4.1 Prescriptions drugs: Medications for Psychological Disorders

Mental Health Medications

Overview

Medications can play a role in treating several mental disorders and conditions. Treatment may also include psychotherapy (also called “talk therapy”) and brain stimulation therapies (less common). In some cases, psychotherapy alone may be the best treatment option. Choosing the right treatment plan should be based on a person’s individual needs and medical situation and under a mental health professional’s care.

The National Institute of Mental Health (NIMH), a federal research agency, does not provide medical advice or referrals. Resources that may help you find treatment services in your area are listed on our Help for Mental Illnesses web page.

NIMH also does not endorse or recommend any particular drug, herb, or supplement. Results from NIMH-supported clinical research trials (What are Clinical Research Trials?) that examine the effectiveness of treatments, including medications, are reported in the medical literature. This health topic webpage is intended to provide basic information about mental health medications. It is not a complete source for all medications available and should not be used as a guide for making medical decisions.

Information about medications changes frequently. Check the U.S. Food and Drug Administration (FDA) website for the latest warnings, patient medication guides, or newly approved medications. Brand names are not referenced on this page, but you can search by brand name on MedlinePlus Drugs, Herbs and Supplements Drugs website. The MedlinePlus website also provides additional information about each medication, including side effects and FDA warnings.

Understanding Your Medications

If you are prescribed a medication, be sure that you:

  • Tell the doctor about all medications and vitamin supplements you are already taking.
  • Remind your doctor about any allergies and any problems you have had with medicines.
  • Understand how to take the medicine before you start using it and take your medicine as instructed.
  • Don’t take medicines prescribed for another person or give yours to someone else.
  • Call your doctor right away if you have any problems with your medicine or if you are worried that it might be doing more harm than good. Your doctor may be able to adjust the dose or change your prescription to a different one that may work better for you.
  • Report serious side effects to the FDA MedWatch Adverse Event Reporting program online at [U.S. Food & Drug (FDA), MedWatch: The FDA Safety Information and Adverse Event Reporting Program] or by phone [1-800-332-1088]. You or your doctor may send a report.

Antidepressants

What are antidepressants?

Antidepressants are medications commonly used to treat depression. Antidepressants are also used for other health conditions, such as anxiety, pain, and insomnia. Although antidepressants are not FDA-approved specifically to treat ADHD, antidepressants are sometimes used to treat ADHD in adults.

The most popular types of antidepressants are called selective serotonin reuptake inhibitors (SSRIs). Explore the information on these SSRI examples:

Other types of antidepressants are serotonin and norepinephrine reuptake inhibitors (SNRIs). SNRIs are similar to SSRIs and include venlafaxine  (ex. Effexor) and duloxetine (ex. Cymbalta).

Another antidepressant that is commonly used is bupropion. Bupropion is a third type of antidepressant which works differently than either SSRIs or SNRIs.  Bupropion is also used to treat seasonal affective disorder and to help people stop smoking.

SSRIs, SNRIs, and bupropion are popular because they do not cause as many side effects as older classes of antidepressants, and seem to help a broader group of depressive and anxiety disorders. Older antidepressant medications include tricyclics, tetracyclics, and monoamine oxidase inhibitors (MAOIs). For some people, tricyclics, tetracyclics, or MAOIs may be the best medications.

How do people respond to antidepressants?

According to a research review by the Agency for Healthcare Research and Quality, all antidepressant medications work about as well as each other to improve symptoms of depression and to keep depression symptoms from coming back. For reasons not yet well understood, some people respond better to some antidepressant medications than to others.

Therefore, it is important to know that some people may not feel better with the first medicine they try and may need to try several medicines to find the one that works for them. Others may find that a medicine helped for a while, but their symptoms came back. It is important to carefully follow your doctor’s directions for taking your medicine at an adequate dose and over an extended period of time (often 4 to 6 weeks) for it to work.

Once a person begins taking antidepressants, it is important to not stop taking them without the help of a doctor. Sometimes people taking antidepressants to feel better and stop taking the medication too soon, and the depression may return. When it is time to stop the medication, the doctor will help the person slowly and safely decrease the dose. It’s important to give the body time to adjust to the change. People don’t get addicted (or “hooked”) on these medications, but stopping them abruptly may also cause withdrawal symptoms.

