Bipolar medications

bipolar medications

New Treatment Options For Bipolar Disorder

Compared to the glut of new medications developed in recent years for the treatment of such serious mental illnesses as schizophrenia and depression, the lack of advances in new drug options for those with bipolar disorder (manic depression) has proven increasingly frustrating and disappointing. Currently, the mood stabilizers available for those with manic depression are limited to the old standby lithium (Eskalith, Cibalith-S, Lithobid) and the newer divalproex sodium (Depakote). While these medications have proven helpful for many, there is a substantial group of those with bipolar disorder who have either not benefited from these options or experience problematic side effects. Furthermore, some feel that lithium and Depakote are better at treating mania than depression, and using antidepressants with these drugs has been known to trigger mania or rapid cycling-conventional antidepressants may not be as effective in treating depressive episodes related to bipolar disorder as they are for treating such episodes in those with unipolar depression. For such reasons, many clinicians have begun to experiment with drugs that are indicated for the treatment of other illnesses, but have proven effective in the treatment of those with bipolar disorder in some studies. This type of medication usage is known as "off label."

Note: It is important to recognize that "off label" usage is generally considered an option only after all traditional treatment methods have failed. Like all medications, these new drugs work differently for different people and each has its own unique side effects. Although the discovery of the effectiveness of these medications in some cases points to a future filled with newer and better options for those with bipolar disorder, many more controlled studies need to be conducted. These drugs have not been approved by the Food and Drug Administration (FDA) for the treatment of bipolar disorder.

The type of medication used most often for bipolar disorder in an "off label" capacity is the group known as anticonvulsants. Used primarily for the treatment of epilepsy, several of these drugs have recently shown promise in treating those with manic depression, particularly in helping stabilize mood.

  • Tegretol (carbamazepine): Due to its apparent effectiveness as a mood stabilizer, Tegretol has become a first-line treatment option even though it has never received FDA approval for the treatment of bipolar disorder. The most common side effects seen with Tegretol include dry mouth and throat, constipation, impaired urination, decreased sense of taste, dizziness, drowsiness, unsteadiness, loss of appetite, nausea, vomiting, indigestion, and diarrhea. Some individuals may also experience clumsiness, double vision, edema (excess of fluid in tissue or body cavity), skin rash, and cardiovascular complications. Additionally, there is the possibility of such life-threatening adverse effects as suppression of blood cells that fight infection or prevent bleeding. The drug can also have negative interactions with Prozac, Luvox, and lithium. Furthermore, it should not be taken with monoamine oxidase inhibitors (MAOIs) and should not be used by those pregnant or nursing. Lastly, regular blood count monitoring and periodic liver function tests are mandatory-due to the induction of enzymes in the liver by carbamazepine, several adverse interactions can occur when it is combined with other drugs.
  • Lamictal (lamotrigine): Several studies (including a randomized, double-blind, placebo-controlled trial presented at the 1998 American Psychiatric Association's annual meeting) indicate that Lamictal may also help stabilize mood in those with bipolar disorder. The drug has been reported as being a more potent antidepressant than Tegretol or Depakote, and it appears to have a low incidence of such side effects as weight gain and hair loss. Although it seems that Lamictal can be taken with MAOIs, taking the drug concurrently with Tegretol may increase the chance of adverse side effects. The most commonly reported side effects are dizziness, headache, double vision, unsteadiness, nausea, blurred vision, sleepiness, rash, and vomiting. Special attention should be paid to skin rashes, which in some extreme cases have developed into the severe disorder known as Stevens-Johnson syndrome or caused death.

    Any noticed rash should be reported immediately to a doctor. The concurrent use of Depakote increases the risk of developing a rash.

  • Neurontin (gabapentin): Also proven effective as a mood stabilizer for those with bipolar disorder, Neurontin is chemically unrelated to any other anticonvulsant. The drug has been the subject of several studies as well, two of which were presented at this year's APA meeting. Like Lamictal, Neurontin has exhibited a lower incidence of side effects (weight gain, hair loss) than lithium and Depakote. As opposed to Lamictal, Neurontin appears to work more in alleviating mania than depression. It also seems to be a more potent antianxiety agent than both Depakote and Tegretol. Additionally, there have been no reports of Neurontin interacting negatively with MAOIs, lithium, Depakote, or Tegretol. Side effects most often noted include sleepiness, dizziness, unsteadiness, nystagmus (rapid, involuntary fluctuation of the eyeballs), tremor, and double vision. A distinct disadvantage to the drug is that it needs to be taken up to four times a day, compared to twice a day for other anticonvulsants.
  • Topamax (topiramate): Yet another anticonvulsant that seems to help regulate mood in those with manic depression, Topamax has been the subject of a few open-label studies. The apparent advantage of this anticonvulsant over the others is that it does not seem to cause weight gain; it may actually help individuals lose weight. On the other hand, Topamax appears to cause more cognitive side effects than the other new drugs. Other commonly reported side effects include sleepiness, dizziness, vision problems, unsteadiness, speech problems, psychomotor slowing, "pins and needles," nervousness, nausea, memory problems, tremor, and confusion. Topamax does not seem to interact negatively with MAOIs, lithium, Lamictal, or Neurontin, but a combination of the drug with Depakote or Tegretol can lower plasma levels of Topamax.
  • ABS-103. This drug is currently in preclinical studies evaluating its treatment potential for epilepsy, migraine headaches, and mania. Evidence suggests it may be as effective as Depakote and not cause as many side effects. In fact, ABS-103 might prove safe for women of childbearing age.

    The new generation of drugs used to treat schizophrenia, known as atypical antipsychotics. have also been explored in some studies as potential treatment options for individuals with bipolar disorder.

    • Zyprexa (olanzapine): Although recently turned down by the FDA to be marketed for the treatment of bipolar disorder, Zyprexa has shown antimanic effectiveness in some trials when used in conjunction with other medication. One adverse effect, excessive weight gain, can be problematic in some patients and may lead to nonadherence.
  • Seroquel (quetiapine fumarate): Another atypical antipsychotic currently being investigated for use in those with bipolar disorder.
  • Substance P-blockers are one other type of newly developed medication that also shows potential promise in helping regulate mood. This class of drugs derives its name from how it works; unlike SSRIs, which work by blocking the brain chemical serotonin, these medications block a brain chemical known as substance P. Substance P was discovered in 1931, and medications designed to work against the chemical have often been used experimentally, but never successfully, in attempts to treat such conditions as chronic pain, migraine headaches, anxiety, and asthma. A recent study of a substance P-blocker called MK-869 found the drug to work as effectively as and cause less of certain sexual side effects than the SSRI Paxil.

    Please remember. While all of the medications mentioned above have proven effective in certain studies, there is still quite a way to go in getting approval by the FDA for their use in the treatment of bipolar disorder. We will keep you notified about any changes in status.

    Reviewed by David J. Kupfer, M.D. Thomas Detre professor and chair for the Department of Psychiatry and director of research at Western Psychiatric Institute and Clinic

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