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Pliva 433 side effects. Trazodone: Uses, Dosage, Side Effects, and Warnings for Depression Treatment

What are the main uses of trazodone. How should trazodone be dosed for depression. What are the common and serious side effects of trazodone. What important warnings should patients know about trazodone.

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What is Trazodone and How Does It Work?

Trazodone is an antidepressant medication used to treat depression in adults. It belongs to a class of drugs called antidepressants, which work by affecting brain chemistry to help stabilize mood. While its exact mechanism of action is not fully understood, trazodone is thought to increase serotonin activity in the brain. Serotonin is a neurotransmitter that plays an important role in regulating mood.

As a generic drug, trazodone is available only as an oral tablet formulation. It does not have a brand-name version currently on the market. Generic medications typically cost less than brand-name drugs while offering the same therapeutic benefits.

Trazodone Dosage and Administration

The appropriate dosage of trazodone can vary based on several factors, including:

  • The severity of depression being treated
  • Patient age
  • Other medical conditions
  • Other medications being taken

Doctors typically start patients on a low dose of trazodone and gradually increase it to find the optimal therapeutic dose. The goal is to prescribe the lowest effective dose that provides symptom relief.

How is trazodone usually dosed for depression? While dosing should always be individualized, a common starting dose is 150 mg per day, often divided into two or three doses. The dose may then be increased gradually up to a maximum of 400 mg daily for outpatients or 600 mg daily for inpatients. However, patients should only take the exact dose prescribed by their doctor.

Common Side Effects of Trazodone

Like all medications, trazodone can potentially cause side effects. Some of the more common side effects include:

  • Drowsiness/sleepiness
  • Dizziness
  • Dry mouth
  • Blurred vision
  • Constipation
  • Weight changes
  • Headache

These common side effects are often mild and may resolve on their own as the body adjusts to the medication. However, patients should inform their doctor if side effects persist or become bothersome.

Serious Side Effects and Warnings

While less common, trazodone can potentially cause more serious side effects that require immediate medical attention. These may include:

  • Serotonin syndrome
  • Irregular or rapid heartbeat
  • Low blood pressure
  • Vision problems
  • Priapism (prolonged erection)
  • Hyponatremia (low blood sodium)

What are the symptoms of serotonin syndrome? This rare but potentially life-threatening condition can cause agitation, confusion, rapid heart rate, dilated pupils, loss of muscle coordination, and fever. Patients should seek emergency medical care if they experience these symptoms.

Black Box Warning for Suicidality

Trazodone carries a black box warning, the most serious type of warning mandated by the FDA. This warning alerts patients and healthcare providers that antidepressants, including trazodone, may increase the risk of suicidal thoughts and behaviors, especially in children, adolescents, and young adults.

The risk appears highest in the first few months of treatment or when changing dosages. Patients, especially younger individuals, should be closely monitored for new or worsening depression, suicidal thoughts or behaviors, or unusual changes in mood or behavior.

Precautions and Contraindications

Certain precautions should be taken when using trazodone:

  • Avoid driving or operating machinery until you know how trazodone affects you, as it may cause drowsiness
  • Use caution when combining with other medications that affect serotonin levels
  • Inform your doctor of all other medications and supplements you take
  • Discuss any history of heart problems, bleeding disorders, or bipolar disorder with your doctor
  • Use with caution in elderly patients, who may be more sensitive to side effects

Can trazodone be used during pregnancy or while breastfeeding? The safety of trazodone during pregnancy and lactation has not been definitively established. Women who are pregnant, planning to become pregnant, or breastfeeding should discuss the potential risks and benefits with their healthcare provider.

Drug Interactions with Trazodone

Trazodone can potentially interact with various medications and substances. Some notable interactions include:

  • Other antidepressants, particularly MAOIs
  • Certain antipsychotics
  • Some antibiotics
  • Antifungal medications
  • Seizure medications
  • Warfarin and other blood thinners
  • Alcohol

How does alcohol interact with trazodone? Combining alcohol with trazodone can increase drowsiness and impair cognitive and motor function. It may also increase the risk of accidental injury. Patients are typically advised to avoid alcohol while taking trazodone.

Monitoring and Follow-up During Trazodone Treatment

Regular follow-up with a healthcare provider is crucial when taking trazodone. This allows for:

  1. Assessment of treatment efficacy
  2. Monitoring for side effects
  3. Dosage adjustments if needed
  4. Screening for emerging suicidal thoughts or behaviors
  5. Evaluation of overall mental health status

How often should patients follow up with their doctor while on trazodone? Initially, follow-ups may be more frequent, perhaps every 1-2 weeks. As treatment stabilizes, visits may become less frequent, but regular check-ins (e.g., every 1-3 months) are typically recommended for ongoing monitoring.

Discontinuing Trazodone Treatment

Patients should not stop taking trazodone abruptly without consulting their healthcare provider. Sudden discontinuation can lead to withdrawal symptoms such as:

  • Nausea
  • Anxiety
  • Agitation
  • Flu-like symptoms
  • Sleep disturbances

How should trazodone be discontinued safely? When stopping trazodone, a gradual tapering of the dose under medical supervision is typically recommended. This approach helps minimize the risk of withdrawal effects and allows for monitoring of any re-emerging depression symptoms.

Alternative Treatment Options for Depression

While trazodone can be effective for many patients, it’s not the only option for treating depression. Other treatment modalities include:

  • Other classes of antidepressants (SSRIs, SNRIs, etc.)
  • Psychotherapy (e.g., cognitive-behavioral therapy)
  • Combination of medication and therapy
  • Electroconvulsive therapy (for severe cases)
  • Transcranial magnetic stimulation
  • Lifestyle modifications (exercise, diet, sleep hygiene)

What factors determine the choice of treatment for depression? The selection of treatment depends on various factors, including the severity of depression, patient preferences, medical history, potential side effects, and response to previous treatments. A personalized approach, often involving a combination of therapies, tends to yield the best outcomes.