What are the possible side effects of antidepressants?

Some antidepressants may cause more side effects than others. You may need to try several different antidepressant medications before finding the one that improves your symptoms and that causes side effects that you can manage.

The most common side effects listed by the FDA include:

  • Nausea and vomiting
  • Weight gain
  • Diarrhea
  • Sleepiness
  • Sexual problems

Call your doctor right away if you have any of the following symptoms, especially if they are new, worsening, or worry you(U.S. Food and Drug Administration, 2011):

  • Thoughts about suicide or dying
  • Attempts to commit suicide
  • New or worsening depression
  • New or worsening anxiety
  • Feeling very agitated or restless
  • Panic attacks
  • Trouble sleeping (insomnia)
  • New or worsening irritability
  • Acting aggressively, being angry, or violent
  • Acting on dangerous impulses
  • An extreme increase in activity and talking (mania)
  • Other unusual changes in behavior or mood

Combining the newer SSRI or SNRI antidepressants with one of the commonly-used “triptan” medications used to treat migraine headaches could cause a life-threatening illness called “serotonin syndrome.” A person with serotonin syndrome may be agitated, have hallucinations (see or hear things that are not real), have a high temperature, or have unusual blood pressure changes. Serotonin syndrome is usually associated with the older antidepressants called MAOIs, but it can happen with the newer antidepressants as well if they are mixed with the wrong medications. For more information, please see the FDA Medication Guide on Antidepressant Medicines.

Antidepressants may cause other side effects that were not included in this list. To report any serious adverse effects associated with the use of antidepressant medicines, please contact the FDA MedWatch program using the contact information at the bottom of this page. For more information about the risks and side effects for each medication, please see Drugs@FDA.

Anti-Anxiety Medications

What are anti-anxiety medications?

Anti-anxiety medications help reduce the symptoms of anxiety, such as panic attacks, or extreme fear and worry. The most common anti-anxiety medications are called benzodiazepines. Benzodiazepines can treat generalized anxiety disorder. In the case of panic disorder or social phobia (social anxiety disorder), benzodiazepines are usually second-line treatments, behind SSRIs or other antidepressants.

Benzodiazepines used to treat anxiety disorders include:

Short half-life (or short-acting) benzodiazepines (such as Lorazepam) and beta-blockers are used to treat the short-term symptoms of anxiety. Beta-blockers help manage physical symptoms of anxiety, such as trembling, rapid heartbeat, and sweating that people with phobias (an overwhelming and unreasonable fear of an object or situation, such as public speaking) experience in difficult situations. Taking these medications for a short period of time can help the person keep physical symptoms under control and can be used “as needed” to reduce acute anxiety. Buspirone (which is unrelated to the benzodiazepines) is sometimes used for the long-term treatment of chronic anxiety. In contrast to the benzodiazepines, buspirone must be taken every day for a few weeks to reach its full effect. It is not useful on an “as-needed” basis.

How do people respond to anti-anxiety medications?

Anti-anxiety medications such as benzodiazepines are effective in relieving anxiety and take effect more quickly than the antidepressant medications (or buspirone) often prescribed for anxiety. However, people can build up a tolerance to benzodiazepines if they are taken over a long period of time and may need higher and higher doses to get the same effect. Some people may even become dependent on them. To avoid these problems, doctors usually prescribe benzodiazepines for short periods, a practice that is especially helpful for older adults (read the NIMH article: Despite Risks, Benzodiazepine Use Highest in Older People), people who have substance abuse problems and people who become dependent on medication easily. If people suddenly stop taking benzodiazepines, they may have withdrawal symptoms or their anxiety may return. Therefore, benzodiazepines should be tapered off slowly.

What are the possible side effects of anti-anxiety medications?

