Bipolar affective disorder

Bipolar disorder, still often referred to colloquially as manic depression, is a mood disorder marked by episodes of clinically significant impairment due to mania or depression.

Bipolar disorder is a serious medical illness that affects millions of people. Bipolar disorder typically develops in early adulthood, but some people develop symptoms as children or late in life. It is often not recognized as an illness, and people may suffer for years before it is properly diagnosed and treated. Like heart disease and diabetes, Bipolar disorder is a long-term illness that must be carefully managed throughout a person's life.

One sufferer of Bipolar disorder wrote: "Manic-depression distorts moods and thoughts, incites dreadful behaviors, destroys the basis of rational thought, and too often erodes the desire and will to live. It is an illness that is biological in its origins, yet one that feels psychological in the experience of it; an illness that is unique in conferring advantage and pleasure, yet one that brings in its wake almost unendurable suffering and, not infrequently, suicide. "I am fortunate that I have not died from my illness, fortunate in having received the best medical care available, and fortunate of having the friends, colleagues, and family that I do."

Emil Kraepelin (1856-1926), a German psychiatrist who first described the illness and coined the term "manic depression", noted in his original delineation of the disease that intervals of acute illness, manic or depressive, were generally punctuated by relatively symptom-free intervals in which a patient was able to function normally.

To that point, there are currently three types of bipolar disorder outlined by the DSM-IV-TR and generally accepted within the medical community: Bipolar I, Bipolar II, and Cyclothymia. Like many disorders involving brain chemistry, bipolar disorder is still under investigation, and symptoms may differ significantly from person to person. Typically, symptoms include periods of euphoria, which alternate with periods of profound depression. In most cases, periods of mood stability complement these periods of instability.

Diagnostic criteria
The DSM-IV-TR details two general profiles of bipolar disorder, Bipolar I and Bipolar II. Bipolar I is characterized by alternating episodes of full-blown mania and depression, while Bipolar II, the less severe and more common type of the disorder, is characterized by episodes of hypomania and depression.

Criteria for a manic episode (DSM-IV-TR)

 * 1) A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least 1 week (or any duration if hospitalization is necessary).
 * 2) During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
 * 3) inflated self-esteem or grandiosity
 * 4) decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
 * 5) more talkative than usual or pressure to keep talking
 * 6) flight of ideas or subjective experience that thoughts are racing
 * 7) distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
 * 8) increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
 * 9) excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., engaging in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
 * 10) The symptoms do not meet criteria for a Mixed Episode.
 * 11) The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.
 * 12) The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

Criteria for a major depressive episode (DSM-IV-TR)

 * 1) Five (or more) of the following symptoms have been present during the same 2-week period and represent a change from previous functioning; at least one of the symptoms is either (1) or (2).
 * 2) depressed mood most of the day, nearly every day, as indicated by either subjective report (e.g., feels sad or empty) or observation made by others (e.g., appears tearful). Note: In children and adolescents, can be irritable mood.
 * 3) markedly diminished interest or pleasure in all, or almost all, activities most of the day, nearly every day (as indicated by either subjective account or observation made by others)
 * 4) significant weight loss when not dieting or weight gain (e.g., a change of more than 5% of body weight in a month), or decrease or increase in appetite nearly every day. Note: In children, consider failure to make expected weight gains.
 * 5) Insomnia or Hypersomnia nearly every day
 * 6) psychomotor agitation or retardation nearly every day (observable by others, not merely subjective feelings of restlessness or being slowed down)
 * 7) fatigue or loss of energy nearly every day
 * 8) feelings of worthlessness or excessive or inappropriate guilt (which may be delusional) nearly every day (not merely self-reproach or guilt about being sick)
 * 9) diminished ability to think or concentrate, or indecisiveness, nearly every day (either by subjective account or as observed by others)
 * 10) recurrent thoughts of death (not just fear of dying), recurrent suicidal ideation without a specific plan, or a suicide attempt or a specific plan for committing suicide
 * 11) The symptoms do not meet criteria for a Mixed Episode.
 * 12) The symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning.
 * 13) The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication) or a general medical condition (e.g., hypothyroidism).
 * 14) The symptoms are not better accounted for by Bereavement, i.e., after the loss of a loved one, the symptoms persist for longer than 2 months or are characterized by marked functional impairment, morbid preoccupation with worthlessness, suicidal ideation, psychotic symptoms, or psychomotor retardation.

