June 1998
Bipolar disorder, or manic-depression, is characterized by moods that swing between
two opposite poles, alternating between periods of mania (exaggerated euphoria) and
depression. The illness is further classified according to symptoms as bipolar I,
bipolar II, and cyclothymic disorder. People with bipolar I disorder may experience depressive
and manic episodes or just manic episodes (although this is very rare). Patients
with bipolar II disorder suffer primarily from depressive episodes with occasional
bouts of hypomania (low-grade manic symptoms), but they do not experience full-blown
manic phases. In cyclothymic disorder, periods of hypomania alternate with depression.
It is not as severe as bipolar II, and I but the condition is more persistent, enduring at least two years, with no break in symptoms that last more than two months.
Cyclothymic disorder may be a precursor to full-blown bipolar disorder in some people
or may continue as a low-grade chronic condition. In most cases of bipolar disorder, the depressive phases far outnumber manic phases, and the cycles of mania and depression
are not regular or predictable. In a subtype of the illness known as rapid cycling,
the manic and depressive stages alternate at least four times a year and in severe cases can progress to several cycles a day. Bipolar disorder has confounded the
medical profession for centuries, but only in the last forty years have doctors begun
to understand the disorder and to develop successful treatments. The other major
mood disorder, unipolar depressive disorder, occurs without episodes of mania and is not
discussed in this report [see
Well-Connected
Report #8, Depression
].
The usual pattern of bipolar disorder is one of increasing intensity and duration
of symptoms that progress slowly over many years. Patients with the disease, however,
may experience symptoms in very different ways.
Symptoms of Depression.
The symptoms of depression experienced in bipolar disorder are almost identical to
those of major clinical depression, which include (1) sad mood, (2) fatigue or loss
of energy, (3) insomnia, excessive sleeping, or shallow, inefficient sleep patterns
with frequent awakenings, (4) weight gain or loss, (5) diminished ability to concentrate
or make decisions, (6) physical agitation or markedly sedentary behavior, (7) feelings
of guilt, pessimism, helplessness and low self-esteem, (8) loss of interest or pleasure in life and (9) thoughts of or attempts at suicide. Depressive episodes associated
with bipolar disorder are less likely to have a specific trigger, are not as long,
and develop more gradually than those caused by major depression. One interesting
study reported that bipolar patients often experienced dreams of death at the low point
of their depression, and these dreams were soon followed by an upward mood change.
Symptoms of Mania.
A manic episode usually comes on suddenly, and it often, but not always, follows a
period of severe depression. An episode lasts for at least a week and can continue
for months. Friends and family members of a person with bipolar disorder who is
entering a manic phase for the first time may be relieved at first by the patient's increased
energy level, gaiety, and sociability. It soon becomes apparent, however, that the
person's mood is too "hyper" and that the behavior is strange. Symptoms of a manic
episode include rapid speech, disconnected thoughts, grandiose ideas, hallucinations
(hearing voices or seeing visions), and extreme irritability. Irritability is most
often the first noticeable change in behavior at the onset of a manic phase. The
patient often requires little sleep; some experts suggest that sleep loss may actually trigger
or intensify mania. Close to 60% of all manic patients experience feelings of omnipotence,
sometimes believing that they are godlike or have celebrity status. Some patients experience intense sexual energy or a marked increase in strength. Hypomania
is a less severe variant of mania; it is of shorter duration, although it lasts at
least four days. Patients with hypomania do not have severely impaired functioning
and generally do not require hospitalization.
Gender.
Between one and two million Americans are thought to suffer from bipolar disorder.
Estimates of the lifetime risk for the disorder run between 1% and 1.5%. There
is some indication that the incidence of bipolar disorder may be increasing, but
more research is needed to confirm this. Bipolar disorder affects both sexes equally, but women
are about three times more likely to experience rapid cycling. (Women have a higher
incidence of depressive cycles than men do, and some experts suggest that antidepressant medications may trigger the rapid cycling.) In any case, rapid cycling occurs
in between 10% and 15% of all bipolar patients.
Age.
In one survey, 59% of bipolar patients had their first symptoms when they were children
or adolescents, and, typically, there was a very long delay until the condition was
diagnosed and treated. One center reported that bipolar disorder in children may
be more common than previously believed. It may be underdiagnosed in this age group
because it can be often confused with attention-deficit hyperactivity disorder.
In addition, symptoms of bipolar disorder may be different in children than in adults
When the onset of the condition occurs at these younger ages, the initial episodes may be
primarily depressive. Irritability is common. Young patients tend to experience
frequent episodes and increasing social problems, even if their family situations
are positive. Manic phases usually begin in adolescence or young adulthood, with average
age of onset being 18. Bipolar disorder, however, can also appear for the first
time in people over forty years of age; in fact, age 40 is another peak onset period
for women. Bipolar disorder that develops in elderly people is less likely to be associated
with a family history of the disorder and more likely to accompany medical and neurologic
problems than earlier-onset bipolar disorder.
Family History.