Like other medications, anti-anxiety medications may cause side effects. Some of these side effects and risks are serious. The most common side effects of benzodiazepines are drowsiness and dizziness. Other possible side effects include:

  • Nausea
  • Blurred vision
  • Headache
  • Confusion
  • Tiredness
  • Nightmares

Tell your doctor if any of these symptoms are severe or do not go away:

  • Drowsiness
  • Dizziness
  • Unsteadiness
  • Problems with coordination
  • Difficulty thinking or remembering
  • Increased saliva
  • Muscle or joint pain
  • Frequent urination
  • Blurred vision
  • Changes in sex drive or ability (The American Society of Health-System Pharmacists, Inc, 2010)

If you experience any of the symptoms below, call your doctor immediately:

  • Rash
  • Hives
  • Swelling of the eyes, face, lips, tongue, or throat
  • Difficulty breathing or swallowing
  • Hoarseness
  • Seizures
  • Yellowing of the skin or eyes
  • Depression
  • Difficulty speaking
  • Yellowing of the skin or eyes
  • Thoughts of suicide or harming yourself
  • Difficulty breathing

Common side effects of beta-blockers include:

  • Fatigue
  • Cold hands
  • Dizziness or light-headedness
  • Weakness

Beta-blockers generally are not recommended for people with asthma or diabetes because they may worsen symptoms related to both.

Possible side effects from buspirone include:

  • Dizziness
  • Headaches
  • Nausea
  • Nervousness
  • Lightheadedness
  • Excitement
  • Trouble sleeping

Anti-anxiety medications may cause other side effects that are not included in the lists above. To report any serious adverse effects associated with the use of these medicines, please contact the FDA MedWatch program using the contact information at the bottom of this page. For more information about the risks and side effects for each medication, please see Drugs@FDA.

Stimulants

What are Stimulants?

As the name suggests, stimulants increase alertness, attention, and energy, as well as elevate blood pressure, heart rate, and respiration (National Institute on Drug Abuse, 2014). Stimulant medications are often prescribed to treat children, adolescents, or adults diagnosed with ADHD.

Stimulants used to treat ADHD include:

Note: In 2002, the FDA approved the non-stimulant medication atomoxetine for use as a treatment for ADHD. Two other non-stimulant antihypertensive medications, clonidine and guanfacine, are also approved for the treatment of ADHD in children and adolescents. One of these non-stimulant medications is often tried first in a young person with ADHD, and if the response is insufficient, then a stimulant is prescribed.

Stimulants are also prescribed to treat other health conditions, including narcolepsy, and occasionally depression (especially in older or chronically medically ill people and in those who have not responded to other treatments).

How do people respond to stimulants?

Prescription stimulants have a calming and “focusing” effect on individuals with ADHD. Stimulant medications are safe when given under a doctor’s supervision. Some children taking them may feel slightly different or “funny”.

Some parents worry that stimulant medications may lead to drug abuse or dependence, but there is little evidence of this when they are used properly as prescribed. Additionally, research shows that teens with ADHD who took stimulant medications were less likely to abuse drugs than those who did not take stimulant medications.

What are the possible side effects of stimulants?

Stimulants may cause side effects. Most side effects are minor and disappear when dosage levels are lowered. The most common side effects include:

  • Difficulty falling asleep or staying asleep
  • Loss of appetite
  • Stomach pain
  • Headache

Less common side effects include:

  • Motor tics or verbal tics (sudden, repetitive movements or sounds)
  • Personality changes, such as appearing “flat” or without emotion

Call your doctor right away if you have any of these symptoms, especially if they are new, become worse, or worry you.

Stimulants may cause other side effects that are not included in the list above. To report any serious adverse effects associated with the use of stimulants, please contact the FDA MedWatch program using the contact information at the bottom of this page. For more information about the risks and side effects for each medication, please see Drugs@FDA.

Antipsychotics

What are antipsychotics?

Antipsychotic medicines are primarily used to manage psychosis. The word “psychosis” is used to describe conditions that affect the mind, and in which there has been some loss of contact with reality, often including delusions (false, fixed beliefs) or hallucinations (hearing or seeing things that are not really there). It can be a symptom of a physical condition such as drug abuse or a mental disorder such as schizophrenia, bipolar disorder, or very severe depression (also known as “psychotic depression”).

Antipsychotic medications are often used in combination with other medications to treat delirium, dementia, and mental health conditions, including:

Antipsychotic medicines do not cure these conditions. They are used to help relieve symptoms and improve quality of life.

Older or first-generation antipsychotic medications are also called conventional “typical” antipsychotics or “neuroleptics”. Some of the common typical antipsychotics include:

Newer or second-generation medications are also called “atypical” antipsychotics. Some of the common atypical antipsychotics include:

According to a  2013 research review by the Agency for Healthcare Research and Quality, typical and atypical antipsychotics both work to treat symptoms of schizophrenia and the manic phase of bipolar disorder.