Criteria for a mixed episode

 * 1) The criteria are met both for a Manic Episode and for a Major Depressive Episode (except for duration) nearly every day during at least a 1-week period.
 * 2) The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or others, or there are psychotic features.
 * 3) The symptoms are not due to the direct physiological effects of a substance (e.g., a illicit drugs, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

Criteria for a hypomanic episode

 * 1) A distinct period of persistently elevated, expansive, or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual non depressed mood.
 * 2) During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree:
 * 3) inflated self-esteem or grandiosity
 * 4) decreased need for sleep (e.g., feels rested after only 3 hours of sleep)
 * 5) more talkative than usual or pressure to keep talking
 * 6) flight of ideas or subjective experience that thoughts are racing
 * 7) distractibility (i.e., attention too easily drawn to unimportant or irrelevant external stimuli)
 * 8) increase in goal-directed activity (either socially, at work or school, or sexually) or psychomotor agitation
 * 9) excessive involvement in pleasurable activities that have a high potential for painful consequences (e.g., the person engages in unrestrained buying sprees, sexual indiscretions, or foolish business investments)
 * 10) The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic.
 * 11) The disturbance in mood and the change in functioning are observable by others.
 * 12) The episode is not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization, and there are no psychotic features.
 * 13) The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g., hyperthyroidism).

According to the DSM-IV-TR, a diagnosis of bipolar I disorder requires at least one manic or mixed episode, but may also include hypomanic or depressive episodes. A depressive episode is not required for a diagnosis of bipolar I disorder.

A diagnosis of bipolar II disorder requires neither a manic nor mixed episode, but requires at least one hypomanic episode and one major depressive episode.

A diagnosis of cyclothymic disorder requires the presence of numerous hypomanic episodes, intermingled with depressive episodes that do not meet the criteria for major depressive episodes.

If an individual clearly seems to be suffering from some type of bipolar disorder but does not meet the criteria for one of the conditions laid out above, he or she receives a diagnosis of Bipolar, Not Otherwise Specified (NOS).

Causes of Relapse of Symptoms and Behaviors to Avoid
A combination of medication and therapy is often used to somewhat suppress the symptoms of Bipolar disorder. Even when on medication, some people might still experience weaker episodes or have a complete manic or depressive episode. There are several factors that could cause someone to relapse into mania or depression:
 * Failure to continue taking the appropriate dose of medication
 * Under or over medicated or on the wrong medication. Generally, taking a lower dosage of a mood stabilizer will cause the patient to relapse into mania. Taking a lower dosage of an antidepressant can cause the patient to relapse into depression, while overdosing can cause the patient to experience mania. Overdosing on either medication can cause serious liver problems and possibly other health problems. During treatment, blood levels are often checked to ensure the appropriate concentrations of the drug(s).
 * Taking other medications that affect brain activity, or using recreational drugs such as marijuana, cocaine, or heroin. For Bipolar patients, mind-altering drugs can cause severe damage.
 * Not getting enough sleep can cause the patient to relapse into mania. It is also important that patients follow a consistent sleep schedule that includes 7-8 hours each night.
 * Avoid caffiene. Excessive amounts can cause relapses into mania.
 * Stress must also be managed appropriately. When not on medication, excessive stress can cause the patient to relapse into mania or depression. Medication raises the stress threshold somewhat, but too much stress can still cause relapses.

Also, patients should not consume excessive amounts of alcohol because that can cause liver damage.

Suicide Warning
Patients with Bipolar often become suicidal. Suicidal symtoms include:
 * talking about feeling suicidal or wanting to die
 * feeling hopeless, that nothing will ever change or get better
 * feeling helpless, that nothing one does makes any difference
 * feeling like a burden to family and friends
 * abusing alcohol or drugs
 * putting affairs in order (e.g., organizing finances or giving away possessions to prepare for one's death)
 * writing a suicide note
 * putting oneself in harm's way, or in situations where there is a danger of being killed

If you are feeling suicidal or know someone who is:
 * call a doctor, emergency room, or 911 right away to get immediate help
 * make sure you, or the suicidal person, are not left alone
 * make sure that access is prevented to large amounts of medication, weapons, or other items that could be used for self-harm

Epidemiology
The lifetime prevalence rate of Bipolar Disorder I and II is thought to be between 0.6 and 2% of the population. Bipolar I disorder is gender-neutral, affecting both women and men equally, according to the DSM. Bipolar II is found more frequently in women. No publication to date has suggested that there is a difference between races in the prevalence of bipolar disorder.

Most frequently, the disorder starts with a depression, and mania or hypomania follows. In the vast majority of cases, the symptoms begin in early adulthood, and continue over the course of the lifespan. There are some occurrences of a single manic episode followed by full recovery with no recurrence; however, these cases are rare enough to suggest some other confounding factors.

For many years it was believed that the bipolar profile emerged in late adolescence and/or young adulthood. Recent research by the National Institute of Mental Health suggests that even young children can suffer from bipolar symptoms or precursors. These precursors can include acute anxiety or panic attacks. Although there is no specific official diagnostic category for this pre-adolescent patient profile, it is often called "pediatric bipolar disorder".

Etiology
There are many theories regarding the development of bipolar disorder. Multiple factors may be involved, such as stressful events or major life transitions, conditions in the womb, past or present drug use (which may complicate diagnoses if present and may lead to misdiagnoses), sleep deprivation, or a family history of bipolar disorder, clinical depression, or schizophrenia. This type of family history creates a genetic vulnerability which can significantly increase the likelihood of developing the disorder.