Complementary and Alternative Approaches

Some patients may explore complementary approaches to managing depression, such as:

  • Mindfulness meditation
  • Acupuncture
  • Herbal supplements (e.g., St. John’s Wort)
  • Yoga or tai chi
  • Light therapy

It’s important to note that while some of these approaches may offer benefits, their efficacy and safety profiles are not as well-established as conventional treatments. Patients should always discuss the use of any complementary therapies with their healthcare provider, especially when used alongside medications like trazodone.

Long-term Outlook and Prognosis

The long-term prognosis for patients taking trazodone for depression can vary widely. Many patients experience significant improvement in their symptoms and quality of life with appropriate treatment. However, depression is often a chronic condition that may require ongoing management.

What factors influence the long-term success of trazodone treatment? Several factors can impact treatment outcomes, including:

  • Adherence to the prescribed treatment regimen
  • Regular follow-up with healthcare providers
  • Engagement in complementary therapies (e.g., psychotherapy)
  • Development of coping strategies and support systems
  • Management of co-occurring mental or physical health conditions

It’s important for patients to work closely with their healthcare team to develop a comprehensive, long-term management plan for their depression. This may involve periodic reassessment of treatment efficacy, consideration of alternative or adjunctive therapies, and ongoing support for maintaining mental health and overall well-being.

Relapse Prevention

Preventing relapse is a crucial aspect of long-term depression management. Strategies for relapse prevention may include:

  1. Continuation of medication even after symptom improvement
  2. Regular check-ins with mental health professionals
  3. Learning to recognize early warning signs of relapse
  4. Developing a crisis plan for managing severe symptoms
  5. Engaging in ongoing therapy or support groups
  6. Maintaining healthy lifestyle habits

How long should patients continue taking trazodone after their depression improves? The duration of treatment can vary, but many experts recommend continuing antidepressant treatment for at least 6-12 months after achieving remission of depressive symptoms. Some patients, particularly those with recurrent depression, may benefit from longer-term maintenance treatment. The decision to continue or discontinue medication should always be made in consultation with a healthcare provider.

Patient Education and Self-Management

Empowering patients with knowledge and self-management skills is crucial for optimal outcomes in depression treatment. Key areas of patient education include:

  • Understanding depression as a medical condition
  • Recognizing symptoms and warning signs
  • Importance of medication adherence
  • Managing side effects
  • Developing healthy coping strategies
  • Importance of lifestyle factors (sleep, diet, exercise)
  • When and how to seek help

What self-management techniques can help patients taking trazodone for depression? Some effective self-management strategies include:

  1. Keeping a mood journal to track symptoms and identify triggers
  2. Setting realistic goals and breaking tasks into manageable steps
  3. Practicing stress-reduction techniques like deep breathing or progressive muscle relaxation
  4. Maintaining a consistent sleep schedule
  5. Engaging in regular physical activity
  6. Building and maintaining social connections
  7. Learning to challenge negative thought patterns

By actively participating in their treatment and developing self-management skills, patients can enhance the effectiveness of their medication regimen and improve their overall quality of life.

Support Systems and Resources

Having a strong support system can significantly impact the success of depression treatment. Patients should be encouraged to:

  • Communicate openly with trusted friends and family members
  • Consider joining support groups for individuals with depression
  • Explore online resources and forums for additional information and peer support
  • Utilize mental health hotlines or crisis services when needed

Healthcare providers can play a crucial role in connecting patients with appropriate resources and support services in their community.

Emerging Research and Future Directions

The field of depression treatment continues to evolve, with ongoing research into new therapeutic approaches and refinements of existing treatments. Some areas of current interest include:

  • Personalized medicine approaches to antidepressant selection
  • Novel drug targets for treatment-resistant depression
  • Combination therapies for enhanced efficacy
  • Non-invasive brain stimulation techniques
  • Digital health interventions and telepsychiatry

What potential future developments might impact trazodone use? While trazodone remains a valuable tool in the treatment of depression, ongoing research may lead to more targeted use of the medication, improved understanding of its mechanisms of action, or development of new formulations with enhanced efficacy or reduced side effects.

As research progresses, patients and healthcare providers should stay informed about emerging treatment options and evolving best practices in depression management. This ongoing learning process can help ensure that patients receive the most appropriate and effective care for their individual needs.

Side Effects, Dosage, Uses, and More

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 about drug effects that may be dangerous.

Drugs used to treat depression, including trazodone, may cause an increase in suicidal thoughts or actions. This risk is higher in children, teenagers, or young adults. It’s also higher within the first few months of treatment with this drug or during dosage changes. You and your family members, caregivers, and doctor should watch for any new or sudden changes in your mood, behaviors, thoughts, or feelings. Trazodone is not approved for use in pediatric patients. Call your doctor right away if you notice any changes.

  1. Trazodone oral tablet is available as a generic drug. It doesn’t have a brand-name version.
  2. Trazodone only comes as a tablet you take by mouth.
  3. Trazodone is used to treat depression.

Trazodone oral tablet is a prescription drug. It’s available only as a generic drug. Generic drugs usually cost less than brand-name drugs.

Why it’s used

Trazodone is used to treat depression in adults.

How it works

Trazodone belongs to a class of drugs called antidepressants. A class of drugs is a group of medications that work in a similar way. These drugs are often used to treat similar conditions.

It isn’t fully understood how trazodone works. It may increase serotonin activity in your brain. Serotonin is a chemical in your brain that can help stabilize your mood.

Trazodone oral tablet may cause drowsiness or sleepiness. You shouldn’t drive, use machinery, or do other activities that require alertness until you know how this drug affects you.

Trazodone can cause mild or serious side effects. The following list contains some of the key side effects that may occur while taking trazodone. This list does not include all possible side effects.

For more information on the possible side effects of trazodone, or tips on how to deal with a troubling side effect, talk with your doctor or pharmacist.

More common side effects

The more common side effects of trazodone can include:

  • swelling
  • sleepiness
  • dizziness
  • diarrhea
  • stuffy nose
  • weight loss
  • blurred vision

These effects may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk to your doctor or pharmacist.