Several atypical antipsychotics have a “broader spectrum” of action than the older medications and are used for treating bipolar depression or depression that has not responded to an antidepressant medication alone.

To find additional antipsychotics and other medications used to manage psychoses and current warnings and advisories, please visit the FDA website.

How do people respond to antipsychotics?

Certain symptoms, such as feeling agitated and having hallucinations, usually go away within days of starting an antipsychotic medication. Symptoms like delusions usually go away within a few weeks, but the full effects of the medication may not be seen for up to six weeks. Every patient responds differently, so it may take several trials of different antipsychotic medications to find the one that works best.

Some people may have a relapse—meaning their symptoms come back or get worse. Usually, relapses happen when people stop taking their medication, or when they only take it sometimes. Some people stop taking the medication because they feel better or they may feel that they don’t need it anymore, but no one should stop taking an antipsychotic medication without talking to his or her doctor. When a doctor says it is okay to stop taking a medication, it should be gradually tapered off— never stopped suddenly. Many people must stay on an antipsychotic continuously for months or years in order to stay well; treatment should be personalized for each individual.

What are the possible side effects of antipsychotics?

Antipsychotics have many side effects (or adverse events) and risks. The FDA lists the following side effects of antipsychotic medicines:

  • Drowsiness
  • Dizziness
  • Restlessness
  • Weight gain (the risk is higher with some atypical antipsychotic medicines)
  • Dry mouth
  • Constipation
  • Nausea
  • Vomiting
  • Blurred vision
  • Low blood pressure
  • Uncontrollable movements, such as tics and tremors (the risk is higher with typical antipsychotic medicines)
  • Seizures
  • A low number of white blood cells, which fight infections

A person taking an atypical antipsychotic medication should have his or her weight, glucose levels, and lipid levels monitored regularly by a doctor.

Typical antipsychotic medications can also cause additional side effects related to physical movements, such as:

  • Rigidity
  • Persistent muscle spasms
  • Tremors
  • Restlessness

Long-term use of typical antipsychotic medications may lead to a condition called tardive dyskinesia (TD). TD causes muscle movements, commonly around the mouth, that a person can’t control. TD can range from mild to severe, and in some people, the problem cannot be cured. Sometimes people with TD recover partially or fully after they stop taking typical antipsychotic medication. People who think that they might have TD should check with their doctor before stopping their medication. TD rarely occurs while taking atypical antipsychotics.

Antipsychotics may cause other side effects that are not included in this list above. To report any serious adverse effects associated with the use of these medicines, please contact the FDA MedWatch program. For more information about the risks and side effects for antipsychotic medications, please visit Drugs@FDA.

Mood Stabilizers

What are mood stabilizers?

Mood stabilizers are used primarily to treat bipolar disorder, mood swings associated with other mental disorders, and in some cases, to augment the effect of other medications used to treat depression. Lithium, which is an effective mood stabilizer, is approved for the treatment of mania and the maintenance treatment of a bipolar disorder. A number of cohort studies describe anti-suicide benefits of lithium for individuals on long-term maintenance. Mood stabilizers work by decreasing abnormal activity in the brain and are also sometimes used to treat:

  • Depression (usually along with an antidepressant)
  • Schizoaffective Disorder
  • Disorders of impulse control
  • Certain mental illnesses in children

Anticonvulsant medications are also used as mood stabilizers. They were originally developed to treat seizures, but they were found to help control unstable moods as well. One anticonvulsant commonly used as a mood stabilizer is valproic acid (also called divalproex sodium). For some people, especially those with “mixed” symptoms of mania and depression or those with a rapid-cycling bipolar disorder, valproic acid may work better than lithium. Other anticonvulsants used as mood stabilizers include:

What are the possible side effects of mood stabilizers?

Mood stabilizers can cause several side effects, and some of them may become serious, especially at excessively high blood levels. These side effects include:

  • Itching, rash
  • Excessive thirst
  • Frequent urination
  • Tremor (shakiness) of the hands
  • Nausea and vomiting
  • Slurred speech
  • Fast, slow, irregular, or pounding heartbeat
  • Blackouts
  • Changes in vision
  • Seizures
  • Hallucinations (seeing things or hearing voices that do not exist)
  • Loss of coordination
  • Swelling of the eyes, face, lips, tongue, throat, hands, feet, ankles, or lower legs

If a person with bipolar disorder is being treated with lithium, he or she should visit the doctor regularly to check the lithium levels his or her blood and make sure the kidneys and the thyroid are working normally.

