Cymbalta doses for anxiety

For nerve pain, anxiety, and more

Cymbalta (duloxetine) is a brand-name prescription medication. The Food and Drug Administration (FDA) has approved it to treat the following conditions in adults:

• generalized anxiety disorder
• major depressive disorder (also known as clinical depression)
• fibromyalgia
• chronic musculoskeletal pain
• pain caused by diabetic neuropathy (nerve damage)

Cymbalta is FDA-approved to treat the following conditions in children:

• generalized anxiety disorder in children ages 7 years and older
• fibromyalgia in children ages 13 years and older

Cymbalta comes as an oral capsule. It’s an antidepressant medication that belongs to a class of drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs).

For information on the dosage of Cymbalta, including its form, strengths, and how to take the drug, keep reading. For a comprehensive look at Cymbalta, see this article.

This article describes typical dosages for Cymbalta provided by the drug’s manufacturer. When taking Cymbalta, always follow the dosage prescribed by your doctor.

Below are Cymbalta dosages that are commonly used for the conditions the drug is prescribed to treat.

Cymbalta form

Cymbalta comes as oral capsules.

Cymbalta strengths

Cymbalta capsules are available in three strengths: 20 milligrams (mg), 30 mg, and 60 mg.

Typical dosages

Typically, your doctor will start you on a low dosage. Then, they’ll adjust it over time to reach the amount that’s right for you. Your doctor will ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.

Dosage for chronic musculoskeletal pain

Chronic musculoskeletal pain is long-term pain in the muscles, bones, joints, tendons, ligaments, or nerves. Examples of this type of pain include back pain and arthritis pain.

The recommended dosage of Cymbalta for chronic musculoskeletal pain in adults is 60 mg once per day.

The typical starting dosage of Cymbalta is 30 mg once per day for the first week. If your condition responds well to the medication, your doctor will likely increase your dosage to 60 mg once per day.

The maximum recommended dosage for this condition is 60 mg per day.

Dosage for fibromyalgia

Cymbalta is approved to treat fibromyalgia in adults. The dosage of Cymbalta for this condition is the same as the dosage for chronic musculoskeletal pain. See the “Dosage for chronic musculoskeletal pain” section above.

Dosage for diabetic nerve pain

The recommended Cymbalta dosage for diabetic neuropathy in adults is 60 mg once per day. Doses higher than 60 mg are not recommended for diabetic neuropathy.

Dosage for anxiety

The recommended dosage of Cymbalta for generalized anxiety disorder depends on your age.

For adults younger than age 65 years, the recommended dosage is 60 mg once per day. Most people can start with this dosage. In some cases, your doctor may prescribe a starting dosage of 30 mg once per day for the first week. Then, they’ll increase your dosage to 60 mg once per day.

For adults ages 65 years and older, the recommended starting dosage is 30 mg once per day for 2 weeks. If you don’t have bothersome side effects, your doctor may increase your dosage to 60 mg once per day.

In adults of any age, the maximum Cymbalta dosage for anxiety is 120 mg per day. However, in clinical studies, doses higher than 60 mg weren’t found to be more effective than 60-mg doses.

For children, see the “Dosage for children” section below.

Dosage for depression

The recommended Cymbalta starting dosage for depression is 40 mg to 60 mg per day.

For the 40-mg dosage, you’ll likely take 20 mg twice per day. For the 60-mg dosage, you’ll likely take 30 mg twice per day or 60 mg once per day.

Most people can start with this dosage. However, in some cases, your doctor may decide to start having you take 30 mg once per day for a week before increasing your dosage.

If needed, your doctor may increase your dosage to a maximum of 120 mg per day to treat depression. However, in clinical studies, doses higher than 60 mg weren’t found to be more effective than 60-mg doses.

Dosage for older adults

In most cases, the dosage of Cymbalta prescribed for older adults is the same as that for adults younger than age 65 years.

However, for generalized anxiety disorder, adults ages 65 years and older should start treatment with a lower dosage than younger adults. For more information, see the “Dosage for anxiety” section above.

Dosage for children

Cymbalta is used to treat fibromyalgia and generalized anxiety disorder in children. The pediatric dose for these conditions is typically lower than the adult dose.

For fibromyalgia in children ages 13 years and older, the recommended starting dosage is 30 mg once per day. If your child doesn’t have bothersome side effects, their doctor may increase their dosage to 60 mg once per day if needed.

For generalized anxiety disorder in children ages 7 years and older, the recommended starting dosage is 30 mg once per day for 2 weeks. If your child doesn’t have bothersome side effects, their doctor may increase their dosage to 60 mg once per day if needed. The recommended Cymbalta dosage range for children is 30 mg to a maximum of 60 mg once per day.

Long-term use

Cymbalta is meant to be used as a long-term treatment. If you and your doctor determine that Cymbalta is safe and effective for you, you’ll likely take it long term.

Exactly how long you’ll take Cymbalta for depends on the condition it’s treating and how well that condition responds to the medication.

Here are answers to some frequently asked questions about Cymbalta’s dosage.

Is Cymbalta prescribed in 90-mg and 120-mg doses?

Yes, Cymbalta can be prescribed in 90-milligram (mg) and 120-mg doses. These doses may be used for depression or anxiety. However, they’re not common because clinical studies haven’t shown them to be more effective than the 60-mg dose.

Cymbalta isn’t prescribed in 90-mg or 120-mg doses for any other conditions.

For more information about the dosage of Cymbalta that’s right for you, talk with your doctor or pharmacist.

When would my doctor recommend the maximum dosage of Cymbalta?

Your doctor may increase your Cymbalta dosage to 120 mg per day for depression or anxiety if lower dosages haven’t worked for you. If the maximum dosage doesn’t work for you, your doctor will likely switch you to a different treatment.

The highest dosage of Cymbalta for depression or anxiety is 120 mg per day. However, this dosage isn’t typically prescribed.

For treating fibromyalgia, chronic musculoskeletal pain, and diabetic nerve pain, dosages above 60 mg per day are not recommended. In clinical studies, the 60-mg doses didn’t show any additional benefit for these conditions. Higher doses of Cymbalta are also associated with more side effects.

If you have questions about the maximum dosage of Cymbalta, talk with your doctor or pharmacist.

What’s considered a low dose of Cymbalta?

A low dose of Cymbalta is 30 mg. A dosage of 30 mg once per day is often prescribed when starting treatment with Cymbalta. Taking a low starting dose can help your body get used to the medication and may help you avoid side effects.

A 30-mg dose is typically prescribed in children. If needed, your child’s doctor may increase their dose.

A low dose may also be used if you take certain other medications. If you take other medications, talk with your doctor before starting treatment with Cymbalta.

If you miss a dose of Cymbalta, take your missed dose as soon as possible. Then, continue with your usual dosing schedule. However, if it’s almost time for your next dose, skip the missed dose and take your next dose as scheduled.

You should not take two doses at once to make up for a missed dose. This may increase your risk of side effects.

To help make sure that you don’t miss a dose, try using a medication reminder. This can include setting an alarm or using a timer. You could also download a reminder app on your phone.

The dosage of Cymbalta that your doctor prescribes will depend on several factors. These include:

• the condition you’re taking Cymbalta to treat and its severity
• other medical conditions you may have
• other medications you take
• your age

Dosage adjustments

Your doctor may adjust your treatment by increasing or lowering your Cymbalta dosage depending on:

• how your condition responds to Cymbalta
• side effects you may have with Cymbalta

You should not adjust your dosage of Cymbalta on your own. Your doctor will help determine what dosage is right for you.

You should take Cymbalta as instructed by your doctor. Cymbalta comes as an oral capsule. You may take your dose with or without food.

If you take Cymbalta once per day, you can take it at any time. However, try to take it around the same time every day.

If you take Cymbalta twice per day, you should take it in the morning and evening. However, try to take your doses around the same time every day.

Cymbalta has the potential to be misused. Misuse refers to using a drug differently than how it was prescribed. This can include taking Cymbalta more often, in a different way, or in a higher dosage than prescribed.

Cymbalta has a potential risk of misuse because it affects brain chemicals that influence mood, behavior, and feelings of reward. Although misuse with Cymbalta is rare, it can occur.

Misusing a drug can cause side effects and lead to overdose. It can also lead to drug dependence and addiction. With drug dependence, your body becomes reliant on a drug to function normally. As a result, you may have withdrawal symptoms when you stop taking it. With drug addiction, you find it difficult to stop misusing a drug, even though it may be causing harm.

Cymbalta isn’t known to be addictive. However, it can cause dependence and withdrawal symptoms if you suddenly stop taking it. For this reason, your Cymbalta dosage should be tapered down gradually when you stop taking it. For more information, see the “Cymbalta and withdrawal and dependence” section below.

If you have concerns about how to take Cymbalta safely, talk with your doctor. They can help you manage your risk of misusing the drug.

If you use more Cymbalta than your doctor prescribes, you may develop serious side effects.

It’s important that you don’t use more Cymbalta than your doctor advises.

Symptoms of an overdose

Symptoms of a Cymbalta overdose can include:

• sleepiness
• vomiting
• fast heartbeat
• dizziness
• fainting
• sweating
• flushed skin
• body tremors
• muscle stiffness
• loss of coordination
• diarrhea
• agitation
• hallucinations (seeing or hearing things that aren’t real)
• seizures
• coma

If you take more than the recommended amount of Cymbalta

Call your doctor right away if you believe you’ve taken too much Cymbalta. Another option is to call the American Association of Poison Control Centers at 800-222-1222 or use its online tool. If you have severe symptoms, immediately call 911 (or your local emergency number) or go to the nearest emergency room.

