Describe the adverse event profile and contraindications of protriptyline.
Summarize interprofessional team strategies for improving care coordination and communication to advance protriptyline and improve patient outcomes.
Access free multiple choice questions on this topic.
Indications
Protriptyline hydrochloride is a tricyclic antidepressant used to improve mood in people with depression.
It is also used for anxiety. Protriptyline was first patented in 1962, and it is sold under many brand names. It is an amine with the empirical formula of CHN. It is a more potent antidepressant and has fewer sedative and tranquilizing effects than other TCAs.
FDA-Approved Uses
[1]
[2]
Results of one study of 25 women who were treated with 20 mg of protriptyline each morning for 12 weeks showed 86% fewer headaches each month, with an average dropping from 28.2 to 11.7 days[3]. More than two-thirds had a 50% reduction in the number of headaches per month. The study also showed an average of 1 pound (0/45 kg) per month of weight loss.
Non-FDA-Approved Uses
One study reported that protriptyline could be helpful in brain-injured adults with attention and behavioral difficulties.[4][1] Research has also shown it to improve the drowsiness, apneic episodes, snoring, and cataplexy related to narcolepsy.[5]
Mechanism of Action
When it comes to mood, the two important chemicals in the brain are serotonin and norepinephrine.
These often decrease in people who are depressed and are the main targets of antidepressants. Protriptyline has the fastest onset of action among other tricyclic antidepressants, and thus clinical effects can occur within the first week of use. It is a secondary tricyclic amine and structurally similar to nortriptyline. It undergoes limited first-pass hepatic metabolism and can cross the blood-brain barrier. Protriptyline has a long half-life of 80 to 200 hours when used long-term, requiring up to a month to reach a steady state. The half-life of protriptyline is approximately 74 hours (greater than three days).
Increases norepinephrine neurotransmission by blocking norepinephrine reuptake pump.
In the frontal cortex, dopamine neurotransmission increases secondary to the norepinephrine reuptake inhibition.[4]
At high doses, protriptyline can increase serotonin neurotransmission.
Protriptyline also can cause calcium-independent cell death.
[6]
[6]Administration
Unlike other tricyclic or tetracyclic antidepressants, which have doses from 75 to 300 mg/day, protriptyline dosing uses much lower doses and then increased as necessary. Unlike other tricyclic and tetracyclic drugs, which often have once a day dosing, dosage for protriptyline is divided into 3 or 4 times a day. When stopping the medication is necessary, taper to avoid the effects of withdrawal.
Protriptyline is available in tablets of 5 or 10 mg.
Initiate at 15 to 40 mg a day, starting with the morning dose.
Divide dose into 3 or 4 doses, not to be taken all at one time.
The maximum dose is 60 mg a day, if necessary, beginning at a lower level and increasing gradually while looking for the patient’s response and any side effects as the dosage increase.
Adverse Effects
Protriptyline, like all TCAs, has multiple adverse effects. Although as effective as SSRIs and SNRIs, TCAs, and MAOs are not first-line treatment due to their side effects.
Among the TCAs, protriptyline is the most likely to cause tachycardia, hypotension, anxiety, and agitation, and for this reason, some European countries have discontinued protriptyline use.[7][8][2][9]
Adverse Effects (like all TCAs)
CNS depression
Convulsions
Cardiac toxicity
Weight gain
Coma
Most Common Adverse Effects
Anxiety
Agitation
Apathy
Anorexia
Nausea
Headache
Diarrhea
Constipation
Urinary retention
Dizziness
Restlessness
Insomnia (decrease of REM sleep)
Nightmares
Hypotension
Hyponatremia
Diaphoresis
Itching
Rash
Blurred vision
Dry mouth Impotence
Change of libido
Impotence
Difficulty having an orgasm
Suicidal thoughts and suicide attempts (black box warning) and risk, especially in that younger than 24 years old, is greater during the initial two months of starting the drug and during dosage adjustment.
