In cases of improvement and sustained recovery, the neuroleptic or benzodiazepine is slowly withdrawn and only the mood-stabilizing drug is continued.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 patient shows signs of shifting to another mood state. If the patient remains stable at that time, the doctor may decide to continue maintenance treatment or to gradually withdraw medications.
Treatment Guidelines for Depressive Episodes
Depressive episodes pose a particular challenge. They are a significant cause of suffering, yet the use of standard antidepressants poses a significant risk for triggering mania. It is also not clear if standard antidepressants work for bipolar depression. In fact, depressive episodes are so difficult to treat that some experts advise patients who do not respond to mood stabilizers to simply expect to endure the depressive episode for about 2 - 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 - 4 weeks, an antidepressant may be added. Antidepressants alone are not recommended. The first choices for antidepressants are bupropion (Wellbutrin) or paroxetine (Paxil). Alternatives include one of the selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine (Prozac), a newer antidepressant such as venlafaxine (Effexor), or a monoamine oxidase inhibitor (MAOI).
Several studies have found no additional benefits from antidepressants. Many studies indicate that antidepressants may cause patients to “switch” to a manic state. Any patient with bipolar disorder who takes antidepressants and who develops symptoms of hypomania should stop taking these drugs, because hypomania is often a sign of impending mania. All antidepressants should be tapered after the mood has been stabilized for a month.
Alternative: Atypical Antipsychotics. An atypical antipsychotic combined with a mood stabilizer is another treatment option. In 2003, the FDA approved a drug (Symbyax) that combines the atypical antipsychotic olanzapine and the SSRI antidepressant fluoxetine. Symbyax is the first drug to be specifically approved for treatment of bipolar depression. In 2006, quetiapine (Seroquel), which is approved for treatment of bipolar mania, received an additional approval for treatment of bipolar depression.
Psychotherapy. Cognitive-behavioral therapy or other psychotherapy programs may help patients endure depressive episodes by developing ways to manage negative thoughts and behaviors.
Other Treatments. Electroconvulsive therapy is another option for depression that does not respond to less intense approaches. Antipsychotic medication may be needed for severely depressed and delusional patients. Small studies indicate that a subgroup of patients may respond to thyrotropin-releasing hormone, a substance that regulates thyroid hormones.
Treatment Guidelines for Mixed Episodes and Rapid Cycling
The first step in treating rapid cycling is to try to identify and resolve other factors, such as drug abuse or hypothyroidism, which may have caused this condition. Many patients may require a combination of medications to control rapid cycling.
- Antidepressants may prompt rapid cycling and should be tapered off.
- Lithium or valproate is a first-line treatment for rapid cycling.
- Lamotrigine is an alternative treatment for rapid cycling.
- Atypical antipsychotics (olanzapine, aripiprazole, ziprasidone, risperidone) are approved to treat mixed episodes. These drugs are used either alone or in combination with lithium or valproate.
- One biological mechanism involved with rapid cycling is an excessive influx of calcium into brain cells. Cardiovascular drugs called calcium channel blockers may be beneficial for ultra-rapid cycling.
- Low thyroid (hypothyroidism) is involved in some cases of rapid cycling. In these cases, levothyroxine, a synthetic derivative of the thyroid hormone T4 (thyroxine), has helped stabilize rapid-cycling patients.
- Electroconvulsive therapy can be useful in emergency situations.
In addition, other measures should be taken:
- Patients should avoid anti-anxiety drugs, alcohol, caffeine, and stimulants.
- Patients should avoid exposure to bright light.
- All efforts should be made to help the patient sleep normally.
Treatment Guidelines for Maintenance
Drugs Used During Maintenance. Relapse occurs in most patients after treatment of acute attacks, and patients who are at high risk for recurring episodes should consider life-long 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 valproate may be better for patients who have had multiple manic episodes. There are some differences in side effects, but the drop-out rates between the drugs are similar. Lithium has proved effective for preventing relapses of manic episodes, but may not work as well for controlling depressive symptoms.
- Lamotrigine, an anti-epileptic drug, was approved in 2003 for long-term maintenance treatment. It is also 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. In 2004, olanzapine became the first atypical antipsychotic to be approved specifically for maintenance treatment.
The general recommendations for maintenance therapy with lithium are as follows:
- The earlier lithium is started in the disease process, the better. Studies suggest that patients 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. In one study, patients who stopped taking it increased their risk of suicide in the first year by 20 times.
- Lithium still works for patients who discontinue and then restart treatment later on. In such cases, however, there may be a greater need for drug combinations. In addition, patients who stop and start again may be at higher risk for hospitalization than those who use the drug continuously.
- For those who want to stop, a gradual discontinuation (over 15 - 30 days) may help to delay recurrence. Stopping lithium quickly poses a high risk for relapse and even for suicide.
Guidelines for the Treatment of Pregnant Patients with Bipolar DisorderInformation on clinical care of pregnant women with bipolar disorder remains very limited. In fact, in one survey, almost half of women with bipolar disorder were discouraged by their doctors from becoming pregnant. Nevertheless, after careful counseling about medications, possibilities for relapse, and disease severity, nearly two-thirds of them decided to attempt pregnancy. Risks for Bipolar Episodes. Some studies suggest the following risks for bipolar episodes during and after pregnancy:
Drugs for Bipolar and Pregnancy. It is not ethical to test drugs during pregnancy, so all known effects of bipolar drugs are reported anecdotally. It is well-known, however, that most mood stabilizers used for bipolar disorder carry a high risk for the fetus, particularly if they are taken during the first trimester. Taking mood stabilizers at the time of delivery may help reduce the risk of manic episodes occurring after the baby is born. However, caution is still advised. Reported effects of drugs taken during pregnancy include:
Electroconvulsive Therapy (ECT). In spite of its bad press, ECT appears to be very beneficial for women with bipolar disorder who become pregnant. The patient should discuss this option with her doctor. |
Treatment Guidelines for Children and Adolescents
Doctors are still trying to decide the best treatment of bipolar disorder in children and adolescents. The drugs used for bipolar disorder have considerable side effects, which may be even more severe in younger people. Parents should consider the potential risks and benefits of treatment for their children.
Lithium and valproate are first-line treatments. Alternative treatments include the antiseizure drug carbamazepine or atypical antipsychotics (olanzapine, quetiapine, risperidone). If the patient does not respond to lithium or valproate treatment, one of these other drugs may be substituted. If treatment with a single drug does not work, a combination of these drugs may be used.
Lithium and valproate are the drugs most studied in children and adolescents. Some evidence suggests that larger rather than smaller doses of valproate or lithium may work best. However, side effects of these drugs in children may include severely impaired thinking, acne, increased urination (lithium), and menstrual irregularities and polycystic ovary syndrome (valproate).
Pediatric prescriptions for atypical antipsychotics have been increasing in recent years. However, the safety and effectiveness of these drugs for children and adolescents has not been established. They appear to work well in the short-term, but a 2006 study noted that there is little available evidence concerning their long-term effects.
Psychotherapy is an important addition to drug treatment. Therapy that includes the entire family is also important.
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