Cymbalta can cause physical dependence.* With physical dependence, your body becomes reliant on a drug to function normally. As a result, you may have withdrawal symptoms if you suddenly stop taking it.

Examples of Cymbalta withdrawal symptoms may include:

• pins and needles or electric shock-like sensations
• headache
• tinnitus (ringing or buzzing in your ears)
• feeling uneasy, irritable, or agitated
• mood shifts
• trouble sleeping
• anxiety
• confusion

To help prevent withdrawal symptoms, you should not stop taking Cymbalta suddenly. If you and your doctor agree that you should stop treatment, your doctor will explain how to reduce your dosage gradually over time. This is called a drug taper. It allows your body to gradually readjust to not having the medication. The length of time this can take varies from person to person.

* Note that dependence is not the same as addiction. See “Cymbalta and misuse” above to learn more about this.

The dosages in this article are typical dosages provided by the drug manufacturer. If your doctor recommends Cymbalta for you, they’ll prescribe the dosage that’s right for you. Always follow the dosage that your doctor prescribes for you.

As with any drug, never change your dosage of Cymbalta without your doctor’s recommendation. If you have questions about the dosage of Cymbalta that’s right for you, talk with your doctor.

Besides learning about dosage, you may want other information about Cymbalta. These additional articles might be helpful to you:

• More about Cymbalta. For information about other aspects of Cymbalta, refer to this article.
• Side effects. To learn about the side effects of Cymbalta, see this article. You can also look at the Cymbalta prescribing information.
• Drug comparison. To find out how Cymbalta compares with other drugs, refer to these sections on Lexapro and Effexor XR.
• Interactions. For more information about Cymbalta’s interactions, see this article.
• Details on your condition. For details on your condition, see our:
  • list of fibromyalgia articles and this article on Cymbalta for fibromyalgia
  • diabetes hub
  • mental health hub
  • lists of depression articles and anxiety articles

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

For nerve pain, anxiety, and more

Cymbalta (duloxetine) is a brand-name prescription medication. The Food and Drug Administration (FDA) has approved it to treat the following conditions in adults:

• generalized anxiety disorder
• major depressive disorder (also known as clinical depression)
• fibromyalgia
• chronic musculoskeletal pain
• pain caused by diabetic neuropathy (nerve damage)

Cymbalta is FDA-approved to treat the following conditions in children:

• generalized anxiety disorder in children ages 7 years and older
• fibromyalgia in children ages 13 years and older

Cymbalta comes as an oral capsule. It’s an antidepressant medication that belongs to a class of drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs).

For information on the dosage of Cymbalta, including its form, strengths, and how to take the drug, keep reading. For a comprehensive look at Cymbalta, see this article.

This article describes typical dosages for Cymbalta provided by the drug’s manufacturer. When taking Cymbalta, always follow the dosage prescribed by your doctor.

Below are Cymbalta dosages that are commonly used for the conditions the drug is prescribed to treat.

Cymbalta form

Cymbalta comes as oral capsules.

Cymbalta strengths

Cymbalta capsules are available in three strengths: 20 milligrams (mg), 30 mg, and 60 mg.

Typical dosages

Typically, your doctor will start you on a low dosage. Then, they’ll adjust it over time to reach the amount that’s right for you. Your doctor will ultimately prescribe the smallest dosage that provides the desired effect.

The following information describes dosages that are commonly used or recommended. However, be sure to take the dosage your doctor prescribes for you. Your doctor will determine the best dosage to fit your needs.

Dosage for chronic musculoskeletal pain

Chronic musculoskeletal pain is long-term pain in the muscles, bones, joints, tendons, ligaments, or nerves. Examples of this type of pain include back pain and arthritis pain.

The recommended dosage of Cymbalta for chronic musculoskeletal pain in adults is 60 mg once per day.

The typical starting dosage of Cymbalta is 30 mg once per day for the first week. If your condition responds well to the medication, your doctor will likely increase your dosage to 60 mg once per day.

The maximum recommended dosage for this condition is 60 mg per day.

Dosage for fibromyalgia

Cymbalta is approved to treat fibromyalgia in adults. The dosage of Cymbalta for this condition is the same as the dosage for chronic musculoskeletal pain. See the “Dosage for chronic musculoskeletal pain” section above.

Dosage for diabetic nerve pain

The recommended Cymbalta dosage for diabetic neuropathy in adults is 60 mg once per day. Doses higher than 60 mg are not recommended for diabetic neuropathy.

Dosage for anxiety

The recommended dosage of Cymbalta for generalized anxiety disorder depends on your age.

For adults younger than age 65 years, the recommended dosage is 60 mg once per day. Most people can start with this dosage. In some cases, your doctor may prescribe a starting dosage of 30 mg once per day for the first week. Then, they’ll increase your dosage to 60 mg once per day.

For adults ages 65 years and older, the recommended starting dosage is 30 mg once per day for 2 weeks. If you don’t have bothersome side effects, your doctor may increase your dosage to 60 mg once per day.

In adults of any age, the maximum Cymbalta dosage for anxiety is 120 mg per day. However, in clinical studies, doses higher than 60 mg weren’t found to be more effective than 60-mg doses.

For children, see the “Dosage for children” section below.

Dosage for depression

The recommended Cymbalta starting dosage for depression is 40 mg to 60 mg per day.

For the 40-mg dosage, you’ll likely take 20 mg twice per day. For the 60-mg dosage, you’ll likely take 30 mg twice per day or 60 mg once per day.

Most people can start with this dosage. However, in some cases, your doctor may decide to start having you take 30 mg once per day for a week before increasing your dosage.

If needed, your doctor may increase your dosage to a maximum of 120 mg per day to treat depression. However, in clinical studies, doses higher than 60 mg weren’t found to be more effective than 60-mg doses.

Dosage for older adults

In most cases, the dosage of Cymbalta prescribed for older adults is the same as that for adults younger than age 65 years.

However, for generalized anxiety disorder, adults ages 65 years and older should start treatment with a lower dosage than younger adults. For more information, see the “Dosage for anxiety” section above.

Dosage for children

Cymbalta is used to treat fibromyalgia and generalized anxiety disorder in children. The pediatric dose for these conditions is typically lower than the adult dose.

For fibromyalgia in children ages 13 years and older, the recommended starting dosage is 30 mg once per day. If your child doesn’t have bothersome side effects, their doctor may increase their dosage to 60 mg once per day if needed.

For generalized anxiety disorder in children ages 7 years and older, the recommended starting dosage is 30 mg once per day for 2 weeks. If your child doesn’t have bothersome side effects, their doctor may increase their dosage to 60 mg once per day if needed. The recommended Cymbalta dosage range for children is 30 mg to a maximum of 60 mg once per day.

Long-term use

Cymbalta is meant to be used as a long-term treatment. If you and your doctor determine that Cymbalta is safe and effective for you, you’ll likely take it long term.

Exactly how long you’ll take Cymbalta for depends on the condition it’s treating and how well that condition responds to the medication.

Here are answers to some frequently asked questions about Cymbalta’s dosage.

Is Cymbalta prescribed in 90-mg and 120-mg doses?

Yes, Cymbalta can be prescribed in 90-milligram (mg) and 120-mg doses. These doses may be used for depression or anxiety. However, they’re not common because clinical studies haven’t shown them to be more effective than the 60-mg dose.

Cymbalta isn’t prescribed in 90-mg or 120-mg doses for any other conditions.

For more information about the dosage of Cymbalta that’s right for you, talk with your doctor or pharmacist.

When would my doctor recommend the maximum dosage of Cymbalta?

Your doctor may increase your Cymbalta dosage to 120 mg per day for depression or anxiety if lower dosages haven’t worked for you. If the maximum dosage doesn’t work for you, your doctor will likely switch you to a different treatment.

The highest dosage of Cymbalta for depression or anxiety is 120 mg per day. However, this dosage isn’t typically prescribed.

For treating fibromyalgia, chronic musculoskeletal pain, and diabetic nerve pain, dosages above 60 mg per day are not recommended. In clinical studies, the 60-mg doses didn’t show any additional benefit for these conditions. Higher doses of Cymbalta are also associated with more side effects.

If you have questions about the maximum dosage of Cymbalta, talk with your doctor or pharmacist.

What’s considered a low dose of Cymbalta?

A low dose of Cymbalta is 30 mg. A dosage of 30 mg once per day is often prescribed when starting treatment with Cymbalta. Taking a low starting dose can help your body get used to the medication and may help you avoid side effects.

A 30-mg dose is typically prescribed in children. If needed, your child’s doctor may increase their dose.

A low dose may also be used if you take certain other medications. If you take other medications, talk with your doctor before starting treatment with Cymbalta.

If you miss a dose of Cymbalta, take your missed dose as soon as possible. Then, continue with your usual dosing schedule. However, if it’s almost time for your next dose, skip the missed dose and take your next dose as scheduled.

You should not take two doses at once to make up for a missed dose. This may increase your risk of side effects.

To help make sure that you don’t miss a dose, try using a medication reminder. This can include setting an alarm or using a timer. You could also download a reminder app on your phone.