Lithium is eliminated from the body through the kidney, so the dose may need to be lowered in older people with reduced kidney function. Also, loss of water from the body, such as through sweating or diarrhea, can cause the lithium level to rise, requiring a temporary lowering of the daily dose. Although kidney functions are checked periodically during lithium treatment, actual damage of the kidney is uncommon in people whose blood levels of lithium have stayed within the therapeutic range.

Mood stabilizers may cause other side effects that are not included in this list. To report any serious adverse effects associated with the use of these medicines, please contact the FDA MedWatch program using the contact information at the bottom of this page. For more information about the risks and side effects for each individual medication, please see Drugs@FDA.

For more information on the side effects of  CarbamazepineLamotrigine, and Oxcarbazepine, please visit MedlinePlus Drugs, Herbs and Supplements.

Some possible side effects linked anticonvulsants (such as valproic acid) include:

  • Drowsiness
  • Dizziness
  • Headache
  • Diarrhea
  • Constipation
  • Changes in appetite
  • Weight changes
  • Back pain
  • Agitation
  • Mood swings
  • Abnormal thinking
  • Uncontrollable shaking of a part of the body
  • Loss of coordination
  • Uncontrollable movements of the eyes
  • Blurred or double vision
  • Ringing in the ears
  • Hair loss

These medications may also:

  • Cause damage to the liver or pancreas, so people taking it should see their doctors regularly
  • Increase testosterone (a male hormone) levels in teenage girls and lead to a condition called polycystic ovarian syndrome (a disease that can affect fertility and make the menstrual cycle become irregular)

Medications for common adult health problems, such as diabetes, high blood pressure, anxiety, and depression may interact badly with anticonvulsants. In this case, a doctor can offer other medication options.

For more information about the risks and side effects for each medication, please see Drugs@FDA.

Special Groups: Children, Older Adults, Pregnant Women

All types of people take psychiatric medications, but some groups have special needs, including:

  • Children and adolescents
  • Older adults
  • Women who are pregnant or who may become pregnant

Children and Adolescents

Many medications used to treat children and adolescents with mental illness are safe and effective. However, some medications have not been studied or approved for use with children or adolescents.

Still, a doctor can give a young person an FDA-approved medication on an “off-label” basis. This means that the doctor prescribes the medication to help the patient even though the medicine is not approved for the specific mental disorder that is being treated or for use by patients under a certain age. Remember:

  • It is important to watch children and adolescents who take these medications on an “off-label: basis.
  • Children may have different reactions and side effects than adults.
  • Some medications have current FDA warnings about potentially dangerous side effects for younger patients.

In addition to medications, other treatments for children and adolescents should be considered, either to be tried first, with medication added later if necessary, or to be provided along with medication. Psychotherapy, family therapy, educational courses, and behavior management techniques can help everyone involved cope with disorders that affect a child’s mental health. Read more about child and adolescent mental health research.

Older Adults

People over 65 have to be careful when taking medications, especially when they’re taking many different drugs. Older adults have a higher risk of experiencing bad drug interactions, missing doses or overdosing.

Older adults also tend to be more sensitive to medications. Even healthy older people react to medications differently than younger people because older people’s bodies process and eliminate medications more slowly. Therefore, lower or less frequent doses may be needed for older adults. Before starting a medication, older people and their family members should talk carefully with a physician about whether a medication can affect alertness, memory, or coordination, and how to help ensure that prescribed medications do not increase the risk of falls.

Sometimes memory problems affect older people who take medications for mental disorders. An older adult may forget his or her regular dose and take too much or not enough. A good way to keep track of medicine is to use a seven-day pillbox, which can be bought at any pharmacy. At the beginning of each week, older adults and their caregivers fill the box so that it is easy to remember what medicine to take. Many pharmacies also have pillboxes with sections for medications that must be taken more than once a day.

For more information and practical tips to help older people take their medicines safely, please see the National Institute on Aging’s Safe Use of Medicines booklet and Taking Medicines on NIHSeniorHealth.gov.