Bipolar disorder often occurs within families. Studies of identical twins raised
apart found that about two-thirds of the pairs shared the disorder when one twin
had it. Among fraternal twins, the risk for the second twin is only 20%. Often,
families of patients with bipolar disorder include members with other psychiatric problems, including
schizoaffective disorder and major depression, which many experts believe are variants
along a single disease spectrum. Studies indicate that a combination of bipolar and panic disorder may be a specific inherited type. It has long been observed
that children of bipolar disorder parents often have a more severe form of the disorder
than do their parents. A recent study indicated that a daughter with bipolar disorder is at particularly high risk for developing a more severe form if her mother has
the disorder. The study also suggested that having parents or other family members
with major depression (particularly if it developed at an early age) is associated
with a higher risk for bipolar disorder.
Attention Deficit Hyperactivity Disorder.
In one study, 65% of adolescents with bipolar disorder met criteria for attention
deficit hyperactivity disorder (ADHD); another study determined that close to 25%
of children diagnosed with ADHD either already have bipolar disorder or go on to
develop it. The risk for both diagnoses was highest in white males. Symptoms were also more
severe in people with both conditions.
Miscellaneous Risk Factors.
The time of the year appears to play a role in increasing the risk for episodes.
In one study, men appeared to have more episodes during the spring and women were
at higher risk during the spring and fall. In both genders, aggressive behavior
peaked in the spring. The rate of the disorder is estimated to be 10 to 20 times higher among
people in the creative arts than in the general population. People who are alcoholic
may also be at higher risk for bipolar disorder.
Personality Traits.
One interesting study defined personality traits associated with bipolar disorder.
Patients tended to lack persistence, avoid harmful situations, and be dependent
on rewards.
Some experts believe that bipolar disorder is only one link on a chain of psychiatric
disorders ranging from schizophrenia to major depression, differing in expression
and severity but sharing a common biologic cause. However, new studies suggest that
these conditions, including bipolar disorder, are distinct and caused by different mechanisms.
For instance, magnetic resonance imaging (MRI) scans of brains of bipolar patients
have revealed structural abnormalities in the hippocampus. This brain territory also shows abnormalities in the brains of people with schizophrenia. In one study
of people with people with bipolar disorder, the left side of the hippocampus was
significantly larger than the right, while in patients with schizophrenia the hippocampus
volume was decreased. In both schizophrenia and bipolar disorder the pathways of
the neurotransmitter dopamine appear to be important. (A neurotransmitter acts as
a chemical messenger between nerve cells.) Dopamine has been a target of scientific
investigation since researchers first observed that certain drugs that reduce the action
of dopamine in the brain also reduce psychotic symptoms.
Although not all cases are familial, genetic factors appear to play a major role in
bipolar disorder. Researchers believe that more than one genetic defect is necessary
to trigger bipolar disorder. Investigators suspect that important genetic abnormalities rest on chromosome 18 and 21. Recently, the first genetic defect specifically
associated with bipolar disorder was identified. The abnormality occurs in a gene
known as human serotonin (5-HT) transporter gene (hSERT). Serotonin is an important
neurotransmitter that plays a prominent role in depression and sleep. Environmental factors
also play a role, since not all cases of bipolar disorder are associated with a family
history of the disease. No single cause may ever been found for this complex disease. When inherited, the disease may increase in severity in subsequent generations,
so affected people may wish to seek genetic counseling. However, there are no genetic
tests available for bipolar disorder, and such counseling should be used for guidance, education, and reassurance about available treatments.
Bipolar disorder can be severe and long-term, or it can be mild with infrequent episodes.
A bipolar patient averages 8 to 10 manic or depressive episodes over a lifetime,
but some people experience much more severe symptoms or rapid cycle (that is, a person may suffer many cycles a day). An estimated 15% to 20% of patients who suffer
from bipolar disorder and who do not receive medical attention commit suicide; in
spite of this, only one-third of bipolar sufferers receive treatment. Even with
therapy, one or more relapses occur in most patients. In addition, treatment does not always
prevent continuing problems in social and psychological functioning, particularly
in patients with dysfunctional families or social groups. One center reported that
recovery was more likely and improvement faster in patients having an illness of shorter
duration, in those coming from a higher social class, and in those complying with
treatment.
Although a small percentage of bipolar patients demonstrate heightened productivity
or creativity during manic phases, more often the distorted thinking and impaired
judgment that are characteristic of manic episodes can lead to dangerous behavior.
In a manic stage, for example, a person may spend money with abandon, financially ruining
himself and his family. Angry, paranoid, and even violent behavior is not uncommon
during a manic episode. Some people may exhibit openly promiscuous activity. Bipolar
patients need an enormous amount of support to help avoid the risky behavior common
in manic episodes and to fight against the low self-esteem and guilt experienced
during the depressed phases. During all stages of the illness, patients need to
be reminded that the mood disturbance will pass and that its severity can be diminished by treatment.
The negative effects on family, partners, and close friends should not be underestimated.