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:

  • Thoughts of suicide and worsening depression. Symptoms include:
    • thoughts about suicide or dying
    • attempts to die by suicide
    • new or worse depression
    • new or worse anxiety
    • feeling very agitated or restless
    • panic attacks
    • insomnia (trouble sleeping)
    • new or worse irritability
    • acting aggressive, angry, or violent
    • acting on dangerous impulses
    • mania (an extreme increase in activity and talking)
    • other unusual changes in behavior or mood
  • Serotonin syndrome. Symptoms include:
    • agitation
    • confusion or trouble thinking
    • hallucinations (seeing or hearing something that isn’t there)
    • problems with coordination
    • fast heart rate
    • tight muscles
    • trouble walking
    • nausea
    • vomiting
    • diarrhea
  • Vision problems. Symptoms include:
    • eye pain
    • changes in your vision, such as blurred vision or visual disturbances
    • swelling or redness in or around your eye
  • Irregular or fast heartbeat
  • Low blood pressure. Symptoms include:
    • dizziness or fainting when you change positions, such as standing up from a sitting position
  • Unusual bruising or bleeding
  • Erection that lasts longer than 4 hours
  • Hyponatremia (low sodium in your blood). Symptoms include:
    • headache
    • weakness
    • confusion
    • trouble concentrating
    • memory problems
    • feeling unsteady when you walk

Suicide prevention

  1. If you think someone is at immediate risk of self-harm or hurting another person:
  2. • Call 911 or your local emergency number.
  3. • Stay with the person until help arrives.
  4. • Remove any guns, knives, medications, or other things that may cause harm.
  5. • Listen, but don’t judge, argue, threaten, or yell.
  6. If you or someone you know is considering suicide, get help from a crisis or suicide prevention hotline. Try the National Suicide Prevention Lifeline at 800-273-8255.

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The trazodone dosage your doctor prescribes will depend on various factors. These include:

  • the type and severity of the condition you’re using the drug to treat
  • your age
  • the form of the drug you take
  • other medical conditions you may have

Typically, your doctor will start you on a low dosage and adjust it over time to reach the dosage that’s right for you. They’ll 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 suit your needs.

Forms and strengths

Generic: Trazodone

  • Form: oral tablet
  • Strengths: 50 mg, 100 mg, 150 mg, 300 mg

Dosage for major depressive disorder

Adult dosage (ages 18 years and older)

  • Typical starting dosage: 150 mg per day in divided doses.
  • Dosage increases: Your doctor may increase your dose by 50 mg per day every 3 or 4 days.
  • Maximum dosage: 400 mg per day in divided doses. If you’re staying in a hospital, the maximum dosage is 600 mg per day.

Child dosage (ages 0–17 years)

This drug hasn’t been studied in children. It shouldn’t be used in people younger than 18 years old.

Trazodone oral tablet is used for long-term treatment. It comes with serious risks if you don’t take it as prescribed.

If you stop taking the drug or don’t take it at all. If you stop taking this drug suddenly or don’t take it, your depression may not get better. You may also have withdrawal symptoms. These include anxiety, agitation, and trouble sleeping. If you need to stop taking this drug, your doctor will slowly lower your dose over time.

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 trazodone in your body. Symptoms of an overdose of this drug can include:

  • an erection that lasts longer than 4 hours
  • seizures
  • changes in the way your heart functions, including QT prolongation (a heart rhythm issue that may cause chaotic or abnormal heartbeats)

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 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. Take your dose as soon as you remember. But if you remember just a few hours before your next scheduled dose, take only one dose. 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. You should have decreased feelings of depression, and your mood should improve.

This drug comes with various warnings.

FDA warning: Suicide risk warning

  • Trazodone has a boxed warning. This is the most serious warning from the Food and Drug Administration (FDA). A boxed warning alerts doctors and patients about drug effects that may be dangerous.
  • Drugs used to treat depression, including trazodone, may cause an increase in suicidal thoughts or actions. This risk is higher in children, teenagers, or young adults. It’s also higher within the first few months of treatment with this drug or during dosage changes. You and your family members, caregivers, and doctor should watch for any new or sudden changes in your mood, behaviors, thoughts, or feelings. Call your doctor right away if you notice any changes.
  • Trazodone is not approved for use in pediatric patients

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Serotonin syndrome warning

This drug can cause a life threatening condition called serotonin syndrome. This risk is higher when you first start taking this drug or during dosage changes.

Your risk may be higher if you also take other drugs that have similar effects as trazodone, such as other drugs used to treat depression.

Symptoms of serotonin syndrome include agitation, hallucinations, confusion or trouble thinking, nausea, vomiting, and diarrhea.

They also include coordination problems, muscle twitching, stiff muscles, racing heart rate, high or low blood pressure, sweating, fever, and coma.

Call your doctor right away if you have these symptoms.

Angle-closure glaucoma warning

This drug can cause your pupils to be slightly bigger and lead to angle-closure glaucoma (a condition that causes increased pressure in your eyes). If you’re at high risk for this condition, your doctor may give you a medication to help prevent it.

Bleeding warning

Taking this drug with other medications that affect your ability to stop bleeding may increase your risk for bleeding. This includes serious, life threatening bleeding, and bleeding-related events, such as nosebleeds, bruising, or skin discoloration due to bleeding below your skin.

These drugs include warfarin, dabigatran, rivaroxaban, and pain medications called nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and aspirin.

Allergy warning

Trazodone can cause a severe allergic reaction. Symptoms can include:

  • trouble breathing
  • swelling of your face, tongue, eyes, or mouth
  • rash, hives (itchy welts), or blisters, alone or with fever or joint pain

If you have an allergic reaction, call your doctor or local poison control center right away. If your symptoms are severe, 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).

Alcohol interaction warning

Consuming drinks that contain alcohol can increase your risk for sleepiness or dizziness from trazodone. If you drink alcohol, talk to your doctor about whether alcohol use is safe for you while you take this drug.

Warnings for people with certain health conditions

For people with heart disease. Ask your doctor whether this drug is safe for you. Taking trazodone may cause irregular heartbeat and a prolonged QT interval (a heart rhythm issue that may cause chaotic or abnormal heart beats). Your doctor may watch you closely if you take this drug.

For people with angle-closure glaucoma. This drug may make your pupils bigger and may cause an angle-closure attack.