The dosage of Cymbalta that your doctor prescribes will depend on several factors. These include:

• the condition you’re taking Cymbalta to treat and its severity
• other medical conditions you may have
• other medications you take
• your age

Dosage adjustments

Your doctor may adjust your treatment by increasing or lowering your Cymbalta dosage depending on:

• how your condition responds to Cymbalta
• side effects you may have with Cymbalta

You should not adjust your dosage of Cymbalta on your own. Your doctor will help determine what dosage is right for you.

You should take Cymbalta as instructed by your doctor. Cymbalta comes as an oral capsule. You may take your dose with or without food.

If you take Cymbalta once per day, you can take it at any time. However, try to take it around the same time every day.

If you take Cymbalta twice per day, you should take it in the morning and evening. However, try to take your doses around the same time every day.

Cymbalta has the potential to be misused. Misuse refers to using a drug differently than how it was prescribed. This can include taking Cymbalta more often, in a different way, or in a higher dosage than prescribed.

Cymbalta has a potential risk of misuse because it affects brain chemicals that influence mood, behavior, and feelings of reward. Although misuse with Cymbalta is rare, it can occur.

Misusing a drug can cause side effects and lead to overdose. It can also lead to drug dependence and addiction. With drug dependence, your body becomes reliant on a drug to function normally. As a result, you may have withdrawal symptoms when you stop taking it. With drug addiction, you find it difficult to stop misusing a drug, even though it may be causing harm.

Cymbalta isn’t known to be addictive. However, it can cause dependence and withdrawal symptoms if you suddenly stop taking it. For this reason, your Cymbalta dosage should be tapered down gradually when you stop taking it. For more information, see the “Cymbalta and withdrawal and dependence” section below.

If you have concerns about how to take Cymbalta safely, talk with your doctor. They can help you manage your risk of misusing the drug.

If you use more Cymbalta than your doctor prescribes, you may develop serious side effects.

It’s important that you don’t use more Cymbalta than your doctor advises.

Symptoms of an overdose

Symptoms of a Cymbalta overdose can include:

• sleepiness
• vomiting
• fast heartbeat
• dizziness
• fainting
• sweating
• flushed skin
• body tremors
• muscle stiffness
• loss of coordination
• diarrhea
• agitation
• hallucinations (seeing or hearing things that aren’t real)
• seizures
• coma

If you take more than the recommended amount of Cymbalta

Call your doctor right away if you believe you’ve taken too much Cymbalta. Another option is to call the American Association of Poison Control Centers at 800-222-1222 or use its online tool. If you have severe symptoms, immediately call 911 (or your local emergency number) or go to the nearest emergency room.

Cymbalta can cause physical dependence.* With physical dependence, your body becomes reliant on a drug to function normally. As a result, you may have withdrawal symptoms if you suddenly stop taking it.

Examples of Cymbalta withdrawal symptoms may include:

• pins and needles or electric shock-like sensations
• headache
• tinnitus (ringing or buzzing in your ears)
• feeling uneasy, irritable, or agitated
• mood shifts
• trouble sleeping
• anxiety
• confusion

To help prevent withdrawal symptoms, you should not stop taking Cymbalta suddenly. If you and your doctor agree that you should stop treatment, your doctor will explain how to reduce your dosage gradually over time. This is called a drug taper. It allows your body to gradually readjust to not having the medication. The length of time this can take varies from person to person.

* Note that dependence is not the same as addiction. See “Cymbalta and misuse” above to learn more about this.

The dosages in this article are typical dosages provided by the drug manufacturer. If your doctor recommends Cymbalta for you, they’ll prescribe the dosage that’s right for you. Always follow the dosage that your doctor prescribes for you.

As with any drug, never change your dosage of Cymbalta without your doctor’s recommendation. If you have questions about the dosage of Cymbalta that’s right for you, talk with your doctor.

Besides learning about dosage, you may want other information about Cymbalta. These additional articles might be helpful to you:

• More about Cymbalta. For information about other aspects of Cymbalta, refer to this article.
• Side effects. To learn about the side effects of Cymbalta, see this article. You can also look at the Cymbalta prescribing information.
• Drug comparison. To find out how Cymbalta compares with other drugs, refer to these sections on Lexapro and Effexor XR.
• Interactions. For more information about Cymbalta’s interactions, see this article.
• Details on your condition. For details on your condition, see our:
  • list of fibromyalgia articles and this article on Cymbalta for fibromyalgia
  • diabetes hub
  • mental health hub
  • lists of depression articles and anxiety articles

Disclaimer: Medical News Today has made every effort to make certain that all information is factually correct, comprehensive, and up to date. However, this article should not be used as a substitute for the knowledge and expertise of a licensed healthcare professional. You should always consult your doctor or another healthcare professional before taking any medication. The drug information contained herein is subject to change and is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. The absence of warnings or other information for a given drug does not indicate that the drug or drug combination is safe, effective, or appropriate for all patients or all specific uses.

instructions for use, home delivery

Description

Round biconvex film-coated tablets, white or almost white. On one side of the tablet there is an engraving in the form of a curved line ( ) &ndash: for a dosage of 30 mg and without it &ndash: for a dosage of 60 mg.

Active ingredients

Duloxetine

Composition nine0005

Excipients: compressible sugar (Compressus MS) &ndash: 100.00 mg/200.00 mg, corn starch &ndash: 14.14 mg/28. 28 mg, magnesium stearate &ndash: 0.75 mg/1.50 mg.

Enteric coating: methacrylic acid-ethylacrylic copolymer (1:1) dispersion (30%) in terms of dry matter - 9.0 mg / 16.0 mg, triethyl citrate - 1.35 mg / 2.40 mg , micronized talc &ndash: 2.69 mg/4.80 mg, titanium dioxide &ndash: 0.39 mg/0.68 mg, simethicone emulsion &ndash: q.s./q.s. nine0005

Pharmacological effect

Duloxetine is an antidepressant, serotonin (5 HT) and norepinephrine (NA) reuptake inhibitor. It weakly inhibits dopamine reuptake without significant affinity for histaminergic, dopaminergic, cholinergic, and adrenergic receptors. The mechanism of action of duloxetine in the treatment of depression is to suppress the reuptake of serotonin and norepinephrine, resulting in increased serotonergic and noradrenergic neurotransmission in the CNS. nine0005

Duloxetine has a central mechanism of action to suppress pain, which is primarily manifested by an increase in the threshold of pain sensitivity in pain syndrome of neuropathic etiology. The pain-suppressing effect of duloxetine is believed to be the result of potentiation of descending inhibitory pain pathways in the central nervous system.

Pharmacokinetics

Absorption: Duloxetine is well absorbed when taken orally. The maximum concentration (Cmax) in plasma is reached 6 hours after ingestion. The absolute oral bioavailability of duloxetine ranges from 32% to 80% (mean 50%). Eating does not affect the maximum concentration, but increases the time to reach it from 6 hours to 10 hours, and this slightly reduces the degree of absorption (approximately 11%). nine0005

Distribution: Duloxetine binds well to plasma proteins (approximately 96%), mainly to albumin and alpha1-glycoprotein. The degree of binding to plasma proteins does not depend on disorders of the liver or kidneys.

Metabolism: Duloxetine is extensively metabolized and its metabolites are excreted primarily in the urine. The metabolic process is carried out with the help of oxidative enzymes (CYP1A2 and polymorphic CYP2D6) followed by conjugation. Both CYP1A2 and CYP2D6 isoenzymes catalyze the formation of two major metabolites: 4-hydroxyduloxetine glucuronide and 5-hydroxy, 6-methoxyduloxetine sulfate. The circulating metabolites of duloxetine do not have pharmacological activity. The pharmacokinetics of duloxetine in patients with reduced CYP2D6 activity has not been specifically studied, but limited data suggest that plasma levels of duloxetine are higher in these patients. nine0005

Elimination: The half-life of duloxetine is 8 to 17 hours (mean 12 hours). After an oral dose, the plasma clearance of duloxetine ranges from 33 to 261 L/hour (average 101 L/hour).

Selected Patient Populations

The pharmacokinetics of duloxetine shows great variability (usually 50-60%) due to gender, age, smoking status and CYP2D6 metabolic status.

Gender: Pharmacokinetic differences have been identified between males and females (mean plasma clearance of duloxetine is lower in women), but these differences are not large enough to warrant dose adjustment based on gender. nine0005

Age: Pharmacokinetic differences have been identified between young and elderly patients (&ge: 65 years) (AUC-area under the concentration-time curve: higher and half-life longer by 25% in older patients), but the magnitude of these differences is insufficient to justify the need for dose adjustments depending on the age of the patient. As a general recommendation, caution should be exercised when treating the elderly.

Impaired renal function: Patients with severe renal impairment (end-stage renal disease (chronic renal failure)) on hemodialysis had twice the Cmax and AUC of duloxetine compared to healthy subjects. Pharmacokinetic data on duloxetine in patients with mild or moderate renal insufficiency are limited. In this regard, the advisability of reducing the dose of the drug in patients with clinically significant renal impairment should be considered. nine0005

Hepatic impairment: Patients with evidence of moderate hepatic impairment (Child-Pugh class B) may experience slow metabolism and excretion of duloxetine from the body. The plasma clearance of duloxetine in these patients was 79% lower, the half-life was 2.3 times longer, and the AUC was 3.7 times higher than in healthy people. The pharmacokinetics of duloxetine and its metabolites have not been studied in patients with mild or severe hepatic impairment.