Often family members feel stigmatized by the presence of a relative with mental
illness and conceal it from acquaintances, particularly if the patient is female
and lives away from home. People with more education are more likely to report being
ostracized by their acquaintances than are those with less education. Even family
members who seek support and education for themselves and for the patient often cannot
tolerate the devastating mood swings, particularly if the patient is verbally or physically
aggressive during a manic episode or goes on spending sprees, putting the family
into debt. As much as loved ones want to sympathize with the patient, it is very
difficult if they are under attack or their lives are in chaos. Very few people, even
those closest to the patient, have the objectivity needed to avoid taking a manic
attack personally. They often see the manic periods as deliberate, since patients
are often highly articulate when they justify their behavior. Many patients are reluctant
to admit that these episodes are part of an illness and not simply extreme, but normal,
characteristics.
The economic burden of bipolar disorder is significant. The National Institute of
Mental Health has estimated that the disorder cost the country $45 billion in 1991,
including direct costs (patient care, suicides, and institutionalizations) and indirect
costs (lost productivity and the criminal justice system)
In spite of the obvious need for professional help, access to medical therapies is
not always available for patients with bipolar disorder. In one major survey, 13%
of patients had no insurance and 15% were unable to afford medical treatment.
If the initial symptoms of bipolar disorder are limited to depression, the condition
is often diagnosed as depression; indeed about 16% of people with bipolar disorder
do not have a manic episode until they have experienced three or more depressive
episodes. An accurate diagnosis is important, particularly in light of a study that reported
a higher incidence of rehospitalization in bipolar patients who were inappropriately
medicated with antidepressants. A family history of manic-depressive illness may
make a physician suspicious, but a diagnosis of bipolar disorder cannot be established
until a manic episode has occurred. The American Psychiatric Association has established
the following criteria for recognizing this phase of bipolar disorder:
A distinct period of abnormally and persistently elevated, expansive, or irritable mood.
During the mood disturbance, at least three of the following symptoms (four, if the primary mood disturbance is irritability):
*inflated self-esteem, grandiosity;
*decreased need for sleep;
* talkativeness;
*flight of ideas or racing thoughts;
*distractibility when confronted by unimportant or irrelevant stimuli;
*increased goal-directed activity (social, sexual, work or school);
*excessive involvement in high-risk activities - e.g., unrestrained shopping, promiscuity.
Mood disturbance severe enough to damage ones job or social functioning or relationships with others, or which requires hospitalization to prevent harm to others or self.
Hallucinations or delusions absent for two weeks or more during normal periods (this would rule-out schizophrenia).
When making a diagnosis of bipolar disorder, it is important that the physician
rule-out other conditions that may be causing symptoms of mania. Hypomania,
the less severe variant of mania, may be difficult to distinguish from normal
joy or euphoria, but it can be differentiated by its persistence for more than
a day; in addition, most hypomanic patients are easily distracted, overly talkative,
and not functioning very well. Severe manic episodes with delusions and hallucinations
may be easily confused with schizophrenia. (African American men, for instance,
are more likely to be diagnosed with schizophrenia than with bipolar disorder.)
Thyroid disorders may cause mood swings, as can adrenal disorders (e.g., Addison's
disease and Cushing's syndrome), vitamin B12 deficiency, certain neurologic
disorders (e.g., Huntington's disease, epilepsy, brain tumors, encephalitis,
multiple sclerosis), and various medications, including some drugs used to treat
anxiety, Parkinson's disease, and depression. Alcoholism and substance abuse
occur often in bipolar patients, sometimes attributed to self-medication. Both
diagnosis and treatment are difficult in such cases, particularly since withdrawal
from opiates or alcohol can cause symptoms of mania or severe depression. Children
or adolescents with manic-depressive illness may be inappropriately diagnosed
with attention deficit hyperactivity disorder; in some cases, ADHD may be a
marker for an emerging bipolar disorder.
Current research is seeking to discover factors in the blood that might help diagnose
bipolar disorder and determine the effectiveness of treatment. Such tests would
be particularly helpful in differentiating attention deficit hyperactivity disorder
from bipolar disorder in young people. One study that measured blood levels of the neurotransmitter
serotonin provides some promise; higher levels were found in children with behavior
disorders and lower levels were found in children with mood disorders. High levels of factors known as G proteins have been detected in both type I and type
II bipolar patients, but studies have been contradictory, and there is no evidence
yet that can be reliably used for diagnostic purposes.
The major goals of treatment are to reduce the frequency, severity, and social and
psychologic consequences of bipolar episodes and to help the patient function as
effectively as possible between episodes. Patients should understand that even with
aggressive therapy relapse of either mania or depression occurs in almost three-quarters
of patients. Even in those who do not relapse, depression is common. First, the
physician will try to determine conditions that might have precipitated the attack
and any accompanying medical or emotional problems that might interfere with or complicate
treatment. The need for hospitalization depends on a number of factors, including
whether the patient is at risk for suicide or harming others and the availability
of social and emotional support. Once a patient is experiencing a severe full-blown manic
attack, medication should be initiated or electroconvulsive therapy begun before
a complete assessment can be made. The preferred class of drugs used for bipolar
disorder are mood stabilizers, but many other types also may be required to manage specific conditions,
including depressive episodes and rapid cycling.
