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Bipolar Disorder

What is bipolar disorder?

Bipolar disorder, or manic depression, is a medical illness that causes extreme shifts in mood, energy, and functioning. These changes may be subtle or dramatic and typically vary greatly over the course of a person’s life as well as among individuals. Over 10 million people in America have bipolar disorder, and the illness affects men and women equally. Bipolar disorder is a chronic and generally life-long condition with recurring episodes of mania and depression that can last from days to months that often begin in adolescence or early adulthood, and occasionally even in children. Most people generally require some sort of lifelong treatment. While medication is one key element in successful treatment of bipolar disorder, psychotherapy, support, and education about the illness are also essential components of the treatment process.

What are the symptoms of mania?

Mania is the word that describes the activated phase of bipolar disorder. The symptoms of mania may include:

  • either an elated, happy mood or an irritable, angry, unpleasant mood
  • increased physical and mental activity and energy
  • racing thoughts and flight of ideas
  • increased talking, more rapid speech than normal
  • ambitious, often grandiose plans
  • risk taking
  • impulsive activity such as spending sprees, sexual indiscretion, and alcohol abuse
  • decreased sleep without experiencing fatigue

What are the symptoms of depression?

Depression is the other phase of bipolar disorder. The symptoms of depression may include:

  • loss of energy
  • prolonged sadness
  • decreased activity and energy
  • restlessness and irritability
  • inability to concentrate or make decisions
  • increased feelings of worry and anxiety
  • less interest or participation in, and less enjoyment of activities normally enjoyed
  • feelings of guilt and hopelessness
  • thoughts of suicide
  • change in appetite (either eating more or eating less)
  • change in sleep patterns (either sleeping more or sleeping less)

What is a "mixed" state?

A mixed state is when symptoms of mania and depression occur at the same time. During a mixed state depressed mood accompanies manic activation.

What is rapid cycling?

Sometimes individuals may experience an increased frequency of episodes. When four or more episodes of illness occur within a 12-month period, the individual is said to have bipolar disorder with rapid cycling. Rapid cycling is more common in women.

What are the causes of bipolar disorder?

While the exact cause of bipolar disorder is not known, most scientists believe that bipolar disorder is likely caused by multiple factors that interact with each other to produce a chemical imbalance affecting certain parts of the brain. Bipolar disorder often runs in families, and studies suggest a genetic component to the illness. A stressful environment or negative life events may interact with an underlying genetic or biological vulnerability to produce the disorder. There are other possible "triggers" of bipolar episodes: the treatment of depression with an antidepressant medication may trigger a switch into mania, sleep deprivation may trigger mania, or hypothyroidism may produce depression or mood instability. It is important to note that bipolar episodes can and often do occur without any obvious trigger.

How is bipolar disorder treated?

While there is no cure for bipolar disorder, it is a treatable and manageable illness. After an accurate diagnosis, most people can achieve an optimal level of wellness. Medication is an essential element of successful treatment for people with bipolar disorder. In addition, psychosocial therapies including cognitive-behavioral therapy, interpersonal therapy, family therapy, and psychoeducation are important to help people understand the illness and to internalize skills to cope with the stresses that can trigger episodes. Changes in medications or doses may be necessary, as well as changes in treatment plans during different stages of the illness.

It is useful to know whether the "mood stabilizing medication" prescribed has been approved by the FDA for use in bipolar disorder:

Medications for Mania:

Currently FDA approved: lithium (Eskalith or Lithobid), divalproex sodium (Depakote), carbamazepine (Tegretol), olanzapine (Zyprexa), risperidone (Risperdal), quetiapine (Seroquel), ziprasidone (Geodon), aripiprazole (Abilify)

At least one adequate well controlled study with positive data: haloperidol (Haldol)

Medications for bipolar depression:

Currently FDA approved: combination of olanzapine and fluoxetine (Symbyax)

Also at least one adequate well controlled study with positive data: quetiapine (Seroquel) and lamotrigine (Lamictal)

Medications for preventing (or delaying) recurrence:

Currently FDA approved: lithium (Eskalith or Lithobid), lamotrigine (Lamictal), olanzapine (Zyprexa), and aripiprazole (Abilify) 

Frequently a combination of two or more medications is used, especially during severe episodes of acute mania or depression.