Breastfeeding: Duloxetine has been studied in 6 women who were breastfeeding up to 12 weeks postpartum. Duloxetine was found in breast milk, and steady state concentrations in breast milk were about a quarter of those in plasma. The amount of duloxetine in breast milk was approximately 7 mcg/day at a dosage of 40 mg twice daily. Breastfeeding did not affect the pharmacokinetics of duloxetine. nine0005

Indications

• depression:
• generalized anxiety disorder:
• pain form of peripheral diabetic neuropathy:
• chronic pain syndrome of the musculoskeletal system (including due to fibromyalgia, chronic pain syndrome in the lower back and osteoarthritis of the knee).

Contraindications

• Hypersensitivity to the active substance or any of the excipients:
• Co-administration with monoamine oxidase inhibitors (MAOIs):
• Liver diseases associated with liver failure:
• Severe renal failure (creatinine clearance (CC) <: 30 ml/min):
• Simultaneous administration of potent inhibitors of the CYP1A2 isoenzyme (fluvoxamine, ciprofloxacin, enoxacin):
• Uncontrolled arterial hypertension:
• Uncompensated angle-closure glaucoma:
• Sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption:
• Children under 18 years of age.

Precautions

Mania and bipolar disorder (including history), convulsions (including history), intraocular hypertension or risk of angle-closure glaucoma attack, history of suicidal thoughts and attempts, increased risk of hyponatremia (elderly patients, cirrhosis of the liver, dehydration, taking diuretics), impaired liver function and renal failure (CC 30-60 ml / min).

Use in pregnancy and lactation

Fertility

In animal studies, duloxetine did not affect male fertility, and effects in females were only seen at animal-toxic doses.

Pregnancy

There are no data on the use of duloxetine in pregnant women. The potential risk to humans is unknown. Therefore, Depratal® should be used during pregnancy only if the potential benefit to the patient justifies the risk to the fetus. Patients should be warned that if they become pregnant or plan to become pregnant while taking duloxetine, they should inform their doctor. nine0005

Epidemiological evidence suggests that the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, especially late in pregnancy, may increase the risk of persistent pulmonary hypertension in newborns. Although there is no study on the relationship between persistent pulmonary hypertension in newborns and the use of SSRIs and norepinephrine, a potential risk cannot be ruled out given the mechanism of action of duloxetine (serotonin reuptake inhibition). nine0005

As with other serotonergic drugs, "withdrawal" syndrome may occur in newborns when duloxetine is used by the mother in late pregnancy. Withdrawal symptoms observed with duloxetine may include hypotension, tremor, hyperexcitability syndrome, feeding difficulties, respiratory distress syndrome, convulsions. Most cases occurred either during childbirth or within a few days of birth. nine0005

Breast-feeding period

Duloxetine passes into breast milk in small amounts (the concentration in the fetus is approximately 0.14% of the concentration in the mother based on mg/kg of body weight). However, because the safety of duloxetine in infants is unknown, the use of Depratal during breastfeeding is not recommended.

Dosage and administration

Inside. The tablets are swallowed whole, without chewing. nine0005

Depression

The initial and recommended maintenance dose is 60 mg once daily with or without food. In clinical studies, the safety of using doses from 60 mg once a day to a maximum dose of 120 mg per day was evaluated. However, there is no clinical evidence that patients who do not respond to the initial recommended dose experience any improvement with dose increases.

Response to therapy is usually observed 2-4 weeks after the start of treatment. nine0005

To avoid relapse after a response to antidepressant therapy is achieved, it is recommended to continue treatment for several months. In patients responding positively to duloxetine therapy and with a history of recurrent episodes of depression, further long-term treatment at a dose of 60 to 120 mg/day should be considered.

Generalized anxiety disorder

The recommended starting dose in patients with generalized anxiety disorder is 30 mg daily with or without food. In case of insufficient response to treatment, the dose can be increased to 60 mg, which is the usual maintenance dose in most patients. nine0005

In patients with comorbid depression, the recommended initial and maintenance dose is 60 mg daily (see also dosage recommendations above).

In clinical studies, doses up to 120 mg per day have been shown to be effective and the safety of such dosages has been evaluated. Therefore, in patients with insufficient response to a dose of 60 mg, an increase in dose to 90 mg or 120 mg is allowed. Dose escalation should be based on clinical response and tolerability. nine0005

After achieving a response to ongoing therapy, it is recommended to continue treatment for several months to avoid relapse.

Painful peripheral diabetic neuropathy

The initial and recommended maintenance dose is 60 mg once daily with or without food. In clinical studies, the safety of doses from 60 mg once a day up to a maximum dose of 120 mg per day, taken in evenly divided doses, was also evaluated. Plasma concentrations of duloxetine vary greatly between individuals, so some patients who do not respond well to 60 mg/day may improve at higher doses. nine0005

Response to treatment should be assessed after 2 months. Patients with poor initial response are unlikely to improve response after this period.

Evaluation of therapeutic response should be carried out regularly (at least once every 3 months).

Chronic musculoskeletal pain syndrome (including due to fibromyalgia, chronic pain syndrome in the lower back and osteoarthritis of the knee)

Initial treatment: the recommended dose of Depratal® is 60 mg once a day. Therapy may be initiated at a dose of 30 mg for one week to allow patients to adjust to the drug before increasing the dose to 60 mg once daily. Evidence that higher doses provide additional benefit is lacking, even in patients who do not respond to therapy with the drug at a dose of 60 mg. Higher doses are associated with a higher incidence of adverse reactions. nine0005

Continued treatment: Efficacy in the treatment of fibromyalgia has been demonstrated in placebo-controlled trials of up to 3 months duration. Efficacy has not been established in longer-term studies, but the decision to continue treatment should be based on the individual patient's response.

Special Patient Populations

Elderly Patients

For elderly patients, an initial dose of 30 mg is recommended for the treatment of generalized anxiety disorder for two weeks prior to initiation of duloxetine at a target dose of 60 mg. Dose adjustment for the treatment of patients for other indications, depending on age is not required. Caution should be exercised in the treatment of the elderly when prescribing a dosage of 120 mg per day for both the treatment of depression and generalized anxiety disorder, since data on the evaluation of the drug at a high dose are limited. nine0005

Patients with impaired liver function

The drug should not be administered to patients with liver disease, as this may lead to worsening of liver disease.

Patients with impaired renal function

Dose adjustment is not required for patients with mild or moderate renal dysfunction (creatinine clearance 30 to 80 ml/min). The use of the drug Depratal® is contraindicated in patients with severe renal insufficiency (creatinine clearance <: 30 ml / min). nine0005

Children

Duloxetine is not recommended for use in children and adolescents under 18 years of age due to insufficient data on its safety and efficacy in this age group.

Withdrawal of therapy

Abrupt discontinuation of the drug should be avoided. When duloxetine treatment is discontinued, the dose should be reduced gradually over a period of 1 to 2 weeks to reduce the risk of developing a "withdrawal" syndrome. If severe symptoms of "withdrawal" syndrome occur after dose reduction or after discontinuation of treatment, resumption of the previously prescribed dose may be considered. Subsequently, the doctor may continue to gradually reduce the dose, but even more gradually. nine0005

Side effects

The most commonly reported side effects in patients treated with duloxetine were nausea, headache, dry mouth, drowsiness and dizziness. However, most of these common side effects were mild to moderate, occurred early in the course of therapy, and subsequently decreased in severity even when therapy was continued.

Description of some adverse events

Discontinuation of duloxetine (especially abruptly) usually results in a "withdrawal" syndrome. Dizziness, sensory disturbances (including paresthesias or electric shock-like sensations, especially in the head), sleep disturbances (including insomnia and deep sleep), fatigue, drowsiness, agitation or anxiety, nausea and/or vomiting, tremor, headache , myalgia, irritability, diarrhoea, hyperhidrosis and dizziness are the most commonly reported reactions. nine0005

These effects are generally mild to moderate and limited with SSRIs and serotonin/norepinephrine reuptake inhibitors (SNRIs), but may be more severe and/or prolonged in some patients. Therefore, when duloxetine treatment is no longer required, a gradual dose reduction is recommended (see sections "Dosing and Administration": and "Special Instructions":).

Short-term use of duloxetine (up to 12 weeks) in patients with painful peripheral diabetic neuropathy showed a slight but statistically significant increase in fasting blood glucose in patients against the background of maintaining a stable concentration of glycated hemoglobin in both those taking duloxetine and in the placebo group . With long-term duloxetine therapy (up to 52 weeks), there was a slight increase in the concentration of glycosylated hemoglobin (HbA1c), which was 0.3% higher than the increase in the corresponding indicator in patients receiving other treatment. Patients treated with duloxetine also experienced slight increases in fasting blood glucose and total cholesterol. In the control group of patients, laboratory studies showed a slight decrease in these parameters. nine0005

The correlated (relative to heart rate) QT interval in patients treated with duloxetine did not differ from that in the placebo group. There were no clinically significant differences between QT intervals, PR, QRS or QTcB intervals in the duloxetine-treated group and in the placebo group.

Overdose

Cases of overdose have been reported with a single oral dose of duloxetine 5400 mg alone or in combination with other medicinal products. There have been some cases of death, primarily with mixed overdoses, while the dose of duloxetine was not more than 1000 mg. nine0005

Signs and symptoms of overdose (duloxetine alone or in combination with other drugs) included drowsiness, coma, serotonin syndrome, convulsions, vomiting, and tachycardia.