Psychiatric Management.
Although bipolar disorder is the result of chemical imbalances in the brain, psychologic
support is a key feature of treatment for all phases of the problem. Psychiatrists
or trained psychologic professionals provide a number of services. They monitor
the patient's on-going status and intervene as early as possible in manic and depressive
episodes in order to reduce the severity of the attack. Psychotherapists and other
mental health professionals can also educate patients about the disorder and its
treatment and can help them to make social and psychologic adaptations and to comply with
drug regimens. Although some patients experience the manic phase as distressing,
many patients avoid treatment because they consider their mania to be positive, creative, and exhilarating. In such cases, education and psychotherapeutic counseling are
necessary to help the patient adjust to the reality of the illness and to understand
the negative consequences of mania. Just as important, therapists and counselors
must help patients cope with feelings of guilt and remorse in response to their actions
during mania and with feelings of imperfection and despair when they acknowledge
their illness. These feelings would be difficult enough in a healthy individual,
but accompanying depression, which places the patient in danger of suicide, often compounds them.
Therapy focused on improving self-esteem, rebuilding social supports, and making
sure the patient complies with medical therapies is essential.
Some patients find that graphing their psychomotor responses (i.e., noting the effect
of their mental states on physical activity) is extremely helpful. The patient makes
a time line across the page and a vertical line on the left side of the time line
with a range from -5 to +5. Minus five indicates the most severe depressive state,
which requires hospitalization; a rating of -5 on psychomotor activity reflects an
inability to function, a severe loss of appetite, and barely enough energy to get
out of bed. As the scale moves up to zero, the depressive state lessens, so that -1 connotes
subdued mood with slightly less energy. Zero is normal. The positive side of the
scale indicates increasing mania. For example, +1 indicates a slightly more active
and energetic state than normal and +5 is the most severe manic state, where the patient
is incapable of slowing down, experiences impaired thinking and judgment, and sleeps
at least two hours less than normal. The patient makes a mark on the scale that
indicates each day's psychomotor state and connects the mark with that of the previous
day's state. The patient also notes any significant emotional or physical events,
menstruation, medications and dosages taken, or any factor that the patient thinks
is salient. After several months, the physician and patient may be able to detect a pattern,
possibly identifying triggers of bipolar episodes that allow the patients to make
adjustments that might reduce the severity of mood swings. For example, if a predictor
for either manic or depressive episodes is insomnia, the physician might prescribe
one of the benzodiazepine anti-anxiety drugs that help people sleep, possibly reducing
the severity of the emerging mania.
Family Support.
It is very important for psychotherapists who treat patients with bipolar disorder
to meet with family, partners, or close friends to help strengthen the social and
emotional supports that are so necessary for patients with bipolar disorder. Unlike
relatives of alcoholic patients who may be encouraged to get tough and to let alcoholics
hit bottom, relatives of bipolar patients must be encouraged to maintain supports
because there is a high risk for suicide if supports evaporate. People with alcoholism
may be able to give up alcohol, but people with bipolar disorder cannot give up their
minds. Family and friends of people with bipolar disorder can offer support by listening
attentively and by being empathic. The patient should not be made to feel guilty;
bipolar disorder results from an imbalance of chemicals in the brain; it is not their
fault. This is not to advise family members of bipolar patients to become enablers;
they must be strong and forceful in getting the patient to comply with treatment,
sometimes even threatening hospitalization if the patient fails to do so. They should
have a hotline number or the number of a psychiatrist authorized to commit the patient,
and they must be willing to carry through with their threats if a patient becomes
violent or the family is on the verge of collapse. Unfortunately, such actions may
not be intuitive, and they take their toll. Loved ones must also care for themselves
or they may follow a path to severe depression themselves. They should try any and
all methods that offer strength and relaxation. Some of these include exercise, stress
reduction and relaxation techniques, holidays away from the patient, or involvement
in hobbies. Support groups are important and are available in most regions.
Mood-Stabilizing Drugs.
Lithium
. Lithium (Carbolith, Duralith, Lithobid, Lithizine, Eskalith, Lithane) has been
the standard mood stabilizing drug for bipolar disorder. It helps prevent relapses
and seems to have a beneficial effect on the psychosocial functioning of bipolar
patients. It is effective in 60% to 80% of all hypomanic and manic episodes, although its
mechanisms are not clear. Some research indicates that patients who experience depressive
symptoms during manic phases may have a lower response to lithium therapy than those who do not. Lithium may take weeks to become effective, so it is not very useful
for the immediate treatment of rapid cycling and mixed states [see below
]. Side effects and toxicity can occur at only slightly higher blood levels of lithium
than those that are effective and safe for the patient. Patients should not become
dehydrated (drinking 2 to 3 quarts of water a day is advisable) and should use normal amounts of salt. Lithium dosages must be tightly controlled by measuring blood
levels frequently during acute attacks and about every three months during maintenance
therapy. Lithium levels in the blood are measured as mEq/L. Safe blood levels are
usually 0.75 to 1.2 mEq/L for most patients during initial treatment and 0.4 to 1 mEq/L
for maintenance therapy.
