Bipolar Disorder
`
`
` in Adults
`
` National Institute of Mental Health
`
`
`
`
`
`
` U.S. Department of HealtH anD HUman ServiceS • national institutes of Health
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Page 1 of 32
`
`JAZZ EXHIBIT 2014
`Ranbaxy Inc. (Petitioner) v. Jazz Pharms. Ireland Ltd. (Patent Owner)
`Case IPR2016-00024
`
`

`
`Page 2 of 32
`
`Page 2 of 32
`
`

`
`Contents
`
`What is bipolar disorder? _____________________________________________ 1
`
`What are the signs and symptoms of bipolar disorder? __________________ 1
`
`How is bipolar disorder diagnosed? ____________________________________ 4
`
`What illnesses often co-exist with bipolar disorder? _____________________ 6
`
`What are the risk factors for bipolar disorder? __________________________ 6
`
`
`
`
`
`Genetics _________________________________________________________ 6
`
`Brain structure and functioning ___________________________________ 7
`
`How is bipolar disorder treated? _______________________________________ 8
`
` Medications ______________________________________________________ 9
`
`
`
`
`
`Psychotherapy __________________________________________________ 14
`
`Other treatments ________________________________________________ 16
`
`What research is NIMH doing to improve treatments
`for bipolar disorder? _________________________________________________ 17
`
`How can I help a friend or relative who has bipolar disorder? ____________ 18
`
`How can caregivers find support? ____________________________________ 19
`
`How can I help myself if I have bipolar disorder? _______________________ 19
`
`Where can I go for help? _____________________________________________ 20
`
`What if I or someone I know is in crisis? _______________________________ 20
`
`Citations ___________________________________________________________ 21
`
`For more information on bipolar disorder ______________________________ 25
`
`Page 3 of 32
`
`

`
`This booklet discusses bipolar disorder in
`adults. For information on bipolar disorder
`in children and adolescents, see the NIMH
`booklet, Bipolar Disorder in Children and
`Adolescents.
`
`Page 4 of 32
`
`

`
`What is bipolar disorder?
`
`
`
`
`
` Bipolar disorder, also known as manic-depressive
`
`
` illness, is a brain disorder that causes unusual
`
`
`
`
`
` shifts in mood, energy, activity levels, and the abil-
`
`
`
`
`
`
`
`
`
` ity to carry out daily tasks. Symptoms of bipolar
`
`
`
`
`
`
`
` disorder can be severe. They are different from
`
`
`
`
`
`
`
` the normal ups and downs that everyone goes
`
`
`
`
`
`
`
` through from time to time. Bipolar disorder symp-
`
`
`
`
`
`
`
` toms can result in damaged relationships, poor
`
`
`
`
`
`
`
`
` job or school performance, and even suicide. But bipolar disorder can be treated,
`
`
`
`
`
`
`
` and people with this illness can lead full and productive lives.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Bipolar disorder often appears in the late teens or early adult years. At least half of
`
` all cases start before age 25.1 Some people have their first symptoms during child-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`hood, while others may develop symptoms late in life.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Bipolar disorder is not easy to spot when it starts. Some people suffer for years
`
`
`
`
`
`
`
`
`
`
`
`before they are properly diagnosed and treated. Like diabetes or heart disease,
`
`
`
`
`
`
`
`
`
`
`
`bipolar disorder is a long-term illness that must be carefully managed throughout
`
`your life.
`
`What are the signs and symptoms of bipolar
`disorder?
`
`
`
`
`
`
`
`
`
`People with bipolar disorder experience unusually intense emotional states that
`
`
`
`occur in distinct periods called “mood episodes.” Each mood episode represents
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`a drastic change from a person’s usual mood and behavior. An overly joyful
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`or overexcited state is called a manic episode, and an extremely sad or hopeless
`
`
`
`
`
`
`
`
`
`
`
`state is called a depressive episode. Sometimes, a mood episode includes symp-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`toms of both mania and depression. This is called a mixed state. People with bipo-
`
`
`
`
`
`
`
`
`
`
`
`
`lar disorder also may be explosive and irritable during a mood episode. Extreme
`
`
`
`
`
`
`
`
`
`
`
`
`changes in energy, activity, sleep, and behavior go along with these changes in
`mood.
`
`
`
`Bipolar Disorder in Adults • 1
`
`Page 5 of 32
`
`

