Side effects, dosage, uses, and more

1. Duloxetine oral capsule is available as both a generic and a brand-name drug. Brand name: Cymbalta.
2. Duloxetine only comes as a capsule you take by mouth.
3. Duloxetine oral capsule is used to treat anxiety, depression, diabetic nerve pain, fibromyalgia, and chronic (long-lasting) muscle and joint pain.

FDA warning: Suicidal thoughts and behaviors

• This drug has a Black Box Warning. This is the most serious warning from the Food and Drug Administration (FDA). A black box warning alerts doctors and patients to potentially dangerous effects.
• This drug may increase the risk of suicidal thoughts and behaviors in people aged 24 years and younger. This drug can make depression worse in the early stages of treatment. Tell your doctor right away if your depression gets worse or if you have thoughts about suicide.

Was this helpful?

• Drowsiness warning: This drug can cause sleepiness or affect your ability to make decisions, think clearly, or react quickly. You shouldn’t drive, use heavy machinery, or do other dangerous activities until you know how the drug affects you.
• Serotonin syndrome warning: This drug affects a chemical in your brain called serotonin. Taking this drug with other medications that affect serotonin may result in increased risk of a serious side effect called serotonin syndrome. Symptoms may include:
  • agitation
  • confusion
  • increased blood pressure or heart rate
  • sweating
  • loss of coordination
• Dizziness and falling warning: This drug can cause a sudden drop in blood pressure if you stand up too fast. This can cause dizziness and increase your risk of falling.

Duloxetine is a prescription drug. It only comes in the form of an oral capsule.

Duloxetine oral capsule is available as the brand-name drugs Cymbalta and Irenka. It’s also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in all strengths or forms as the brand-name drug.

Why it’s used

Duloxetine oral capsule is used to treat:

• generalized anxiety disorder
• major depressive disorder
• nerve pain caused by diabetes
• fibromyalgia pain
• chronic muscle and joint pain

How it works

Duloxetine belongs to a class of drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs).

It works by balancing chemicals in your brain that cause depression and anxiety. By balancing these chemicals, this drug also helps inhibit pain signals from your nerves to your brain.

Duloxetine oral capsule can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You shouldn’t drive, use heavy machinery, or do other dangerous activities until you know how it affects you. It can also cause other side effects.

More common side effects

In adults, the more common side effects of duloxetine can include:

• nausea
• dry mouth
• sleepiness
• fatigue
• constipation
• loss of appetite
• increased sweating
• dizziness

In children, the more common side effects of duloxetine can include:

• nausea
• decreased weight
• dizziness
• diarrhea
• stomach pain

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Liver damage. Symptoms can include:
  • itching
  • pain in the right side of your upper abdomen
  • dark-colored urine
  • yellowing of your skin or the whites of your eyes
• Changes in blood pressure. Symptoms can include:
  • dizziness or fainting when standing. This may occur more often when you first start duloxetine or when you increase the dose.
• Serotonin syndrome. Symptoms can include:
  • agitation
  • hallucinations
  • coma
  • coordination problems or muscle twitching
  • racing heart
  • high or low blood pressure
  • sweating or fever
  • nausea, vomiting, or diarrhea
  • muscle rigidity
  • dizziness
  • flushing
  • tremor
  • seizures
• Abnormal bleeding. Duloxetine may increase your risk of bleeding or bruising, especially if you take warfarin or nonsteroidal anti-inflammatory drugs.
• Severe skin reactions. Symptoms can include:
  • skin blisters
  • peeling rash
  • sores in your mouth
  • hives
• Manic episodes in people with depression or bipolar disorder. Symptoms can include:
  • greatly increased energy
  • severe trouble sleeping
  • racing thoughts
  • reckless behavior
  • unusually grand ideas
  • excessive happiness or irritability
  • talking more or faster than usual
• Vision problems. Symptoms can include:
  • eye pain
  • changes in vision
  • swelling or redness in or around your eye
• Seizures or convulsions
• Low salt (sodium) levels in your blood. Symptoms can include:
  • headache
  • weakness or feeling unsteady
  • confusion, problems concentrating, or thinking or memory problems
• Problems with urination. Symptoms can include:
  • decrease in your urine flow
  • trouble passing urine

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.

Duloxetine oral capsule can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with duloxetine are listed below.

Serotonergic drugs

Taking these drugs with duloxetine may increase your risk of serotonin syndrome, which can be fatal. If you take any of these drugs, your doctor will start you on a lowered dosage of duloxetine and monitor you for signs of serotonin syndrome. Symptoms can include agitation, sweating, muscle twitches, and confusion.

Examples of serotonergic drugs include:

• selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and sertraline
• serotonin-norepinephrine reuptake inhibitors (SSNRIs) such as venlafaxine
• tricyclic antidepressants (TCAs) such as amitriptyline and clomipramine
• monoamine oxidase inhibitors (MAOIs) such as selegiline and phenelzine
• the opioids fentanyl and tramadol
• the anxiolytic buspirone
• triptans
• lithium
• tryptophan
• amphetamines
• St. John’s wort

Schizophrenia drug

Taking thioridazine with duloxetine can increase the amount of thioridazine in your body. This may increase your risk of arrhythmia (abnormal heart rate).

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Taking duloxetine with NSAIDs may increase your risk of abnormal bleeding. Examples of NSAIDs include:

• ibuprofen
• indomethacin
• naproxen

Mental health drug

Taking aripiprazole with duloxetine may increase the amount of aripiprazole in your body. This can lead to increased side effects.

Anticoagulants (blood thinners)

Taking blood thinners with duloxetine may increase your risk of abnormal bleeding. Examples of blood thinners include:

• apixaban
• warfarin
• clopidogrel
• dabigatran
• edoxaban
• prasugrel
• rivaroxaban
• ticagrelor

Gaucher disease drug

Taking eliglustat with duloxetine can increase the amount of eliglustat in your body. This may cause side effects on your heart.

Drug for depression and stopping smoking

Taking bupropion with duloxetine may increase the amount of duloxetine in your body. This may increase your risk of seizures.

Cancer drug

Taking doxorubicin with duloxetine may increase the amount of doxorubicin in your body. This can cause increased side effects.

Antibiotic

Taking ciprofloxacin with duloxetine may increase the amount of duloxetine in your body. Avoid taking these drugs together.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

Duloxetine oral capsule drug comes with several warnings.

Alcohol interaction warning

Drinking heavily while taking this drug increases your risk of severe liver injury. Talk to your doctor about how much alcohol you drink before starting duloxetine.

Allergy warning

This drug can cause a severe allergic reaction. Symptoms may include:

• trouble breathing
• swelling of your throat or tongue
• hives

If you develop these symptoms, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Warnings for people with certain health conditions

For people with liver disease: Avoid taking this drug if you have chronic liver disease or cirrhosis of the liver. You may have trouble clearing the drug from your body. This can lead to further liver damage.

For people with kidney disease: Avoid taking this drug if you have severe kidney disease or if you receive dialysis. Your kidneys may have trouble removing the drug from your body. This could lead to a buildup of the drug and increase your risk of side effects.