Rare, More Serious Adverse Effects
Hepatic failure
Increased intraocular pressure
Induction of mania
Paralytic ileus
Extrapyramidal symptoms
QTc prolongation, arrhythmia, tachycardia, myocardial infarction
Stroke, seizures, coma
Sudden death
Contraindications
Tricyclic antidepressants have many side effects, some of which are life-threatening. Among the tricyclic antidepressants, protriptyline is the most potent and most likely to cause hypotension, agitation, and cardiac effects. For this reason, protriptyline has multiple contraindications, including people with the following [7][9][8][9]:
Heart problems such as prolonged QTC interval, uncompensated heart failure, arrhythmias, heart block, palpitations, hypotension, hypertension, and recent myocardial infarction.
Use of drugs that inhibit TCA metabolism, inhibit CYP450 2D6, or prolong QTc interval.
(Look for hypokalemia before starting protriptyline.)Use of tramadol (increase the risk of seizures with TCAs), and people with a seizure disorder require careful monitoring.
Use of anticholinergic drugs (risk of hyperthermia and paralytic ileus).
Use of SSRIs, SNRIs, and MAOIs to prevent serotonin syndrome, hypertensive crisis or hypotensive crisis, hyper-pyretic, and convulsions, a washout period of at least 14 days must take effect before starting one of these drugs.
Weight gain concerns and/or metabolic syndrome.
Psychosis due to TCAs aggravating psychotic symptoms
Possible pregnancy or women who are breastfeeding (due to potential adverse effects to the fetus such as fetal malformations, lethargy, and withdrawal symptoms. protriptyline is classified in pregnancy category C)
Age younger than 12 due to the increased risk of suicidal thoughts/suicidal attempts in children
History of hypersensitivity to protriptyline
Hyperthyroidism, urinary retention, and angle-closure glaucoma merit closer monitoring.
Renal or hepatic impairment may need to lower dose and may need to monitor closely.
Consumption of alcohol should also be avoided due to the additive CNS effects.
(Look for hypokalemia before starting protriptyline.)
Monitoring
Protriptyline’s initial dose is 15 mg per day divided into 3 or 4 doses per day, with a max dose of 60 mg per day. However, taking more than recommended or taking the daily dose at one time can have significant consequences which can manifest in cardiac arrhythmias or EKG changes, especially QRS-widening hypotension, confusion, visual hallucinations, delusions, ataxia, tremors, syndrome of inappropriate ADH, tinnitus, hyperactive reflexes, muscle rigidity stupor, convulsions, coma, and even death.[2][7]
ECG is a recommendation and close monitoring for patients over the age of 50, especially in those taking more than 20 mg per day, due to sensitivity to anticholinergic, cardiovascular, hypotensive, and sedative effects.
Like other antidepressants, protriptyline increases suicidal ideation and attempts in children, adolescents, and young adults.
It is not recommended in patients under the age of 12 or intended for those under the age of 6.
Toxicity
Tricyclic antidepressants, like all antidepressants, are used in a group of patients that are already at increased risk of attempted suicide. Thus, overdose with such drugs is something that needs to have a plan at hand. Furthermore, TCAs are often used in drug-resistant depression, which makes them even more of a risk than the first-line SSRIs and SNRIs. Thus protriptyline is a very potent TCA and a dangerous drug for overdose.
Treatment of protriptyline toxicity includes gastrointestinal decontamination with gastric lavage and activated charcoal l and treating the symptoms that arise due to the overdose as necessary; for example, norepinephrine and IV fluids for hypotension, IV sodium bicarbonate for prolonged QRS duration, and benzodiazepines for anxiety, agitation, or seizures.
Enhancing Healthcare Team Outcomes
Protriptyline is an older tricyclic antidepressant which has little use today.:max_bytes(150000):strip_icc()/nexplanon-birth-control-implant-faq-9068641-5c8ad59046e0fb00014a9688.png)
Healthcare workers, including the pharmacist and prescribing nurse, should be familiar with newer antidepressants, which are much safer. Patients already on protriptyline should be gradually weaned off and started on the newer antidepressants if there are no contraindications.
Review Questions
Access free multiple choice questions on this topic.
Comment on this article.
References
- 1.