`
`Symptoms of bipolar disorder are described below.
`
`
`
`
`
`
`
`
`
`
`
` Symptoms of depression or a
`
` depressive episode include:
`
`
` Mood Changes
`
`• An overly long period of feeling
`
`
`
`
`
`
`sad or hopeless
`
`
`• Loss of interest in activities once
`
`
`
`
`
`
`enjoyed, including sex.
`
`
`
`Behavioral Changes
`
`• Feeling overly tired or “slowed
`
`
`
`
`
`down”
`• Having problems concentrat-
`
`
`
`ing, remembering, and making
`
`
`
`decisions
`• Being restless or irritable
`
`
`
`
`• Changing eating, sleeping, or
`
`
`
`
`other habits
`
`• Thinking of death or suicide, or
`
`
`
`
`
`
`attempting suicide.
`
`
`
`
` Symptoms of mania or a manic
`
` episode include:
`
`
`
`
`
`
`
` Mood Changes
`• An overly long period of feeling
`
`
`
`
`
`
`“high,” or an overly happy or out-
`
`
`
`
`
`
`going mood
`
`• Extreme irritability.
`
`
`Behavioral Changes
`• Talking very fast, jumping from
`
`
`
`
`
`one idea to another, having racing
`
`
`
`
`
`thoughts
`• Being unusually distracted
`
`
`
`•
`Increasing activities, such as
`
`
`
`
`taking on multiple new projects
`
`
`
`
`• Being overly restless
`
`
`
`• Sleeping little or not being tired
`
`
`
`
`
`
`• Having an unrealistic belief in your
`
`
`
`
`
`
`abilities
`• Behaving impulsively and engag-
`
`
`
`
`ing in pleasurable, high-risk
`
`
`
`behaviors.
`
`
`
`
`
`
`
`
`
`2 • National Institute of Mental Health
`
`
`
`
`
`Page 6 of 32
`
`

`
` Bipolar disorder can be present even when mood swings
`
`
`
`
`
`
`
`
`
`
`
` are less extreme. For example, some people with bipolar
`
`
`
`
`
` disorder experience hypomania, a less severe form of
`
`
`
`
`
`
`
` mania. During a hypomanic episode, you may feel very
`
`
`
`
`
`
`
`
` good, be highly productive, and function well. You may
`
`
`
`
`
`
`
`
` not feel that anything is wrong, but family and friends
`
`
`
`
`
`
`
`
`
` may recognize the mood swings as possible bipolar dis-
`
`
`
`
`
`
`
`
` order. Without proper treatment, people with hypomania
`
`
`
`
`
`
` may develop severe mania or depression.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Bipolar disorder may also be present in a mixed state, in which you might experi-
`
`
` ence both mania and depression at the same time. During a mixed state, you might
`
`
`
`
`
`
`
`
`
`
`
` feel very agitated, have trouble sleeping, experience major changes in appetite,
`
`
`
`
`
`
`
`
`
`
`
` and have suicidal thoughts. People in a mixed state may feel very sad or hopeless
`
`
`
`
`
`
`
`
`
`
`
`
`
` while at the same time feel extremely energized.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Sometimes, a person with severe episodes of mania or depression has psychotic
` symptoms too, such as hallucinations or delusions. The psychotic symptoms tend
`
`
`
`
`
`
`
`
`
`
` to reflect the person’s extreme mood. For example, if you are having psychotic
`
`
`
`
`
`
`
`
`
`
`
` symptoms during a manic episode, you may believe you are a famous person,
`
`
`
`
`
`
`
`
`
`
`
`
` have a lot of money, or have special powers. If you are having psychotic symptoms
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` during a depressive episode, you may believe you are ruined and penniless, or you
`
`
`
`
`
`
`
`
`
`
`
`
`
` have committed a crime. As a result, people with bipolar disorder who have psy-
`
`
`
`
`
`
`
`
`
`
`
`
`
` chotic symptoms are sometimes misdiagnosed with schizophrenia.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` People with bipolar disorder may also abuse alcohol or substances, have relation-
`
` ship problems, or perform poorly in school or at work. It may be difficult to recog-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` nize these problems as signs of a major mental illness.
`
`
`
`
`
`
`
`
`
`
`
`Bipolar Disorder in Adults • 3
`
`Page 7 of 32
`
`