For people with diabetes: This drug may affect your blood sugar levels. If you have diabetes, your doctor may want you to monitor your levels more closely and may need to change the dosage of your diabetes medication.

For people with bladder problems: This drug may affect your ability to urinate. Talk to your doctor if you have any problems with urine flow.

For people with bipolar disorder: This drug may cause mania or hypomania. If you or someone in your family has bipolar disorder, tell your doctor before starting duloxetine.

For people with bleeding problems: This drug may increase your risk of bleeding or bruising. If you already have bleeding problems or take certain medications, your risk may be higher. Before taking this drug, tell your doctor if you have any bleeding problems.

For people with glaucoma: This drug can increase your risk of having a glaucoma attack. If you have glaucoma, tell your doctor before starting this drug.

For people with high blood pressure: This drug may increase your blood pressure. If you already have high blood pressure, let your doctor know before starting duloxetine.

For people with a history of seizures or convulsions: This drug may cause seizures or convulsions. If you already experience these, your risk may be even higher if you take this drug. Tell your doctor about any seizures or convulsions before starting duloxetine.

For people with low sodium levels in the blood: This drug can cause very low sodium levels in your blood. If you already have a low sodium level, talk with your doctor before starting duloxetine.

Warnings for other groups

For pregnant women: This drug is a category C pregnancy drug. That means two things:

1. Research in animals has shown adverse effects to the fetus when the mother takes the drug.
2. There haven’t been enough studies done in humans to be certain how the drug might affect the fetus.

Talk to your doctor if you’re pregnant or plan to become pregnant. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

If you take this drug during pregnancy, you can take part in a registry that monitors outcomes in women exposed to duloxetine during pregnancy. To enroll, talk to your doctor or call 1-866-814-6975.

For women who are breastfeeding: This drug may pass into breast milk. If you take this drug while you breastfeed, your baby may have side effects of the drug. Tell your doctor if you wish to breastfeed. You may need to decide whether to breastfeed or take this drug.

For seniors: If you’re aged 65 years or older and you take this drug, you may be at a greater risk of falls due to blood pressure changes. You may also be at greater risk of low sodium (salt) in your blood. Symptoms may include:

• headache
• weakness or feeling unsteady
• confusion, problems concentrating, or thinking or memory problems

For children: This drug hasn’t been proved to be safe or effective in treating generalized anxiety disorder in children younger than 7 years. It hasn’t been proved to be safe or effective in treating other conditions in children younger than 18 years.

This dosage information is for duloxetine oral capsule. All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:

• your age
• the condition being treated
• the severity of your condition
• other medical conditions you have
• how you react to the first dose

Forms and strengths

Generic: Duloxetine

• Form: oral delayed-release capsule
• Strengths: 20 milligrams (mg), 30 mg, 40 mg, and 60 mg

Brand: Cymbalta

• Form: oral delayed-release capsule
• Strengths: 20 mg, 30 mg, 60 mg

Dosage for major depressive disorder

Adult dosage (ages 18 years and older)

• Typical starting dosage: 30–60 mg per day.
• Typical maintenance dosage: Total daily dose of 40 mg (given as 20-mg doses twice daily) or 60 mg (given either once daily or as 30-mg doses twice daily).
• Maximum dosage: 120 mg per day.

Child dosage (ages 0–17 years)

Dosage for people younger than 18 years hasn’t been established.

Dosage for generalized anxiety disorder

Adult dosage (ages 18–64 years)

• Typical starting dosage: 30–60 mg per day.
• Typical maintenance dosage: 60 mg per day.
• Maximum dosage: 120 mg per day.

Child dosage (ages 7–17 years)

• Typical starting dosage: 30 mg per day for 2 weeks.
• Typical maintenance dosage: 30–60 mg per day.
• Maximum dosage: 120 mg per day.

Child dosage (ages 0–6 years)

Dosage for people younger than 7 years hasn’t been established.

Senior dosage (ages 65 years and older)

• Typical starting dosage: 30 mg per day for 2 weeks.
• Typical maintenance dosage: 60 mg per day.
• Maximum dosage: 120 mg per day.

Nerve pain caused by diabetes

Adult dosage (ages 18–64 years)

• Typical starting dosage: 60 mg per day.
• Maximum dosage: 60 mg per day.

Child dosage (ages 0–17 years)

Dosage for people younger than 18 years hasn’t been established.

Dosage for fibromyalgia

Adult dosage (ages 18 years and older)

• Typical starting dosage: 30 mg per day for 1 week.
• Typical maintenance dosage: 30–60 mg per day.
• Maximum dosage: 60 mg per day.

Child dosage (ages 13–17 years)

• Typical starting dosage: 30 mg per day for 1 week.
• Typical maintenance dosage: 30–60 mg per day.
• Maximum dosage: 60 mg per day.

Child dosage (ages 0–12 years)

Dosage for people younger than 13 years hasn’t been established.

Dosage for chronic muscle and joint pain

Adult dosage (ages 18 years and older)

• Typical starting dosage: 30 mg per day for 1 week.
• Typical maintenance dosage: 60 mg per day.
• Maximum dosage: 60 mg per day.

Child dosage (ages 0–17 years)

Dosage for people younger than 18 years hasn’t been established.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Duloxetine oral capsule is a long-term medication. It comes with risks if you don’t take it as prescribed by your doctor.

If you stop taking the drug or don’t take it at all: If you don’t take the drug, your symptoms won’t get better and could get worse. If you stop this drug quickly, you may have serious side effects, including:

• anxiety
• irritability
• feeling tired or problems sleeping
• headache
• sweating
• dizziness
• electric shock-like sensations
• vomiting or nausea
• diarrhea

If you miss doses or don’t take the drug on schedule: Your medication may not work as well or may stop working completely. For this drug to work well, a certain amount needs to be in your body at all times.

If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:

• tiredness
• seizures
• dizziness
• increased heart rate
• high blood pressure
• vomiting

If you think you’ve taken too much of this drug, call your doctor or seek guidance from the American Association of Poison Control Centers at 1-800-222-1222 or through their online tool. But if your symptoms are severe, call 911 or go to the nearest emergency room right away.

What to do if you miss a dose: If you miss a dose, take it as soon as you remember. However, if it’s just a few hours until your next dose, skip the missed dose and take your next dose on schedule. Never try to catch up by taking two doses at once. This could result in dangerous side effects.

How to tell if the drug is working: The symptoms of the condition being treated should improve.

Keep these considerations in mind if your doctor prescribes duloxetine oral capsule for you.

General

Don’t crush or chew the delayed-release capsule.

Storage

• Store this drug at room temperature between 68°F and 77°F (20°C and 25°C).
• Keep this drug away from light.
• Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
• Don’t worry about airport X-ray machines. They won’t damage your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled container with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Clinical monitoring

Your doctor may monitor you for new or worsening suicidal thoughts or behaviors.

Prior authorization

Many insurance companies require prior authorization for this drug. This means your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.

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 other 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.