Wilens TE, Biederman J, Abrantes AM, Spencer TJ. A naturalistic assessment of protriptyline for attention-deficit hyperactivity disorder. J Am Acad Child Adolesc Psychiatry. 1996 Nov;35(11):1485-90. [PubMed: 8936915]
- 2.
Furukawa TA, McGuire H, Barbui C. Meta-analysis of effects and side effects of low dosage tricyclic antidepressants in depression: systematic review. BMJ. 2002 Nov 02;325(7371):991. [PMC free article: PMC131022] [PubMed: 12411354]
- 3.
Cohen GL. Protriptyline, chronic tension-type headaches, and weight loss in women.
Headache. 1997 Jul-Aug;37(7):433-6. [PubMed: 9277026]- 4.
Bansode SB, Jana AK, Batkulwar KB, Warkad SD, Joshi RS, Sengupta N, Kulkarni MJ. Molecular investigations of protriptyline as a multi-target directed ligand in Alzheimer’s disease. PLoS One. 2014;9(8):e105196. [PMC free article: PMC4139341] [PubMed: 25141174]
- 5.
Smith IE, Quinnell TG. Pharmacotherapies for obstructive sleep apnoea: where are we now? Drugs. 2004;64(13):1385-99. [PubMed: 15212557]
- 6.
Cheng HH, Chou CT, Liang WZ, Kuo CC, Shieh P, Wang JL, Jan CR. Effect of Protriptyline on [Ca²⁺]i and Viability in MDCK Renal Tubular Cells. Chin J Physiol. 2017 Apr 30;60(2):114-123. [PubMed: 28468029]
- 7.
Elonen E, Mattila MJ, Saarnivaara L. Cardiovascular effects of amitriptyline, nortriptyline, protriptyline and doxepin in conscious rabbits. Eur J Pharmacol. 1974 Sep;28(1):178-88. [PubMed: 4430320]
- 8.
Anderson IM. Meta-analytical studies on new antidepressants.
Br Med Bull. 2001;57:161-78. [PubMed: 11719915]- 9.
Elonen E, Mattila MJ. Cardiovascular effects of amitriptyline, nortriptyline, protriptyline, and doxepin in conscious rabbits after subacute pretreatment with protriptyline. Med Biol. 1975 Aug;53(4):238-44. [PubMed: 1186320]
Headache. 1997 Jul-Aug;37(7):433-6. [PubMed: 9277026]:max_bytes(150000):strip_icc()/side-effects-of-flagyl-metronidazole-1941759-FINAL-7b1b3d3abd1c4b7789af8de7e97386ab.png)
Br Med Bull. 2001;57:161-78. [PubMed: 11719915]Disclosure: Moadh Saef declares no relevant financial relationships with ineligible companies.
Disclosure: Musa Yilanli declares no relevant financial relationships with ineligible companies.
Disclosure: Abdolreza Saadabadi declares no relevant financial relationships with ineligible companies.
💊 Ingredients of Amitriptyline ✅ Use of Amitriptyline Save Search for analogues Interaction Description of the active ingredients of the preparation Amitriptyline The scientific information provided is general and cannot be used to make decisions. Update date: 2021.12.06 Marketing authorization holder: DALHIMFARM JSC ATX code: N06AA09 (Amitriptyline) Active substance: Rec.INN WHO registered Dosage form
Release form, packaging and composition |
In anxiety-depressive conditions, it reduces anxiety, agitation and depressive manifestations.