`
`How is bipolar disorder diagnosed?
`
`
`
`
`
`
`
`
`
`
`
` Bipolar disorder usually lasts a lifetime. Episodes of mania and depression typically
`
`
` come back over time. Between episodes, many people with bipolar disorder are
`
`
`
`
`
`
`
`
`
` free of symptoms, but some people may have lingering symptoms.
`
`
`
`
`
`
`
`
`
`
`
`
` Doctors diagnose bipolar disorder using guidelines from the Diagnostic and
`
`
`
`
`
`
`
` Statistical Manual of Mental Disorders (DSM). To be diagnosed with bipolar
`
`
`
`
`
`
`
`
`
`
`
` disorder, the symptoms must be a major change from your normal mood or
`
`
`
`
`
`
`
`
`
`
`behavior. There are four basic types of bipolar disorder:
`
`
`
`
`
`
`
`
`
`
`
` 1. Bipolar I Disorder—defined by manic or mixed episodes that last at least seven
`
`
`
`
`
`
`
`
`
`
`
`
`
` days, or by manic symptoms that are so severe that the person needs immedi-
`
`
`
`
`
`
`
`
`
`
`
`
` ate hospital care. Usually, depressive episodes occur as well, typically lasting at
`
`
`
`
`
`
`
`
`
`
`
` least 2 weeks.
`
`
` 2. Bipolar II Disorder—defined by a pattern of depressive episodes and hypo-
`
`
`
`
`
`
`
`
`
`
`
` manic episodes, but no full-blown manic or mixed episodes.
`
`
`
`
`
`
`
`
` 3. Bipolar Disorder Not Otherwise Specified (BP-NOS)—diagnosed when symp-
`
`
`
`
`
`
`
`
`
` toms of the illness exist but do not meet diagnostic criteria for either bipolar I
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` or II. However, the symptoms are clearly out of the person’s normal range of
`
`
`
`
`
`
`
`
`
`
`
`
`behavior.
`
` 4. Cyclothymic Disorder, or Cyclothymia—a mild form of bipolar disorder.
`
`
`
`
`
`
`
`
` People with cyclothymia have episodes of hypomania as well as mild depres-
`
`
`
`
`
`
`
`
`
`
`
`
` sion for at least 2 years. However, the symptoms do not meet the diagnostic
`
`
`
`
`
`
`
`
`
`
`
`
` requirements for any other type of bipolar disorder.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`4 • National Institute of Mental Health
`
`
`
`
`
`Page 8 of 32
`
`

`
`A severe form of the disorder is called Rapid-cycling
`
`
`
`
`
`
`
`
` Bipolar Disorder. Rapid cycling occurs when a person has
`
`
`
`
`
`
`
`
` four or more episodes of major depression, mania, hypo-
`
`
`
`
`
`
`
`
` mania, or mixed states, all within a year.2 Rapid cycling
`
`
`
`
`
`
`
`
`
`
` seems to be more common in people who have their first
`
`
`
`
`
`
`
`
`
`
` bipolar episode at a younger age. One study found that
`
`
`
`
`
`
`
`
`
` people with rapid cycling had their first episode about
`
`
`
`
`
`
`
`
` 4 years earlier—during the mid to late teen years—than
`
`
`
`
`
`
`
` people without rapid cycling bipolar disorder.3 Rapid
`
`
`
`
`
`
`
` cycling affects more women than men.4 Rapid cycling can come and go.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` When getting a diagnosis, a doctor or health care provider should conduct a physi-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` cal examination, an interview, and lab tests. Currently, bipolar disorder cannot be
`
`
`
`
`
`
`
`
`
`
` identified through a blood test or a brain scan, but these tests can help rule out
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` other factors that may contribute to mood problems, such as a stroke, brain tumor,
`
`
`
`
`
`
`
`
`
`
`
`
`
` or thyroid condition. If the problems are not caused by other illnesses, your health
`
`
`
`
`
`
`
`
`
`
`
`
`
` care provider may conduct a mental health evaluation or provide a referral to a
`
`
`
`
`
`
`
`
`
`
`
`
`
` trained mental health professional, such as a psychiatrist, who is experienced in
`
`
`
`
`
`
`
`
`
`
`
` diagnosing and treating bipolar disorder.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` The doctor or mental health professional should discuss with you any family his-
`
`
`
`
` tory of bipolar disorder or other mental illnesses and get a complete history of
`
`
`
`
`
`
`
`
`
` symptoms. The doctor or mental health professional should also talk to your close
`
`
`
`
`
`
`
`
`
`
`
`
`
` relatives or spouse about your symptoms and family medical history.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` People with bipolar disorder are more likely to seek help when they are depressed
` than when experiencing mania or hypomania.5 Therefore, a careful medical his-
`
`
`
`
`
`
`
`
`
`
`tory is needed to assure that bipolar disorder is not mistakenly diagnosed as major
`
`
`
`
`
`
`
`
`
`
`
`
`
`depression. Unlike people with bipolar disorder, people who have depression only
`
`
`
`
`
`
`
`
`
`
`(also called unipolar depression) do not experience mania.
`
`
`
`
`
`
`
`
`Bipolar disorder can worsen if left undiagnosed and untreated. Episodes may
`
`
`
`
`
`
`
`
`
`become more frequent or more severe over time without treatment.6 Also, delays in
`
`
`
`
`
`
`
`
`
`
`
`
`getting the correct diagnosis and treatment can contribute to personal, social, and
`
`
`
`
`
`
`
`
`
`
`
`work-related problems.7 Proper diagnosis and treatment help people with bipo-
`
`
`
`
`
`
`
`
`
`lar disorder lead healthy and productive lives. In most cases, treatment can help
`
`
`
`
`
`
`
`
`
`
`
`
`reduce the frequency and severity of episodes.
`
`
`
`
`
`
`
`
`
`Bipolar Disorder in Adults • 5
`
`Page 9 of 32
`
`

