Treatment Options for Bipolar Disorder

Drug Therapy for Bipolar Disorder

Drug therapy is usually the first-line of therapy used in treating acute episodes of bipolar disorder.

Medications chosen for treatment of bipolar disorder are usually determined by:

  • Treatment history
  • Type of bipolar disorder
  • Severity and current state of mood
  • Side effects of each drug

Women who are trying to conceive, who are pregnant, or who are nursing should discuss with their doctors the benefits and risks involved in continuing treatment with any medication.

There are three types of medications utilized in the treatment of bipolar disorder.

  • Mood stabilizers
  • Antipsychotics
  • Antidepressants

Mood Stabilizers

Mood stabilizers are drugs that provide acute relief from mania, provide acute relief from depression, and prevent recurrences of mania or depression.

The most commonly used mood stabilizers are:

  • Lithium (Eskalith, Lithobid, Lithonate)
  • Divalproex sodium (Depakote)
  • Carbamazepine (Tegretol, Carbatrol)
  • Oxcarbazepine (Trileptal)
  • Lamotrigine (Lamictal)
  • Gabapentin (Neurontin)
  • Topiramate (Topomax)
Lithium

Lithium is a naturally occurring element. Its efficiency for treatment was discovered in the 1950's and it was approved by the U.S. Food and Drug Administration (FDA) for treating mania in 1995. It is very effective for pure mania and depression and can be combined with other medications for enhanced effect. It is less effective for rapid cycling or mixed episodes. Lithium has also been shown to reduce the risk of suicide.

Studies indicate that up to 64% of bipolar patients do not respond to lithium. Nonresponding patients include those experiencing:

  • Mixed states
  • Personality disorders
  • Comorbid substance abuse
  • Mixed cycling
  • Previously failed trials of lithium

When lithium is discontinued, there is usually an abrupt rebound effect with an increase in manic or depressive symptoms. The risk is reduced by lowering the dosage of the drug over several months.

Side effects include:

  • Weight gain
  • Tremor
  • Nausea
  • Increased urination

Long term side effects may include renal, thyroid, and cardiovascular problems. Side effects can be minimized by regularly monitoring blood levels of lithium and adjusting the medication as needed.

Divalproex Sodium

This drug was used for many decades as an anticonvulsant. It was approved by the FDA for treatment of mania in 1995. Divalproex is also effective for:

  • Mania
  • Mixed manic episodes
  • Rapid cycling
  • Comorbid conditions (e.g., substance abuse or anxiety)

Divalproex differs from lithium in that it can be given initially in large doses to achieve a rapid response to acute mania or depression.

Side effects may include:

  • Weight gain
  • Sedation
  • Tremor
  • Gastrointestinal disturbances
  • Liver inflammation

Monitoring the blood levels and adjusting the medication accordingly can minimize most side effects.

There is some evidence that divalproex may cause hormonal changes in adolescent girls and may be related to the development of Polycystic Ovary Syndrome (PCOS) in women who began taking the drug before the age of 20. Consequently, hormone levels of any young woman taking divalproex must be carefully monitored.

Carbamazepine and Oxcarbazepine

These two closely related drugs (carbamazepine was reformulated into oxcarbazepine) were originally developed as anticonvulsants. They have similar properties to divalproex and are effective for mania and mixed episodes.

Side effects may include:

  • Sedation
  • Gastrointestinal upset
  • Bone marrow suppression
  • Liver inflammation

Bone marrow suppression and liver inflammation are very rare side effects and can be minimized by monitoring blood levels and adjusting doses of medication accordingly.

Carbamazepine may interact with certain medications so it is important for the physician to know which drugs the patient is taking before prescribing carbamazepine. Oxcarbazepine is better-tolerated and easier to use.

Lamotrigine

This is a relatively new medication that is indicated for prevention of relapses of depression in bipolar disorder.

Side effects may include:

  • Dizziness
  • Headaches
  • Vision difficulties
  • Serious rash (rare) - increasing the dosage very slowly can minimize this side effect.

Lamotrigine is generally considered to have fewer side effects than most of the other mood stabilizers.

Gabapentin

Though this drug is used as a mood stabilizer, there is relatively little research regarding its efficacy when used for bipolar disorder. It appears to be helpful in reducing anxiety.

Gabapentin does not interact with most medications so it can be added to other mood stabilizers to enhance their effect.

Side effects include:

  • Fatigue
  • Sedation
  • Dizziness
Topiramate

Preliminary research indicates that topiramate may be effective for mania in adolescents. It is different than the other drugs in that it does not cause weight gain and may even help in weight loss.

Side effects may include:

  • Sedation
  • Dizziness
  • Cognitive disturbances
  • Memory difficulties

Topiramate should not be taken by people with kidney stones.

Evidence suggests that abrupt discontinuation of mood stabilizers, especially lithium, is associated with very high relapse rates within several months, even after many years of mood stability. Recommendations are that, when necessary, discontinuation should occur slowly over time.

Antipsychotics

Antipsychotics are used to treat mania as well as control hallucinations or delusions that can occur with severe mania or depression. Antipsychotics are commonly combined with other drugs (e.g., mood stabilizers) but also can be used alone.