The "kindling" theory asserts that people who are genetically predisposed toward bipolar disorder experience a series of stressful events, each of which lowers the threshold at which mood changes occur. Eventually, the mood episode itself is sufficient to trigger recurring difficulties.

As with nearly all psychiatric or psychological phenomena, the etiology of bipolar disorder is thought to include a complex interplay between environmental stimuli (stressful life events, drug use, etc.) and genetic vulnerability. While bipolar disorder has a strong genetic component, the concordance rate between MZ (identical) twins, who share 100% of their DNA, is not 100%. Therefore, environmental and genetic factors must be at play.

Many drugs, legal and illegal, may initiate a manic episode. The mania induced by such drugs, including antidepressant medications and stimulants (e.g. Adderall or methamphetamines), may or may not resolve when the medication is discontinued. When a patient with a history of manic episodes requires an antidepressant because of a serious depression, a doctor typically will tread carefully, prescribing a low dose and, ideally, closely monitoring the patient for any signs of an excessive mood shift toward the manic side of the spectrum.

Comorbid conditions
Several disorders may occur simultaneously with bipolar I and II disorders. As these disorders are not all episodic, they may present themselves during the course of both mood mood stability. Further, the medications used to manage the symptoms of bipolar disorders may be ineffective against the symptoms of comorbid disorders, and, in some cases, are contraindicated because they aggravate other conditions. Anxiety disorders or obsessive-compulsive disorder (mild or severe) may occur in conjunction with bipolar disorder. Other co-occurring symptomologies may include panic disorder, social phobia, suicidal ideation, substance dependence, and somatization disorders. Another comorbid condition that often confuses the diagnosis in the juvenile population is ADHD. ADHD and bipolar disorder co-occur frequently, perhaps due to their overlapping symptom profiles or to the prescription of stimulant medications to juveniles with ADHD.

Cycles in bipolar disorder
The cycles of bipolar disorder may be long or short, and the ups and downs may be of different magnitudes: for instance, a person suffering from bipolar disorder may suffer a protracted mild depression followed by a shorter and intense mania. The depressed periods may seem much worse following a manic period from the point of view of the patient.

Severe depression or mania may be accompanied by symptoms of psychosis. These symptoms include hallucinations (hearing, seeing, or otherwise sensing the presence of stimuli that are not there) and delusions (false personal beliefs that are not subject to reason or contradictory evidence and are not explained by a person's cultural concepts). Paranoid (see paranoia) thoughts, which cause the patient to believe that he or she is being persecuted or monitored by some powerful entity such as the government or a hostile force, may be present. Intense and unusual religious beliefs may also be present, such as patients' strong insistance that they have a God-given role to play in the world, a great and historic mission to accomplish, or even that they possess supernatural powers. Delusions in a depression may be far more distressing, sometimes taking the form of intense guilt for supposed wrongs that the patient believes he or she has inflicted on others.

Mania
Researchers at Duke University have refined Kraepelin’s four classes of mania to include hypomania (featuring mainly euphoria), severe mania (including euphoria, grandiosity, high levels of sexual drive, irritability, volatility, psychosis, paranoia, and aggression), extreme mania (most of the displeasures, hardly any of the pleasures) a.k.a. dysphoric mania, and two forms of mixed mania (where depressive and manic symptoms collide).

Hypomania
Hypomania is a less severe form of mania without progression to psychosis. Many of the symptoms of mania are present, but to a lesser degree than in overt mania. People with hypomania are generally perceived as being energetic, euphoric, overflowing with new ideas, and sometimes highly confident and charismatic, yet they are sufficiently capable of coherent thought and action to participate in everyday life.

It is questionable whether hypomania occurs without being part of a cycle of mania or depression. Patients rarely, if ever, seek out a psychiatrist complaining of hypomania. Johns Hopkins psychologist John Gartner in The Hypomanic Edge contends that many famous people – including Christopher Columbus, Alexander Hamilton, Andrew Carnegie, Louis B Mayer, and Craig Venter (who mapped the human genome) - owed their ideas and drive (and eccentricities) to their hypomanic temperaments. The creativity and risky behavior associated with hypomania (and bipolar disorder in general) may suggest why it has survived evolutionary pressures.

Although hypomania sounds in many ways like a desirable condition, it can have significant downsides. Many of the negative symptoms of mania can be present; the primary differentiating factor is the absence of psychosis. Many hypomanic patients have symptoms of disrupted sleep patterns, irritability, racing thoughts, obsessional traits, and poor judgment. Hypomania, like mania, can be associated with recklessness, excessive spending, risky hypersexual activity, general lack of judgment and out-of-character behaviour that the patient may later regret and may cause significant social, interpersonal, career and financial problems.

Hypomania can also signal the beginning of a more severe manic episode, and in people who know that they suffer from bipolar disorder, can be viewed as a warning sign that a manic episode is on the way, allowing them to seek medical treatment while they are still sufficiently self-aware before full-blown mania occurs.