`
`What illnesses often co-exist
`with bipolar disorder?
`
`
`
`
`
`
` Substance abuse is very common among people
`
` with bipolar disorder, but the reasons for this link are
`
`
`
`
`
`
`
`
` unclear.8 Some people with bipolar disorder may try to
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`treat their symptoms with alcohol or drugs. Substance
`
`
`
`
`
`
`
`abuse can also trigger or prolong bipolar symptoms,
`
`
`
`
`
`
`
`and the behavioral problems associated with mania can
`
`
`
`
`lead to drinking too much.
`
`
`
`
`
`
`
`
`
`
`Anxiety disorders, such as post-traumatic stress disorder (PTSD) and social
`
`
`
`
`
`
` phobia, also can co-occur with bipolar disorder.9, 10, 11 Bipolar disorder can co-
`
`
`
`
`
`
` occur with attention deficit hyperactivity disorder (ADHD) as well, which has some
`
`
`
`
`
`
`
`
`
`
`
` symptoms that overlap with bipolar disorder, such as restlessness and being easily
`
`
`
`
`
`
`
`
`
`
`
`
` distracted. However, the symptoms of ADHD are persistent, whereas those of
`
`
`
`
`
`
`
`
`
` bipolar disorder are episodic.
`
`
`
`
` In addition, people with bipolar disorder are at higher risk for thyroid disease,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` migraine headaches, heart disease, diabetes, obesity, and other physical ill-
` nesses.12, 13 These illnesses may cause symptoms of mania or depression, or they
`
`
`
`
`
`
`
`
`
`
`
` may be caused by some medications used to treat bipolar disorder.
`
`
`
`
`
`
`
`
`
`
`
`
`
`What are the risk factors for bipolar disorder?
`
`
`
`
`
`
`
`
`
`
`
`Scientists are studying the possible causes of bipolar disorder. Most agree that
`
`
`
`
`
`
`
`
`
`
`
`
`
`there is no single cause. Rather, many factors likely act together to produce the
`
`
`
`
`
`
`illness or increase risk for developing it.
`
`Genetics
`
`
`
`
`
`
`
`
`
`
`
`Bipolar disorder tends to run in families. Some research has suggested that
`
`
`
`
`
`
`
`
`
`
`
`
`
`people with certain genes are more likely to develop bipolar disorder than others.14
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Children with a parent or sibling who has bipolar disorder are much more likely to
`
`
`
`
`
`
`
`
`
`
`
`
`
`develop the illness, compared with children who do not have a family history of
`
`
`
`
`
`
`
`
`
`
`
`bipolar disorder.15 However, most children with a family history of bipolar disorder
`
`
`
`
`will not develop the illness.
`
`
`
`
`
`
`
`6 • National Institute of Mental Health
`
`
`
`
`
`Page 10 of 32
`
`