For people with a history of mania or bipolar disorder. You may have a higher risk for manic episodes. If you have a history of mania or bipolar disorder, your doctor may need to prescribe a different medication.

Warnings for other groups

For pregnant women. There haven’t been enough studies done in humans to be certain how this drug might affect a pregnancy.

Research in animals has shown negative effects to the fetus when the mother takes this drug. However, animal studies don’t always predict the way humans would respond.

Talk to your doctor if you’re pregnant or planning to become pregnant. This drug should only be used if the potential benefit justifies the potential risk to the fetus. Call your doctor right away if you become pregnant while taking this drug.

There’s a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants during pregnancy. To take part in the National Pregnancy Registry for Antidepressants, call 844-405- 6185 or visit their website.

Women who are breastfeeding. Trazodone may pass into breast milk and may cause side effects in a child who is breastfed. Talk to your doctor if you breastfeed your child. You may need to decide whether to stop breastfeeding or stop taking this medication.

For seniors. The kidneys of older adults may not work as well as they used to. This can cause your body to process drugs more slowly. As a result, more of a drug stays in your body for a longer time. This raises your risk of side effects.

If you’re over the age of 65 years, you may be at higher risk for developing side effects while taking this drug. This includes hyponatremia (low salt levels in your blood).

For children. The safety and effectiveness of this drug haven’t been established in children. This drug shouldn’t be used in people younger than 18 years.

Trazodone oral tablet can interact with several other medications. Different interactions can cause different effects. For instance, some can interfere with how well a drug works, while others can cause increased side effects.

Below is a list of medications that can interact with trazodone. This list does not contain all drugs that may interact with trazodone.

Before taking trazodone, be sure to tell your doctor and pharmacist about all prescription, over-the-counter, and other drugs you take. Also tell them about any vitamins, herbs, and supplements you use. Sharing this information can help you avoid potential interactions.

If you have questions about drug interactions that may affect you, ask your doctor or pharmacist.

Drugs you should not use with trazodone

Do not take these drugs with trazodone. Doing so can cause dangerous effects in your body. Examples of these drugs include:

  • Monoamine oxidase inhibitors (MAOIs), such as isocarboxazid, phenelzine, tranylcypromine, or selegiline. You shouldn’t take trazodone with MAOIs or within 14 days of taking them. Taking these drugs together raises your risk for serotonin syndrome.

Interactions that can cause more side effects

Taking trazodone with certain medications may cause more side effects. These drugs include:

  • Central nervous system (CNS) depressants such as pentobarbital and secobarbital. Trazodone may make your response to barbiturates and other CNS depressants stronger.
  • Warfarin. Taking trazodone with warfarin can increase your risk for bleeding. Your doctor will watch you closely.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs) or aspirin. Trazodone may increase your risk of bleeding when used with these drugs.
  • Depression drugs, such as citalopram, fluoxetine, paroxetine, sertraline, venlafaxine, duloxetine, and St. John’s wort. Taking these drugs together may increase your risk of serotonin syndrome. This condition can be life threatening.
  • Digoxin. Taking trazodone with digoxin may increase the levels of digoxin in your body. This could increase your risk of side effects from digoxin. These include vomiting, dizziness, vision problems, and irregular heart rate. Your doctor may monitor the level of digoxin in your blood if you take these drugs together.
  • Phenytoin. Taking trazodone with phenytoin may increase the levels of phenytoin in your body. This could increase your risk for side effects from phenytoin. These include constipation, changes in mood, confusion, and balance problems. Your doctor may monitor the level of phenytoin in your blood if you take these drugs together.
  • Ketoconazole or ritonavir. The level of trazodone in your body may increase if you take it with ketoconazole, ritonavir, or other drugs that increase levels of trazodone. This can increase your risk of side effects from trazodone. These include serotonin syndrome and vision problems. Your doctor may lower your trazodone dosage if you take drugs that can increase trazodone levels.

Interactions that can make drugs less effective

Certain drugs may decrease the levels of trazodone in your body and make your dosage of trazodone less effective. You doctor may need to increase your dosage of trazodone when you take it with these drugs.

These drugs include:

  • Phenytoin and carbamazepine

Keep these considerations in mind if your doctor prescribes trazodone oral tablet for you.

General

  • Take trazodone shortly after a meal or snack.
  • You should swallow this drug whole. You can also break it in half along the score line (indented line down the center of the tablet) and swallow it. Don’t chew or crush trazodone tablets.

Storage

  • Store trazodone at room temperature. Keep it between 68°F and 77°F (20°C and 25°C).
  • Keep it away from light.

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

  • 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 can’t hurt your medication.
  • You may need to show airport staff the pharmacy label for your medication. Always carry the original prescription-labeled box 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

You and your doctor should monitor certain health issues. This can help make sure you stay safe while you take this drug. These issues include:

  • Eye health. You may be at risk for angle-closure glaucoma. Your doctor may do an eye exam and treat you if needed.
  • Mental health and behavioral problems. You and your doctor should watch for any changes in your behavior and mood. This drug can cause new mental health and behavior issues. It can also make problems you already have worse.

Prior authorization

Many insurance companies may require a 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: Healthline 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.

Dosage, Benefits, Side Effects & Other Risks

Trazodone is an antidepressant that is sometimes prescribed as a sleep aid. It is not addictive and may offer additional benefits over other sleep aids for certain conditions, such as sleep apnea.

Insomnia is more than not being able to get a good night’s sleep. Having trouble falling asleep or staying asleep can affect every aspect of your life, from work and play to your health. If you’re having trouble sleeping, your doctor may have discussed prescribing trazodone to help.

If you’re thinking of taking trazodone (Desyrel, Molipaxin, Oleptro, Trazorel, and Trittico), here’s important information for you to consider.

Trazodone is a prescription medication approved for use by the Food and Drug Administration (FDA) as an antidepressant.

This medicine works in multiple ways in your body. One of its actions is to regulate the neurotransmitter serotonin, which helps brain cells communicate with each other and influences many activities such as sleep, thoughts, mood, appetite, and behavior.