Treatment of overdose

No specific antidote known, but if serotonin syndrome occurs, corrective treatment with cyproheptadine and the use of methods to normalize body temperature are possible. Fresh air must be provided. Monitoring of cardiac activity and vital signs is recommended, along with appropriate symptomatic and supportive treatment. nine0005

Gastric lavage may be indicated if performed shortly after ingestion of duloxetine or as part of symptomatic treatment. Activated charcoal may be used to limit absorption.

Duloxetine has a large volume of distribution, so forced diuresis, hemoperfusion, and exchange perfusion are unlikely to be helpful.

Interaction with other drugs

Monoamine oxidase inhibitors (MAOIs). Due to the risk of developing serotonin syndrome, duloxetine should not be used concomitantly with nonselective irreversible MAOIs and for at least 14 days after cessation of MAOI treatment. Based on the duration of the half-life of duloxetine, at least 5 days must elapse after discontinuation of duloxetine before the start of MAOIs (see section "Contraindications":). nine0005

Simultaneous use of duloxetine with selective reversible MAOIs such as moclobemide is also not recommended (see section "Special Instructions" :) despite the fact that the risk of serotonin syndrome is lower.

The antibiotic linezolid is a non-selective, reversible MAOI and should not be given to patients receiving duloxetine (see section "Special Instructions":).

CYP1A2 isoenzyme inhibitors. Due to the fact that the CYP1A2 isoenzyme is involved in the metabolism of duloxetine, the simultaneous use of duloxetine with inhibitors of CYP1A2 may lead to higher plasma concentrations of duloxetine. Fluvoxamine, a potent inhibitor of CYP1A2, at a dose of 100 mg once daily reduced the mean plasma clearance of duloxetine by approximately 77% and increased AUC0&ndash:t by six times. Therefore, duloxetine should not be taken in combination with CYP1A2 inhibitors such as fluvoxamine (see section 'Contraindications'). Caution should be exercised when prescribing duloxetine with certain quinolone antibiotics, which are also inhibitors of the CYP1A2 isoenzyme. When used together, smaller doses of duloxetine should be used. nine0005

Drugs metabolized by CYP1A2 isoenzyme. The simultaneous use of duloxetine (60 mg twice a day) did not significantly affect the pharmacokinetics of theophylline, which is metabolized by the CYP1A2 isoenzyme. Duloxetine is unlikely to have a clinically significant effect on the metabolism of substrates of the CYP1A2 isoenzyme.

Drugs metabolized by the CYP2D6 isoenzyme. Duloxetine is a moderate inhibitor of the CYP2D6 isoenzyme. When taking duloxetine at a dose of 60 mg twice a day, along with a single dose of desipramine, a substrate of the CYP2D6 isoenzyme, the AUC of desipramine increased three times. Co-administration of duloxetine (40 mg twice daily) increased the steady state concentration of tolterodine (2 mg twice daily) by 71% but did not affect the pharmacokinetics of its active 5-hydroxy metabolite. Thus, caution should be exercised when using duloxetine with drugs that are predominantly metabolized by the CYP2D6 system (risperidone, tricyclic antidepressants such as nortriptyline, amitriptyline and imipramine), especially if they have a narrow therapeutic index (such as flecainide, propafenone and metoprolol). nine0005

CYP2D6 isoenzyme inhibitors. Since the CYP2D6 isoenzyme is involved in the metabolism of duloxetine, the simultaneous use of duloxetine with potential inhibitors of the CYP2D6 isoenzyme may lead to an increase in the concentration of duloxetine. Paroxetine (20 mg once daily) reduced the mean clearance of duloxetine by approximately 37%. When using duloxetine inhibitors of the CYP2D6 isoenzyme (for example, SSRIs), caution should be exercised.

Medicinal products affecting the central nervous system. The risk of using duloxetine in combination with other CNS active drugs has not been systematically evaluated. Caution should be exercised when duloxetine is used in combination with other drugs or substances that act on the CNS, especially those that have a similar mechanism of action, including alcohol, and sedative drugs (eg, benzodiazepines, opioid analgesics, antipsychotics, phenobarbital, sedative antihistamines). nine0005

Serotonin syndrome. In rare cases, serotonin syndrome has been observed with the combined use of SSRIs, for example, paroxetine, fluoxetine, and serotonergic drugs. Caution should be exercised when co-administering duloxetine with serotonergic antidepressants such as SSRIs, tricyclic antidepressants (clomipramine or amitriptyline), St. section "Special Instructions" :). nine0005

Oral contraceptives and other steroid preparations. The results of in vitro studies in vitro show that duloxetine does not induce the catalytic activity of the CYP3A isoenzyme. Specific in vivo drug interaction studies have not been conducted.

Anticoagulants and antithrombotics. Caution should be exercised when co-administering duloxetine with anticoagulants or antithrombotic agents due to the potentially increased risk of bleeding associated with pharmacodynamic interactions. In addition, an increase in INR (International Normalized Ratio) values ​​was noted when duloxetine was taken concomitantly with warfarin. However, co-administration of duloxetine and warfarin under stable conditions in healthy volunteers in a clinical pharmacology study did not result in a clinically significant change in INR from baseline or in the pharmacokinetics of the R or S isomer of warfarin. nine0005

Antacids and h3-histamine receptor antagonists. Co-administration of duloxetine with antacids containing aluminum and magnesium, or duloxetine with famotidine, did not significantly affect the rate or extent of absorption of duloxetine at a dose of 40 mg.

CYP1A2 isoenzyme inducers. Population pharmacokinetic analysis showed that compared with non-smoking patients, in smoking patients, the plasma concentration of duloxetine is almost 50% lower. Drugs highly bound to plasma proteins. Duloxetine is highly protein bound (>: 90%. Therefore, the administration of duloxetine to a patient who is taking another drug that is highly bound to plasma proteins may lead to an increase in the concentration of the free fractions of both drugs.

Special instructions

Manic state and seizures

Depratal® should be used with caution in patients with manic episodes or a diagnosis of bipolar disorder and/or seizures in history.

Mydriasis (dilated pupil)

Cases of mydriasis have been reported while taking duloxetine. Therefore, caution should be exercised when prescribing Depratal®: to patients with increased intraocular pressure or to persons at risk of developing acute angle-closure glaucoma.

Blood pressure and heart rate

In isolated cases, duloxetine has been associated with increased blood pressure and clinically significant hypertension in some patients. This may be due to the noradrenergic action of duloxetine. Cases of hypertensive crisis have been reported in connection with the use of duloxetine, especially in patients with prior hypertension. Therefore, in patients with hypertension and/or other heart conditions, blood pressure monitoring is recommended, especially during the first month of treatment. Duloxetine should be used with caution in patients who experience an increase in heart rate or high blood pressure. Caution should also be exercised when duloxetine is taken with drugs that may reduce its metabolism (see section "Interaction with other drugs":). For patients who experience a persistent increase in blood pressure while taking duloxetine, either dose reduction or gradual discontinuation of the drug is recommended. Patients with uncontrolled hypertension should not take duloxetine. nine0005

Serotonin syndrome

As with other serotonergic agents, serotonin syndrome, a potentially life-threatening condition, may occur during treatment with duloxetine, especially when used concomitantly with other serotonergic agents, including SSRIs, selective norepinephrine reuptake inhibitors (SNRIs) , tricyclic antidepressants or triptans) and drugs that interfere with serotonin metabolism, such as MAOIs, antipsychotics, or other dopamine antagonists that may affect serotonergic neurotransmitter systems (see sections "Contraindications" and "Interaction with other medicinal products":). nine0005

Symptoms of serotonin syndrome may include mental status changes (eg, agitation, hallucinations, coma), autonomic instability (eg, tachycardia, labile blood pressure, pyrexia), neuromuscular aberrations (eg, hyperreflexia, incoordination), and/or gastrointestinal intestinal symptoms (eg, vomiting, diarrhea).

If concomitant therapy with duloxetine and other serotonergic agents that may affect the serotonergic and/or dopaminergic neurotransmitter systems is clinically warranted, careful monitoring of the patient is recommended, especially during initiation of treatment and dose escalation. nine0005

St. John's wort (Hypericum perforatum)

Adverse reactions may be more common when duloxetine is co-administered with herbal preparations containing St. John's wort (Hypericum perforatum).

Suicidal behavior

The risk of suicide and self-harm exists in all patients with depression and some other mental disorders. This danger persists until the patient goes into significant remission.

Since improvement may not occur during the first few weeks of treatment or more, patients should be closely monitored until significant improvement occurs. Clinical experience shows that the risk of suicide may increase in the early stages of recovery.

Patients with a history of suicide attempts, or those who exhibit significant suicidal ideation prior to treatment, have been found to be at greater risk of suicidal thoughts or suicidal behavior. Patients in this group require careful monitoring during treatment. Cases of suicidal thoughts and suicidal behavior have been reported both during duloxetine therapy or at the beginning of treatment, and after discontinuation of treatment. Analytical reviews of the results of a number of studies using antidepressants for the treatment of mental disorders indicate an increased risk of developing suicidal thoughts and / or suicidal behavior in children, adolescents and adults under 25 years of age compared with placebo. Patients (and their caregivers) should be warned to monitor any clinical deterioration, suicidal behavior or thoughts, and unusual changes in behavior and seek immediate medical attention if these symptoms occur. nine0005

Increased risk of bleeding

There have been reports of bleeding abnormalities such as bruising, purpura and gastrointestinal bleeding with SSRIs and SNRIs, including duloxetine. Caution is advised in patients taking anticoagulants and/or drugs known to affect platelet function (eg, non-steroidal anti-inflammatory drugs or acetylsalicylic acid) and in patients with a history of bleeding tendency.