Medication specifics and possible side effects:

Lithium has long been used as a first line treatment for acute mania in people with bipolar disorder for more than 50 years. It generally has more positive impact when used earlier, rather than later, in the course of bipolar disorder. Research shows it is most effective in those individuals with a family history of the illness, and in those experiencing the bipolar I sequence of swings between mania and depression with return to normal function between episodes.

Like all medications, lithium treatment produces side effects. The most common ones are dose-related and can be effectively managed, but for about 30 percent of people who try it, lithium is not tolerable. Lithium side effects may include frequent urination, excessive thirst, weight gain, memory problems, hand tremors, gastrointestinal problems, hair loss, acne, and water retention. There are two important lithium side effects, that can be effectively monitored by a simple blood test: 1)hypothyroidism, which mimics depression and can be easily treated, and 2) less commonly, damage to kidney functions.

Anti-convulsants: The Food and Drug Administration (FDA) approved divalproex sodium (Depakote) in 1995 for treating bipolar episodes. Originally approved in 1983 as a drug to treat epilepsy, Depakote was found to be as effective as lithium for treating acute mania, and appears to be better than lithium in treating the more complex bipolar subtypes of rapid cycling and dysphoric mania, as well as co-morbid substance abuse. In addition, Depakote may be safely given in larger doses to treat acute episodes, and works faster in this situation than lithium. The generic version of this drug is valproic acid. Some people find that the generic version produces more gastrointestinal distress than Depakote.

Depakote may also produce sedation and gastrointestinal distress, but these side effects often resolve during the first six months of treatment, or with dose adjustment. Another dose-related side effect is weight gain, and rare liver and pancreatic function problems may develop while taking Depakote. However, Depakote is generally well-tolerated, and is now prescribed far more often then lithium. Recent controlled trials indicate that the combination of Depakote and lithium is more effective in preventing relapse and recurrence than treatment with lithium alone.

Lamictal (lamotrigine), another anti-convulsant, is effective in the treatment of acute depression in bipolar I and II and in promoting remissions between episodes. For most people, Lamictal has a very tolerable side effect profile. Rarely, this medication can cause a rash serious enough to cause a medical emergency. The risk of this one potentially serious side effect can be reduced by starting with a low dose and going slowly in increasing the dose.

Use of Antidepressants

Standard antidepressant medications (those approved for the treatment of unipolar depression) have not yet been proven effective for bipolar depression. Although the evidence supporting their use for bipolar depression is limited to small or less rigorous studies, these medications remain the most commonly used treatment for bipolar depression. The data from larger studies finds neither evidence of benefit nor evidence that these agents cause large numbers of depressed patients to switch into mania.

Use of Antipsychotic Medications as Mood Stabilizers

To control acute episodes, antipsychotic medications may be used alone (monotherapy), or added to anti-convulsant medications (combination therapy). Medication guidelines now recommend the combination of these two medications as most effective for acute manic episodes. Because the older typical antipsychotic medications run the risk of causing permanent movement disorder, and have been associated with depression when used over the long term, the new atypical antipsychotics are now preferred for this purpose. All the new atypicals are effective in the treatment of acute and mixed mania. Olanzapine (Zyprexa) and risperidone (Risperdal) are FDA-approved for this purpose.

Finding the right preventive/maintenance medicine is an art informed by science and your own observations. Not all medicines that work in the acute phase of mania are as strong in preventing the next episode, so this is an area to explore.

Side effects of the atypicals are different than with first-generation antipsychotics (such as Haldol), although sedation, weight gain, and risk of diabetes are problems associated with many of the new antipsychotics. Clozapine and olanzapine, both effective antipsychotics and mood stabilizers, offer the most risk in this area. Weight gain is a serious clinical concern related to all atypical antipsychotics, and to anti-convulsants as well. Not only can weight gain lead to adult onset also known as type 2 diabetes and cardiovascular diseases, but being overweight is also now the leading cause of medication non-adherence. Doctors advise weekly monitoring of weight in the early stages of taking these medications, along with regular exercise and healthy diets, and people must be willing to make lifestyle changes to maintain optimal health. The FDA has noted an association between all atypical antipsychotics and the risk of diabetes. As the science develops in this area, it will continue to inform medicine choices for the person that best reflect their risks and benefits.             

Reviewed by Ken Duckworth, MD, October 2006

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