| B02.2 | Herpes zoster with other nervous system complications |
| F20 | Schizophrenia |
| F21 | Schizotypal disorder |
| F22 | Chronic delusional disorders |
| F23 | Acute and transient mental disorders |
| F25 | Schizoaffective disorders |
| F29 | Non-organic psychosis, unspecified |
| F32 | Depressive episode |
| F33 | Recurrent depressive disorder |
| F40 | Phobic anxiety disorders (including agoraphobia, social phobias) |
F41. 2 | Mixed anxiety and depressive disorder |
| F50.2 | Bulimia nervosa |
| F90.0 | Activity and attention disorders |
| F91.9 | Conduct disorder, unspecified |
| F98.0 | Inorganic enuresis |
| G43 | Migraine |
| G44.2 | Tension headache |
| G50.1 | Atypical facial pain |
| G53.0 | Neuralgia after herpes zoster (B02.2) |
| G60 | Hereditary and idiopathic neuropathy |
| G61 | Inflammatory polyneuropathy |
G62. 1 | Alcoholic polyneuropathy |
| G63.2 | Diabetic polyneuropathy |
| K25 | Gastric ulcer |
| K26 | Duodenal ulcer |
| M79.2 | Neuralgia and neuritis, unspecified |
| R52.2 | Other persistent pain (chronic) |
Dosage regimen
The method of administration and dosing regimen of a particular drug depends on its form of release and other factors. The optimal dosage regimen is determined by the doctor. Compliance of the dosage form of a particular drug with indications for use and dosing regimen should be strictly observed.
For oral administration, the initial dose is 25-50 mg at night.
Then, within 5-6 days, the dose is individually increased to 150-200 mg / day (most of the dose is taken at night). If there is no improvement within the second week, the daily dose is increased to 300 mg. With the disappearance of signs of depression, the dose is reduced to 50-100 mg / day and therapy is continued for at least 3 months. In elderly patients with mild disorders, the dose is 30-100 mg / day, usually 1 time / day at night, after achieving a therapeutic effect, they switch to the minimum effective dose – 25-50 mg / day.
For nocturnal enuresis in children aged 6-10 years – 10-20 mg / day at night, aged 11-16 years – 25-50 mg / day.
V / m – the initial dose is 50-100 mg / day in 2-4 injections. If necessary, the dose can be gradually increased to 300 mg / day, in exceptional cases – up to 400 mg / day.
Side effects
From the nervous system: drowsiness, asthenia, syncope, restlessness, disorientation, agitation, hallucinations (especially in elderly patients and in patients with Parkinson’s disease), anxiety, restlessness, manic state, hypomanic condition, aggressiveness, memory impairment, depersonalization, increased depression, decreased ability to concentrate, insomnia, nightmares, yawning, activation of psychotic symptoms, headache, myoclonus, dysarthria, tremor (especially of the hands, head, tongue), peripheral neuropathy (paresthesia ), myasthenia gravis, myoclonus, ataxia, extrapyramidal syndrome, increased frequency and intensification of epileptic seizures, changes in the EEG.
From the side of the cardiovascular system: orthostatic hypotension, tachycardia, conduction disturbances, dizziness, non-specific changes on the ECG (ST interval or T wave), arrhythmia, blood pressure lability, intraventricular conduction disturbance (expansion of the QRS complex, changes in the PQ interval, bundle branch block).
From the digestive system: nausea, heartburn, vomiting, gastralgia, increase or decrease in appetite (weight gain or decrease), stomatitis, change in taste, diarrhea, darkening of the tongue; rarely – liver dysfunction, cholestatic jaundice, hepatitis.
On the part of the endocrine system: testicular edema, gynecomastia, mammary gland enlargement, galactorrhea, changes in libido, decreased potency, hypo- or hyperglycemia, hyponatremia (decreased production of vasopressin), syndrome of inappropriate ADH secretion.
From the side of the hematopoietic system: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia.
Allergic reactions: skin rash, pruritus, urticaria, photosensitivity, swelling of the face and tongue.
Effects due to anticholinergic activity: dry mouth, tachycardia, disturbances of accommodation, blurred vision, mydriasis, increased intraocular pressure (only in persons with a narrow anterior chamber angle of the eye), constipation, paralytic ileus, urinary retention, decreased sweating, confusion, delirium, or hallucinations.
Other: hair loss, tinnitus, edema, hyperpyrexia, swollen lymph nodes, pollakiuria, hypoproteinemia.
Contraindications for use
Acute period and early recovery period after myocardial infarction, acute alcohol intoxication, acute intoxication with hypnotics, analgesics and psychotropic drugs, angle-closure glaucoma, severe disorders of AV and intraventricular conduction (blockade of the bundle branches, AV blockade II degree), lactation period, children under 6 years of age (for oral administration), children under 12 years of age (for intramuscular and intravenous administration), simultaneous treatment with MAO inhibitors and the period 2 weeks before their use, increased sensitivity to amitriptyline.