`
`
`
`
`
`
`
`
`
`
` Technological advances are improving genetic research on bipolar disorder. One
`
`
`
`
`
` example is the launch of the Bipolar Disorder Phenome Database, funded in part
`
`
`
`
`
`
`
` by NIMH. Using the database, scientists will be able to link visible signs of the
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` disorder with the genes that may influence them.16
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Scientists are also studying illnesses with similar symp-
`
` toms such as depression and schizophrenia to identify
`
`
`
`
`
`
` genetic differences that may increase a person’s risk for
`
`
`
`
`
`
`
`
` developing bipolar disorder.17, 18, 19 Finding these genetic
`
`
`
`
`
`
`
`
` “hotspots” may also help explain how environmental fac-
`
`
`
`
`
`
` tors can increase a person’s risk.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` But genes are not the only risk factor for bipolar disorder.
`
`
` Studies of identical twins have shown that the twin of a
`
`
`
`
`
`
`
`
` person with bipolar illness does not always develop the disorder, despite the fact
`
`
`
`
`
`
`
`
`
`
`
`
`that identical twins share all of the same genes. Research suggests that factors
`
`
`
`
`
`
`
`
`
`
`
`
`besides genes are also at work. It is likely that many different genes and environ-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`mental factors are involved. However, scientists do not yet fully understand how
`
`
`
`
`
`
`
`
`
`
`
`these factors interact to cause bipolar disorder.
`
`
`
`
`
`
`
`
`
`
` Brain structure and functioning
`
`
`
`
` Brain-imaging tools, such as functional magnetic resonance imaging (fMRI) and
`
`
`
`
`
` positron emission tomography (PET), allow researchers to take pictures of the
`
`
`
`
`
`
`
`
`
`
` living brain at work. These tools help scientists study the brain’s structure and
`
`
`
`
`
`
`
`
`
`
`
`
`activity.
`
`
`
`
`
`
`
`
`
`
`
`
`
` Some imaging studies show how the brains of people with bipolar disorder may
`
`
` differ from the brains of healthy people or people with other mental disorders.
`
`
`
`
`
`
`
`
`
`
`
` For example, one study using MRI found that the pattern of brain development in
`
`
`
`
`
`
`
`
`
`
`
`
` children with bipolar disorder was similar to that in children with “multi-dimensional
`
`
`
`
`
`
`
`
`
`
`
` impairment,” a disorder that causes symptoms that overlap somewhat with bipolar
`
`
`
`
`
`
`
`
`
`
`
` disorder and schizophrenia.20 This suggests that the pattern of brain development
`
`
`
`
`
`
`
`
`
`in the two conditions may be associated with the risk for unstable moods.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Another MRI study found that the brain’s prefrontal cortex in adults with bipo-
`
`
`
`
`
`
`
`
`
`
`
`
`lar disorder tends to be smaller and function less well compared to adults who
`
`
`
`
`
`
`
`
`
`
`
`
`
` don’t have bipolar disorder.21, 22 The prefrontal cortex is a brain structure involved
`
`
`
`
`
`
`
`
`
`
`
`
` in “executive” functions such as solving problems and making decisions. This
`
`
`
`
`
`
`
`
`
`
`
`
`
`Bipolar Disorder in Adults • 7
`
`Page 11 of 32
`
`

`
`
`
`
`
`
`
`
`
`
` structure and its connections to other parts of the brain
` mature during adolescence, suggesting that abnormal
`
`
`
`
`
` development of this brain circuit may account for why the
`
`
`
`
`
`
`
`
`
` disorder tends to emerge during a person’s teen years.23
`
`
`
`
`
`
`
`
`
` Pinpointing brain changes in youth may help us detect ill-
`
`
`
`
`
`
`
`
`
` ness early or offer targets for early intervention.
`
`
`
`
`
`
`
`
` The connections between brain regions are important
`
`
`
`
`
`
` for shaping and coordinating functions such as forming
`
`
`
`
`
`
`
` memories, learning, and emotions, but scientists know little
`
`
`
`
`
`
`
`
`
`
`
` about how different parts of the human brain connect. Learning more about these
`
`
`
`
`
`
`
`
` connections, along with information gained from genetic studies, helps scientists
`
`
`
`
`
`
`
`
`
` better understand bipolar disorder. Scientists are working towards being able to
`
`
`
`
`
`
`
`
`
`
` predict which types of treatment will work most effectively.
`
`
`
`
`
`
`
`
`
`How is bipolar disorder treated?
`
`
`
`
`
`
`
`
`
`
`
`
`
` Bipolar disorder cannot be cured, but it can be treated effectively over the long-
`
`
`
` term. Proper treatment helps many people with bipolar disorder—even those with
`
`
`
`
`
`
`
` the most severe forms of the illness—gain better control of their mood swings and
`
`
`
`
`
`
`
`
`
`
`
`
`
` related symptoms.24, 25, 26 But because it is a lifelong illness, long-term, continuous
`
`
`
`
`
`
`
`
`
`
`
`
` treatment is needed to control symptoms.27
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` However, even with proper treatment, mood changes can occur. In the NIMH-
`
`
`
` funded Systematic Treatment Enhancement Program for Bipolar Disorder
`
`
`
`
` (STEP-BD) study—the largest treatment study ever conducted for bipolar
`
`
`
`
`
`
`
`
`
` disorder—almost half of those who recovered still had lingering symptoms. Having
`
`
`
`
`
`
`
`
`
` another mental disorder in addition to bipolar disorder increased one’s chances for
`
`
`
`
`
`
`
`
`
`
`
` a relapse.28 For more information about STEP-BD, see http://www.nimh.nih.gov/
`
`
`
`
`
`
`
`
`trials/practical/step-bd/index.shtml.
`
`Treatment is more effective if you work closely with a doctor and talk openly about
`
`
`
`
`
`
`
`
`
`
`
`
`
`your concerns and choices. An effective maintenance treatment plan usually
`
`
`
`
`
`
`
`
`
`includes a combination of medication and psychotherapy.
`
`
`
`
`
`
`
`
`
`
`
`
`
`8 • National Institute of Mental Health
`
`
`
`
`
`Page 12 of 32
`
`