Side effects, dosage, uses, and more

1. Duloxetine oral capsule is available as both a generic and a brand-name drug. Brand name: Cymbalta.
2. Duloxetine only comes as a capsule you take by mouth.
3. Duloxetine oral capsule is used to treat anxiety, depression, diabetic nerve pain, fibromyalgia, and chronic (long-lasting) muscle and joint pain.

FDA warning: Suicidal thoughts and behaviors

• This drug has a Black Box Warning. This is the most serious warning from the Food and Drug Administration (FDA). A black box warning alerts doctors and patients to potentially dangerous effects.
• This drug may increase the risk of suicidal thoughts and behaviors in people aged 24 years and younger. This drug can make depression worse in the early stages of treatment. Tell your doctor right away if your depression gets worse or if you have thoughts about suicide.

Was this helpful?

• Drowsiness warning: This drug can cause sleepiness or affect your ability to make decisions, think clearly, or react quickly. You shouldn’t drive, use heavy machinery, or do other dangerous activities until you know how the drug affects you.
• Serotonin syndrome warning: This drug affects a chemical in your brain called serotonin. Taking this drug with other medications that affect serotonin may result in increased risk of a serious side effect called serotonin syndrome. Symptoms may include:
  • agitation
  • confusion
  • increased blood pressure or heart rate
  • sweating
  • loss of coordination
• Dizziness and falling warning: This drug can cause a sudden drop in blood pressure if you stand up too fast. This can cause dizziness and increase your risk of falling.

Duloxetine is a prescription drug. It only comes in the form of an oral capsule.

Duloxetine oral capsule is available as the brand-name drugs Cymbalta and Irenka. It’s also available as a generic drug. Generic drugs usually cost less than the brand-name version. In some cases, they may not be available in all strengths or forms as the brand-name drug.

Why it’s used

Duloxetine oral capsule is used to treat:

• generalized anxiety disorder
• major depressive disorder
• nerve pain caused by diabetes
• fibromyalgia pain
• chronic muscle and joint pain

How it works

Duloxetine belongs to a class of drugs called serotonin-norepinephrine reuptake inhibitors (SNRIs).

It works by balancing chemicals in your brain that cause depression and anxiety. By balancing these chemicals, this drug also helps inhibit pain signals from your nerves to your brain.

Duloxetine oral capsule can cause sleepiness or may affect your ability to make decisions, think clearly, or react quickly. You shouldn’t drive, use heavy machinery, or do other dangerous activities until you know how it affects you. It can also cause other side effects.

More common side effects

In adults, the more common side effects of duloxetine can include:

• nausea
• dry mouth
• sleepiness
• fatigue
• constipation
• loss of appetite
• increased sweating
• dizziness

In children, the more common side effects of duloxetine can include:

• nausea
• decreased weight
• dizziness
• diarrhea
• stomach pain

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life-threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

• Liver damage. Symptoms can include:
  • itching
  • pain in the right side of your upper abdomen
  • dark-colored urine
  • yellowing of your skin or the whites of your eyes
• Changes in blood pressure. Symptoms can include:
  • dizziness or fainting when standing. This may occur more often when you first start duloxetine or when you increase the dose.
• Serotonin syndrome. Symptoms can include:
  • agitation
  • hallucinations
  • coma
  • coordination problems or muscle twitching
  • racing heart
  • high or low blood pressure
  • sweating or fever
  • nausea, vomiting, or diarrhea
  • muscle rigidity
  • dizziness
  • flushing
  • tremor
  • seizures
• Abnormal bleeding. Duloxetine may increase your risk of bleeding or bruising, especially if you take warfarin or nonsteroidal anti-inflammatory drugs.
• Severe skin reactions. Symptoms can include:
  • skin blisters
  • peeling rash
  • sores in your mouth
  • hives
• Manic episodes in people with depression or bipolar disorder. Symptoms can include:
  • greatly increased energy
  • severe trouble sleeping
  • racing thoughts
  • reckless behavior
  • unusually grand ideas
  • excessive happiness or irritability
  • talking more or faster than usual
• Vision problems. Symptoms can include:
  • eye pain
  • changes in vision
  • swelling or redness in or around your eye
• Seizures or convulsions
• Low salt (sodium) levels in your blood. Symptoms can include:
  • headache
  • weakness or feeling unsteady
  • confusion, problems concentrating, or thinking or memory problems
• Problems with urination. Symptoms can include:
  • decrease in your urine flow
  • trouble passing urine

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this information includes all possible side effects. This information is not a substitute for medical advice. Always discuss possible side effects with a healthcare provider who knows your medical history.

Duloxetine oral capsule can interact with other medications, vitamins, or herbs you may be taking. An interaction is when a substance changes the way a drug works. This can be harmful or prevent the drug from working well.

To help avoid interactions, your doctor should manage all of your medications carefully. Be sure to tell your doctor about all medications, vitamins, or herbs you’re taking. To find out how this drug might interact with something else you’re taking, talk to your doctor or pharmacist.

Examples of drugs that can cause interactions with duloxetine are listed below.

Serotonergic drugs

Taking these drugs with duloxetine may increase your risk of serotonin syndrome, which can be fatal. If you take any of these drugs, your doctor will start you on a lowered dosage of duloxetine and monitor you for signs of serotonin syndrome. Symptoms can include agitation, sweating, muscle twitches, and confusion.

Examples of serotonergic drugs include:

• selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine and sertraline
• serotonin-norepinephrine reuptake inhibitors (SSNRIs) such as venlafaxine
• tricyclic antidepressants (TCAs) such as amitriptyline and clomipramine
• monoamine oxidase inhibitors (MAOIs) such as selegiline and phenelzine
• the opioids fentanyl and tramadol
• the anxiolytic buspirone
• triptans
• lithium
• tryptophan
• amphetamines
• St. John’s wort

Schizophrenia drug

Taking thioridazine with duloxetine can increase the amount of thioridazine in your body. This may increase your risk of arrhythmia (abnormal heart rate).

Nonsteroidal anti-inflammatory drugs (NSAIDs)

Taking duloxetine with NSAIDs may increase your risk of abnormal bleeding. Examples of NSAIDs include:

• ibuprofen
• indomethacin
• naproxen

Mental health drug

Taking aripiprazole with duloxetine may increase the amount of aripiprazole in your body. This can lead to increased side effects.

Anticoagulants (blood thinners)

Taking blood thinners with duloxetine may increase your risk of abnormal bleeding. Examples of blood thinners include:

• apixaban
• warfarin
• clopidogrel
• dabigatran
• edoxaban
• prasugrel
• rivaroxaban
• ticagrelor

Gaucher disease drug

Taking eliglustat with duloxetine can increase the amount of eliglustat in your body. This may cause side effects on your heart.

Drug for depression and stopping smoking

Taking bupropion with duloxetine may increase the amount of duloxetine in your body. This may increase your risk of seizures.

Cancer drug

Taking doxorubicin with duloxetine may increase the amount of doxorubicin in your body. This can cause increased side effects.