There are two kinds of antipsychotics:

  • "Typical" or older antipsychotics
  • "Atypical" or newer antipsychotics
"Typical" Antipsychotics

Drugs in this category include:

  • Haloperidol (Haldol)
  • Perphenazine (Trilafon)
  • Chloropromazine (Thorazine)

Side effects may include:

  • Tardive dyskinesia - repetitive, involuntary, purposeless movements of the tongue, lips, arms, and other parts of the body
  • Muscle stiffness
  • Restlessness
  • Tremors
"Atypical" Antipsychotics

The atypical antipsychotics are a newer generation of drugs being used to treat bipolar disorder. Atypical antipsychotics include:

  • Olanzapine (Zyprexa)
  • Quetiapine (Seroquel) - This is the first antipsychotic medication approved by the U.S. Food and Drug Administration (FDA) for the treatment of both the manic and depressive phases of bipolar disorder
  • Risperidone (Risperdal)
  • Clozapine (Clozaril)
  • Ziprasidone (Geodon)
  • Aripiprazole (Abilify)

In general, the newer atypical antipsychotics are less likely to cause certain distressing side effects associated with older antipsychotics, such as tardive dyskinesia (involuntary movement of muscles) and elevated levels of the hormone prolactin that can lead to menstrual problems, breast changes, and infertility.

Atypical antipsychotics are not, however, totally free of side-effects the most common of which include:

  • Weight gain
  • Drowsiness and somnolence
  • Dizziness
  • Nausea
  • Hyperglycemia (high levels of glucose in the blood)
  • Increased risk of diabetes
  • Agranulocytosis - depression of white blood cells called granulocytes which leads to increased susceptibility to infections. This side-effect is of particularly associated with clozapine. Although other antipsychotics can cause agranulocytosis, the risk for developing this condition is about 10 times higher with clozapine.

To limit side effects, antipsychotics are usually initiated at a low dose and increased slowly with regular monitoring of the blood. Dosages can also be adjusted to minimize side effects. If a patient cannot tolerate atypical antipsychotics, typical antipsychotics are an alternative.

Antidepressants

On October 15, 2004, the U.S. Food and Drug Administration (FDA) issued a Public Health Advisory, asking manufacturers of all antidepressant drugs to revise the labeling for their products to include a boxed warning and expanded warning statements that alert health care providers to an increased risk of suicidality (suicidal thinking and behavior) in children and adolescents being treated with these agents, and additional information about the results of pediatric studies. On May 2, 2007, the FDA expanded the warning regarding suicidality to include young adults between the ages of 18-24. The FDA also informed these manufacturers that it has determined that a Patient Medication Guide (MedGuide), which will be given to patients receiving the drugs to advise them of the risk and precautions that can be taken, is appropriate for these drug products.

The American Psychiatric Association recommends conservative use of antidepressants in the treatment of bipolar disorder for the following reasons:

  • They have not been shown to significantly prevent suicide and reduce mortality
  • They have not been shown to be more effective than mood stabilizers
  • They are less effective than mood stabilizers in preventing relapse of depressive episodes
  • They may actually increase the risk of mania and long-term worsening of bipolar disorder

Antidepressants must be used together with mood stabilizers in the treatment of bipolar disorder. They are not used as first-line treatment for bipolar depression; however, if the situation warrants physicians may first consider the use of the following three:

  • Bupropion (Wellbutrin)
  • Selective serotonin reuptake inhibitors (SSRIs)
  • Venlafaxine (Effexor)
Bupropion

Side effects may include:

  • Dry mouth
  • Headache
  • Nausea/vomiting
  • Fatigue
Selective Serotonin Reuptake Inhibitors (SSRIs)

Drugs in the category of SSRIs include:

  • Fluoxetine (Prozac)
  • Fluvoxamine (Luvox)
  • Paroxetine (Paxil)
  • Sertraline (Zoloft)

Side effects of SSRIs can include:

  • Dizziness
  • Tremor
  • Fatigue
  • Decreased sex drive
Venlafaxine (Effexor)

Side effects may include:

  • Sweating
  • Nausea
  • Dry mouth
  • Dizziness
  • Tremor

In June 2004, the U.S. Food and Drug Administration (FDA) and Wyeth Pharmaceuticals notified healthcare professionals of revisions to the WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION sections of labeling to alert healthcare providers about the following important safety issue:

Neonates exposed to Effexor, other SNRIs (Serotonin and Norepinephrine Reuptake Inhibitors), or SSRIs (Selective Serotonin Reuptake Inhibitors), late in the third trimester of pregnancy have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery.

Other antidepressants may be used in the treatment of bipolar depression. They are not preferred, however, because of reduced efficacy and/or potentially more severe side effects. These antidepressants include:

  • Mirtazapine (Remeron)
  • Monamine oxidase inhibitors - phenelzine (Nardil) and tranylcypromine (Parnate)

Monoamine oxidase inhibitors require special dietary considerations.

  • Tricyclic antidepressants:

    • amitriptyline (Elavil)
    • desipramine (Norpramin, Pertofrane)
    • imipramine (Trofranil)
    • nortriptyline (Pamelor)

Tricyclic antidepressants are more likely to have side effects or to cause mania or rapid cycling than other antidepressants.