Hyponatremia

Cases of hyponatremia have been reported very rarely (in some cases, serum sodium was below 110 mmol/l). Hyponatremia can be caused by syndrome of inappropriate secretion of anticancer hormone (SIADH). Most of these cases have been reported in the elderly, especially in combination with a history or condition predisposing to changes in body fluid balance. Caution should be exercised in patients at increased risk of hyponatremia, such as elderly patients with liver cirrhosis or dehydrated patients or patients receiving diuretics. nine0005

Withdrawal Syndrome:

Withdrawal symptoms are common when treatment is discontinued, especially if treatment is discontinued abruptly. In clinical studies, adverse events observed with abrupt discontinuation of treatment were present in approximately 45% of patients treated with Depratal® and in 23% of patients treated with placebo.

The risk of withdrawal symptoms seen with SSRIs and SNRIs may depend on several factors, including the duration and size of the dose, and the rate of dose reduction. The most commonly reported reactions are listed in the "Side effect" section:. nine0005

These symptoms are generally mild to moderate, but may be severe in some patients. They usually occur within the first few days after stopping treatment, but there have also been very rare reports of such symptoms in patients who accidentally missed a dose. As a rule, these symptoms resolve on their own within 2 weeks, although in some people they can last 2-3 months or more. Therefore, when stopping treatment, it is recommended to reduce the dose of duloxetine gradually over at least 2 weeks in accordance with the needs of the patient (see section "Dosage and Administration":). nine0005

Akathisia / psychomotor restlessness

The use of duloxetine has been associated with the development of akathisia, characterized by subjectively unpleasant or anxious restlessness and the need to move frequently, inability to sit or stand still. This most likely occurs within the first few weeks of treatment. For patients who develop these symptoms, an increase in dose is not recommended.

Hepatitis / Elevated liver enzymes

Cases of liver damage, including elevated liver enzymes, have been reported in association with duloxetine. Most of these cases occurred in the first months of treatment, were transient and disappeared spontaneously. A serious increase in liver enzymes (10 times or more above the upper limit of normal), as well as liver damage of cholestatic or mixed origin, were rare, and in some cases were associated with excessive alcohol consumption or with previous liver disease, duloxetine should be used with caution in patients, who drink alcohol or take other drugs that can cause liver damage, or who have liver disease. nine0005

Monoamine oxidase inhibitors (MAOIs)

Serious reactions, sometimes fatal, have been reported in patients taking a serotonin reuptake inhibitor in combination with an MAOI, including hyperthermia, rigidity, myoclonus, peripheral disturbances with possible sharp fluctuations in vital signs functions and changes in mental status, including marked arousal with a transition to delirium and coma. These reactions have also been observed in patients who had their serotonin reuptake inhibitor discontinued shortly before MAOIs. In some cases, patients experienced symptoms characteristic of neuroleptic malignant syndrome. The effects of the combined use of duloxetine and MAOIs have not been evaluated in humans or animals. Therefore, given the fact that duloxetine is both a serotonin and norepinephrine reuptake inhibitor, it is not recommended to use duloxetine in combination with an MAOI or for at least 14 days after stopping MAOI treatment. Based on the length of the half-life of duloxetine, a break of at least 5 days after the end of duloxetine should be taken before taking MAOIs. nine0005

Sugar

Depratal® enteric tablets: contain compressed sugar, including sucrose. Patients with rare hereditary problems of fructose intolerance, glucose malabsorption, galactose malabsorption, or isomaltase sucrase deficiency should not take this drug.

Special patient populations

Children and adolescents under 18 years of age

Depratal® should not be used in the treatment of children and adolescents under 18 years of age. Suicide-related behaviors (suicide attempts and suicidal thoughts), hostility (predominantly aggression, oppositional behavior and anger) were observed more frequently in clinical studies among children and adolescents treated with antidepressants compared with those treated with placebo. If a treatment decision is made based on clinical need, the patient should be carefully monitored for suicidal symptoms. In addition, there are no long-term data on the safety of children and adolescents in terms of growth, maturation and the development of cognitive and behavioral characteristics. nine0005

Elderly patients

Data on the use of the drug Depratal® 120 mg in elderly patients with major depressive disorder and generalized anxiety disorder are limited. Therefore, caution should be exercised when treating the elderly with the maximum dosage.

Impaired liver or kidney function

In patients with severe renal impairment (CC <: 30 ml / min) or severe liver failure, an increase in plasma concentrations of duloxetine is observed. If duloxetine is clinically warranted in such patients, lower initial doses should be used. nine0005

Storage conditions

At temperatures not exceeding 25 °C.

Keep out of reach of children.

Depression

Russian Academy of Medical Sciences
SCIENTIFIC CENTER FOR MENTAL HEALTH









DEPRESSION (from hope to certainty).
(INFORMATION FOR PATIENTS AND THEIR FAMILIES)

MOSCOW
2008

Oleichik I. V. - Candidate of Medical Sciences, Leading Researcher of the Department for the Study of Endogenous Mental Disorders and Affective States

© 2008, Oleichik I.V. nine0337 © 2008, NTsPZ RAMS

The vast experience accumulated by mankind and reflected in many literary works convincingly shows that sadness (sadness, spleen) has always gone side by side with people, being one of the natural human emotions. None of us is immune from failures, illness, breakups, loss of loved ones, financial collapse. Each person can face something inevitable and inevitable, when it seems that life loses its meaning, and despair becomes boundless. However, normally, sadness, sadness and melancholy, as natural reactions to traumatic events, weaken over time and the person's condition returns to normal without special treatment. The situation is different with depressions, which are mental disorders that differ from natural physiological reactions in greater intensity, special severity of experiences and persistence of manifestations. True depression rarely goes away on its own, requiring persistent, sometimes long-term treatment. nine0337 A depressive state (from the Latin word depressio - suppression, oppression) is a disease that concerns not only an individual specific sick person, but is also a significant burden of modern society, since it is spreading more and more widely in the world, causing enormous damage to the health of the population and the state. economy. And this applies to all countries, regardless of their level of social development. Every year, at least 200 million people in the world fall ill with depression. Perhaps these figures are even higher, since most victims of depression do not seek help because they are not aware of the painfulness of their condition. Scientists have calculated that almost one in five people who have reached adulthood will experience at least one episode of depression during their lifetime. nine0337 In the most general sense, a depressive state is one of the possible forms of a person's response to the impact of stress factors. In some cases, depression can be triggered by external negative influences, for example, mental trauma, excessive educational or work overload, infection or other serious somatic disease, traumatic brain injury, changes in the hormonal background, which is especially important for the female body, regular certain medications, such as hormones, blood pressure medications, alcohol or other drug abuse. In other cases, depressive states develop as a manifestation of such mental illnesses, in which the main influence is heredity or characteristics of the nervous system (cyclothymia, dysthymia, manic-depressive psychosis, schizophrenia, etc.). If, based on the description of depressive symptoms set out later in our brochure, you realize that you have indeed developed a depressive state, do not fall into despair, do not “try to control yourself”, remember that depression is not a manifestation of weakness of will or character, on the contrary, weakening of volitional qualities is one of the main symptoms of depression. Depression is a disease like rheumatism, arthritis or hypertension, it responds well to treatment, resulting in almost always a full recovery. You should not blame yourself for the occurrence of depression, it does not indicate either your fault, or your weakness, or the possible development of a more severe mental pathology. Below we will tell you about the symptoms of depression, which can be extremely diverse. nine0005