Antibiotic

Taking ciprofloxacin with duloxetine may increase the amount of duloxetine in your body. Avoid taking these drugs together.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs interact differently in each person, we cannot guarantee that this information includes all possible interactions. This information is not a substitute for medical advice. Always speak with your healthcare provider about possible interactions with all prescription drugs, vitamins, herbs and supplements, and over-the-counter drugs that you are taking.

Duloxetine oral capsule drug comes with several warnings.

Alcohol interaction warning

Drinking heavily while taking this drug increases your risk of severe liver injury. Talk to your doctor about how much alcohol you drink before starting duloxetine.

Allergy warning

This drug can cause a severe allergic reaction. Symptoms may include:

• trouble breathing
• swelling of your throat or tongue
• hives

If you develop these symptoms, call 911 or go to the nearest emergency room.

Don’t take this drug again if you’ve ever had an allergic reaction to it. Taking it again could be fatal (cause death).

Warnings for people with certain health conditions

For people with liver disease: Avoid taking this drug if you have chronic liver disease or cirrhosis of the liver. You may have trouble clearing the drug from your body. This can lead to further liver damage.

For people with kidney disease: Avoid taking this drug if you have severe kidney disease or if you receive dialysis. Your kidneys may have trouble removing the drug from your body. This could lead to a buildup of the drug and increase your risk of side effects.

For people with diabetes: This drug may affect your blood sugar levels. If you have diabetes, your doctor may want you to monitor your levels more closely and may need to change the dosage of your diabetes medication.

For people with bladder problems: This drug may affect your ability to urinate. Talk to your doctor if you have any problems with urine flow.

For people with bipolar disorder: This drug may cause mania or hypomania. If you or someone in your family has bipolar disorder, tell your doctor before starting duloxetine.

For people with bleeding problems: This drug may increase your risk of bleeding or bruising. If you already have bleeding problems or take certain medications, your risk may be higher. Before taking this drug, tell your doctor if you have any bleeding problems.

For people with glaucoma: This drug can increase your risk of having a glaucoma attack. If you have glaucoma, tell your doctor before starting this drug.

For people with high blood pressure: This drug may increase your blood pressure. If you already have high blood pressure, let your doctor know before starting duloxetine.

For people with a history of seizures or convulsions: This drug may cause seizures or convulsions. If you already experience these, your risk may be even higher if you take this drug. Tell your doctor about any seizures or convulsions before starting duloxetine.

For people with low sodium levels in the blood: This drug can cause very low sodium levels in your blood. If you already have a low sodium level, talk with your doctor before starting duloxetine.

Warnings for other groups

For pregnant women: This drug is a category C pregnancy drug. That means two things:

1. Research in animals has shown adverse effects to the fetus when the mother takes the drug.
2. There haven’t been enough studies done in humans to be certain how the drug might affect the fetus.

Talk to your doctor if you’re pregnant or plan to become pregnant. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

If you take this drug during pregnancy, you can take part in a registry that monitors outcomes in women exposed to duloxetine during pregnancy. To enroll, talk to your doctor or call 1-866-814-6975.

For women who are breastfeeding: This drug may pass into breast milk. If you take this drug while you breastfeed, your baby may have side effects of the drug. Tell your doctor if you wish to breastfeed. You may need to decide whether to breastfeed or take this drug.

For seniors: If you’re aged 65 years or older and you take this drug, you may be at a greater risk of falls due to blood pressure changes. You may also be at greater risk of low sodium (salt) in your blood. Symptoms may include:

• headache
• weakness or feeling unsteady
• confusion, problems concentrating, or thinking or memory problems

For children: This drug hasn’t been proved to be safe or effective in treating generalized anxiety disorder in children younger than 7 years. It hasn’t been proved to be safe or effective in treating other conditions in children younger than 18 years.

This dosage information is for duloxetine oral capsule. All possible dosages and forms may not be included here. Your dose, form, and how often you take it will depend on:

• your age
• the condition being treated
• the severity of your condition
• other medical conditions you have
• how you react to the first dose

Forms and strengths

Generic: Duloxetine

• Form: oral delayed-release capsule
• Strengths: 20 milligrams (mg), 30 mg, 40 mg, and 60 mg

Brand: Cymbalta

• Form: oral delayed-release capsule
• Strengths: 20 mg, 30 mg, 60 mg

Dosage for major depressive disorder

Adult dosage (ages 18 years and older)

• Typical starting dosage: 30–60 mg per day.
• Typical maintenance dosage: Total daily dose of 40 mg (given as 20-mg doses twice daily) or 60 mg (given either once daily or as 30-mg doses twice daily).
• Maximum dosage: 120 mg per day.

Child dosage (ages 0–17 years)

Dosage for people younger than 18 years hasn’t been established.

Dosage for generalized anxiety disorder

Adult dosage (ages 18–64 years)

• Typical starting dosage: 30–60 mg per day.
• Typical maintenance dosage: 60 mg per day.
• Maximum dosage: 120 mg per day.

Child dosage (ages 7–17 years)

• Typical starting dosage: 30 mg per day for 2 weeks.
• Typical maintenance dosage: 30–60 mg per day.
• Maximum dosage: 120 mg per day.

Child dosage (ages 0–6 years)

Dosage for people younger than 7 years hasn’t been established.

Senior dosage (ages 65 years and older)

• Typical starting dosage: 30 mg per day for 2 weeks.
• Typical maintenance dosage: 60 mg per day.
• Maximum dosage: 120 mg per day.

Nerve pain caused by diabetes

Adult dosage (ages 18–64 years)

• Typical starting dosage: 60 mg per day.
• Maximum dosage: 60 mg per day.

Child dosage (ages 0–17 years)

Dosage for people younger than 18 years hasn’t been established.

Dosage for fibromyalgia

Adult dosage (ages 18 years and older)

• Typical starting dosage: 30 mg per day for 1 week.
• Typical maintenance dosage: 30–60 mg per day.
• Maximum dosage: 60 mg per day.

Child dosage (ages 13–17 years)

• Typical starting dosage: 30 mg per day for 1 week.
• Typical maintenance dosage: 30–60 mg per day.
• Maximum dosage: 60 mg per day.

Child dosage (ages 0–12 years)

Dosage for people younger than 13 years hasn’t been established.

Dosage for chronic muscle and joint pain

Adult dosage (ages 18 years and older)

• Typical starting dosage: 30 mg per day for 1 week.
• Typical maintenance dosage: 60 mg per day.
• Maximum dosage: 60 mg per day.

Child dosage (ages 0–17 years)

Dosage for people younger than 18 years hasn’t been established.

Disclaimer: Our goal is to provide you with the most relevant and current information. However, because drugs affect each person differently, we cannot guarantee that this list includes all possible dosages. This information is not a substitute for medical advice. Always speak with your doctor or pharmacist about dosages that are right for you.

Duloxetine oral capsule is a long-term medication. It comes with risks if you don’t take it as prescribed by your doctor.

If you stop taking the drug or don’t take it at all: If you don’t take the drug, your symptoms won’t get better and could get worse. If you stop this drug quickly, you may have serious side effects, including:

• anxiety
• irritability
• feeling tired or problems sleeping
• headache
• sweating
• dizziness
• electric shock-like sensations
• vomiting or nausea
• diarrhea

If you miss doses or don’t take the drug on schedule: Your medication may not work as well or may stop working completely. For this drug to work well, a certain amount needs to be in your body at all times.

