Bipolar disorder is a recurrent disease that can be unpredictable. It is treatable, however, and many people have healthy and productive lives. The major goals of treatment are to:
- Treat and reduce the severity of acute episodes of mania or depression when they occur
- Reduce the frequency of episodes
- Avoid cycling from one phase to another
- Help the person function as well as possible between episodes
Challenges of Bipolar Treatment
The treatments for bipolar disorder, while very effective, pose some specific challenges for the person:
- Mood variations in bipolar disorder are not predictable, so it is sometimes difficult to tell if a person is responding to treatment or naturally emerging from a bipolar phase.
- A person with bipolar disorder cannot always reliably inform the doctor about the state of the illness.
- The person is likely to need more than one medication during the course of the disease. This increases the risk for side effects. Noncompliance is common.
- People may have more than one mental health or medical problem and need different drugs to treat each condition. Such medications can interact with drugs used to treat bipolar disorder or increase side effects.
- Treatment strategies for children and the elderly have not been intensively studied and have not been clearly defined.
- People need to monitor their condition on a lifelong basis.
Specific Drugs and Other Treatments Used in Bipolar Disorder
Drugs Used in Bipolar Disorder
Mood stabilizing drugs are the mainstay for people with bipolar disorder. They are defined as drugs that are effective for acute episodes of mania and depression and that can be used for maintenance. The standard first-line mood stabilizers are lithium and valproate. Both drugs stimulate the release of the neurotransmitter glutamate, although they appear to work through different mechanisms. Other drugs may also be used. Drugs to treat bipolar disorder should be prescribed and managed by a psychiatrist.
The following are some of the standard drugs used for treatment of bipolar disorder:
- Lithium. Lithium has been used for years for bipolar disorder. It remains the best drug for people with pure mania characterized by euphoria and pure depression. Although imperfect, it is also an effective long-term drug for many people with other bipolar subtypes.
- Antiseizure Drugs. Valproate (valproic acid, generic) carbamazepine (Tegretol, Carbatrol, Equetro, generic), oxcarbazepine (Trileptal, generic), and lamotrigine (Lamictal, generic) are the antiseizure drugs used most often in treating bipolar illness. Other antiseizure drugs used or investigated for bipolar include gabapentin (Neurontin, generic), zonisamide (Zonegran, generic), and topiramate (Topamax, generic). To date, it is not clear if any of these newer drugs are useful for the treatment of acute mania.
- Atypical Antipsychotics. Drugs known as atypical antipsychotics are used to treat schizophrenia and also have mood stabilizing properties that are applicable to bipolar disorder. They may be used either alone or in combination with lithium or valproate. Atypical antipsychotics approved for treating bipolar disorder include olanzapine (Zyprexa, generic), risperidone (Risperdal, generic), quetiapine (Seroquel, generic), ziprasidone (Geodon, generic), aripiprazole (Abilify), asenapine (Saphris), and cariprazine (Vraylar).
- Antidepressants. Antidepressants alone are not recommended, but may sometimes be used for depressive symptoms that do not respond to lithium and antiseizure drugs. The first choices for antidepressants are bupropion (Wellbutrin, generic) or a selective serotonin reuptake inhibitor (SSRI) such as fluoxetine (Prozac, generic) or paroxetine (Paxil, generic).
These drugs may be used singly or in various combinations. Other drugs, such as typical antipsychotics or anti-anxiety drugs, are used as necessary.
Electroconvulsive therapy (ECT) is a treatment that may be helpful for select people who require stabilization or who have severe mania or depression.
In addition to medical treatments, psychotherapy and sleep management are also parts of bipolar disorder treatment. They can help reduce symptoms and prevent relapse.
Treatment for Manic Episodes
Step 1. Determine the Need for Hospitalization and Eliminate Triggers
The first step in treating an acute manic episode is to rule out any life-threatening conditions and eliminate any triggers, such as antidepressants or other substances that can elevate moods. People often require hospitalization at the onset of acute mania.
Step 2. Control Symptoms of Mania with a Mood Stabilizer
Initiation of a mood-stabilizing drug is the critical first step. It may take several weeks for a mood stabilizer to take effect, and other drugs may be needed.
- Either valproate or lithium is the standard first drug for most manic episodes. Lithium is effective for most hypomanic and manic episodes.
- Carbamazepine may be used in place of valproate to treat people with multiple manic episodes, mixed episodes, and rapid cycling. Combinations of these mood stabilizers may be used if the person does not respond to a single drug.