Use in pregnancy and lactation
Amitriptyline should not be used during pregnancy, especially in the first and third trimesters, except in cases of emergency. Adequate and strictly controlled clinical studies of the safety of the use of amitriptyline during pregnancy have not been conducted.
Amitriptyline should be phased out at least 7 weeks before expected delivery to avoid neonatal withdrawal.
In experimental studies amitriptyline was teratogenic.
Contraindicated during lactation. It is excreted in breast milk and may cause drowsiness in infants.
Use in hepatic impairment
Use with caution in hepatic impairment.
Use in impaired renal function
Use with caution in impaired renal function.
Pediatric use
Contraindication: children under 6 years of age (for oral administration), children under 12 years of age (for intramuscular and intravenous administration).
Use in elderly patients
In elderly patients, it can provoke the development of drug-induced psychoses, mainly at night (after discontinuation of the drug pass within a few days), and also cause paralytic ileus.
Special instructions
Use with caution in ischemic heart disease, arrhythmia, heart block, heart failure, myocardial infarction, arterial hypertension, stroke, chronic alcoholism, thyrotoxicosis, against the background of therapy with thyroid drugs, with impaired liver and / or kidney function.
During therapy with amitriptyline, care must be taken when abruptly moving to an upright position from a lying or sitting position.
Abrupt discontinuation may lead to withdrawal syndrome.
Amitriptyline at doses greater than 150 mg/day lowers the seizure threshold; the risk of developing epileptic seizures in predisposed patients should be taken into account, as well as in the presence of other factors that increase the risk of developing a convulsive syndrome (including with brain damage of any etiology, simultaneous use of antipsychotic drugs, during the period of refusal of ethanol or withdrawal of drugs, with anticonvulsant activity).
Consideration should be given to the possibility of suicide attempts in patients with depression.
Should only be used in combination with electroconvulsive therapy under close medical supervision.
In predisposed patients and elderly patients, it can provoke the development of drug-induced psychoses, mainly at night (after discontinuation of the drug pass within a few days).
May cause paralytic ileus, predominantly in patients with chronic constipation, the elderly, or in patients requiring bed rest.
Before general or local anesthesia, the anesthesiologist should be warned that the patient is taking amitriptyline.
With prolonged use, an increase in the frequency of caries is observed. May increase the need for riboflavin.
Amitriptyline can be used no earlier than 14 days after discontinuation of MAO inhibitors.
Do not use simultaneously with adreno- and sympathomimetics, incl. with epinephrine, ephedrine, isoprenaline, norepinephrine, phenylephrine, phenylpropanolamine.
Use with caution concomitantly with other anticholinergic drugs.
Avoid drinking alcohol while taking amitriptyline.
Influence on the ability to drive vehicles and mechanisms
During the period of treatment, one should refrain from potentially hazardous activities that require increased attention and rapid psychomotor reactions.
Drug interactions
When used simultaneously with drugs that have a depressant effect on the central nervous system, a significant increase in the inhibitory effect on the central nervous system, hypotensive effect, and respiratory depression is possible.
When used simultaneously with drugs with anticholinergic activity, it is possible to increase anticholinergic effects.
With simultaneous use, it is possible to increase the effect of sympathomimetic drugs on the cardiovascular system and increase the risk of developing cardiac arrhythmias, tachycardia, and severe arterial hypertension.
When used simultaneously with antipsychotics (neuroleptics), metabolism is mutually inhibited, while the threshold for convulsive readiness decreases.
When used simultaneously with antihypertensive agents (with the exception of clonidine, guanethidine and their derivatives), it is possible to increase the antihypertensive effect and the risk of developing orthostatic hypotension.
With simultaneous use with MAO inhibitors, the development of a hypertensive crisis is possible; with clonidine, guanethidine – it is possible to reduce the hypotensive effect of clonidine or guanethidine; with barbiturates, carbamazepine – it is possible to reduce the effect of amitriptyline due to an increase in its metabolism.
A case of the development of serotonin syndrome with simultaneous use with sertraline is described.