If you take too much: You could have dangerous levels of the drug in your body. Symptoms of an overdose of this drug can include:

• tiredness
• seizures
• dizziness
• increased heart rate
• high blood pressure
• vomiting

If you think you’ve taken too much of this drug, call your doctor or seek guidance from the American Association of Poison Control Centers at 1-800-222-1222 or through their online tool. But if your symptoms are severe, call 911 or go to the nearest emergency room right away.

What to do if you miss a dose: If you miss a dose, take it as soon as you remember. However, if it’s just a few hours until your next dose, skip the missed dose and take your next dose on schedule. Never try to catch up by taking two doses at once. This could result in dangerous side effects.

How to tell if the drug is working: The symptoms of the condition being treated should improve.

Keep these considerations in mind if your doctor prescribes duloxetine oral capsule for you.

General

Don’t crush or chew the delayed-release capsule.

Storage

• Store this drug at room temperature between 68°F and 77°F (20°C and 25°C).
• Keep this drug away from light.
• Don’t store this medication in moist or damp areas, such as bathrooms.

Refills

A prescription for this medication is refillable. You should not need a new prescription for this medication to be refilled. Your doctor will write the number of refills authorized on your prescription.

Travel

When traveling with your medication:

• Always carry your medication with you. When flying, never put it into a checked bag. Keep it in your carry-on bag.
• Don’t worry about airport X-ray machines. They won’t damage your medication.
• You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled container with you.
• Don’t put this medication in your car’s glove compartment or leave it in the car. Be sure to avoid doing this when the weather is very hot or very cold.

Clinical monitoring

Your doctor may monitor you for new or worsening suicidal thoughts or behaviors.

Prior authorization

Many insurance companies require prior authorization for this drug. This means your doctor will need to get approval from your insurance company before your insurance company will pay for the prescription.

There are other drugs available to treat your condition. Some may be better suited for you than others. Talk to your doctor about other drug options that may work for you.

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 other 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.

The use of duloxetine, a dual reuptake inhibitor, in the treatment of painful diabetic neuropathy | Guryeva

Diabetic neuropathy is known to be a common complication of diabetes mellitus and is registered in 30% of patients on the basis of the hospital registry, in 25% of patients during large-scale population studies [1]. The incidence is 2% per year. Symmetrical distal polyneuropathy (DSN) is the most common type of diabetic disorder, accounting for about 80% of all cases of diabetic neuropathy. The main etiological factors associated with DPN are the duration of the disease, poor glycemic control, age, smoking, and dyslipidemia [2, 3]. Pain is the most common disturbing symptom, forcing the patient to seek medical attention [4]. Not only diabetic polyneuropathy, but focal and multifocal diabetic neuropathies, such as isolated cranial nerve palsy or proximal motor neuropathy of the lower extremities, can be accompanied by pain. The incidence of painful diabetic neuropathy according to studies varies from 8 to 26% among diabetic patients, depending on the criteria for assessing pain [5]. Distal symmetric polyneuropathy is combined with autonomic disorders.

The onset of DPN is usually sudden and, in the absence of early intervention, the course is chronic and progressive. A decrease or loss of function of thin nerve fibers leads to a violation of pain perception (pain from hot touch and injection), as well as temperature perception – cold (Aδ) and heat (C-fibers). When thick (Aα and Aβ) nerve fibers are involved, nerve conduction velocity slows down and sensitivity to touch, pressure, and vibration decreases, which in severe cases can lead to sensory ataxia (ataxic gait).

Involvement of sensory fibers in the process causes “positive symptoms”, which include paresthesia, dysesthesia and pain, and may also be accompanied by “negative” symptoms – a decrease in sensitivity.

Persistent or episodic pain is usually localized in the feet, increases at night and decreases during walking. Patients describe the pain as deep aching, but also as a stabbing or burning sensation in the legs. Pain caused by stimuli that are not usually accompanied by pain—allodynia and hyperalgesia —significant pain caused by stimuli that are usually accompanied by mild pain—may also be present. The pain may at the same time be accompanied by a decrease in sensitivity. Neuropathic pain in diabetes mellitus persists for several years in a number of patients, causing both physical and emotional suffering, while in others it disappears completely or partially, despite a progressive decrease in the function of fine nerve fibers. Pain remission is associated with sudden metabolic changes, short duration of pain, prior weight loss, and less severe sensory loss [6].

Chronic pain is a common condition, accompanied by a decrease in quality of life and is associated with disability, however, one third of patients do not receive any treatment, 40% of patients receive inadequate therapy, and only 2% are treated by pain specialists [7].

Although the pathogenesis of pain has not yet been sufficiently elucidated, it is clear that chronic neuropathic pain arises as a result of damage and impaired adaptation mechanisms in both the peripheral and central nervous systems.

Primary pain receptors (nociceptors) are sensory endings of nerves located in various tissues and organs. The transmission and perception of pain is a two-way process and is carried out through ascending and descending neuronal pathways. Following tissue damage, there is a massive release of inflammatory mediators – histamine, prostaglandins and bradykinin, which activate and sensitize nociceptors. Further, the pain impulse through the primary afferent neurons enters the synapses of the posterior horns of the spinal cord, where the impulse passes to second-order neurons, while substance P is released into the intersynaptic gap. Through the second-order neurons of the posterior horns, the pain impulse ascends along the anterolateral spinothalamic tract, affecting the synapses in the thalamus, and then enters the somatosensory area of ​​the cerebral cortex for interpretation. In turn, the brain modulates ascending impulses through descending neuronal mechanisms that exercise their control through descending spinothalamic pathways [8]. Among various modulators and neurotransmitters, serotonin (5-hydroxytryptophan, 5-HT) and norepinephrine (NA) are especially important [9]. Experimental animal studies have demonstrated the involvement of the serotonergic and noradrenergic systems in pain modulation [10]. The descending pathways are designed to suppress incoming stimuli from the gastrointestinal tract and the musculoskeletal systems. Dysfunction of these pathways is accompanied by increased sensitivity to pain and even painful responses to normal non-painful stimuli. Thus, an increase in the content of 5-HT and NA is accompanied by an endogenous analgesic effect, acting through a descending inhibitory neuronal pathway at the level of the brain and spinal cord [11].

Painful diabetic neuropathy is the result of both metabolic and microcirculatory disturbances in neurons caused by chronic hyperglycemia, which lead to pathological impulses from peripheral nociceptors recognized by the brain as pain. Over time, “central sensitization” occurs, leading to further intensification and chronicization of pain. Central sensitization leads to neuronal plasticity and changes in pain conduction, which eventually transform into states where a small painful stimulus can be recognized as very strong, or pain can persist even in the absence of any stimuli [12].