Step 3. Addition of Other Treatments
Other treatments may be added to speed recovery, treat any psychosis, and achieve remission:
- If the person does not respond fully within a week and symptoms are more severe, antipsychotics may be added to mood stabilizers. Atypical antipsychotics are more likely to be used first. They include olanzapine (Zyprexa, generic), risperidone (Risperdal, generic), quetiapine (Seroquel, generic), ziprasidone (Geodon, generic), aripiprazole (Abilify), cariprazine (Vraylar), and asenapine (Saphris).
- Older antipsychotic drugs (also called typical antipsychotics), such as haloperidol (Haldol, generic), may be used for acute mania. They may be more likely to cause extrapyramidal effects, which disrupt motor control, and are not generally used on a long-term basis.
- Benzodiazepines, such as clonazepam (Klonopin, generic) or lorazepam (Ativan, generic), are anti-anxiety drugs that may be beneficial if the person is experiencing severe mania.
- ECT. This non-drug treatment may help people who do not respond to medication.
Step 4. Withdrawal of Some Drug Treatments
In cases of improvement and sustained recovery, the antipsychotic or benzodiazepine drugs are slowly withdrawn and only the mood-stabilizing drug is continued.
Step 5. Continuation of Mood Stabilizers
Mood stabilizers are typically continued for about 8 weeks, unless the person shows signs of shifting to another mood state. If the person remains stable at that time, the doctor may decide to continue maintenance treatment or to gradually withdraw medications.
Treatment for Depressive Episodes
Depressive episodes are a particular challenge because many antidepressant drugs pose a risk for triggering mania. It is not clear if standard antidepressants work for bipolar depression. Depressive episodes are very difficult to control and people who do not respond to mood stabilizers may endure prolonged depressive episodes up to 2 to 3 months.
Lithium or lamotrigine are the standard first-line treatments for depressive episodes. Many studies indicate that lithium works better for controlling manic states, and that lamotrigine works better for bipolar depression.
If improvement does not occur within 2 to 4 weeks, an antidepressant may be added. Antidepressants alone are not recommended. The first choices for antidepressants are bupropion (Wellbutrin, generic) or SSRI such as fluoxetine (Prozac, generic).
Other drugs are also approved specifically for treatment of bipolar depression. Symbyax combines the atypical antipsychotic olanzapine with the SSRI antidepressant fluoxetine. Quetiapine (Seroquel, generic) is an atypical antipsychotic which is approved for both treatment of bipolar mania and bipolar depression. Lurasidone (Latuda) is an atypical antipsychotic approved for treating adults with depression associated with bipolar I disorder. It can be used either alone or in combination with lithium or valproate.
Cognitive-behavioral therapy (CBT) or other psychotherapy programs may help people cope with depressive episodes by developing ways to manage negative thoughts and behaviors. ECT is another treatment option for severe depression.
Treatment for Maintenance
Drugs Used During Maintenance
Relapse occurs in most people after treatment of acute attacks, and people who are at high risk for recurring episodes should consider lifelong maintenance therapy. This usually involves mood-stabilizing drugs:
- Lithium is a first-line mood stabilizer used in maintenance therapy. The anti-epileptic drug valproate is also a first-line treatment. In general, the two work equally well, although there are some differences in side effects.
- Lamotrigine, another anti-epileptic drug, is approved as a maintenance treatment for bipolar I disorder and may also be used as a first-line drug for treating depressive episodes.
- Carbamazepine and oxcarbazepine are other anti-epileptic drugs used as alternative maintenance treatments.
- Atypical antipsychotics may be used for maintenance, particularly in combination with a mood stabilizer.
The general recommendations for maintenance therapy with lithium are as follows:
- Lithium can help reduce the risk for suicide. The earlier lithium is started in the disease process, the better. Studies suggest that people on long-term lithium therapy have survival rates comparable to the general population, but those who permanently drop out of therapy have significantly lower survival rates due to an increased suicide risk.
- People who stop lithium and then start again may be at higher risk for hospitalization and are more likely to need more than one drug.
- For those who want to stop, a gradual discontinuation (over 15 to 30 days) may help to delay recurrence. Stopping lithium quickly poses a high risk for relapse and for suicide.
Treatment for Rapid Cycling
The first step in treating rapid cycling is to try to identify and resolve other factors, such as drug abuse or hypothyroidism (underactive thyroid), which may have caused this condition. Antidepressants, particularly SSRIs, may contribute to rapid cycling and are usually tapered off.
