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What’s Next for Bipolar Treatment?

By Paula Zimbrean, MD, as told to Hallie Levine

Over the last 2 decades, there have been huge advancements in the treatment of bipolar disorder. We’ve learned that there are several types: bipolar I, bipolar II, and cyclothymic. All present differently and require different treatments.

We’ve gotten better at teasing out if symptoms are truly due to bipolar disorder or something else. And we’ve developed groundbreaking new treatments that are easier on the body and make it possible for people with bipolar disorder to live full lives. Here’s what I’m most excited about.

We’ve moved away from lithium.

A study published in the American Journal of Psychiatry looked at data collected over 2 decades — from 1997 to 2016 — and found that patients today are much more likely to be prescribed an antipsychotic or an antidepressant medication than a mood stabilizer like lithium. There’s no doubt lithium is an important drug

when it comes to bipolar disorder, and it’s very effective. But it carries a risk of side effects, especially at high doses, including both kidney and thyroid disease. I’ve worked with patients who took lithium for many years who eventually required kidney transplants. The good news is today we know much more about lithium and how it works, so when we do need to use it, we prescribe much lower doses.

Over the last couple of decades, we’ve also realized that some of the anticonvulsant medications, such as carbamazepine, lamotrigine, and valproate are effective ways to treat the mania from bipolar disorder. At the same time, a group of drugs known as second-generation antipsychotics became available, too. These medications, which include aripiprazole, cariprazine, lumateperone,olanzapine, quetiapine, and risperidone, among others, carry lower risk of side effects than earlier antipsychotics. These side effects include weight gain, elevated cholesterol and blood sugar levels, and tardive dyskinesia — stiff, jerky movements of the face and body.

There are even more of these being approved. Some seem to carry a much lower risk of side effects such as weight gain or elevated cholesterol or blood sugars. Some also appear less likely to interact with other medications, which is something I worry about daily as a prescriber.

There are more long-term medications.

Another important step forward has been the availability of long-acting atypical antipsychotics. These drugs play an important role in treating bipolar disorder, since there’s often a high rate of noncompliance. But medications such as aripiprazole monohydrate and risperidone are now available as long-acting injectables, given in your doctor’s office every 2 weeks or once a month. This is much more acceptable to people with bipolar disorder, especially those who are active and don’t want to think about taking a pill every single day. Research shows these long-term injectables improve recovery outcomes. People are more likely to stick to treatment and gain control of symptoms. Hopefully, we will see more and more of them in the future.

We’re shifting toward gene therapy.

We know there are specific genes associated with your risk of developing bipolar disorder. Just this past year, the largest genetic study of bipolar disorder thus far was able to identify 64 different spots on the genome that raise your odds of bipolar disorder. But we’re not quite there yet when it comes to making the leap that modifying certain genes will cure the disease. The hope is eventually we’ll be able to apply what’s known as precision medicine to bipolar disorder. Ideally, we’ll analyze a patient’s gene to figure out which targeted treatments and therapies they’ll most benefit from, just like we do for patients with other conditions, such as breast cancer.

There are drugs to treat unwanted side effects.

One of the reasons people don’t stick to their medication regime is because of side effects like weight gain or tardive dyskinesia. But we’re learning that there are other drugs we can give them to counter these side effects. For example, we now often use metformin to help reverse rises in blood sugar, or the anticonvulsant drug topiramate to offset weight gain. While you never want to give patients too many prescriptions, these drugs can ward off some of the adverse effects that make it hard for some people to take antipsychotic medication long term. Eventually, we hope pharmacies will be able to combine two to three different drugs to maximize a treatment’s effectiveness and reduce the risk of side effects.

Nondrug therapies are on the rise.

Electroconvulsant treatment can be effective for bipolar disorder that hasn’t responded to medications. It’s when an electric current is sent through the brain to cause a controlled seizure. But it requires general anesthesia and has side effects such as confusion, headache, and nausea. Now, researchers are studying whether transcranial magnetic stimulation (TMS), a noninvasive procedure that uses magnetic fields to stimulate brain nerve cells, is effective. Early research is promising, especially for the depressive stages of bipolar disorder.

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