Recent studies have shown that diabetes affects all levels of the nervous system, from the peripheral nerve to the brain [13]. Magnetic resonance imaging confirmed a lesion of the type of demyelination at the level of the spinal cord already in the early stages of neuropathy, identical to the consequences observed in spinal cord injury 145]. Magnetic resonance spectroscopy studies show the presence of thalamic dysfunction in diabetic sensorimotor polyneuropathy [15]. Thus, diabetes has a much more generalized effect on the nervous system than previously thought.

Dysfunction of the noradrenergic and/or serotonergic systems of the brain and spinal cord has common psychopharmacological mechanisms involved in the development of both pain and depression. The use of antidepressants has been shown in animal experiments to cause the growth of hippocampal neurons and thus induce neurogenesis. This property of antidepressants promotes neuroplasticity, and thus helps to influence the main symptoms of depression associated with mood and motivation. Studies show that “dual action” drugs that act on both the serotonin and norepinephrine systems have the most significant effect on both depression and chronic pain [11].

Chronic pain associated with diabetic neuropathy ranks second in the structure of neuropathic pain after back pain. Treatment of pain involves the impact on the pathophysiological mechanisms of its formation. The main goal of this approach is to ensure the analgesic activity of the drug or drug combinations while reducing the number of side effects, which improves the patient’s adherence to treatment.

The management of pain associated with diabetic peripheral nervous system disease is a difficult task. The progression of DPN largely depends on the severity of diabetes and the degree to which glycemic control is maintained over time. In the treatment of pain, various non-drug methods of treatment are used (acupuncture, magnetotherapy, transcutaneous electrical nerve stimulation, massage, etc.), the effectiveness of which remains unproven [13]. Currently, drug therapy is the most effective in the treatment of neuropathic pain [14, 15]. It should immediately be emphasized that simple analgesics and non-steroidal anti-inflammatory drugs in the treatment of pain in DPN are not recommended due to their inefficiency and the high frequency of adverse events with long-term use (complications from the gastrointestinal tract, liver and blood).

The main groups of drugs for the treatment of neuropathic pain in DPN are: antidepressants, anticonvulsants, opioid analgesics (Table 1).

Currently, the possibility of pathogenetic treatment of painful neuropathy is being discussed. The results obtained in multicenter placebo-controlled studies on the use of alpha-lipoic (thioctic) acid show the possibility of short-term relief of pain symptoms accompanying mild or moderate neuropathy, which recovers 3-6 months after discontinuation of the drug [16, 17]. Long-term treatment of severe persistent pain generally requires the administration of systemic or topical pharmacological agents with analgesic activity alone or in combination.

Tricyclic antidepressants (TCAs) have long existed as first-line therapy for the treatment of painful diabetic neuropathy. Amitriptyline given in gradually increasing doses of 10 to 150 mg per day. (see Table 1), provides an analgesic effect, regardless of the antidepressant effect in 7-58% of patients, which may not occur immediately, but after 2-3 weeks from the start of treatment.

TCAs inhibit the reuptake of serotonin and norepinephrine, reduce sympathetic activity, and act on receptors of the central nervous system. The use of TCAs is limited by known intolerable side effects such as sedation, blurred vision, dry mouth, orthostatic hypertension, and cardiac arrhythmias.

Currently, there is ample evidence of the effectiveness and validity of antidepressant treatment of neuropathic pain syndrome. Tricyclic antidepressants inhibit the reuptake of 5-HT and NA, but they have additional effects on muscarinic, histamine, and a-adrenergic receptors, thereby exhibiting side effects that limit their use [18]. Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine and citalopram, have no clear evidence of analgesic effect, although preclinical studies have shown their effect on pain [8].

Recently, interest has been shown in the so-called “dual-acting inhibitors”, which simultaneously reduce the reuptake of both serotonin and norepinephrine, which include duloxetine and milnacipram. The results obtained in numerous animal studies in experimental models of chronic pain have convincingly shown that the effect on the serotonergic and noradrenergic systems is more effective than on the serotonergic system alone. At the same time, the perception of pain is inhibited both at the level of the posterior horns of the spinal cord and at the level of supraspinal mechanisms (transmission of central pain).

A particularly effective and well-studied selective and balanced inhibitor of dual action is duloxetine (Cymbalta), the effect of which, apparently, is mediated by effects on a1-adrenergic receptors and 5-HT2 receptors [31]. The effect of duloxetine on neuropathic pain has been studied in animal models (rat models) [11]. It has been shown to be similar to paroxetine in its effect on 5-HT and to desipramine in its ability to maintain NA levels. Compared to other dual-acting inhibitors (venflaxin and milnacipran), it was superior in efficacy. This effect was dose-dependent, did not cause neurological deficit, and had a positive effect on mechanical allodynia. Thus, the potential use of duloxetine in the treatment of persistent neuropathic pain conditions in humans has been substantiated.

The effectiveness of duloxetine for the treatment of painful diabetic peripheral neuropathy has been proven in three double-blind, placebo-controlled studies [21-24]. These studies included 1139 patients with type 1 and type 2 diabetes mellitus and pain diabetic neuropathy lasting more than 6 months; all had a 12-week duloxetine fixed-dose phase.

In the first study (Goldstein et al 2005) [21], patients received 20 mg, 60 mg once and 60 mg twice daily, and placebo for 12 weeks. The second (Raskin et al. 2006) [22] and the third (Wernicke et al. 2006) studies compared doses of duloxetine 60 and 120 mg daily with placebo, also given for 12 weeks. The second and third studies had an extended open-label phase comparing duloxetine with conventional treatment. The main objective of this phase of the study was to assess the safety and satisfaction of patients with treatment, as well as assess the quality of life (EQ-5D).

The mean age of the patients included in the studies was 60 years, the duration of diabetes was 11.7 years, and the duration of neuropathy was 3.9 years (Table 2). All patients had symptoms of painful diabetic neuropathy of a typical symmetrical nature, which lasted at least 6 months. Pain intensity was ≥4 on the mean pain intensity scale over 24 hours (maximum 10). The level of glycated hemoglobin at inclusion was ≤12%, i.e. patients were mostly in a state of poor glycemic control. In order to avoid an indirect effect of duloxetine by acting on the depressive component of pain, patients with depressive symptoms, as well as other mental and somatic diseases that could affect the outcome of treatment, were excluded from the study. The study assessed the primary criteria for effectiveness – the scale of average pain intensity within 24 hours Likert; Secondary efficacy measures included Most Intense Pain Scale and Nocturnal Pain Intensity, Brief Description of Pain (BPI), Clinical Global Impression of Severity (CGI), Patient Global Impression of Improvement (PGI-Improvement), Short McGill Pain Inventory, Dynamic Allodynia, Short Health Inventory (SF-36). In all three studies, patients with symptomatic episodes of depression were excluded from the study.

The result of treatment in studies was a reduction of more than 30% in the average daily pain intensity. If duloxetine at a dose of 60 mg and 120 mg per day was superior to the placebo effect, then at a dose of 20 mg it did not differ from placebo (Fig. 2 and 3). After the analysis, it turned out that the change in the results of some psychological tests may also indicate the influence of depression on the result of pain reduction. However, this indirect component of the effect of duloxetine on pain is small and amounted to no more than 20%.