When used simultaneously with sucralfate, the absorption of amitriptyline is reduced; with fluvoxamine – increases the concentration of amitriptyline in the blood plasma and the risk of developing a toxic effect; with fluoxetine – the concentration of amitriptyline in the blood plasma increases and toxic reactions develop due to inhibition of the CYP2D6 isoenzyme under the influence of fluoxetine; with quinidine – it is possible to slow down the metabolism of amitriptyline; with cimetidine – it is possible to slow down the metabolism of amitriptyline, increase its concentration in blood plasma and develop toxic effects.
When used simultaneously with ethanol, the effect of ethanol is enhanced, especially during the first few days of therapy.
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Amitriptyline . Description of the drug in the reference book Vidal.
Rec.INN drug interaction Included in preparations: Pharmacological action Antidepressant from the group of tricyclic compounds, dibenzocycloheptadine derivative. The mechanism of antidepressant action is associated with an increase in the concentration of noradrenaline in synapses and/or serotonin in the CNS due to inhibition of neuronal reuptake of these mediators. With prolonged use, it reduces the functional activity of β-adrenergic receptors and serotonin receptors in the brain, normalizes adrenergic and serotonergic transmission, restores the balance of these systems, disturbed during depressive states. In anxiety-depressive conditions, it reduces anxiety, agitation and depressive manifestations. It also has some analgesic effect, which is believed to be related to changes in the concentrations of monoamines in the CNS, especially serotonin, and effects on endogenous opioid systems. It has a pronounced peripheral and central anticholinergic effect due to its high affinity for m-cholinergic receptors; a strong sedative effect associated with affinity for histamine H 1 receptors, and alpha-adrenergic blocking action. The mechanism of therapeutic action in bulimia nervosa has not been established (possibly similar to that in depression). Amitriptyline has been shown to be clearly effective in bulimic patients both without depression and in its presence, while a decrease in bulimia can be observed without a concomitant weakening of the depression itself. Efficacy in bedwetting appears to be due to anticholinergic activity leading to increased bladder distensibility, direct β-adrenergic stimulation, α-adrenergic agonist activity associated with increased sphincter tone and central blockade of serotonin uptake. It has an antiulcer effect, the mechanism of which is due to the ability to block histamine H 2 receptors in the parietal cells of the stomach, as well as to have a sedative and m-anticholinergic effect (in case of gastric ulcer and duodenal ulcer, it reduces pain, accelerates the healing of the ulcer). Reduces blood pressure and body temperature during general anesthesia. Antidepressant effect develops within 2-3 weeks after the start of use. PharmacokineticsThe bioavailability of amitriptyline is 30-60%. Plasma protein binding 82-96%. V d – 5-10 l/kg. Metabolized to form the active metabolite nortriptyline. T 1/2 – 31-46 hours Excreted mainly by the kidneys. Indications of the active substance |
Does not inhibit MAO.
| B02.2 | Herpes zoster with other nervous system complications |
| F20 | Schizophrenia |
| F21 | Schizotypal disorder |
| F22 | Chronic delusional disorders |
| F23 | Acute and transient mental disorders |
| F25 | Schizoaffective disorders |
| F29 | Non-organic psychosis, unspecified |
| F32 | Depressive episode |
| F33 | Recurrent depressive disorder |
| F40 | Phobic anxiety disorders (including agoraphobia, social phobias) |
F41. 2 | Mixed anxiety and depressive disorder |
| F50.2 | Bulimia nervosa |
| F90.0 | Activity and attention disorders |
| F91.9 | Conduct disorder, unspecified |
| F98.0 | Inorganic enuresis |
| G43 | Migraine |
| G44.2 | Tension headache |
| G50.1 | Atypical facial pain |
| G53.0 | Neuralgia after herpes zoster (B02.2) |
| G60 | Hereditary and idiopathic neuropathy |
| G61 | Inflammatory polyneuropathy |
G62. 1 | Alcoholic polyneuropathy |
| G63.2 | Diabetic polyneuropathy |
| K25 | Gastric ulcer |
| K26 | Duodenal ulcer |
| M79.2 | Neuralgia and neuritis, unspecified |
| R52.2 | Other persistent pain (chronic) |
Dosing regimen
For oral administration, the initial dose is 25-50 mg at night. Then, within 5-6 days, the dose is individually increased to 150-200 mg / day (most of the dose is taken at night). If there is no improvement within the second week, the daily dose is increased to 300 mg. With the disappearance of signs of depression, the dose is reduced to 50-100 mg / day and therapy is continued for at least 3 months.