Manifestations of depression

Manifestations of depression can be very different. Depressive states can be manifested by a violation of almost all aspects of mental life: mood, memory, will, activity, which is expressed in the appearance of sadness, sadness, mental and muscle retardation, lasting at least 2 weeks. Depressed mood during depression can manifest itself as mild sadness, sadness, and boundless despair. Often it is accompanied by a feeling of melancholy, unbearable heaviness in the soul, with excruciating pain behind the sternum, a feeling of hopelessness, deep depression, hopelessness, helplessness, despair and uncertainty. At the same time, the patient is completely immersed in his gloomy experiences, and external events, even the most joyful ones, do not affect him, do not affect his mood, and sometimes even worsen the latter. A constant "companion" of a depressive mood is also anxiety of varying severity: from mild anxiety or tension to violent excitement, riot. Anxiety and bad mood arise at the mere thought of the need to make some kind of decision or change your plans due to suddenly changed circumstances. Anxiety can also manifest itself on the physical (bodily) level in the form of belching, intestinal cramps, loose stools, frequent urination, shortness of breath, palpitations, headaches, increased sweating, etc.
The picture of depression is complemented by the disappearance of desires, interests, a pessimistic assessment of everything around, ideas of one's own low value and self-blame. Deficiency of vital impulses is manifested in patients with a variety of symptoms - from lethargy, physical weakness to a state of weakness, loss of energy and complete impotence. Where an important decision is required, a choice between different options, human activity is sharply hampered. Depressed people are well aware of this: they complain that insignificant everyday tasks, small issues that used to be solved almost automatically, take on the significance of complex, painful, insoluble problems. At the same time, a person feels that he began to think, act and speak slowly, notes the suppression of instincts (including food and sexual instincts), the suppression or loss of the instinct of self-preservation and the lack of the ability to enjoy life up to complete indifference to what used to be liked evoked positive emotions. nine0337 People suffering from depression often feel "stupid", "mentally retarded", "feeble-minded". Thinking in depression becomes viscous, painful, requires special efforts, one mental image is hardly forced out by the next. The sick person is oppressed by the feeling of his own intellectual insolvency, professional collapse. Depressed patients can hardly describe their painful experiences to the doctor. Only after getting out of depression, many of them say that the mood at that moment was lowered, thinking was slow, all undertakings (including treatment) seemed in vain, and the years lived were empty and useless. However, at the time of the first visit to the doctor, they could not explain this because of the almost complete absence of thoughts in their heads, “para-lich of thinking”. With depression, there are also often complaints of memory loss, which is why those suffering from it assume that they have "Alzheimer's disease", "schizophrenia", "senile dementia", which is not true. Especially often these complaints are found in depressions that develop in adolescence. nine0337 Typical story
Aleksey, 18 years old, 1st year student of a technical university, describes his condition during depression in this way:
“From childhood, I was fond of technology and modeling, I could read special literature for hours, won school and regional olympiads in mathematics and physics. After graduating from school, my dream came true - I brilliantly passed the exams to a prestigious university. Then it seemed to me that the whole world was at my feet, I flew with happiness "as if on wings." In September, I happily began to study. At the beginning, everything worked out well, but after 2 months I began to notice that it was becoming increasingly difficult for me to absorb what I read, I did not remember the simplest text, I could not solve problems that I used to “click like nuts”. Trying to achieve success through many hours of brainstorming or drinking a few cups of coffee led to the fact that I completely stopped thinking about anything. It seemed to me that I was "finally and irreversibly stupid." At night I sobbed, wrapped in a blanket and thought about how best to commit suicide. Luckily, I met a senior in the library and shared my problems with him. My new acquaintance said that he experienced something similar and advised me to contact the psychiatrist of the student clinic. After the examination, I was diagnosed with juvenile depression and sent for treatment to a specialized medical center. After 2 months, I felt completely healthy, returned to my studies and caught up with my classmates. nine0005

Depression can also be accompanied by real setbacks: for example, a decrease in academic performance, the quality of work, family conflicts, sexual disorders and their consequences for personal relationships. As a rule, the significance of these failures is exaggerated and as a result there is a false sense of the irreparability of what happened, "the collapse of all hopes."
Another generally recognized danger of depression is the possibility of suicidal thoughts, which often lead to suicide attempts. The condition of a person suffering from depression can suddenly deteriorate sharply, which happens either without clear external causes, or under the influence of traumatic situations, unpleasant news. It is during these hours, and sometimes even minutes, that a fatal decision is made. Factors that increase the risk of suicide in depression are past suicide attempts, the severity and duration of the depressive state, the presence of anxiety in its structure, prolonged insomnia, loneliness or alienation in the family, alcohol and drug abuse, loss of work and a sharp change in lifestyle, as well as relatives commit suicide. nine0337 Typical story
Eugene E., 35 years old, leading manager of the company.
Almost all my life, my career went “on the ascending”, the goals set were clear, clear and achievable. The marriage was extremely harmonious, two beloved children grew up. He devoted almost all the time to the affairs of the company, occasionally, once every 1-2 months, he escaped with his family out of town, to the country. He often lacked sleep, stayed late at work, took home assignments, and was deeply worried about the affairs of the company. Gradually, irritability, fatigue, insomnia, difficulty concentrating appeared, more and more often he suffered a “fiasco” in intimate life. Thoughts appeared that life was lived in vain, that it is a "chain of tragic mistakes" that led to a dead end. He began to believe that the choice of work, friends, family was wrong, for which now "retribution has come." Analyzing the past years for a long time, he found more and more evidence and examples of his "duplicity, hypocrisy, insincerity, etc." I realized that the only way to solve all problems is to voluntarily leave this life. At the same time, he believed that by this act he would free the family from the “burden”, “loser”, “loser”. I decided, having locked myself in the garage, to get poisoned by the exhaust gases of the car. However, by chance, in a semi-conscious state, he was discovered by an employee of a garage cooperative. He explained what happened as an "accident". The thought of leaving life did not leave the patient. I decided to shoot myself with a gas pistol, which I had long ago acquired for self-defense. After a shot in the mouth, in a serious condition, he was taken to the Research Institute. Sklifasovsky, from where he was discharged a week later. The alarmed wife, suspecting something was wrong, decided to consult her husband with a psychiatrist. He was admitted to the clinic. He agreed to this only out of respect for family relations, he himself believed that treatment by psychiatrists was completely useless, because. his situation is hopeless and no medicines will help here, but will only "stupefy" his psyche. However, after two weeks of taking a modern antidepressant, the patient's point of view changed. Everything began to look not so bleak and hopeless, interest in work and life in general returned, I began to feel more cheerful, more energetic, interest in intimate life appeared. He took work to the clinic, called up colleagues. After two months of treatment, he fully returned to his usual life. With bewilderment, he recalled his thoughts about insolvency, the collapse of life, suicide. He took the drug prophylactically for about six months, then, on the recommendation of a doctor, he gradually reduced the dose and stopped taking it. Over the next two years, the condition remained stable, career growth continued, another child was born. nine0005

Depression is also characterized by sleep disturbances, which occur in approximately 80% of patients. As a rule, these are early awakenings with the inability to fall asleep, lack of a sense of sleep, difficulty falling asleep. These disorders, as well as restless sleep with unpleasant dreams, are often the very first symptoms of incipient depression.
If the depression is not deep, it is sometimes difficult to recognize it. This is due to the fact that people are ashamed to tell others about their problems, to admit to "weaknesses". Quite often, especially in Russia, depressive states are masked by alcohol abuse (“vodka heals”). In addition, often patients suffering from depression, in order to "shake themselves up", "throw into all serious", engage in casual sex, are fond of gambling or extreme sports, leave to serve on a contract in "hot spots", lead an idle lifestyle with constant attendance at entertainment events. Surrounding people, relatives who do not have psychiatric knowledge, often accuse them of debauchery, drunkenness, riotous lifestyle, parasitism. Meanwhile, this behavior is a kind of “cry for help”, an attempt to fill the spiritual emptiness brought by depression with new acquaintances and impressions. nine0337 Depressive conditions can occur in shallow forms that are easily treatable, but at least a third of depressions are more severe. Such depressions are characterized by:
- ideas of guilt, sometimes reaching the degree of delirium, i.e. unshakable conviction in their sinfulness, low value (patients consider themselves great sinners, believe that because of them all relatives and Mankind will die, that they are “moral freaks” from birth, supposedly deprived of the foundations of morality and a sense of empathy for other people that they have no place on earth They find in their past numerous "confirmations" of what has been said above, they believe that the doctor and other patients are aware of these transgressions and express contempt and indignation with their facial expressions and gestures, but in the words “they hide, deny the obvious. ” Both the patients themselves and their relatives must remember this in order to prevent the impending threat in time: remove all firearms, piercing and cutting objects, ropes, potent drugs and poisonous close household fluids, close windows or shutters, do not let the patient go anywhere alone.If these ideas become persistent and cannot be dissuaded, it is urgent to seek advice from a psychiatrist. neurological institution or call a psychiatrist at home. nine0337 - mood swings during the day: in typical cases, the patient, waking up, immediately feels longing. Sometimes, even before full awakening, through a dream he experiences a painful premonition of a heavy coming morning. In the evening, the state of health improves somewhat.
- the patient may experience a feeling of unmotivated hostility towards relatives, friends, constant internal discontent and irritation, which makes him unbearable for the family.
- in a number of people suffering from depression, constant doubts, fear for the health and well-being of loved ones, obsessive ones, come to the fore. arising against the will, ideas about the misfortunes and troubles of family members. nine0005

Typical story
Dmitry Petrovich, 58 years old, teacher.
“After minor troubles at work, I began to feel incomprehensible anxiety and agitation. Unpleasant thoughts came into my head that I did something wrong at work, because of which I double-checked everything many times and went home later than everyone else. But even at home, the anxiety did not let go: as soon as the daughter or wife lingered for at least half an hour, terrible pictures of traffic accidents or violence were drawn in the imagination. I fell asleep only in the morning, got up broken and felt sleepy all day. I took Valerian, Corvalol, but it practically did not help. At work, they hinted whether I should take a vacation. Friends advised me to consult a neuropathologist, but he did not find his pathology and sent me to a psychiatrist. I was diagnosed with anxiety depression. After a course of outpatient treatment, I completely recovered. ” nine0005