Even at lower doses, trazodone can cause you to feel relaxed, tired, and sleepy. It does this by blocking chemicals in the brain that interact with serotonin and other neurotransmitters, such as, 5-HT2A, alpha1 adrenergic receptors, and h2 histamine receptors.

This effect may be one of the main reasons trazodone works as a sleep aid.

FDA Warning about trazodone

Like many antidepressants, trazodone has been issued a “Black Box Warning” by the FDA.

Taking trazodone has increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients. People taking this medication should be closely monitored for worsening symptoms and emergence of suicidal thoughts and behaviors. Trazodone is not approved for use in pediatric patients.

Though the FDA has approved trazodone for use as a treatment for depression in adults, for many years doctors have also prescribed it as a sleep aid.

The FDA approves medications to treat specific conditions based on clinical trials. When doctors prescribe the medicine for conditions other than what was approved by the FDA, it is known as off-label prescribing.

Off-label use of a medication is a widespread practice. Twenty percent of medications are prescribed off-label. Physicians can prescribe medications off-label based on their experience and judgment.

Trazodone is most often prescribed at doses between 25mg to 100mg as a sleep aid.

However, studies show lower dosages of trazodone are effective and may cause less daytime sleepiness and fewer side effects because the drug is short acting.

Experts recommend cognitive behavioral therapy and other behavioral modifications as the first treatment for insomnia and sleep problems.

If these treatment options are not effective for you, your doctor may prescribe trazodone for sleep. Your doctor may also prescribe it if other sleep medications, such as Xanax, Valium, Ativan, and others (short- to medium-acting benzodiazepine medications), haven’t worked for you.

A few advantages of trazodone include:

  • Effective treatment for insomnia. A 2017 review of studies of trazodone use for insomnia found the medication was effective for primary and secondary insomnia in low doses.
  • Reduced cost. Trazodone is less expensive than some newer insomnia medicines because it is available generically.
  • Not addictive. Compared to other medications, such as the benzodiazepine class of medications like Valium and Xanax, trazodone is not addictive.
  • May help prevent age-related mental decline. Trazodone might help improve slow wave sleep. This may slow certain types of age-related mental decline like memory in older adults.
  • May be a better choice if you have sleep apnea. Some sleep medications may negatively affect obstructive sleep apnea and sleep arousal. A small 2014 study found that 100mg of trazodone had a positive impact on sleep arousal.

Trazodone may cause some side effects, especially when first starting the medication.

This is not a complete list of side effects. Discuss concerns with your doctor or pharmacist if you feel you are experiencing side effects or have other worries about your medicine.

Some common side effects of trazodone include:

  • sleepiness
  • dizziness
  • fatigue
  • nervousness
  • dry mouth
  • weight changes (in approximately 5 percent of people taking it)

Although rare, trazodone can cause serious reactions. Call 911 or local emergency services if you are experiencing any life-threatening symptoms such as difficulty breathing.

According to the FDA, serious risks include:

  • Thoughts of suicide. This risk is higher in young adults and children.
  • Serotonin syndrome. This occurs when too much serotonin builds up in the body and may lead to serious reactions. The risk of serotonin syndrome is higher when taking other medications or supplements that raise serotonin levels such as some migraine medications. Symptoms include:
    • hallucinations, agitation, dizziness, seizures
    • increased heart rate, body temperature, headaches
    • muscle tremor, rigidity, trouble with balance
    • nausea, vomiting, diarrhea
  • Cardiac arrhythmias. The risk of changes in heart rhythm is higher if you already have heart problems.
  • Priapism. This is a risk of an erection lasting a long time which is painful.
  • Hypotension. This sudden drop in blood pressure may occur more often when you stand up from sitting.
  • Increased risk of bleeding. Taking medications that interfere with blood clotting like blood thinner such as Warfarin, Heparin, or Plavix increase this risk.
  • Mania. Individuals may experience euphoria, hyperactivity, or excessive excitement.
  • Blurred vision.
  • Hyponatremia. Sodium imbalance in the blood may occur. Symptoms include:
    • headache
    • confusion
    • weakness
    • unsteadiness
    • seizures
  • Discontinuation syndrome. Trazodone, unlike benzodiazepines, is not addictive. However, because your body can become used to trazodone, it is important to talk with your doctor about the best way to slowly stop the medicine. Suddenly stopping trazodone may cause withdrawal symptoms.

Trazodone overdose

There have been reports of overdose with trazodone use. These risks are higher with drinking alcohol, taking benzodiazepines, and other central nervous system depressant drugs that can slow your breathing and reactions.

Drug overdose can be fatal. If you suspect you have taken too much trazodone, call 911 or local emergency services and seek medical attention immediately.

symptoms of overdose

Symptoms of trazodone overdose include:

  • drowsiness
  • seizures
  • vomiting
  • heart rhythm changes
  • respiratory arrest (stop breathing)

Trazodone is an older medication approved for use by the FDA in 1981 as an antidepressant. Although trazodone use for sleep is common, according to recent guidelines published by the American Academy of Sleep Medicine, trazodone should not be the first line of treatment for insomnia.

Given in lower doses, it may cause less daytime sleepiness or drowsiness. Trazodone is not addictive, and common side effects are dry mouth, drowsiness, dizziness, and lightheadedness.

Trazodone may offer benefits in certain conditions such as sleep apnea over other sleep aids.