Bipolar depression
People with bipolar disorder, generally speaking, are depressed far more often than they are manic. According to the Stanley Foundation Bipolar Network, bipolar patients spend three times more days in depression than they do in mania, however, there are cases of Bipolar I in which patients are primarily manic. For bipolar II patients, a study by Hagop Akiskal of the University of California, San Diego revealed this population was depressed 37 times more than they were hypomanic.

A 2003 study by Robert Hirschfeld of the University of Texas, Galveston found bipolar patients fared worse in their depressions than unipolar patients. (See Bipolar Depression.)

Cognition
Numerous studies show that bipolar disorder affects a patient's ability to think and perform mental tasks, even in states of remission. Deborah Yurgelun-Todd of McLean Hospital in Belmont, Massachusetts has argued these deficits should be included as a core feature of bipolar disorder. By the same token, research by Kay Jamison of Johns Hopkins University and others has attributed high rates of creativity and productivity to individuals with bipolar disorder. (See Brain Damage.) There may be no conflict here: Cognitive dysfunction does not necessarily bar creativity.

The Mood Spectrum Perspective
Clinical depression and bipolar disorder are classified as separate illnesses, but psychiatry is increasingly viewing them as part of an overlapping spectrum that also includes anxiety and psychosis.

In a 2003 study, Akiskal and Judd re-examined data from the landmark Epidemiological Catchment Area study from two decades before. The original study found that .08 percent of the population surveyed had experienced a manic episode at least once (the diagnostic threshold for bipolar I) and .05 a hypomanic episode (the diagnostic threshold for bipolar II). But by tabulating survey responses to include criteria below the diagnostic radar, such as one or two symptoms over a short time period, the authors of the study recalculated the data to arrive at an additional 5.1 percent of the population, adding up to a total of 6.4 percent of the entire population who could conceivably be thought of as having bipolar disorder.

There is also a case that clinical depression can be bipolar disorder waiting to happen. In a 2005 study, Jules Angst and his colleagues at Zurich University tracked 406 patients with major mood disorders over a 20-year period. Of 309 patients presenting with depression, 121 (39.2 percent) eventually manifested as bipolar (24.3 percent to bipolar I, 14.9 percent to bipolar II). In all, more than 50 percent of the study population turned out to have bipolar disorder. This could also be attributed to the fact that most cases of bipolar disorder are first misdiagnosed as depression.

Environmental factors affecting mood in bipolar disorder
In mid-2003, a twin study was published concerning environmental factors and bipolar disorder. The bipolar twin was found to be far more affected by changes in sunlight. Longer nights resulted in changes in mood and length of sleep to a far greater extent than the healthy twin. Sunny days also did more to improve mood. In fact, natural light in general was found to have a profound positive effect upon the well-being of the bipolar twin.

Paradoxically, in the 2004 publication of a study using Tel Aviv's public psychiatric hospitals, it was found that "Admission rates of bipolar depressed patients increase during spring/summer and correlate with maximal environmental temperature". Unipolar depressed patient admission had no such correlation. High temperature points in the month, as well as high temperature months, were found to be correlated with depressive episodes in admissions.

In contrast, it has been found that the bipolar cycle tends towards extreme mania in the mid-to-late-summer, followed by an inevitable crash into depression with the ending of the manic episode coupled with the decreasing natural light in autumn.

Treatment of bipolar disorder
There is no cure for bipolar disorder; the emphasis is on management of the symptoms. A variety of medications are used to treat bipolar disorder; many people with bipolar disorder require multiple medications. Some people with bipolar disorder supplement or replace their Western medication with herbal or holistic options. Still, even with optimal medication treatment, many people with the illness have some residual symptoms or relapses of depression or mania. Cognitive therapy may work to lessen the severity of mood swings by recognizing and managing triggering symptoms or events. Interpersonal and Social Rhythm Therapy (ISPRT) emphasizes the regulation of sleep, diet and exercise to prevent episodes, along with teaching coping skills; it is well-documented that sleep disruptions can trigger manic episodes.

Principles
Medications called mood stabilizers are used to prevent or mitigate manic or depressive episodes. Because mood stabilizers are generally more effective at treating mania than bipolar depression, periods of depression are sometimes also treated with antidepressants. However, as stated above, antidepressants carry the risk of inducing mania, especially in bipolar patients who are not taking a mood stabilizer.

In severe cases where the mania or the depression is severe enough to cause psychosis (and recently sometimes in less severe cases as well, although this remains controversial), The antipsychotic drugs may also be used. A new class of "atypical" antipsychotics has also become more widely used for bipolar episodes. The FDA has only approved them for acute episodes, if at all (with the exception of olanzapine, which is approved as a mood stabilizer). Like most doctors, psychiatrists use medication for "off-label" uses, even when such uses are not supported by available research. It is becoming accepted practice to use atypical antipsychotics as mood stabilizers at this point, and there is support in the literature for their effectiveness in mood stabilization.