In elderly patients with mild disorders, the dose is 30-100 mg / day, usually 1 time / day at night, after achieving a therapeutic effect, they switch to the minimum effective dose – 25-50 mg / day.
For nocturnal enuresis in children aged 6-10 years – 10-20 mg / day at night, aged 11-16 years – 25-50 mg / day.
V / m – the initial dose is 50-100 mg / day in 2-4 injections. If necessary, the dose can be gradually increased to 300 mg / day, in exceptional cases – up to 400 mg / day.
Side effects
From the nervous system: drowsiness, asthenia, syncope, restlessness, disorientation, agitation, hallucinations (especially in elderly patients and in patients with Parkinson’s disease), anxiety, restlessness, manic state, hypomanic condition, aggressiveness, memory impairment, depersonalization, increased depression, decreased ability to concentrate, insomnia, nightmares, yawning, activation of psychotic symptoms, headache, myoclonus, dysarthria, tremor (especially of the hands, head, tongue), peripheral neuropathy (paresthesia ), myasthenia gravis, myoclonus, ataxia, extrapyramidal syndrome, increased frequency and intensification of epileptic seizures, changes in the EEG.
From the side of the cardiovascular system: orthostatic hypotension, tachycardia, conduction disturbances, dizziness, non-specific changes on the ECG (ST interval or T wave), arrhythmia, blood pressure lability, intraventricular conduction disturbance (expansion of the QRS complex, changes in the PQ interval, bundle branch block).
From the digestive system: nausea, heartburn, vomiting, gastralgia, increase or decrease in appetite (weight gain or decrease), stomatitis, change in taste, diarrhea, darkening of the tongue; rarely – liver dysfunction, cholestatic jaundice, hepatitis.
On the part of the endocrine system: testicular edema, gynecomastia, mammary gland enlargement, galactorrhea, changes in libido, decreased potency, hypo- or hyperglycemia, hyponatremia (decreased production of vasopressin), syndrome of inappropriate ADH secretion.
From the side of the hematopoietic system: agranulocytosis, leukopenia, thrombocytopenia, purpura, eosinophilia.
Allergic reactions: skin rash, pruritus, urticaria, photosensitivity, swelling of the face and tongue.
Effects due to anticholinergic activity: dry mouth, tachycardia, disturbances of accommodation, blurred vision, mydriasis, increased intraocular pressure (only in persons with a narrow anterior chamber angle of the eye), constipation, paralytic ileus, urinary retention, decreased sweating, confusion, delirium, or hallucinations.
Other: hair loss, tinnitus, edema, hyperpyrexia, swollen lymph nodes, pollakiuria, hypoproteinemia.
Contraindications for use
Acute period and early recovery period after myocardial infarction, acute alcohol intoxication, acute intoxication with hypnotics, analgesics and psychotropic drugs, angle-closure glaucoma, severe disorders of AV and intraventricular conduction (blockade of the bundle branches, AV blockade II degree), lactation period, children under 6 years of age (for oral administration), children under 12 years of age (for intramuscular and intravenous administration), simultaneous treatment with MAO inhibitors and the period 2 weeks before their use, increased sensitivity to amitriptyline.
Use in pregnancy and lactation
Amitriptyline should not be used during pregnancy, especially in the first and third trimesters, except in cases of emergency. Adequate and strictly controlled clinical studies of the safety of the use of amitriptyline during pregnancy have not been conducted.
Amitriptyline should be phased out at least 7 weeks before expected delivery to avoid neonatal withdrawal.
In experimental studies amitriptyline was teratogenic.
Contraindicated during lactation. It is excreted in breast milk and may cause drowsiness in infants.