Even mildly elevated concentrations (1.4 to 2 mEq/L) of lithium can cause toxic reactions,
including trembling hands, nausea, increased urine output, and loss of coordination.
When lithium levels are between 2 and 2.5 mEq/L, more severe reactions can occur, including convulsions, uncontrolled jerky movements in arms and legs, blurred vision,
nausea and vomiting, stupor, and even coma. Blood levels over 2.5 mEq/L can be fatal.
Physicians should test the blood periodically to be sure that drug levels are within a safe range; patients or their families should notify their physician at the
sign of any suspicious symptoms or illnesses. Children under six who have been treated
with lithium for bipolar disorder or very aggressive behavior are reported to have
a high rate of severe side effects, particularly central nervous system problems in
the first week. Lithium should only be prescribed in young children by physicians
very experienced in the effects of the drug on children.
Patients should be aware of medications or conditions that may elevate the levels
of lithium in the blood, increasing the risk of toxicity. Such conditions include
fever, diabetes, weight-loss diets, salt restricted diets, and diarrhea. Because
lithium is eliminated from the body by the kidneys, any drugs that alter the kidneys' actions
may increase lithium blood levels and should be used with great caution. Some nonsteroidal
anti-inflammatory drugs (NSAIDs) may effect kidney function and lithium levels. Thiazide diuretics, used for high blood pressure or fluid retention, cause the greatest
increase in lithium blood levels. ACE inhibitors, drugs used for hypertension and
congestive heart failure, may also increase lithium blood levels, and there have
been reports of interactions between lithium and antipsychotics, anticonvulsants, and
calcium channel blockers (drugs commonly used in combination with lithium). Although,
the risks associated with these drugs are very low, caution is needed. Interesting
research is underway on the effects of seasonal change on lithium blood levels; for
instance, one study has found that they are higher in summer in men, which indicates
that lower doses may be needed for men during that season. If toxicity occurs, the
drug is stopped immediately and the patients is given fluids and drugs to increase excretion
of lithium salts. Gastric lavage, a procedure that rinses the stomach may be used
to treat very recent overdoses. Hemodialysis, a procedure that filters lithium out
of the blood, may also be performed.
Long-term use of lithium is not without problems even for patients who do not experience
toxic responses, and noncompliance is common. One study of lithium users found that
patients took their medication only 34% of the time. Another reported that nearly a third of patients eventually went off the drug. In addition to side effects from
high drug levels of lithium, some patients may experience an unpleasant taste in
the mouth, hair loss, or weight gain (which is a frequent reason for noncompliance
and relapse). Lithium can also cause skin eruptions that can resemble acne; the drug can
also worsen psoriasis. Eventually, lithium may cause thyroid problems; up to 20%
of patients who take lithium develop symptomatic hypothyroidism, and another 20%
to 30% develop hypothyroidism without symptoms. Patients may stop using lithium because of
blunted sexual drive, dulled emotions and mental acuity, memory loss, and lack of
motor coordination. Recent studies have reported that it may reduce sensitivity
to light and affect color recognition slightly, which might cause problems with night driving.
This effect occurs regardless of how long a person has been on the drug. Experts
recommend that patients wear sunglasses outside and avoid extensive exposure to bright
light.
Some patients regret the loss of their manic episodes and the feelings of exhilaration
and creativity that sometimes accompany them. In one small study of artists with
bipolar disorder, one-quarter found no change in creative output, another quarter
felt their work had declined, and half felt that lithium had improved their output. Despite
the potential side effects, however, lithium has been in use for more than 40 years
and physicians are confident that the drug can be taken safely by most patients,
even for life. A recent study reported that taking it for at least five years significantly
reduced the time spent in the hospital.
Valproate and Other Anti-Epileptic Drugs
. About 20% to 40% of patients do not respond to lithium. Valproate (Depakote),
also called valproic acid, and carbamazepine (Epitol, Tegretol) are drugs ordinarily
used for epilepsy; either one may be an alternative for patients who do not tolerate
or respond to lithium. In fact, experts now recommend a combined program of valproate
and lithium as first-line treatment for manic episodes in bipolar patients. Both
drugs stimulate the release of the neurotransmitter glutamate, although they appear
to work through different mechanisms. For patients who do not respond to standard treatment,
combinations of carbamazepine, valproate, and lithium should be tried. For hospitalized
patients, taking either a combination of carbamazepine and lithium or valproate appears to reduce the length of hospital stays when compared to taking lithium alone.