Some people have reported that antipsychotics cause mania, panic attacks, or psychosis. Any agitation should be reported to the doctor immediately. Antipsychotics also carry a risk of causing tardive dyskinesia, a potentially disfiguring and sometimes irreversible movement disorder that may case the arms, legs, face or head to jerk or twitch. The risk is thought to be proportionate to the length of duration of neuroleptic/antipsychotic use (roughly 5% per year in non-elderly patients) and has recently been linked to an equally high occurrence in both typical and atypical antipsychotics, in contrast to claims of lower risks when the atypicals were introduced. Patients and physicians need to be careful to watch for symptoms of this side effect carefully so that an antipsychotic can be reduced in dosage, or changed to another medication, before the condition progresses. The doctor should, of course, be consulted about any change in dosage. The only antipsychotic with no apparent association with tardive dyskinesia is clozapine.

Medications work differently in each person, and it takes considerable time to determine in any particular case whether a given drug is effective at all, since bipolar disorder is by nature episodic, and patients may experience remissions whether or not they receive treatment. For this reason, neither patients nor their doctors should expect immediate relief, although psychosis with mania can respond quickly to antipsychotics, and bipolar depression can be alleviated quickly with electroconvulsive therapy (ECT). Many doctors emphasize that patients should not expect full stabilization for at least 3-4 weeks (some antidepressants, for example, take 4-6 weeks to take effect), and should not “give up” on a medication prematurely, nor should they discontinue medication with the disappearance of symptoms as the depression may return.

Compliance with medications can be a major problem, because some people as they become manic lose the awareness of having an illness, and they therefore discontinue medications. Patients also often quit taking medication when symptoms disappear, erroneously thinking themselves "cured", and some people enjoy the effects of unmedicated hypomania.

Depression does not respond instantaneously to resumed medication, typically taking 2–6 weeks to respond. Mania may disappear slowly, or it may become depression. Other reasons cited by individuals for discontinuing medication are side effects, expense, and the stigma of having a psychiatric disorder. In a relatively small number of cases stipulated by law (varying by locality but typically, according to the law, only when a patient poses a threat to himself or others), patients who do not agree with their psychiatric diagnosis and treatment can legally be required to have treatment without their consent. Throughout North America and the United Kingdom, involuntary treatment or detention laws exist for severe cases of bipolar disorder and other mental illnesses.

Prognosis
While bipolar disorder can be one of the most severe and devastating medical conditions, indeed the sixth highest cause of disability in the world according to the World Health Organization, fortunately many individuals with bipolar disorder can also live full and mostly happy lives with correct management of their condition. Compared to patients with schizophrenia, persons with bipolar disorder are more likely to have periods of normal functioning in the absence of medication. Although schizophrenic patients may have remissions with relatively high levels of functioning, schizophrenic patients tend to suffer some impairment during these intervals in contrast to persons with bipolar disorder who often appear completely healthy when they are between mood swings.

Lithium salts
The use of lithium salts as a treatment of bipolar disorder was first discovered by Dr. John Cade, an Australian psychiatrist who published a paper on the use of lithium in 1949.

Lithium salts had long been used as a first-line treatment for bipolar disorder. In ancient times, doctors would send their mentally ill patients to drink from "alkali springs" as a treatment. They did not know it, but they were really prescribing lithium, which was present in high concentration in the waters. The therapeutic effect of lithium salts appears to be entirely due to the lithium ion, Li+. The two lithium salts used for bipolar therapy are lithium carbonate (mostly) and lithium citrate (sometimes). Approved for the treatment of acute mania in 1970 by the FDA, lithium has been an effective mood-stabilizing medication for many people with bipolar disorder. Lithium is also noted for reducing the risk of suicide. Although lithium is among the most effective mood stabilizers, persons taking it may experience side effects similar to the effects of ingesting too much table salt, such as high blood pressure, water retention, and constipation. Regular blood testing is required when taking lithium to determine the correct lithium levels since the therapeutic dose is close to the toxic dose.

The mechanism of lithium salt treatment is believed to work as follows: some symptoms of bipolar disorder appear to be caused by the enzyme inositol monophosphatase (IMPase), an enzyme that splits inositol monophosphate into free inositol and phosphate. It is involved in signal transduction and is believed to create an imbalance in neurotransmitters in bipolar patients. The lithium ion is believed to produce a mood stabilizing effect by inhibiting IMPase by substituting for one of two magnesium ions in IMPase's active site, slowing down this enzyme.

Lithium orotate is used as an alternative treatment to lithium carbonate by some sufferers of bipolar disorder, mainly because it is available without a doctor's prescription. It is sometimes sold as "organic lithium" by nutritionists, as well as under a wide variety of brand names. There seems to be little evidence for its use in clinical treatment in preference to lithium carbonate.