The results of the studies showed that the analgesic effect of duloxetine develops quickly – after a week of treatment with both 60 mg and 120 mg duloxetine. The reduction in pain was statistically significant and remained significant throughout the 12 weeks of treatment. The magnitude of pain reduction was 65% for 60 mg, 64% for 120 mg in the first study, 63% and 69%, respectively, in the second study and significantly exceeded the placebo response rate (42%). It was found that changes in the Beck Anxiety Scale did not affect the outcome, but analysis of the Beck Depression Scale showed a moderate effect on the pain score. Thus, it was concluded that the direct effect of duloxetine on the daily average pain scale is 88.6%, and the indirect effect reaches 11.4%.

As a result of the studies, both primary: pain intensity (average, strongest and weakest), assessed on a 24-hour intensity scale, and secondary criteria were significantly different compared to placebo. Patients also noted an improvement in health status in certain domains of the SF-36 scale, as well as in quality of life (EQ-5D).

The safety and tolerability of duloxetine was assessed in three studies, as well as in three extended (52 weeks) open-label comparative studies [23, 25, 26]. The study was not completed due to side effects in 20% of patients in the placebo group, 20.9% of patients receiving 60 mg and 25.8% of patients receiving 120 mg of duloxetine. A study of the safety and tolerability of duloxetine (Cymbalty) showed a dose-related dependence of side effects of the drug, the most typical of which is at a dose of 60 mg per day. were nausea (22%), dizziness (13%), drowsiness (18%), constipation (11%) and weakness (7%) [23, 25, 26]. These side effects were observed slightly more often when taking 120 mg of duloxetine per day. However, in most patients, side effects were moderate to mild, regardless of the type of treatment.

When compared with standard therapy in open-label 52-week studies (amitriptyline, carbamazepine, gabapentin and venlaflaxine), duloxetine showed sufficient safety and tolerability. The most common (more than 10%) side effects when taking duloxetine were nausea, and with standard therapy – peripheral edema, pain in the extremities, drowsiness and dizziness [27].

During the studies, insignificant changes in the level of glycated hemoglobin and lipids were noted, but only the change in high density lipoproteins was statistically significant in all three studies [12].

The impact of duloxetine on quality of life was evaluated in an extended 52-week phase of the study. In the domains of bodily pain, physical condition and physical functions, a positive effect of the drug was noted. For other SF-36 domains, the changes were negative, but to a lesser extent compared to the changes in the standard treatment groups [12]. On a quality-of-life scale, duloxetine significantly outperformed standard treatment.

Duloxetine is metabolized in the liver under the influence of the cytochrome P450 enzyme with the appearance of two active metabolites, its half-life is 12 hours [28]. Excretion of the drug occurs mainly through the kidneys (70%). The use of duloxetine in patients with renal insufficiency requires caution. After taking 60 mg of simbalta, the maximum plasma concentration of the drug and the distribution of the drug are approximately 2 times higher in patients with end-stage renal disease on hemodialysis than in patients with normal renal function. However, the elimination half-life is the same in both groups. Population pharmacokinetic analysis has shown that in mild to moderate renal insufficiency (creatinine clearance 30-80 ml/min. ), there is no significant effect on the pharmacokinetics of duloxetine. Cymbalta is not recommended for patients with end-stage renal disease and creatinine clearance less than 30 ml/min.

The effectiveness of duloxetine, as well as the incidence of side effects in the treatment of diabetic neuropathy, does not differ significantly with increasing age of patients. However, when prescribing the drug to elderly patients, caution is required when increasing the dose of the drug [11]. During pregnancy, especially in the third trimester, it is desirable to reduce the dose as much as possible [29].

With a sharp withdrawal of the drug, phenomena such as dizziness, nausea, headache, paresthesia may occur. The frequency of these symptoms is small and is about 2%, and therefore it is recommended to gradually reduce the dose of the drug.

Thus, neuropathic pain in diabetes mellitus is complex and, unlike nociceptive pain, is caused by disorders in both the peripheral and central nervous systems. More and more data is accumulating, indicating a whole range of disorders, including changes in the structure and function of the spinal cord, thalamic neuronal dysfunction, and a decrease in the inhibitory effect of descending neuronal pathways. Progress in the study of the pathogenesis of neuropathy opens up new ways to search for drugs that have a direct effect on the pathophysiological mechanisms of pain. The use of duloxetine (Cymbalty), a balanced selective double serotonin and norepinephrine reuptake inhibitor, in patients with diabetes mellitus occupies an important place in the complex treatment of painful diabetic neuropathy.

1. Ziegler D., Rathmann W. Dickhause T., Meisinger C., MielckA., KORA Study Group. Prevalence of polyneuropathy in prediabetes and diabetes is associated with abdominal obesity and macroangiopathy: the MONIKA/KORA Augsburg Surveys S2 and S3.Diabetes Care 2008; 31:464-469.

2. J.Show. P.Z.Zimmet, F.A.Gries and D.Ziegler. Epidemiology of Diabetic Neuropathy. In: Gries FA, Cameron NE, Low PA, Ziegler D (eds) Textbook of diabetic neuropathy. 2003; Thieme, Stuttgart, pp. 64-82.

3. Tesfaye S, Kempler P. Diabetologia 2005; 48:805-807.

4. Sindrup S.H., Jensen T.S. Efficacy of pharmacological treatment of neuropathic pain: an update and effect related to mecanosm of drug action. Pain 1999; 83:389-400.

5. Davies M., Brophy S., Williams R., Taylor A. The prevalence, severity, and impact of painful diabetic neuropathy in type 2 diabetes. Diabetes care 2006: 29; 1580-1522.

6. Ziegler D. Painful diabetic neuropathy:treatment and future aspects. Diabetes Metab Res Rev 2008:24(supple 1): 52-57.

7. Breivik H, Collett B., Ventafridda V., Cohen R. and Callacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur J Pain. 2006 May;10(4): 287-333.

8. Moshizucki D. Serotonin and noradrenalin reuptake inhibitors in animal models of pain. Hum Psychopharmacol Clin Exp 2004; 19:S15-S19.

9. Kranzler J.D., Gendreau JR, Rao SG.2002 The psychopharmacology of fybromyalgia: a drug development perspective. Psychopharmacol Bull 36; 165-213.

10. Fishbain D.2000 Evidence-based data on pain relief with antidepressants. Ann Med 32:305-316.

11. Delgado P.L. Common pathways of depression and pain. J Clin Psychiatry 2004;65(suppl 12):16-20.

12. Smith T and Nicholson RA . Review of duloxetine in the management of diabetic peripheral neuropathic pain. Vasc Health and Risk Management 2007: 3(6) 833-844.

13. Kapur D.,Neuropathic pain and diabetes. Diabetes Metab Res Rev 2003; 19:9-15.

14. Dejong RN. CNS manifestation of diabetes mellitus Postgrad Med 1977; 61:101-107.

15. Tesfay S, Selvarajah D, Emery CJ et al. Thalamic sensory neuronal dysfunction in distal symmetrical polyneuropathy. Diabetologia 47 (Suppl 1): A365.