Although both these drugs are comparable to lithium in long-term effectiveness,
patients face a higher risk for breakthrough depression with these drugs than they
do with lithium. One study found that valproate appears to work more quickly than the other
drugs. The side effects of valproate are usually minor, occurring early in therapy,
and then subsiding. In some studies, nearly half the patients taking valproate initially experienced gastrointestinal problems (nausea, vomiting, heartburn). People
also may have headaches, visual disturbances, ringing in the ear, hair loss, weight
gain, agitation, or odd movements. Women may experience menstrual irregularities,
and the risk for polycystic ovaries seems to increase. (These side effects also appear
in women using other anti-epileptic drugs, but a recent study reported that the risk
for those taking valproate was higher.) Valproate is, however, the preferred drug
for women taking oral contraceptives. The drug significantly increases the risk for birth
defects when taken by pregnant women. Other serious but rare side effects include
liver damage, convulsions, and coma. A recent study of epileptic patients who had
taken valproate for longer than a year found an association between long-term treatment
and the development of hearing loss, cognitive impairment and symptoms of Parkinson's
disease; these disturbing side effects resolved after valproate therapy was discontinued.
Initial side effects for carbamazepine (Tegretol) are similar to those of valproate.
Increased appetite with weight gain, tremor, and hair loss may be more severe with
valproate than carbamazepine; skin reactions, on the other hand, may be less severe.
In about 6% of patients, skin reactions are so severe that the drug has to be discontinued.
In about 10% of those taking the drug, a decrease in white blood cells occurs.
This is generally not serious unless the patient has an infection. Other blood conditions can arise that are potentially serious. Patients should be sure to inform
the doctor if they develop a sore throat, fever, easy bruising, or unusual bleeding.
Water retention can be a problem in older people. Like valproate, it increases
the risk for birth defects.
Another anti-epileptic drug showing promise for bipolar disorder is lamotrigine (Lamictal),
which was originally derived from an antimalarial drug. It appears to be beneficial
for both depressive and manic phases. It also may be effective either alone or in combination with other drugs for rapid cycling. The most common reason for withdrawing
from the drug is development of a rash, which occurs in 10% of patients taking lamotrigine.
Other potential side effects include nausea, dizziness, blurred vision, and sleepiness.
Electroconvulsive Therapy.
Commonly called shock treatment, electroconvulsive therapy (ECT) has received bad
press since it was introduced in the 1930s. This is unfortunate, since over the
years it has been refined and may now even be safer than lithium for patients who
are pregnant or who have certain types of heart problems. In a review of studies, about 80%
of ECT-treated patients experienced improvement. The procedure first involves administering
a muscle relaxant and short-acting anesthetic; then a small amount of current is
sent to the brain, causing a generalized seizure that lasts for about 40 seconds.
People can experience temporary confusion and memory lapses, headache, nausea, muscle
soreness, and heart disturbances. The response to ECT is usually very fast, and
the patient often needs less medication afterward. ECT may be used for patients who need
immediate stabilization of their condition and cannot wait for medications to be
become effective, for those who cannot tolerate or do not respond to medications,
or simply for those who prefer ECT. It is also useful for people who suffer suicidal thoughts
and guilt during the depressive phase, and for manic behavior. It may be particularly
useful for elderly patients
Treating Bipolar Phases and Other Conditions.
Treatment of Manic Episodes.
Some experts have found that patients whose first episode is manic respond better
to treatment and have less risk for rapid cycling than those who first enter treatment
during a depressive episode. Patients often require hospitalization at the onset
of acute mania. If the patient is experiencing severe symptoms, including psychosis or
violent behavior, the physician may administer one of the antipsychotic drugs known
as neuroleptics, e.g., haloperidol (Haldol), or one of the antianxiety drugs known
as a benzodiazepine, usually clonazepam (Klonopin) or lorazepam (Ativan). These drugs are
used to sedate and calm the patient and to control the symptoms. Neuroleptics can
cause severe side effects that disturb motor control to which bipolar patients are
particularly susceptible, and many experts now believe that benzodiazepines should be tried
first. The benzodiazepines may be combined with a mood-stabilizing drug, usually
lithium. When the acute phase of the manic episode passes the neuroleptic or benzodiazepine drug is slowly withdrawn and only the mood-stabilizing drug is continued.
Treatment of Depressive Episodes.
A combination of psychotherapy and drugs is generally recommended for depression.
Some experts believe about half the patients with depressive episodes will respond
to lithium at low doses. If improvement does not occur within two to four weeks,
then an antidepressant drug may be added; caution is necessary because antidepressants may
trigger manic reactions and increase the risk for rapid cycling. Patients at risk
for a rapid cycling or manic response from antidepressants should usually continue
on a mood-stabilizing drug, generally lithium, and psychiatric management should be intensified.
Patients should be taken off antidepressants if they develop hypomania, which is
often a sign of impending mania. The antidepressant buproprion (Wellbutrin), a unique drug that is related to amphetamines, appears to have a lower risk for triggering
mania than others. Drugs known as monoamine oxidase inhibitors (MAOIs), particularly
tranylcypromine (Parnate), are also beneficial. (It should be noted that while taking MAOIs, hypertension can occur from eating certain foods having a high tyramine content.