Anticonvulsant mood stabilizers
Anticonvulsant medications, particularly valproate and carbamazepine, have been used as alternatives or adjuncts to lithium in many cases. Valproate (Depakote and Depakene, Epival) was FDA approved for the treatment of acute mania in 1995, and is now considered by some doctors to be the first line of therapy for bipolar disorder. For some, it is preferable to lithium because its side effect profile seems to be less severe, compliance with the medication is better, and fewer breakthrough manic episodes occur. However, valproate is not as effective as lithium in preventing or managing depressive episodes, so patients taking valproate may also need an antidepressant as an adjunct medicinal therapy. Some research suggests that different combinations of lithium and anticonvulsants may be helpful. Anticonvulsants are also used in combination with antipsychotics. Newer anticonvulsant medications, including lamotrigine and oxcarbemazepine, are also effective as mood stabilizers in bipolar disorder. Lamotrigine is particularly promising, as it alleviates bipolar depression and prevents recurrence at higher rates. Topiramate has not done well in clinical trials; it seems to help a few patients very much but most not at all. It appears to be useful in some treatment resistant cases. Gabapentin has failed to distinguish itself from placebo as a mood stabilizer.

According to studies conducted in Finland in patients with epilepsy, valproate may increase testosterone levels in teenage girls and produce polycystic ovary syndrome in women who began taking the medication before age 20. Increased testosterone can lead to polycystic ovary syndrome with irregular or absent menses, obesity, and abnormal growth of hair. Therefore, young female patients taking valproate should be monitored carefully by a physician. It should be noted, however, that the therapeutic dose for a patient taking valproate for epilepsy is very different than the therapeutic dose of valproate for an individual with bipolar disorder.

Other anticonvulsants effective in some cases and being studied closer include phenytoin, levitiracetam, pregabalin and valnoctimide. Clonazepam and other benzodiazepines are also antimanic agents.

Atypical antipsychotic drugs
The newer atypical antipsychotic drugs such as risperidone, quetiapine, and olanzapine are often used in acutely manic patients, because these medications have a rapid onset of psychomotor inhibition, which may be lifesaving in the case of a violent or psychotic patient. Parenteral and orally disintegrating (in particular, Zydis wafers) forms are favoured in emergency room settings. These drugs can also be used as adjunctives to lithium or anticonvulsants in refractory bipolar disorder and in prevention of mania recurrence. In light of recent evidence, olanzapine (Zyprexa) has been FDA approved as an effective monotherapy for the maintenance of bipolar disorder. A head-to-head randomized control trial in 2005 has also shown olanzapine monotherapy to be just as effective and safe as lithium in prophylaxis. Eli Lilly also offers Symbyax, a combination of olanzapine and fluoxetine.

Omega-3 fatty acids
Omega-3 fatty acids may also be used as a treatment for bipolar disorder, particularly as a supplement to medication. An initial clinical trial by Stoll et. al. produced positive results. However, since 1999 attempts to confirm this finding of beneficial effects of omega-3 fatty acids in several larger double-blind clinical trials have produced inconclusive results. It was hypothesized that the therapeutic ingredient in omega-3 fatty acid preparations is eicosapentaenoic acid (EPA) and that supplements should be high in this compound to be beneficial. Omega-3 fatty acids may be found in fish, fish oils, and to a lesser degree in other foods such as flaxseed, flaxseed oil and walnuts. Researchers have not determined if flaxseed oil or supplements have the same effect that was observed when bipolar patients were given omega-3 fatty acids through fish products.

Psychotherapy
Certain types of psychotherapy or psychosocial interventions, generally used in combination with medication, often can provide tremendous additional benefit. These include cognitive-behavioral therapy, interpersonal and social rhythm therapy, interpersonal group therapy, family systems therapy, and psychoeducation. Although bipolar patients will not be cured of the illness through "talking," therapy often can be invaluable in helping to address the effects of disruptive manic or depressive episodes that have hurt a patient's career, relationships or self-esteem. Therapy is available not only from psychiatrists but from social workers, psychologists and other licensed counselors.

Electroconvulsive therapy
Electroconvulsive therapy (ECT) is sometimes used to treat severe bipolar depression in cases where other treatments have failed. Although it has proved to be a highly effective treatment, doctors are reluctant to use it except as a treatment of last resort because of the side-effects and possible complications of ECT, particularly when repeated treatments ("maintenance ECT") are needed.

Medical Marijuana
There are many anecdotal claims that medical marijuana can help control the mood swings associated with bipolar disorder. The euphoriant effect of THC can elevate depressive phases, while the tranquilizing effects of THC are effective at controlling manic phases. This is only a theory. It should be noted that THC has different effects on different brains, and some studies suggest that marijuana can actually increase anxiety and depression. While most anti-depressants take several weeks to work at full strength, smoked marijuana is effective in minutes, and eaten marijuana is effective within an hour or two. Also, negative side effects associated with pharmaceutical anti-depressants such as nausea, sleep disruption, and loss of libido are usually non-existant with medical marijuana. Of course, marijuana legality issues makes this treatment medically unavailable and/or difficult to obtain for those looking for an alternative.

Some controlled medical studies have concluded that data suggests adults do not increase their risk for depression by using marijuana.