Formin Pliva – instructions for use, doses, side effects, reviews of the drug Formin Pliva: – Encyclopedia of drugs RLS

2012

Date of approval: 09/27/2012

Content

  • Active substance
  • ATX
  • Pharmacological group
  • Nosological classification (ICD-10)
  • Compound
  • pharmachologic effect
  • Dosage and administration
  • Release form
  • Manufacturer
  • Terms of dispensing from pharmacies
  • Storage conditions
  • Best before date
  • Reviews

Active ingredient

Metformin* (Metformin*)

ATX

A10BA02 Metformin

Pharmacological group

Hypoglycemic agent for oral use of the biguanide group
[Hypoglycemic synthetic and other agents]

Nosological classification (ICD-10)

List of ICD-10 codes

Composition

film-coated
1 tab.
active ingredient:
metformin hydrochloride 850 mg
excipients: sodium carboxymethyl starch – 34 mg; corn starch – 17 mg; povidone – 68 mg; colloidal silicon dioxide – 11.9 mg; magnesium stearate – 5.1 mg
film coating: hypromellose – 8 mg; titanium dioxide (E171) – 3.2 mg; propylene glycol 0.616 mg; macrogol 6000 – 0.616 mg; talc – 5.1 mg
Film-coated tablets 1 tab.
Active ingredient:
metformin hydrochloride 1000 mg
excipients: hypromellose 15000 cPs – 35.2 mg; povidone – 53 mg; magnesium stearate – 5.8 mg
foil sheath: hypromellose 5 cPs – 11.5 mg; macrogol 6000 – 2.3 mg; titanium dioxide (E 171) – 9. 2 mg

Pharmacological action

Pharmacological action

hypoglycemic .

Dosage and administration

Information for healthcare professionals only.
Are you a healthcare professional?

By mouth , during or immediately after a meal. Tablets should be taken whole, without chewing and with a sufficient amount of liquid (200 ml of water).

Film-coated tablets, 850 mg

Monotherapy and combination therapy with other oral hypoglycemic agents. Initial dose – 1 tab. (850 mg) 1 time per day in the evening. After 7-15 days, in the absence of adverse effects from the gastrointestinal tract, 1 table is prescribed. (850 mg) 2 times a day, morning and evening. Perhaps a further gradual increase in dose depending on the concentration of glucose in the blood.

The maintenance dose is 1700 mg/day. To reduce side effects from the gastrointestinal tract, the dose should be divided into 2 doses. The maximum daily dose is 2550 mg / day, divided into 3 doses.

If you plan to switch to Formin Pliva from another hypoglycemic agent, you should stop taking the other agent and start taking Formin Pliva at the dose indicated above.

Combination with insulin. Formin Pliva and insulin can be used as a combination therapy to achieve better glycemic control.

Formin Pliva is taken at the usual starting dose of 850 mg 2 to 3 times daily. The dose of insulin is selected based on the results of determining the concentration of blood glucose. After 10-15 days, the dose is adjusted depending on the blood glucose concentration. The maximum daily dose of metformin in combined treatment is 1700 mg / day, divided into 2 doses.

In elderly patients the daily dose should not exceed 850 mg/day.

Film-coated tablets, 1000 mg

The dose of Formin Pliva is determined individually, taking into account the level of glucose in the blood. The initial dose is, as a rule, 500-1000 mg (1/2-1 table) per day, a further gradual increase in dose is possible depending on the effect of therapy.

Maintenance daily dose of the drug is 1000-2000 mg (table 1-2) per day. The maximum daily dose is 3000 mg (table 3), the appointment of higher doses does not increase the effect of the treatment.

The course of treatment with the drug is long.

Due to the increased risk of developing lactic acidosis, the dose of the drug must be reduced in severe metabolic disorders.

Presentation

Film-coated tablets, 850 mg. 10 tab. in a PVC/PVDC/aluminum foil blister. 3 or 6 blisters in a cardboard box.

Film-coated tablets, 1000 mg. 15 tab. in a PVC/aluminum foil blister. 2 or 4 blisters in a cardboard box.

Producer

Film-coated tablets, 850 mg

Pliva Hrvatska doo, Prylaz Barun Filipovića 25, 10000 Zagreb, Republic of Croatia.

Address for receiving claims: 119049, Moscow, st. Shabolovka, 10, building. 1.

Tel.: (495) 644-22-34; fax: (495) 644-22-35/36.

Film-coated tablets, 1000 mg

Pliva Hrvatska d.o.o., Prylaz Barun Filipovića 25, 10000 Zagreb, Republic of Croatia

or Dragenofarm Apotheker Puschl GmbH & Co. KG, Gelstraße 1, 84529 Tittmoning, Germany.

Address for receiving claims: 119049, Moscow, st. Shabolovka, 10, building. 1.

Tel.: (495) 644-22-34; fax: (495) 644-22-35/36.

Terms of dispensing from pharmacies

By prescription.

Storage conditions

At a temperature not higher than 25 °C.

Keep out of reach of children.

Expiry date

4 years.

Do not use after the expiry date which is stated on the pack.

Side effects of second generation antiepileptic drugs | Belousov

Annotation

This article discusses the side effects and frequency of their occurrence in 6 modern second-generation antiepileptic drugs (PEP-II): gabapentin (GBP) – Neurontin, Pfizer and other generics; lamotrigine (Ltd. ) – Lamictal, GlaxoSmithKline and other generics; levetiracetam (LEV) – Keppra, Pliva; oxcarbazepine (OKS) – Trileptal, Novartis; pregabalin (PHB) – Lyrica, Pfizer; topiramate (TPM) – Topamax, Janssen-Cilag and other generics. All data on the side effects of PEP-II are from controlled clinical trials. Compared to first generation drugs (AED-I), most AED-II have much fewer side effects associated with stimulation or inhibition of enzyme activity, such as cognitive, hormonal, and others. This simplifies therapy and improves patient compliance, which is absolutely essential for the successful management of patients with partial or generalized epilepsy. AED-II expands the arsenal of treatments and is a new step in optimizing individual therapy for epilepsy. Although these drugs are safer and better tolerated, most of them still cause adverse side effects.

Introduction

This article discusses the side effects and incidence of six current second-generation antiepileptic drugs (AED-II): iki;

  • lamotrigine (Ltd) – Lamictal, GlaxoSmithKline and other generics;
  • levetiracetam (LEV) – Keppra, Pliva;
  • oxcarbazepine (OKS) – Trileptal, Novartis;
  • pregabalin (PHB) – Lyrica, Pfizer;
  • topiramate (TPM) – Topamax, Janssen-Cilag and other generics.
  • All AED-II side effect data are from controlled clinical trials.

    Compared to first generation drugs (AED-I): phenobarbital (PB), primidone (PRD), phenytoin (PNT), carbamazepine (CBZ), valproic acid (VPA), most AED-II have much fewer side effects, associated with stimulation or inhibition of enzyme activity, for example, cognitive, hormonal, and others. This simplifies therapy and improves patient compliance, which is absolutely essential for the successful management of patients with partial or generalized epilepsy [25]. AED-II expands the arsenal of treatments and is a new step in optimizing individual therapy for epilepsy.