Such foods include aged cheeses, most red wines, vermouth, dried meats and fish,
canned figs, fava beans, and concentrated yeast products. If MAOIs are taken with
certain drugs, including some common over-the-counter cough medications, severe hypertension
or toxic reactions can occur. It is very important, therefore, that the patient
discusses with the physician any other medications being taken.) The antidepressants known as tricyclics have most often been implicated in causing a switch to a manic
response. Such drugs include amitriptyline (Elavil, Endep), desipramine (Norpramin),
doxepin (Sinequan), imipramine (Tofranil), amoxapine (Asendin) and nortriptyline
(Pamelor, Aventyl). The serotonin reuptake inhibitors, such as fluoxetine (Prozac), sertraline
(Zoloft), and paroxitine (Paxil) are being used to treat bipolar depression, but
their long-term benefits have not yet been determined. Electroconvulsive therapy
also helps patients who do not respond to medication. Some patients become severely
depressed and delusional, and they require an antipsychotic medication. Small studies
indicate that a subgroup of patients may respond to thyrotropin-releasing hormone,
a substance that regulates thyroid hormones, which are produced in a brain structure
called the hypothalamus.
Treatment of Mixed Episodes and Rapid Cycling.
At one time, patients with rapid cycling were treated with a single drug, but over
the years regimens have changed. Now, treatment typically involves the use of three
or four drugs. A combination of lithium and valproate appears to be more effective
in preventing relapse than use of lithium alone, although with co-administration the risk
for side effects is greater. Another approach uses valproate first, followed by
carbamazepine, and then a combination of carbamazepine and lithium. The newer antiepileptic drug lamotrigine may prove effective for rapid cyclers who have severe depression.
Because one biologic mechanism involved with rapid cycling is an excessive influx
of calcium into brain cells, a calcium channel blocker, such as nimodipine, is proving to be beneficial. Nimodipine has been shown to reduce hypomania and is particularly
effective when added to carbamazepine. Rapid cycling between manic and depressive
poles has also been treated with antidepressants, but experts now believe they should
be avoided or used with caution (particularly tricyclic antidepressants). Thyroxin
has also been prescribed, but tolerance to this thyroid hormone tends to develop.
In one small study, the stimulant methylphenidate (Ritalin) or dextroamphetamine
(Dexedrine) were added to standard bipolar treatment. These drugs, commonly prescribed for
attention deficit hyperactivity disorder, appeared to be effective in reducing racing
thoughts, irritability, and grandiose thinking (although not psychosis) in most patients. The study was very small, however, and more work is needed before the benefits
of these drugs are proved. Electroconvulsive therapy can be useful in emergency
situations.
Maintenance Therapy.
Relapse occurs in most patients after treatment of acute attacks, and patients who
are at high risk for recurring episodes should consider lifelong maintenance therapy.
Lithium is the primary medication, although some patients often benefit from valproate or carbamazepine. Lithium maintenance therapy has the longest track record of safety
and efficacy, and its use is associated with significant reductions in both depressive
and manic episodes, particularly in type II bipolar patients. In one study, the
earlier lithium was started the more effective it was. Studies are showing that patients
on long-term lithium therapy have survival rates comparable to the general population,
but those who drop out of therapy have significantly lower survival rates. Patients who decide against maintenance therapy and who stop lithium after successful
treatment also may be at increased risk for ineffective lithium re-treatment if they
relapse, particularly if there is a long duration between the withdrawal from lithium
and the relapse. One study reported, however, that the effectiveness of lithium was
similar during initial and repeat courses of treatment, although during the second
period there was a greater need for combinations of drugs. Some researchers have
found that patients who stop taking lithium and then start again experience significantly more
psychiatric hospitalizations than those who use the drug continuously. A gradual
discontinuation (over 15 to 30 days) may help to delay recurrence. Clozapine (Clozaril) or risperidone (Risperidal), drugs used for schizophrenia, may prove to be beneficial
in some patients for maintenance therapy when used alone or with lithium. One small
study found that risperidone was helpful in certain (but not most) patients for break-through episodes of either depression or mania that occurred during maintenance
therapy. Some studies are finding that maintenance electroconvulsive (ECT) therapy
may be helpful for those who do not respond to medications. In one study bipolar
patients who had intractable recurrent episodes were maintained on monthly ECT treatments
for more than a year and a half. Without this treatment, these patients spent an
average of almost half a year in the hospital, suffering at least three episodes
annually; after ECT treatment, all of the rapid cyclers achieved full or partial remission.
Treatment during Pregnancy.
Women with bipolar disorder are at particularly high-risk for mania in the postpartum
period; in one study, 20% of women were hospitalized within 90 days after giving
birth. Taking mood stabilizers at the time of delivery has been shown to significantly
reduce this risk, but these drugs carry their own dangers. Antiepileptic drugs taken
by pregnant women greatly increase the risk for physical malformations, developmental
delay, and spina bifida in babies. An increased incidence of heart defects and other birth defects have been found in babies whose mothers used lithium in the first three
months of pregnancy, but recent studies indicate that it may be safer for the fetus
than previously believed. Physicians may now prescribe lithium at the time of delivery with some confidence that it will not harm the mother or baby; however, caution
is still advised. Mothers who are taking lithium should not nurse their babies,
since lithium is concentrated in breast milk.