`
`Medications
`
`
`
`
`
`
`
`
` Different types of medications can help control symptoms of
`
` bipolar disorder. Not everyone responds to medications in
`
`
`
`
`
`
` the same way. You may need to try several different medica-
`
`
`
`
`
`
`
`
`
`
` tions before finding ones that work best for you.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Keeping a daily life chart that makes note of your daily
`
`
` mood symptoms, treatments, sleep patterns, and life events
`
`
`
`
`
` can help you and your doctor track and treat your illness
`
`
`
`
`
`
`
`
`
`
`
` most effectively. If your symptoms change or if side effects become intolerable,
`
`
`
`
`
`
`
`
`
` your doctor may switch or add medications.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` The types of medications generally used to treat bipolar disorder include mood
`
`
`
` stabilizers, atypical antipsychotics, and antidepressants. For the most up-to-date
`
`
`
`
`
`
`
` information on medication use and their side effects, contact the U.S. Food and
`
`
`
`
`
`
`
`
`
`
`
`
`
` Drug Administration (FDA).
`
`
`
`
` Mood stabilizers are usually the first choice to treat bipolar disorder. In general,
`
`
`
`
`
`
`
`
`
`
`
`
`
` people with bipolar disorder continue treatment with mood stabilizers for years.
`
`
`
`
`
`
`
`
`
`
`
`
` Lithium (also known as Eskalith or Lithobid) is an effective mood stabilizer. It was
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` the first mood stabilizer approved by the FDA in the 1970’s for treating both manic
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` and depressive episodes.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Anticonvulsants are also used as mood stabilizers. They were originally developed
`
`
`
` to treat seizures, but they also help control moods. Anticonvulsants used as mood
`
`
`
`
`
`
`
`
`
`
`
` stabilizers include:
`
`
`
`• Valproic acid or divalproex sodium (Depakote), approved by the FDA in 1995
`
`
`
`
`
`
`
`
`
`
`
`
` for treating mania. It is a popular alternative to lithium. However, young women
`
`
`
`
`
`
`
`
`
`
`
`
` taking valproic acid face special precautions. See the sidebar, “Should young
`
`
`
`
`
`
`
`
`
`
` women take valproic acid?”
`
`
`
`• Lamotrigine (Lamictal), FDA-approved for maintenance treatment of bipolar
`
`
`
`
`
`
`
`
` disorder. It is often effective in treating depressive symptoms.
`
`
`
`
`
`
`
`
`• Other anticonvulsant medications, including gabapentin (Neurontin), topiramate
`
`
`
`
`
`
`
` (Topamax), and oxcarbazepine (Trileptal).
`
`
`
`
`
`
`Bipolar Disorder in Adults • 9
`
`Page 13 of 32
`
`

`
`
`
`
`
`
`
`
`
`
`Valproic acid, lamotrigine, and other anticonvulsant medications have an FDA
`
`
`
`
`
`
`
`
`
`
`
`
`warning. The warning states that their use may increase the risk of suicidal
`
`
`
`
`
`
`
`
`
`thoughts and behaviors. People taking anticonvulsant medications for bipolar or
`
`
`
`
`
`
`
`
`
`
`
`other illnesses should be monitored closely for new or worsening symptoms of
`
`
`
`
`
`
`
`
`
`
`
`depression, suicidal thoughts or behavior, or any unusual changes in mood or
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`behavior. If you take any of these medications, do not make any changes to your
`
`
`
`
`
`dosage without talking to your doctor.
`
`
`
`
`
`
`
` What are the side effects of mood stabilizers?
` Lithium can cause side effects such as:
`
`
`
`
`
`
`
`
`
`• Restlessness
`• Dry mouth
`
`• Bloating or indigestion
`
`
`
`• Acne
`• Unusual discomfort to cold temperatures
`
`
`
`
`• Joint or muscle pain
`
`
`
`
`• Brittle nails or hair.
`
`
`
`
`
`
`
`
`
`When taking lithium, your doctor should check the levels of lithium in your blood
`
`
`
`
`
`
`
`
`
`
`
`
`
`regularly, and will monitor your kidney and thyroid function as well. Lithium treat-
`
`
`
`
`
`
`
`
`
`
`
`
`ment may cause low thyroid levels in some people.29 Low thyroid function, called
`
`
`
`
`
`
`
`
`
`
`
`
`hypothyroidism, has been associated with rapid cycling in some people with bipo-
`
`
`
`
`
`
`
`
`
`
`
`lar disorder, especially women.
`
`
`
`
`Because too much or too little thyroid hormone can lead to mood and energy
`
`
`
`
`
`
`
`
`
`
`
`
`
`changes, it is important that your doctor check your thyroid levels carefully. You
`
`
`
`
`
`
`
`
`
`
`
`
`may need to take thyroid medication, in addition to medications for bipolar disor-
`
`
`
`
`
`
`
`
`
`
`
`
`der, to keep thyroid levels balanced.
`
`
`
`
`
`
`Common side effects of other mood stabilizing medications include:
`
`
`
`
`
`
`
`
`
`• Drowsiness
`• Dizziness
`• Headache
`• Diarrhea
`• Constipation
`
`
`
`
`
`
`
`10 • National Institute of Mental Health
`
`
`
`
`
`
`
`Page 14 of 32
`
`