- in many cases, depression is characterized by unpleasant sensations in the body, disturbances in the activity of internal organs in the absence of objective signs of true somatic, i.e. non-mental illness. At the same time, many patients constantly report pain, internal discomfort. Some complain of headaches, pains in the stomach, joints, lower back, others - of disorders in the intestines: constipation, indigestion, irritation of the colon, others pay attention to a decrease in sexual desire and potency. In women, menstruation often becomes painful and irregular. Approximately 50% of depressed people at the doctor's office complain of such physical ailments, without mentioning the depressed mood or state of mind underlying the depression. Experiencing chronic pain or other unpleasant sensations in the body, patients may not realize that they are suffering from depression, even with severe melancholy, considering the latter a reaction to painful bodily discomfort. nine0337 - some patients are convinced that they have some rare and difficult to diagnose disease and insist on numerous examinations in general medical institutions. Doctors call this condition masked (hidden) depression, in which a person may experience pain in the head, in the limbs, behind the sternum, in the abdomen and in any other parts of the body, he may be haunted by anxious fears, he may suffer from insomnia or, on the contrary, too much sleep. nine0337 - Patients may experience disturbances in the cardiovascular system, skin itching or lack of appetite. All of these are manifestations of depression.
- the pathological sensations that patients experience during such depressions are quite real, painful, but they are the result of a special mental state, and not an internal disease. It must be remembered that the frequency of latent depressions exceeds the number of explicit ones many times over.
- with such depression, patients, as a rule, also have a changed attitude towards food: they can go without food for a long time and not feel hungry, and sitting down at the table, eat only 1-2 spoons - they have neither strength nor desire for more . nine0337 - a sign of depression can serve as a weight loss of more than 5 kg. within a month. In some people, especially women, the appetite for depression, on the contrary, increases, sometimes reaching the level of excruciating hunger, accompanied by severe weakness and pain in the epigastric region. In some cases, food is taken in excess due to an increased craving for sweets or attempts to distract oneself from painful thoughts by frequent eating.
Thus, we see that depression is a disease with many different manifestations that do not go away on their own, requiring special, sometimes long-term, medical intervention. Therefore, when the symptoms described above appear, it is necessary to seek help from a psychiatrist who will prescribe and monitor antidepressant treatment. nine0005

TREATMENT OF DEPRESSIVE DISORDERS

To date, it can be argued that the vast majority of cases of depression respond well to treatment. According to modern views, effective treatment of depression consists of a combination of pharmacotherapy, psychotherapy and, if necessary, other types of treatment. At the same time, the main role in therapy, of course, belongs to antidepressants - drugs specially designed for the treatment of various types of depression. nine0337 The creation of antidepressants is based on the discovery of scientists that depression develops as a result of a violation of the mechanism of biochemical transmission of nerve impulses in the brain regions responsible for mood, behavior, response to stress, sleep and wakefulness, appetite and some other functions. To ensure the coordination of the work of all these functional divisions, the brain sends special "commands" to them in the form of chemical impulses transmitted from the processes of one nerve cell (neuron) to the processes of another. This transmission is carried out with the help of chemical mediators (neurotransmitters), which, after transmitting a signal, partially return to the original neuron. This process is called neurotransmitter reuptake. Thanks to him, the number of mediators in the microscopic space between the processes of neurons (in the so-called synaptic cleft) decreases, which means that the necessary signals are transmitted worse. Numerous studies have shown that mediators of various structures, in particular, norepinephrine and serotonin, are involved in the transmission of signals that ensure the normal functioning of the nervous system. The first of them has a general activating effect, maintains the level of wakefulness of the body and takes part in the formation of adaptive reactions, and the second has the main antidepressant effect, controls impulsive actions, anxiety, aggressiveness, sexual behavior, falling asleep, feeling of pain, therefore serotonin is called sometimes a "good mood" regulator. A decrease in the number of mediators in the synaptic cleft causes symptoms of depression, while an increase, on the contrary, prevents their appearance. The ability of some drugs in one way or another to increase the concentration of mediators in the synaptic cleft allows them to be used as antidepressants. nine0337 Now antidepressants are used in Russia, which can be conditionally divided into 4 generations according to the time of creation.
The first antidepressants to find wide clinical use were tricyclic drugs: amitriptyline and imipramine. They have a fairly powerful effect on most depressive states by blocking the reuptake of both norepinephrine and serotonin. However, the real clinical effect of these drugs is significantly offset by their undesirable side effects, which drastically reduce the quality of life of patients during treatment. Side effects of tricyclic antidepressants arise due to the nonspecificity of their effect on receptor structures. Acting in addition to the serotonin and norepinephrine system and other neurotransmitters (acetylcholine, histamine, dopamine), these antidepressants cause side effects such as urinary retention, dry mucous membranes, constipation, palpitations, fluctuations in blood pressure, confusion, tremor, sexual dysfunction. functions, weight gain. In such cases, it is necessary to prescribe other drugs to correct side effects or reduce the therapeutic dose of drugs, which naturally affects the effectiveness of the antidepressant action. It has been observed that up to 50% of patients refuse to take tricyclic antidepressants due to severe side effects. For the same reason, physicians are less likely to prescribe these drugs to patients on an outpatient basis. nine0337 The situation was somewhat improved by the introduction into practice of drugs of the second generation - tetracyclic antidepressants, which, along with the ability to block the reuptake of norepinephrine and serotonin, could also affect some other receptors. Being analogues of tricyclic compounds, these drugs have antidepressant activity comparable to them, but unlike their predecessors, they are safer, since they cause unwanted side effects much less often. In addition to the antidepressant, mianserin (lerivon) has a clear sedative, anti-anxiety and hypnotic effect. Maprotiline (Ludiamil) has a mild balanced antidepressant effect. In general, these drugs are able to cure mild to moderate depression, but are ineffective in patients with severe depression. nine0337 To date, antidepressants of the 3rd generation, such as fluoxetine (Prozac), fluvoxamine (Fevarin), paroxetine (Paxil), sertraline (Zoloft), citalopram (Cipralex) and some other drugs that selectively (selectively) affect the serotonin metabolism system, have received widespread recognition today. , preventing its reuptake in the synaptic cleft. Based on the mechanism of action, these antidepressants are combined into a group of selective serotonin reuptake inhibitors. In addition to treating depression, they are used to correct eating disorders, level panic disorders, so-called social phobias, various obsessive-compulsive disorders and chronic pain symptoms. These drugs have gained popularity due to the possibility of a once-daily intake, concomitant anti-anxiety effect, the presence of a psychostimulant component and a small number of side effects. In addition, they have low toxicity and are well tolerated by elderly patients. However, some researchers note their lack of effectiveness in the treatment of severe forms of depressive states, probably associated with selective activity in relation to only one neurotransmitter - serotonin. It should be noted that in recent years, some American scientists have associated the use of these drugs with an increased risk of suicide, which, however, is not proven. nine0337 Considering the high frequency of side effects in some of the above drugs and the insufficient antidepressant activity in others, psychopharmacologists have taken the path of developing more effective antidepressants - IV generation drugs that selectively block the reuptake of both serotonin and noradrenaline, without affecting other mediators. system and with minor side effects. Currently, 3 drugs meet these requirements: milnacipran (Ixel), duloxetine (Cymbalta) and venlafaxine (Effexor). Their antidepressant activity in the treatment of patients with severe and moderate depression has been confirmed in a number of specially conducted studies, which at the same time showed that these drugs are well tolerated. nine0337 It should be noted that antidepressants of plant origin (negrustin, gelarium hypericum, deprim, etc. ) can be effective in mild depressive states, but there are no reliable data guaranteeing their effectiveness. The opinion of a number of doctors that all depression can be treated with herbs or, say, acupuncture, should be recognized as unfounded.
For extremely severe depressions that do not improve despite the use of the most powerful antidepressants, electroconvulsive therapy (ECT) can be effective, but this situation is extremely rare and requires careful justification by the commission of doctors and the consent of the patient. nine0337 An important additional role in antidepressant therapy, especially with concomitant anxiety, is played by tranquilizers - anti-anxiety drugs, such as Xanax, phenazepam, diazepam, nitrazepam, atarax, etc. Drugs that can, when taken systematically, prevent mood swings in various depressive disorders include so-called mood stabilizers or mood stabilizers - lithium preparations, carbamazepine, valproic acid salts, lamotrigine, topiramate. With their systematic intake in most patients, the clinical manifestations of depression either completely disappear or become rare and mild, requiring no hospitalization and not significantly affecting the ability to work. nine0337 Antipsychotics play a significant role in the treatment of certain forms of depression. These include both traditional drugs - fluanxol, triftazin, eglonil, teralen, neuleptil, sonapax, and atypical antipsychotics that are gaining more and more recognition among doctors: seroquel, solian, zeldox, rispolept, abilify, serdolect and others.
In drug therapy of depressive conditions, an unconventional, strictly individual approach is used, with the obligatory provision of fruitful cooperation between the patient and the doctor. Otherwise, there may be a violation of medical recommendations regarding doses and regimens for taking medications. The patient's faith in the possibility of recovery, the absence of prejudice against the "harm" caused by psychotropic drugs, the systematic observance of the prescriptions prescribed by the doctor largely contribute to the achievement of therapeutic success. nine0337 Drug treatment of depression takes time. You should not expect a complete cure already in the first days of taking the drug. It must be remembered that all modern antidepressants begin to act on depressive symptoms no earlier than 1-2 weeks after the start of treatment. Cancellation of an antidepressant, as well as its appointment, should be carried out only by a doctor. Cancellation is usually made no earlier than 6 months from the normalization of the mental state. Even after the complete disappearance of all symptoms of depression, do not rush to stop taking the drug yourself, as there is a risk of an exacerbation of the disease. Therefore, doctors recommend continuing to take the antidepressant for a certain period of time. A common mistake is the premature withdrawal of drugs soon after a significant improvement in the condition or due to "forgetfulness". To avoid this, try to include the drug in the list of daily urgent matters - for example, store it in the bathroom and take it after hygiene procedures. When planning a trip, calculate exactly how many tablets you need for the entire period of absence from home.

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