Abilify (aripiprazole) is an atypical antipsychotic medication commonly used to treat schizophrenia and acute mania. In 2005, the Food and Drug Administration (FDA) approved its use in the maintenance treatment of bipolar disorder – to prevent the recurrence of mood episodes. Unfortunately, evidence proving the effectiveness of Abilify as a maintenance medication for bipolar disorder is scarce and questionable.

Exposing the Truth

An article published this week in the open access journal PLoS Medicine (Tsai et al) looks critically at the scientific evidence that supports such widespread use of this medicine for maintenance treatment of bipolar disorder.

This month’s edition of Discovery’s Edge, Mayo Clinic’s Online Research Magazine, features an article entitled “The Genomics of Bipolar Disorder.” The article looks at biobanking – a practice in which research centers store a lot of information on thousands of people with certain disorders, in this case bipolar. Mayo Clinic, in conjunction with several other research centers, is collecting blood samples and clinical information from 2,000 patients. This information is stored anonymously, and researchers can use this high volume of data to look at specific questions about bipolar disorder.

The primary focus of this work is related to genomics – looking at genetic associations to bipolar disorder. The work is not just about which genes and genetic variations contribute to causing bipolar disorder, but also examines subtypes of bipolar disorder and patterns of medication response. Partly due to genetic differences, people experience different benefits and side effects to the same medications.

A recent study published in the Journal of Clinical Psychiatry entitled “Are Mood Disorders and Obesity Related? A Review for the Mental Health Professional” (McElroy, Susan L.; Kotwal, Renu; Malhotra, Shishuka; Nelson, Erik B.; Keck, Paul E., Jr.; Nemeroff, Charles B.) reveals a possible connection between obesity and mood disorders including major depressive disorder and bipolar disorder.

The study found that:

• Children and adolescents with major depressive disorder may be at increased risk for developing obesity.
• Patients with bipolar disorder may have elevated rates of overweight, obesity, and abdominal obesity. (Abdominal obesity is specifically related to higher risk of cardiovascular disease.)
• Persons living with obesity who seek weight-loss treatment may have elevated rates of depressive and bipolar disorders.
• Obesity is associated with major depressive disorder in females.
• Abdominal obesity may be associated with depressive symptoms in females and males.
• Most overweight and obese persons do not have mood disorders.

Kim Asks…

Is there a way to combat the headaches and joint pains when taking the lithium?

Dr. Fink Answers…

Hi, Kim. Good question. Most importantly discuss these side effects with your doctor immediately. Your doctor may want to run a blood test to determine your lithium level and make sure your lithium level is not toxic. Headaches can indicate toxicity. Headaches may also be a sign of dehydration, which can occur with lithium, so keeping hydrated is important.

Until recently, doctors and researchers had believed that brain volume loss in schizophrenia was caused primarily by the disease itself. One recent study, however, questions this long-held belief and identifies antipsychotics, the medications most commonly used to treat schizophrenia, as the more likely culprits.

With the increased long-term use of antipsychotics to treat schizophrenia and other forms of mental illness, especially bipolar mania, it’s important to determine whether the illness or the medication (or both) contribute to the potential loss of brain volume.

In an article published in the Archives of General Psychiatry (February, 2011) entitled “Long-term Antipsychotic Treatment and Brain Volumes,” Beng-Choon Ho, MRCPsych, et al. conclude the following:

One of the problems with using traditional anti-depressants, especially selective serotonin reuptake inhibitors (SSRI’s) to treat bipolar depression is the potential risk of triggering a switch from depression to mania. Another issue is that traditional anti-depressants may not be effective in treating depression in some patients.

SSRI’s work by inhibiting the reabsorption of the neurotransmitter serotonin, effectively increasing the level of serotonin in the synapses of the brain – the space between the brain cells (neurons). This reduces the symptoms of depression and anxiety in many people.

While insufficient serotonin may be one cause of depression, researchers are exploring another possible cause – dysregulation of glutamate. Glutamate is the most abundant excitatory neurotransmitter in the body. Riluzole (Rilutek), a prescription drug commonly used to treat Lou Gehrig’s disease, amyotrophic lateral sclerosis (ALS), reduces the release of glutamate while increasing its uptake. Some studies have shown that Riluzole is effective in treating acute bipolar depression alone or in combination with other anti-depressants.

In an article published in this month’s Biological Psychiatry entitled “Structural Magnetic Resonance Imaging in Bipolar Disorder: An International Collaborative Mega-Analysis of Individual Adult Patient Data” (Hallahan et al.), researchers pulled together a large number of magnetic resonance imaging studies to compare the brains of people with bipolar disorder to those of healthy control subjects. Their goal was to make sense of some of the conflicting data that had come out of the studies individually.

Using so many studies, from research groups all over the world, the authors are able to examine all of the results together and come up with some more comprehensive findings. This is called a “meta- analysis.” “Mega-analysis” is an informal term that describes a huge meta-analysis.

Continue reading… »

The U.S. Food and Drug Administration (FDA) is informing healthcare professionals that it has updated the Pregnancy section of drug labels for the entire class of antipsychotic drugs. The new drug labels now contain more and consistent information about the potential risk for abnormal muscle movements (extrapyramidal signs or EPS) and withdrawal symptoms in newborns whose mothers were treated with these drugs during the third trimester of pregnancy.

For details, see http://www.fda.gov/Drugs/DrugSafety/ucm243903.htm

Important: Do not stop taking your antipsychotic medication if you become pregnant. Consult your healthcare professional before making any changes to your medication. Abruptly stopping antipsychotic medication can cause significant complications in your treatment.

Photo by Frank de Kleine, available under a Creative Commons attribution license.

Cecie Asks…

I’ve been told that it has become increasingly the norm to only take the anti-psychotic medications and the heavier hitting mood-stabilizers for a limited period of time to get the moods and scary thoughts under control (when you feel an episode “coming on” or to recover from an episode you were unable to avoid) and then to stop them when you are stabilized.

I guess the idea is…

1. You don’t have to be under the effects of these medications any longer that is absolutely necessary.
2. These medications are actually more effective when used for only a short period of time, during the “acute” phase of the illness.

My questions are:

1. Is this something you recommend to some/all of your patients?
2. How long can I expect to be on an anti-psychotic medication and stronger mood-stabilizer after a manic episode with psychotic features?

As we have noted in several posts, the depressive pole of bipolar disorder is often the more challenging to treat. In most cases, conventional antidepressants may require three to four weeks or even longer to become effective. In addition, most if not all of the most effective antidepressants may push a person with bipolar disorder from a depressive cycle into a mania.

For these reasons and others, researchers are constantly on the lookout for new treatments for depression that provide faster relief and have a more neutral side effect profile. Some medications that show promise are already in use in other medical applications. Back in August of this year, we wrote about one of these promising medications, Ketamine – originally used as an anesthetic.

Another medication that has shown some promise is scopolamine, which traditionally has been used to prevent nausea and vomiting caused by motion sickness.