`
`• Heartburn
`• Mood swings
`
`• Stuffed or runny nose, or other cold-like symptoms.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`These medications may also be linked with rare but serious side effects. Talk with
`
`
`
`
`
`
`
`
`
`
`
`
`
`your doctor or a pharmacist to make sure you understand signs of serious side
`
`
`
`
`
`
`
`
`
`
`
`effects for the medications you’re taking. If extremely bothersome or unusual side
`
`
`
`
`
`
`
`
`effects occur, tell your doctor as soon as possible.
`
`
`
`
`
`
` Should young women take valproic acid?
`
`
`
`
`
`
`
` Valproic acid may increase levels of testosterone (a male hormone) in teenage girls. It could lead
`
`
`
`
`
`
`
`
`
`
` to a condition called polycystic ovary syndrome (PCOS) in women who begin taking the medica-
`
`
`
`
`
`
`
`
`
`
`
`
` tion before age 20.30, 31 PCOS can cause obesity, excess body hair, an irregular menstrual cycle,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` and other serious symptoms. Most of these symptoms will improve after stopping treatment with
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` valproic acid.32 Young girls and women taking valproic acid should be monitored carefully by a
`
`doctor.
`
` Atypical antipsychotics are sometimes used to treat symptoms of bipolar disor-
`
`
`
`
`
`
`
`
`
`
` der. Often, these medications are taken with other medications, such as antide-
`
`
`
`
`
`
`
`
`
`
`
` pressants. Atypical antipsychotics include:
`
`
`
`
`• Olanzapine (Zyprexa), which when given with an antidepressant medication,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`may help relieve symptoms of severe mania or psychosis.33 Olanzapine can be
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`taken as a pill or a shot. The shot is often used for urgent treatment of agitation
`
`
`
`
`
`
`
`
`
`
`
`
`associated with a manic or mixed episode. Olanzapine can be used as main-
`
`
`
`
`
`
`
`
`
`
`tenance treatment as well, even when psychotic symptoms are not currently
`present.
`• Aripiprazole (Abilify), which is used to treat manic or mixed episodes.
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`Aripiprazole is also used for maintenance treatment. Like olanzapine, aripipra-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`zole can be taken as a pill or a shot. The shot is often used for urgent treatment
`
`
`of severe symptoms.
`• Quetiapine (Seroquel), risperidone (Risperdal) and ziprasidone (Geodon) also are
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`prescribed to relieve the symptoms of manic episodes.
`
`
`
`Bipolar Disorder in Adults • 11
`
`Page 15 of 32
`
`