Use in hepatic impairment
Use with caution in hepatic impairment.
Use in impaired renal function
Use with caution in impaired renal function.
Pediatric use
Contraindication: children under 6 years of age (for oral administration), children under 12 years of age (for intramuscular and intravenous administration).
Use in elderly patients
In elderly patients, it can provoke the development of drug-induced psychoses, mainly at night (after discontinuation of the drug pass within a few days), and also cause paralytic ileus.
Special instructions
Use with caution in ischemic heart disease, arrhythmia, heart block, heart failure, myocardial infarction, arterial hypertension, stroke, chronic alcoholism, thyrotoxicosis, against the background of therapy with thyroid drugs, with impaired liver and / or kidney function.
During therapy with amitriptyline, care must be taken when abruptly moving to an upright position from a lying or sitting position.
Abrupt discontinuation may lead to withdrawal syndrome.
Amitriptyline at doses greater than 150 mg/day lowers the seizure threshold; the risk of developing epileptic seizures in predisposed patients should be taken into account, as well as in the presence of other factors that increase the risk of developing a convulsive syndrome (including with brain damage of any etiology, simultaneous use of antipsychotic drugs, during the period of refusal of ethanol or withdrawal of drugs, with anticonvulsant activity).
Consideration should be given to the possibility of suicide attempts in patients with depression.
Should only be used in combination with electroconvulsive therapy under close medical supervision.
In predisposed patients and elderly patients, it can provoke the development of drug-induced psychoses, mainly at night (after discontinuation of the drug pass within a few days).
May cause paralytic ileus, predominantly in patients with chronic constipation, the elderly, or in patients requiring bed rest.
Before general or local anesthesia, the anesthesiologist should be warned that the patient is taking amitriptyline.
With prolonged use, an increase in the frequency of caries is observed. May increase the need for riboflavin.
Amitriptyline can be used no earlier than 14 days after discontinuation of MAO inhibitors.
Do not use simultaneously with adreno- and sympathomimetics, incl. with epinephrine, ephedrine, isoprenaline, norepinephrine, phenylephrine, phenylpropanolamine.
Use with caution concomitantly with other anticholinergic drugs.
Avoid drinking alcohol while taking amitriptyline.
Influence on the ability to drive vehicles and mechanisms
During the period of treatment, one should refrain from potentially hazardous activities that require increased attention and rapid psychomotor reactions.
Drug interactions
When used simultaneously with drugs that have a depressant effect on the central nervous system, a significant increase in the inhibitory effect on the central nervous system, hypotensive effect, and respiratory depression is possible.
When used simultaneously with drugs with anticholinergic activity, it is possible to increase anticholinergic effects.
With simultaneous use, it is possible to increase the effect of sympathomimetic drugs on the cardiovascular system and increase the risk of developing cardiac arrhythmias, tachycardia, and severe arterial hypertension.
When used simultaneously with antipsychotics (neuroleptics), metabolism is mutually inhibited, while the threshold for convulsive readiness decreases.
When used simultaneously with antihypertensive agents (with the exception of clonidine, guanethidine and their derivatives), it is possible to increase the antihypertensive effect and the risk of developing orthostatic hypotension.
With simultaneous use with MAO inhibitors, the development of a hypertensive crisis is possible; with clonidine, guanethidine – it is possible to reduce the hypotensive effect of clonidine or guanethidine; with barbiturates, carbamazepine – it is possible to reduce the effect of amitriptyline due to an increase in its metabolism.
A case of the development of serotonin syndrome with simultaneous use with sertraline is described.
When used simultaneously with sucralfate, the absorption of amitriptyline is reduced; with fluvoxamine – increases the concentration of amitriptyline in the blood plasma and the risk of developing a toxic effect; with fluoxetine – the concentration of amitriptyline in the blood plasma increases and toxic reactions develop due to inhibition of the CYP2D6 isoenzyme under the influence of fluoxetine; with quinidine – it is possible to slow down the metabolism of amitriptyline; with cimetidine – it is possible to slow down the metabolism of amitriptyline, increase its concentration in blood plasma and develop toxic effects.