One opinion popular among proponents of medical marijuana suggests that since plants cannot be patented, and because marijuana is easily grown, there has been a concerted effort by the pharmaceutical industry to suppress the use of medical marijuana as a treatment for many disorders and illnesses, including bipolar disorder. In contrast, a UK company, GW Pharmaceuticals, has recently begun marketing Sativex, which is a whole-plant Cannabis extract, and is also pursuing studies of its use for various illnesses, such as cancer and depression.

Alternative treatments
Complementary non-Western treatments, such as acupuncture and orthomolecular therapy, are used by people with bipolar disorder, and some research shows that some of them may have some scientific merit.

Treatment issues
Nearly all bipolar treatment studies have involved treating patients in the acute (initial) mania stage, where use of medication may be justified in removing a patient from danger. Less is known, however, about long-term treatment, where relapse prevention and full remission are the main treatment goals.

Until recently, depression was largely overlooked in bipolar disorder. The anticonvulsant medication, lamotrigine is often used for treating bipolar depression, particularly where other drugs have failed and the patient's disorder has a strong depressive component. New clinical trials are finding that certain new-generation antipsychotics such as olanzapine and quetiapine show some beneficial effect in treating bipolar depression. Lithium also has a mild antidepressant effect.

Because there is a danger of antidepressant medications such as SSRIs switching bipolar patients into mania, these medications are used with caution, nearly always with a mood stabilizer..

Heritability
Bipolar disorder appears to run in families. The rate of suicide is higher in people who have bipolar disorder than in the general population. In fact, people with bipolar disorder are about twice as likely to commit suicide as those suffering from major depression (12% to 6%).

More than two-thirds of people with bipolar disorder have at least one close relative with the disorder or with unipolar major depression, indicating that the disease has a genetic component. Studies seeking to identify the genetic basis of bipolar disorder indicate that susceptibility stems from multiple genes. Scientists are continuing their search for these genes using advanced genetic analytic methods and large samples of families affected by the illness. The researchers are hopeful that identification of susceptibility genes for bipolar disorder, and the brain proteins they code for, will make it possible to develop better treatments and preventive interventions targeted at the underlying illness process.

Recent genetic research
Bipolar disorder is considered to be a result of complex interactions between genes and environment. The monozygotic concordance rate for the disorder is 70%. This means that if a person has the disorder, an identical twin has a 70% likelihood of having the disorder as well. Dizygotic twins have a 23% concordance rate.

In 2003, a group of American and Canadian researchers published a paper that used gene linkage techniques to identify a mutation in the GRK3 gene as a possible cause of up to 10% of cases of bipolar disorder. This gene is associated with a kinase enzyme called G protein receptor kinase 3, which appears to be involved in dopamine metabolism, and may provide a possible target for new drugs for bipolar disorder.

Medical imaging
Researchers are using advanced brain imaging techniques to examine brain function and structure in people with bipolar disorder, particularly using the functional MRI and positron emission topography. An important area of neuroimaging research focuses on identifying and characterizing networks of interconnected nerve cells in the brain, interactions among which form the basis for normal and abnormal behaviors. Researchers hypothesize that abnormalities in the structure and/or function of certain brain circuits could underlie bipolar and other mood disorders and studies have found anatomical differences in areas such as the subgenual prefrontal cortex and hippocampus. Better understanding of the neural circuits involved in regulating mood states, and genetic factors such as the FAT-0 chromosome linked to bipolar disorder, may influence the development of new and better treatments and may ultimately aid in early diagnosis and even a cure.

Personality types
An evolving literature exists concerning the nature of personality and temperament in bipolar disorder patients, compared to major depressive disorder (unipolar) patients and non-sufferers. Such differences may be diagnostically relevant. Using MBTI continuum scores, bipolar patients were significantly more extroverted, intuitive and perceiving, and less introverted, sensing, and judging  than were unipolar patients. This suggests that there might be a correlation between the Jungian extraverted intuiting process and bipolar disorder.

Research into new treatments
In late 2003, researchers at McLean Hospital found tentative evidence of improvements in mood during EP-MRSI imaging, and attempts are being made to develop this into a form which can be evaluated as a possible treatment.

NIMH has initiated a large-scale study at twenty sites across the U.S. to determine the most effective treatment strategies for people with bipolar disorder. This study, the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD), will follow patients and document their treatment outcome for 5 to 8 years. For more information, visit the Clinical Trials page of the NIMH Web site.

Transcranial magnetic stimulation is another fairly new technique being studied.

Pharmaceutical research is extensive and ongoing, as seen at clinicaltrials.gov.

Gene therapy and nanotechnology are two more areas of future development.

Bipolar disorder and creativity


Many artists, musicians, and writers have experienced its mood swings, and some credit the condition with their creativity. However, this disease ruins many lives, and it is associated with a greatly increased risk of suicide. Psychiatrist Kay Jamison, who herself has bipolar disorder and is considered a leading expert on the disease, has written several books that explore this idea, including "Touched with Fire". Research indicates that while mania may contribute to creativity (see Andreasen, 1988), hypomanic phases, such as those experienced in Bipolar II and cyclothymia, actually contribute more (see Richards, 1988). This is perhaps due to the distress and impairment associated with full-blown mania, which may be preceded by symptoms of hypomania (i.e. increased energy, confidence, activity) but soon spirals into a state much too debilitating to allow much creative endeavor.