`
`
`
`
`
`
`
`
` What are the side effects of atypical antipsychotics?
`
` If you are taking antipsychotics, you should not drive until you have adjusted to
`
`
`
`
`
`
`
`
`
`
` your medication. Side effects of many antipsychotics include:
`
`
`
`
`
`
`
`
`
`
`
`
`• Drowsiness
`• Dizziness when changing positions
`
`
`
`• Blurred vision
`
`
`• Rapid heartbeat
`
`
`• Sensitivity to the sun
`
`
`
`
`• Skin rashes
`
`
`• Menstrual problems for women.
`
`
`
`
`
`
`
`Atypical antipsychotic medications can cause major weight gain and changes in
`
`
`
`
`
`
`
`
`
`
`your metabolism. This may increase your risk of getting diabetes and high cho-
`
`
`
`
`
`
`
`
`
`
`
`
`lesterol.34 Your doctor should monitor your weight, glucose levels, and lipid levels
`
`
`
`
`
`
`
`
`
`
`
`regularly while you are taking these medications.
`
`
`
`
`
`
`
`In rare cases, long-term use of atypical antipsychotic drugs may lead to a condi-
`
`
`
`
`
`
`
`
`
`
`
`
`
`tion called tardive dyskinesia (TD). The condition causes uncontrollable muscle
`
`
`
`
`
`
`
`
`
`movements, frequently around the mouth. TD can range from mild to severe. Some
`
`
`
`
`
`
`
`
`
`
`
`
`people with TD recover partially or fully after they stop taking the drug, but others
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`do not.
`
`
`Antidepressants are sometimes used to treat symptoms of depression in bipolar
`
`
`
`
`
`
`
`
`
`
`disorder. Fluoxetine (Prozac), paroxetine (Paxil), sertraline (Zoloft), and bupropion
`
`
`
`
`
`
`
`
`(Wellbutrin) are examples of antidepressants that may be prescribed to treat symp-
`
`
`
`
`
`
`
`
`
`
`
`toms of bipolar depression.
`
`
`
`
`However, taking only an antidepressant can increase your risk of switching to
`
`
`
`
`
`
`
`
`
`
`
`mania or hypomania, or of developing rapid-cycling symptoms.35 To prevent this
`
`
`
`
`
`
`
`
`
`
`switch, doctors usually require you to take a mood-stabilizing medication at the
`
`
`
`
`
`
`
`
`
`
`
`same time as an antidepressant.
`
`
`
`
`
`
`
`
`
`12 • National Institute of Mental Health
`
`
`
`
`
`
`
`Page 16 of 32
`
`

`
`Report any concerns about side
`effects to your doctor right away.
`You may need a change in the
`dose or a different medication.
`You should not stop taking a
`medication without talking to your
`doctor first. Suddenly stopping a
`medication may lead to “rebound”
`or worsening of bipolar disorder
`symptoms. Other uncomfortable or
`potentially dangerous withdrawal
`effects are also possible.
`
` What are the side effects of
`
`
`
`
`antidepressants?
`
`
` Antidepressants can cause:
`
`
`
`• Headache
`• Nausea (feeling sick to your stomach)
`
`
`
`
`
`• Agitation (feeling jittery)
`
`
`
`• Sexual problems, which can affect both
`
`
`
`
`
`
` men and women. These include reduced
`
`
`
`
`
` sex drive and problems having and
`
`
`
`
`
` enjoying sex.
`
`
`
`
`
`
`
`
`
` Some antidepressants are more likely to
`
`
`
` cause certain side effects than other types.
`
`
`
`
`
`
`
`
`
` Your doctor or pharmacist can answer questions about these medications. Any
`
`
`
`
`
`
`
`
` unusual reactions or side effects should be reported to a doctor immediately.
`
`
`
`
`
`
`
`
`
`
`
`
` FDA Warning on Antidepressants
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` Antidepressants are safe and popular, but some studies have suggested that they may have unin-
`
`
`
` tentional effects on some people, especially in adolescents and young adults. The FDA warning
`
`
`
`
`
`
`
`
`
`
`
` says that patients of all ages taking antidepressants should be watched closely, especially during
`
`
`
`
`
`
`
`
`
`
`
`
` the first few weeks of treatment. Possible side effects to look for are depression that gets worse,
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` suicidal thinking or behavior, or any unusual changes in behavior such as trouble sleeping, agita-
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` tion, or withdrawal from normal social situations. For the latest information, see the FDA website
`
`
`
`
`
`
`
`
`
`
`
`
`
`
` at http://www.fda.gov.
`
`
`
`
`Bipolar Disorder in Adults • 13
`
`Page 17 of 32
`
`

`
`
`
`
`
`
`
`
` Should women who are pregnant or may become
` pregnant take medication for bipolar disorder?
`
`
`
`
`
`
` Women with bipolar disorder who are pregnant or may become pregnant
`
`
`
`
`
`
`
`
`
` face special challenges. Mood stabilizing medications can harm a devel-
`
`
`
`
`
`
`
`
`
`
`
`
`
` oping fetus or nursing infant.36 But stopping medications, either suddenly
`
`
`
`
`
`
`
`
`
`
`
`
`
`
`or gradually, greatly increases the risk that bipolar symptoms will recur
`
`during pregnancy.37
`
`
`
`
`
`
`
`
`
`Lithium is generally the preferred mood-stabilizing me