Rapid cycling can be challenging to control and there is no consensus on how which drugs are most effective in treating it. People may need to try different medications to see what works.
In general, lithium and valproate are the first-line treatments for rapid cycling associated with bipolar I disorder, and lamotrigine for bipolar II disorder. Atypical antipsychotics such as aripiprazole, olanzapine, and quetiapine may also be tried. ECT may be useful in some situations.
In addition, other measures should be taken:
- People should avoid anti-anxiety drugs, alcohol, caffeine, and stimulants.
- People should avoid exposure to bright light.
- All efforts should be made to help the person sleep normally.
Treatment for Pregnant Patients
Treatment of pregnant women with bipolar disorder poses specific challenges. All psychiatric medications can cross the placenta into amniotic fluid. These drugs can also enter breast milk. While certain types of medications present more risks to the fetus than others, not taking medications also carries substantial risks. Untreated women may be less likely to receive appropriate prenatal care, and more likely to engage in risky behaviors, including alcohol and tobacco use. Non-treatment may also cause difficulties with mother-infant bonding and disruptions in the family environment.
A woman with bipolar disorder who is considering pregnancy should consult with her gynecologist/obstetrician, psychiatrist, and primary care physician. Close follow-up with all of these providers should take place during the pregnancy.
The American College of Obstetricians and Gynecologists (ACOG) has guidelines for psychiatric drug treatment during pregnancy:
- When possible, a single medication at a higher dosage is preferred over multiple medications.
- Lithium is associated with a small increased risk for heart defects and other birth defects in the fetus.
- For a pregnant woman with mild bipolar disorder, the medication may be gradually tapered off before conception. Women who are at moderate risk for relapse are often asked to stop taking lithium until the fetus' organ formation is complete. Women at high risk for bipolar disorder relapse may need to continue taking lithium throughout the pregnancy.
- Women should have their lithium levels closely monitored during pregnancy. Lithium levels in the blood that were previously stable may change during pregnancy.
- If lithium was taken during the first trimester, ultrasound and perhaps echocardiography are generally performed to evaluate the fetal heart.
- Women who must take lithium during pregnancy should take the lowest possible dosage and stop the drug 1 to 2 days before delivery. Mothers who are taking lithium should not nurse their babies, since lithium is concentrated in breast milk.
For antiseizure drugs, valproate should not be used during the first trimester of pregnancy, if possible. Valproate is specifically associated with neural tube, craniofacial, and heart birth defects as well as growth delay and cognitive impairment. Carbamazepine may also increase facial malformation but, like lamotrigine, is considered a safer drug than valproate for use during pregnancy.
For atypical antipsychotics, safety data is limited and there have been no long-term studies on the effects of children exposed to these drugs during pregnancy. Some studies indicate that these drugs can increase the risk of low birth weight. In general, doctors do not recommend the routine use of atypical antipsychotics during pregnancy.
For antidepressants, doctors decide on the appropriateness of these drugs on a case-by-case basis. The SSRI paroxetine should be avoided by women who plan on becoming pregnant as this drug significantly increases the risk of fetal heart defects. Other SSRIs are generally considered safe for use during pregnancy and breastfeeding.
Treatment for Children and Adolescents
Doctors are still trying to decide the best treatment approaches to bipolar disorder in children and adolescents. The drugs used for bipolar disorder have considerable side effects, which may be more severe in young people. Parents should consider the potential risks and benefits of treatment for their children.
Lithium is generally used as the first-line treatment, with valproate or atypical antipsychotics as alternatives. If treatment with a single drug does not work, a combination of drugs may be used. For atypical antipsychotic drugs, risperidone (Risperdal, generic), aripiprazole (Abilify), quetiapine (Seroquel, generic), and olanzapine (Zyprexa, generic) are approved for the treatment of mania in children and adolescents with bipolar disorder.
When prescribing atypical antipsychotics to children and adolescents, the benefits of treatment must be weighed against the potential harms of side effects. Atypical antipsychotics can increase the risk for weight gain and type 2 diabetes, heart problems, increased prolactin levels, sedation, and movement disorders (extrapyramidal side effects). Doctors need to carefully monitor pediatric patients for potential development of any of these side effects.
Psychotherapy is also an important addition to drug treatment. Therapy that includes the entire family is important. ECT may benefit adolescents who have not been helped by medication.