    Although these drugs are safer and better tolerated, most of them still cause adverse side effects. The table summarizes the frequency of occurrence of the most common side effects of some AED-II.

    Table. Frequency of side effects of some new antiepileptic drugs, modified from [7]

    9 0068

    TPM*

    n=113 (%)

    Weight Loss 0068

    Side effect

    90 271 GBP

    n=543 (%)

    LTD

    n=711 (%)

    CNS

    25 (3. 5)

    14 (12.4)

    Ataxia

    7 (1.3)

    16 (2.3)

    14 (12.4)

    90 002 Speech disorder

    4 (0.7)

    21 (3.0) 900 05

    8 (7.1)

    Nystagmus

    4 (0.7)

    3 (2.7)

    Paresthesia

    12 (10.6)

    Tremor 0068

    4 (0.7)

    5 (4.4)

    Impaired coordination of movements

    Mental state

    7 (6. 2)

    10 (1.8)

    7 (1.0) 9Weakness

    6 (1.1)

    9 0270 –

    Psychomotor retardation

    15 (13.3)

    8 (7.1)

    Difficulty in concentration

    Memory impairment (8.0)

    (4.4)

    Depression/psychosis

    2 (1.8)

    General condition

    Visual impairment

    11 (9. 7)

    Rash (0.7)

    Nausea

    9 (1.3)

    90 002 Vomiting

    5 (0.7)

    6 ( 5.3)

    Diarrhea

    2 (0.3)

    9027 0 –

    Constipation

    4 (3.5)

    Dyspepsia

    3 (0.4) 9 0005

    3 (2.7)

    Insomnia

    5 (4. 4)

    * – Low dose (200-400 mg/day) ; GBP – gabapentin ; LTD – lamotrigine ; TPM – Topiramate .

    Gabapentin (GBP). The most common side effects of GBP are drowsiness, weakness, dizziness, and weight gain [9]. GBP does not change the performance of the liver, kidneys and endocrine system and does not affect the cellular composition of the blood. Several cases of movement disorders have been described [20]. Data on a possible teratogenic effect in humans is insufficient.

    Lamotrigine (Ltd). The most common side effect of LTD is exanthema [17], which rarely manifests as Stevens-Johnson syndrome or Lyell’s syndrome. The development of exanthema in most cases can be avoided by slowly increasing the dose. When a rash appears, the drug is immediately canceled, since in most cases the exanthema is irreversible. Other rare side effects are vetiligo, gastrointestinal symptoms, drowsiness, nausea, diplopia, idiosyncratic thrombocytopenia, leukopenia, and transaminase elevation [13].

    The development of blepharospasm has been described with the use of LTD [27]. As a result of the interaction of LTD with CBZ, vitiligo and nausea may occur, which are eliminated by reducing the dose of CBZ.

    No teratogenic effects have been found in animal experiments, but there are insufficient data on effects in humans. To date, 707 pregnant women treated with LTD monotherapy have reported a 2.8% incidence of fetal developmental disorders; with monotherapy with other AEDs, this figure is 3.3-4.5%, according to the Register of Pregnant Women Taking Lamotrigine [14]. According to one North American registry, the incidence of cleft palate is 8.9cases per 1000 children, but this figure needs to be confirmed. LTD passes into breast milk [19].

    In general, LTD is well tolerated. In some studies, the use of LTD even found mood stabilization, antidepressant effect, improvement of attention and cognitive functions [26]. In 6.4% of patients, sleep disturbances are observed, which are partially eliminated by taking the drug in the morning or in the middle of the day [22].

    Levetiracetam (LEV) – Studies to date suggest that LEV is well tolerated [5]. A positive effect on the quality of life of patients was also noted [6]. The most common side effects are drowsiness, asthenia and dizziness [1], with drowsiness more common at higher doses of the drug [2]. Gastrointestinal phenomena (anorexia, diarrhea) and side effects from the central nervous system (amnesia, ataxia, insomnia, nervousness, tremor, vitiligo), as well as diplopia and skin reactions, are less common. Emotional instability and aggressiveness may develop.

    Oxcarbazepine (OCS). The most common side effects of ACS are headache, vitiligo, drowsiness, nausea, diplopia, vomiting, and ataxia [3]. In general, the drug is well tolerated, and side effects are less common than with CBZ [8]. Often they can be avoided by carefully increasing the initial dose (600 mg / week). It should be remembered that ACS can cause hyponatremia up to <125 mmol/l [12], which in rare cases is accompanied by confusion. OCS has less effect on free testosterone levels than CBZ due to its weak drug interaction potential [10]. This may be important given the risk of erectile dysfunction and hypogonadism. In addition to testosterone levels, after switching from CBZ to ACS, the level of total cholesterol also normalizes [4].

    Pregabalin (PHB). The most common side effects in controlled clinical trials were dizziness (38%), drowsiness (28%), ataxia (19.5%), and weight gain (15.9%) at the maximum dose of 600 mg [4].

    Topiramate (TPM). Long-term studies have shown good tolerability and no withdrawal symptoms [21]. The most common side effect was dose-dependent weight loss [23]. In addition, side effects from the central nervous system were observed – a decrease in concentration, psychomotor retardation, speech impairment, dizziness, drowsiness, weakness, confusion and ataxia. Perhaps the development of paresthesia associated with inhibition of the activity of carbonic anhydrase. Attention should be paid to the fact that TBI contributes to the formation of calcium-phosphate kidney stones due to the weakening of the excretion of citrates in the urine and, accordingly, the increase in urine pH. In some cases, the use of TPM may cause symptoms of glaucoma. There are insufficient data on the use of the drug during pregnancy, so TBI should be used during pregnancy only after a careful assessment of the risk-benefit ratio. Monotherapy at doses of 100-200 mg is generally better tolerated than combination therapy.