16. Ziegler D, Ametov A, Barinov A, et al. Oral Treatment With A-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy The SYDNEY 2 trial. Diabetes Care 2006; 29:2365-70.

17. Ziegler D. Treatment of neuropathic pain. In: Gries FA, Cameron NE, Low PA, Ziegler D (eds) Textbook of diabetic neuropathy. Thieme, Stuttgart, p. 211-224.

18. MacFarlane BV, Wright A, O’Callaghan J, Benson HA.1997. Chronic neuropathic pain and its control by drugs. Pharmacology and Theraputics 75, 1-19.

19. Yokogawa F, Kiuchi Y, ishikawa Y et al. 2002. An investigation of monoamine receptors involved in aminoceptive effects of antidepressants. Anesth Analg 95:163-168.

20. Iyengar S, Webster AA, Hemrick-Luecke SK, et al. 2004. Efficacy of Duloxetine, a potent and balanced serotonon-norepinephrine reuptake inhibitor in persistent pain models in rats. J Parm Experim Therap, 311:576-584.

21. Golstein DJ, Lu Y, Detke MJ, Lee TC, Iyengar S. 2005. Duloxetine vs placebo in patients with painful diabetic neuropathy. Pain 116, S. 109-118.

22. Raskin J., Smith T.R., Wong K.et al. 2006 Duloxetine versus routine care in the long term Management of diabetic peripheral neuropathic pain. J. Palliat Med, 9:29-40.

23. Wernicke JF, Pritchett YL, D’SousaDN, et al. 2006a A randomized controlled trial of doloxetine in diabetic peripheral neuropathic pain. Neurology, 67: 1411-20.

24. Wernike J, Lu Y, D’Souza DN, Waninger A, Tran P. Antidepressants: Duloxetine at doses of 60 mg QD and 60 mg BID is effective in treatment of diabetic neuropathic pain (DNP). In: Abstracts of the 2d Joint scientific meeting of the American pain society. May 2004. J. Pain 2004;5(3 suppl 1), S 48.

25. Duloxetine (Cymbalta) for diabetic neuropathic pain. The medical letter. On drugs and theraputics. Published by the medical letter inc/ NY. Vol.47 (issue 1215|1216), 2005. 67-68.

26. Wernicke JF, Raskin J., Rosen A., et al. 2006b Duloxetin in long term management of diabetic peripheral neuropathic pain: an open label, 52 week extention of a randomized controlled clinical trial. Curr the Res Clin Exp, 67;283-304.

27. Raskin J, Smith TR, Wong K. et al. Duloxetine versus Routine Care in the long-Term management of diabetic peripheral neuropathic pain, J Palliative Med , Vol. 9, No.1 2006, p. 29-40.

28. Tesfaye S., Chaturvedi N, Eaton SEM, Ward JD, Fuller JH. Cardiovascular risk factors predict the development of diabetic peripheral neuropathy. Diabetes 2000, 49(Suppl 1): A34.

29. Smith T.R. Duloxetine in diabetic neuropathy. Expert Opin. Pharmacother. 2006, 7(2), p. 215-223.

Why do neurologists prescribe antidepressants?

A couple of decades ago, the use of psychotropic drugs was the exclusive prerogative of the psychiatrist. Therefore, it seems to me that fear and distrust remain in relation to this class of drugs.

However, the trends of modern medicine are such that a neurologist working based on the principles of evidence-based medicine and adhering to international clinical recommendations should understand psychotropic drugs, as they allow the doctor to improve the patient’s quality of life, avoid endless and useless consultations with doctors and additional expensive examinations.

In this article I will talk about the main types of psychotropic drugs that a neurologist can prescribe on an outpatient basis: tranquilizers / anxiolytics, antidepressants, neuroleptics, antiepileptic drugs.

Some basics. How does our brain work?

Brain is a lot of neuron cells. Neurons transmit information to each other with the help of molecules – neurotransmitters.
There are a lot of neurotransmitters: acetylcholine, histamine, serotonin, dopamine, GABA, etc.
The mediator is ejected from the process of one neuron and “sits down” on the receptor, which is located on the process or body of another neuron.

Some neurotransmitters activate another neuron, some inhibit it.

The mechanism of action of most psychotropic drugs is associated with exposure to receptors for certain mediators – one or several at once.

What is the fundamental difference between classes of psychotropic drugs?

1. Tranquilizers (anxiolytics, anti-anxiety drugs)

Representatives: benzodiazepines (phenazepam, alprozalam, clonazepam), hydroxyzine (atarax), tofisopam (grandaxin), etifoxine (stresa m) and others.

Act on the receptors of “brake” mediators. Due to this, they have a calming, sedative effect. The drugs differ in the “strength” of the impact and the severity of the calming effect.

The effect develops quickly but does not last long.

When indicated: if you need to quickly relieve anxiety, panic attacks, correct insomnia, reduce anxiety before surgery or medical interventions, to reduce the side effects of antidepressants at the beginning of their use.

Course duration: short, no more than 4 weeks, especially benzodiazepine drugs, which may develop tolerance with longer use.

Tranquilizers are not sold without a prescription. Some drugs are released only on a special prescription with a number and series.

2. Antidepressants
These include tricyclic antidepressants (amitriptyline, clomipramine), selective serotonin reuptake inhibitors (escitalopram, sertraline, fluoxetine and others), selective serotonin and norepinephrine reuptake inhibitors (venlafaxine, duloxet in) and others.

Old groups of antidepressants act on receptors of several types of mediators at once, this causes a large number of uncomfortable side effects (weight gain, drowsiness, arrhythmia, increased intraocular pressure, and others).

The more modern the drug, the more “pointed” its effect. Some drugs act on a specific subtype of neurotransmitter receptor. This reduces the likelihood of side effects, but their effectiveness remains high.

In order to minimize the side effects of antidepressants, which can be especially disturbing at the beginning of treatment, the doctor will select the optimal dosage increase regimen (with the lowest possible dose and a gradual gradual increase) and drug withdrawal.

The effect of this group of drugs unfolds within 2-3-4 weeks, however, after the drug is discontinued, a “tail” of their positive action remains for some time.

The course of treatment is long, not less than 6 months.

When properly prescribed, taking into account the individual characteristics of the patient and his comorbidities, taking antidepressants, even long-term, is safe.
Antidepressants are not addictive or addictive.

Used for: anxiety, phobias, panic attacks, as part of the treatment of post-traumatic disorder and reaction to a stressful event, insomnia, chronic headaches, chronic back pain, painful polyneuropathies, psychogenic dizziness, irritable bowel syndrome, somatization disorders.

Antidepressants are prescribed by a physician and are not available without a prescription.

3. Antipsychotics
Of the most commonly prescribed by a neurologist are quetiapine, olanzapine, risperidone, alimemazine (teraligen). In Russian realities, sulpiride (eglonil) is also often used, although in my opinion its appointment is not entirely justified.

The main target is dopamine receptors. The indications are rather narrow and specific.
Often prescribed in addition to antidepressants.

Each neuroleptic has its own nuances of increasing the dosage and stopping the drug. Also not sold without a prescription.