Many famous people are believed to have been affected by bipolar disorder, based on evidence in their own writings and contemporaneous accounts by those who knew them. Bipolar disorder is found in disproportionate numbers in people with creative talent such as artists, musicians, authors, poets, and scientists, and it has been speculated that the mechanisms which cause the disorder may be related to those responsible for creativity in these persons. Many of the historical creative talents commonly cited as bipolar were "diagnosed" retrospectively after their deaths and thus the diagnoses are unverifiable; however, in cases diagnosed in recent decades there does seem to be at least some correlation between bipolar disorder and creativity.

The possible explanation for this is that hypomanic phases of the illness allow for heightened concentration on activities and the manic phases allow for around-the-clock work with minimal need for sleep. Another theory is that the rapid thinking associated with mania generates a higher volume of ideas, and as well associations drawn between a wide range of seemingly unrelated information. The increased energy also allows for greater volume of production. See list of people believed to have been affected by bipolar disorder.

Bipolar Disorder and Medical Marijuana

 * The Use of Cannabis as a Mood Stabilizer in Bipolar Disorder: Anecdotal Evidence and the Need for Clinical Research
 * Medicinal Uses of Marijuana: Psychological Disorders
 * New Study: Marijuana Users Less Depressed
 * Medical Cannabis Resource Center-Bipolar Information Pages
 * Cannabis and Depression by Jay R. Cavanaugh, Ph.D.
 * GW Pharmaceuticals
 * 'Assessment Worksheet for Evaluating Petitions to Expand the List of "Debilitating Medical Conditions" Under the Oregon Medical Marijuana Act'

Research

 * NAMI index of research studies
 * Juvenile Bipolar Research
 * Bipolar Disorder in Children - Reviews of recent findings and research
 * Mood Disorder Research Group (UK)
 * Bipolar Twin Study, Institute of Psychiatry, London - Seeking further volunteers
 * Omega-3 Fatty Acids Evaluated for Bipolar Disorder. Psychiatric Times December 1999  Vol. XVI  Issue 12
 * Anticonvulsants and antipsychotics in the treatment of bipolar disorder - 2004, a literature review.
 * Psychosocial Approaches in the Management of Bipolar Disorder - another review article.
 * New Research in Bipolar Disorder - a website by a scientist who researches bipolar disorder.

Evidence-based medicine

 * Evidence-based guidelines for treating bipolar disorder: recommendations from the British Association for Psychopharmacology
 * Affective disorders - Cochrane systematic reviews
 * Cochrane Collaboration Depression, Anxiety and Neurosis Group

Other resources

 * HealthyPlace.com Bipolar Community - Comprehensive information about Bipolar disorder in adults and children. Includes causes for Bipolar, treatment, medications and alternative remedies. Online bipolar tests, journals, support groups, bipolar chat and bulletin boards.
 * Facts about Bipolar Disorder
 * NIMH information
 * Bipolar disorder and manic depression information - MayoClinic.com
 * Helpguide: Bipolar Disorder: Signs, Symptoms and Treatment
 * Mental Health: A Report of the Surgeon General - Chapter 4 section 3 - Mood Disorders
 * Bipolar Happens Resource written by a person suffering with bipolar disorder for over 20 years. Focuses on how a person can manage bipolar disorder.
 * Coping With Bipolar Proven techniques to help co-manage and cope with bipolar disorder in a loved one. Compiled by a NAMI faculty member from thousands of bipolar victims and co-victims.
 * Alternative Depression Therapy Alternative and Holistic approaches to the treatment of Bipolar Disorder and Depression. Written by a licensed psychotherapist specializing in mood disorders.
 * The Psychological Effects of Cannabis
 * Symptoms of depressive/manic episodes

News stories

 * Q&A: Cannabis and health Cannabis classification news in the UK.
 * UCSD Researchers Identify Gene Involved In Bipolar Disorder
 * Unique Type Of MRI Scan Shows Promise In Treating Bipolar Disorder
 * Two mental diseases appear to be linked: reports on apparent link of protein kinase C to both bipolar disorder and schizophrenia
 * A list of famous people (including Canadians) can be found at http://www.mooddisorderscanada.ca/depression/print/p_famous.htm

تعكر المزاج الثنائي القطب Maniodepresivní psychóza Maniodepressiv sindslidelse Bipolare Störung

Desorden bipolar Trouble bipolaire Trastorno bipolar 조울증 Psicosi maniaco-depressiva הפרעה דו-קוטבית Maniakinė depresija Bipolaire stoornis 双極性障害 Choroba afektywna dwubiegunowa Distúrbio bipolar Биполярное аффективное расстройство Kaksisuuntainen mielialahäiriö Bipolärt syndrom