    Conclusion

    PEP-I (FB, PRD, FNT, CBZ, VPC) have an increased ability to develop side effects due to the activation/inhibition of enzyme activity. In addition to impaired cognitive functions and functions of the endocrine system, long-term use of these drugs may be accompanied by changes in bones (osteoporosis) and connective tissue (gingival hyperplasia, Dupuytren’s contracture, hypertrichosis, etc.). In addition, hormonal and metabolic disorders lead to sexual dysfunction [10, 11, 15, 16, 18].

    These side effects are unlikely for most AED-IIs, so it is now possible to improve treatment tolerance. In controlled trials, the rate of early discontinuation of HBP, LEV, LTD, ACS, PHB, and TPM was less than for CBA, VPC, and FNT [24].

    Thus :

    • the use of PEP-II improves tolerability and compliance;
    • AED-II have better safety and possibly less teratogenicity than AED-I.

    Currently, epileptologists expect the emergence of a new generation of AEDs: ganaloxone, BIA2-093, brivaracetam, fluorofelbamate, charcoseride, remazemide, safinamide, styripentol, talampanel, SPD 421, retigabine and others, which are still undergoing preclinical and clinical studies.

    1. Ben-Menachem E. & Falter U. (2000). Efficacy and tolerability of levetiracetam 3000 mg/d in patients with refractory partial seizures: a multicenter, double-blind, responder-selected study evaluating monotherapy. European Levetiracetam Study Group. Epilepsia 41, 1276-1283.

    2. Betts T., Waegemans T. & Crawford P. (2000). A multicentre, double-blind, randomized, parallel group study to evaluate the tolerability and efficacy of two oral doses of levetiracetam, 2000 mg daily and 4000 mg daily, without titration in patients with refractory epilepsy. Seizure 9, 80-87.

    3. Bill P.A., Vigonius U., Pohlmann H., Guerreiro C.A., Kochen S., Saffer D., et al. (1997). A double-blind controlled clinical trial of oxcarbazepine versus phenytoin in adults with previously untreated epilepsy. Epilepsy Res 27, 195-204.

    4. Blum D.E. (1998). New drugs for persons with epilepsy. Adv Neurol 76, 57-87.

    5. Cereghino J.J., Biton V., Abou K.B., Dreifuss F., Gauer L.J. & Leppik I. (2000). Levetiracetam for partial seizures: results of a double-blind, randomized clinical trial. Neurology 55, 236-242.

    6. Cramer J.A., Arrigo C., Van-Hammee G., Gauer L.J. & Cereghino J.J. (2000). Effect of levetiracetam on epilepsy-related quality of life. N132 Study Group. Epilepsia 41, 868-874.

    7. Cramer J.A., Fisher R., Ben-Menachem E., French J. & Mattson R. (1999). New antiepileptic drugs: comparison of key trials. Epilepsia 40, 590-600.

    8. Dam M., Ekberg R., Loyning Y., Waltimo O. & Jakobsen K. (1989). A double-blind study comparing oxcarbazepine and carbamazepine in patients with newly diagnosed, previously untreated epilepsy. Epilepsy Res 3, 70-76.

    9. Gidal B.E., Maly M.M., Nemire R.E. & Haley K. (1995). Weight gain and gabapentin therapy [letter]. Ann Pharmacother 29, 1048-1054.

    10. Herzog A., Drislane F.W. & Schomer D.I. (2003). Differential antiepileptic drug effects on sex hormones and reproductive hormones: a comparison between lamotrigne and enzyme-inducing antiepileptic drugs. Epilepsia 44(9), 107-115.

    11. Isojaervi J.I.T., Pakarinen A.J., Rautio A., Pelkonen O. & Myllylae V.V. (1995). Serum sex hormone levels after replacing carbamazepine with oxcarbazepine. Eur J Clin Pharmacol 47(5), 462-464.

    12. Johannessen A.C. & Nielsen O.A. (1987). Hyponatremia induced by oxcarbazepine. Epilepsy Res 1, 155-156.

    13. Kilpatrick E.S., Forrest G. & Brodie M.J. (1996). Concentration-effect and concentration-toxicity relations with lamotrigine: a prospective study. Epilepsia 37, 534-538.

    14. Lamotrigine pregnanacy registry, January 2006, GlaxoSmithKline.

    15. Martin R., Kuzniecky R. & Ho S. (1999). Cognitive effects of topiramate, gabapentine and lamotrigine in healthy young adults. Neurology 52(2), 321-327.

    16. Meador K.J., Loring D.W., Ray P.G., Murro, A.M., King D.W., Perrine K.R. et al. (2001). Differential cognitive and behavioral effects of carbamazepine and lamotrigine. Neurology 56, 177-1182.

    17. Messenheimer J.A. & Guberman A.H. (2000). Rash with lamotrigine: dosing guidelines [letter]. Epilepsia 41, 488.

    18. Pack A.M., Olarte L.S. & Morell M.J. (2003). Bone mineral density in an outpatient population receiving enzyme-inducing antiepileptic drugs. Epilepsy Behav 4, 169-174.

    19. Rambeck B., Kurlemann G., Stodieck S.R., May T.W. & Jurgens U. (1997). Concentrations of lamotrigine in a mother on lamotrigine treatment and her newborn child. Eur J Clin Pharmacol 51, 481-484.

    20. Reeves A.L., So E.L., Sharbrough F.W. & Krahn L.E. (1996). Movement disorders associated with the use of gabapentin. Epilepsia 37, 988-990.

    21. Ritter F., Glauser T.A., Elterman R.D. & Wyllie E. (2000). Effectiveness, tolerability, and safety of topiramate in children with partial-onset seizures. Topiramate YP Study Group. Epilepsia 41(1), 82-85.

    22. Sadler M. (1999). Lamotrigine associated with insomnia. Epilepsia 40, 322-325.

    23. Sander J.W. (1997). Practical aspects of the use of topiramate in patients with epilepsy. Epilepsia 38(1), 56-58.

    24. Stefan H., Feuerstein T.J. Novel anticonvulsant drugs. Pharmacology & Therapeutics 113 (2007) 165-183

    25. Steinhoff B.J., Hirsch E, Mutani R. & Nakken K.