National Foundation for Depressive Illness
P.O. Box 2257
New York, NY 10116
call (212-268-4260) or (800-239-1265) or on the Internet (http://www.depression.org/)
National Depressive and Manic-Depressive Association
730 N. Franklin St.
Suite 501, Chicago, Ill. 60610
call (800-826-3632) or (312-642-0049) on the Internet (http://www.ndmda.org/)
Makes referrals to local support services and offers a free information package.
Depression and Related Disorders Association
Meyer 3-181, 550 bldg.
600 North Wolfe Street
Baltimore, Maryland
call (410-955-4647) or on the Internet (http://infonet.welch.jhu.edu/departments/drada/default/)
Lithium Information Center
8000Excelsior Drive, Suite 302
Madison, Wisconsin 53717-1914
call (608-836-8070) or fax (608-836-8033)
General information is provided over the phone; literature searches on specific topics
cost a nominal fee. The center also publishes many patient guides and reference
books.
National Institute of Mental Health
D/ART/ (Depression Awareness, Recognition, and Treatment) Program
Room 15-C-05
5600 Fishers Lane
Rockville, MD 20857
call (800-421-4211) or on the Internet (http://www.nimh.nih.gov/)
National Alliance for the Mentally Ill (NAMI)
200 N. Glebe Rd.
Arlington, VA 22203-3754
call (800-950-6264) or on the Internet (http://www.nami.org/)
NAMI is a national grass roots organization providing ways for self-help and support
organizations to individuals and families of people with psychologic disorders.
Bipolar Network News
c/o Stanley Foundation
5430 Grosvenor Lane, Suite #200
Bethesda, MD 20814.
call (800-518-7326) or write for a free subscription to Bipolar Network News (a joint
project of NAMI and NIMH).
Association for the Advancement of Behavior Therapy
305 Seventh Avenue
16th Floor
New York, NY 10001
call (212-647-1890) or (800-685-AABT)
Offers information packets that include list of behavior therapists, fact sheets on
various psychologic problems, and methods for choosing a behavior therapist.
National Mental Health Association
1021 Prince St.
Alexandria, VA 22314-2971
call (800-969-6642) or on the Internet (http://www.nmha.org)
This organizations will give the names and numbers of regional chapters and also provides
information on 200 mental health topics.
Expert Knowledge Systems
PO Box 917
Independence VA 23248
fax (540 773 2347) or on the Internet (.psychguides.com">www.psychguides.com)
This physician group offers excellent detailed information on bipolar disorder.
On the Internet
Mental Health Net (http://www.cmhc.com/)
Internet Mental Health (http://www.mentalhealth.com/)
is a free encyclopedia of mental health information.
Bipolar mood disorders in the elderly. Psychiatry Clinics of North America,
3/20/97
Effects of chronic lithium treatment on retinal electrophysiologic function.
And Lithium decreases retinal sensitivity, but this is not comulative with years
of treatment. Biol Psychiatry 1997
Expanded trinucleotide CAG repeats in families with bipolar affective disorders.
Biol Psychiatry 1997
Panic disorder with familial bipolar disorder. Biol Psychiatry 1997
A pilot study of lithium carbonate plus divalproex sodium for the continuation
and maintenance treatment of patients with bipolar I disorder. Journal of Clinical
Psychiatry, March 1997
Well-Connected reports are written and updated by experienced medical writers and reviewed and edited by the in-house editors and a board of physicians at Harvard Medical School and Massachusetts General Hospital. The reports are distinguished from other information sources available to patients and health care consumers by their quality, detail of information and currency. These reports are not intended as a substitute for medical professional help or advice but are to be used only as an aid in understanding current medical knowledge. A physician should always be consulted for any health problem or medical condition. The reports may not be copied without the express permission of the publisher.
Board of Editors
Harvey Simon, M.D., Editor-in-Chief, Massachusetts Institute of Technology; Physician, Massachusetts General Hospital
Masha J. Etkin, M.D., Gynecology, Harvard Medical School; Physician, Massachusetts General Hospital
John E. Godine, M.D., PhD, Metabolism, Harvard Medical School; Associate Physician, Massachusetts General Hospital
Daniel Heller, M.D., Pediatrics, Harvard Medical School; Associate Pediatrician, Massachusetts General Hospital; Active Staff, Children's Hospital
Irene Kuter, M.D., D. Phil, Oncology, Harvard Medical School; Assistant Physician, Massachusetts General Hospital
Paul C. Shellito, M.D., Surgery, Harvard Medical School; Associate Visiting Surgeon, Massachusetts General Hospital
Theodore A. Stern, M.D., Psychiatry, Harvard Medical School; Psychiatrist and Chief, Psychiatric Consultation Service, Massachusetts General Hospital
Carol Peckham, Editorial Director
Cynthia Chevins, Publisher
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