Women who are pregnant or who may become pregnant

The research on the use of psychiatric medications during pregnancy is limited. The risks are different depending on which medication is taken, and at what point during the pregnancy the medication is taken. Decisions on treatments for all conditions during pregnancy should be based on each woman’s needs and circumstances, and based on a careful weighing of the likely benefits and risks of all available options, including psychotherapy (or “watchful waiting” during part or all of the pregnancy), medication, or a combination of the two. While no medication is considered perfectly safe for all women at all stages of pregnancy, this must be balanced for each woman against the fact that untreated serious mental disorders themselves can pose a risk to a pregnant woman and her developing fetus. Medications should be selected based on available scientific research, and they should be taken at the lowest possible dose. Pregnant women should have a medical professional who will watch them closely throughout their pregnancy and after delivery.

Most women should avoid certain medications during pregnancy. For example:

  • Mood stabilizers are known to cause birth defects. Benzodiazepines and lithium have been shown to cause “floppy baby syndrome,” in which a baby is drowsy and limp, and cannot breathe or feed well. Benzodiazepines may cause birth defects or other infant problems, especially if taken during the first trimester.
  • According to research, taking antipsychotic medications during pregnancy can lead to birth defects, especially if they are taken during the first trimester and in combination with other drugs, but the risks vary widely and depend on the type of antipsychotic taken. The conventional antipsychotic haloperidol has been studied more than others and has been found not to cause birth defects. Research on the newer atypical antipsychotics is ongoing.

Antidepressants, especially SSRIs, are considered to be safe during pregnancy. However, antidepressant medications do cross the placental barrier and may reach the fetus. Birth defects or other problems are possible, but they are very rare. The effects of antidepressants on childhood development remain under study.

Studies have also found that fetuses exposed to SSRIs during the third trimester may be born with “withdrawal” symptoms such as breathing problems, jitteriness, irritability, trouble feeding, or hypoglycemia (low blood sugar). Most studies have found that these symptoms in babies are generally mild and short-lived, and no deaths have been reported. Risks from the use of antidepressants need to be balanced with the risks of stopping medication; if a mother is too depressed to care for herself and her child, both may be at risk for problems.

In 2004, the FDA issued a warning against the use of certain antidepressants in the late third trimester. The warning said that doctors may want to gradually taper pregnant women off antidepressants in the third trimester so that the baby is not affected. After a woman delivers, she should consult with her doctor to decide whether to return to a full dose during the period when she is most vulnerable to postpartum depression.

After the baby is born, women and their doctors should watch for postpartum depression, especially if a mother stopped taking her medication during pregnancy. In addition, women who nurse while taking psychiatric medications should know that a small amount of the medication passes into the breast milk. However, the medication may or may not affect the baby depending s on the medication and when it is taken. Women taking psychiatric medications and who intend to breastfeed should discuss the potential risks and benefits with their doctors.

Contact FDA MedWatch

About the FDA

The FDA is responsible for protecting the public health by ensuring the safety, efficacy, and security of drugs (medications), biological products, medical devices, our nation’s food supply, cosmetics, and products that emit radiation.

FDA is also responsible for advancing public health by helping to speed innovations that make medicines more effective, safer, and more affordable and by helping the public get accurate science-based information they need to use medicines and foods to maintain and improve their health.

Reporting Serious Problems to the FDA

Visit FDA’s MedWatch to voluntarily report a serious adverse effect, product quality problem, product use error or product failure that you suspect is associated with the use of an FDA-regulated drug, biologic, medical device, dietary supplement or cosmetic. You can also report suspected counterfeit medical products to the FDA through MedWatch. You can also use the contact information provided below: 1-800-332-1088; 1-800-FDA-0178 Fax; Report a Serious Problem: MedWatch Online Regular Mail: Use postage-paid FDA Form 3500 Mail to: MedWatch, 5600 Fishers Lane, Rockville, MD 20857

Required for class assignment: Podcast to listen to for assignment (click on Listen Now): To The Best Of Your Knowledge, A Pill That Saves Your Life But Destroys Your Body
Optional: Additional reading for those of you who want to learn more:  Reducing Disorder Biologically: Drug and Brain Therapy

 

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Drugs, Health & Behavior Copyright © 2018 by Jacqueline Schwab and Denise Salters is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License, except where otherwise noted.

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