Have you seen a Vraylar commercial? A woman is having a manic episode. She has Post-it Notes everywhere and as the camera pulls back we see that she is working in an office that is supported by a gigantic house of cards. Here’s a link so you can see it for yourself. The announcer tells us that Vraylar is approved for bipolar I disorder. Then we see the woman smiling and looking relaxed and playing with her children, presumably thanks to cariprazine (Vraylar). So, what’s the straight and skinny on this medicine?
Bipolar Disorder | Formerly Manic Depression:
The field of psychiatry has lots of confusing categories for mental illnesses. Prior to 1980 many health professionals used the term manic depression to describe a condition where patients cycled between melancholy and mania. In other words, they might feel wired, energetic and euphoric for days or weeks at a time. Other symptoms might include fast talking, illusions of grandeur, reduced need for sleep and abnormal behavior (shopping binges or bad financial investments).
The flip side of the coin is depression. People can fall into a deep, dark pit of despair. Some patients become lethargic and have great difficulty concentrating or making decisions. They may feel helpless and hopeless.
Now that manic depression is officially called bipolar disorder, there are some sub-categories. There’s bipolar I, bipolar II and “mixed episodes.” They all involve cycles of depression and mania but vary in degree. If you would like to learn more about what it is like to suffer from this condition, please listen to our interview with Jaime Lowe. It is part of a show on low-dose lithium. Here is a link to the free podcast or streaming audio.
The question at hand, however, is how safe and effective is Vraylar for helping people with bipolar disorder?
Cariprazine Side Effects:
If you watch the TV commercials for this drug you might be a little taken aback by the severity of the potential side effects. That said, there’s a common strategy employed during most direct-to-consumer prescription drug ads. When the announcer starts rattling off a long list of serious complications, the people on the screen seem to be smiling and having all sorts of fun. The visual images contradict the scary side effects. Here is what the announcer says about Vraylar:
“Vraylar should not be used in elderly patients with dementia due to increased risk of death or stroke. Call your doctor about fever, stiff muscles or confusion which may mean a life-threatening reaction or uncontrollable muscle movements which may be permanent. Side effects may not appear for several weeks. High cholesterol and weight gain, high blood sugar, which can lead to coma or death, decreased white blood cells which can be fatal, dizziness upon standing, falls, seizures, impaired judgement, heat sensitivity and trouble swallowing may occur…Ask your doctor about Vraylar.”
We always encourage people who watch prescription drug ads on television to close their eyes when the announcer starts listing side effects. That way they won’t be distracted by the visual images of people having fun.
Making Sense of Serious Adverse Reactions:
It is important to understand that cariprazine is an atyplical antipsychotic medication. It has been approved to treat schizophrenia as well as bipolar disorder. Vraylar is not an antidepressant.
Antipsychotic medications have a long history of serious side effects. Cariprazine is no exception. One of the big worries has a fancy neurological name: “extrapyramidal symptoms” or EPS. It means the drug impacts brain neurochemicals, sometimes irreversibly.
Patients develop very disturbing movement disorders. These include uncontrollable muscular contractions, jerky movements, spasms, restlessness and irritability (akathisia), fidgeting, rocking, pacing, lip smacking, drooling and grimacing. I have seen such complications in patients. EPS is a profoundly life-altering condition.
The announcer on the TV commercial glides over the phrase “uncontrollable muscle movements which may be permanent.” We doubt that many viewers understand how devastating this problem could be.
In its medical review the FDA notes that:
“…akathisia is a very disturbing adverse reaction for patients, and that if left untreated it can lead to suicide and other dangerous behavior (motor restlessness, pacing, intentional self-injury, violence directed at others).”
Other Vraylar Side Effects:
In addition to the adverse reactions mentioned in the TV commercial, here are some other complications to be aware of:
- Digestive distress (abdominal pain, constipation, diarrhea, nausea, vomiting, indigestion, dry mouth)
- Psychological difficulties (insomnia, anxiety, agitation)
- Headache, dizziness, sleepiness, fatigue
- High blood pressure
- Blurred vision
- Weight gain
A Note of Special Concern:
Cariprazine and its byproducts build up in the body over time. In other words, if you start taking the drug on Monday, it will gradually accumulate in the body over the next week. Each additional dose will increase exposure to the medicine. The FDA notes:
“…there was an approximate 25-fold increase in total exposure between Day 1 and Day 14.”
That is why patients must be very vigilant for side effects after a few weeks of treatment. The doctor may need to make dosage adjustments to prevent adverse reactions. Women may be more susceptible to this effect than men.
Some people may think uncontrollable muscle movements are minor side effects. We do not agree:
Unanswered Questions About Toxicity:
The FDA notes that there were concerns regarding “preclinical pulmonary pathology.” In other words, lung inflammation. There was also a “…lingering safety concern regarding the potential for adrenal insufficiency…” Both conditions are caused by something called phospholipidosis. This is complicated, but boils down to drug-induced changes in tissue. The FDA admits that it doesn’t know how serious the problem may be.
Drug Interactions with Cariprazine:
There is substantial risk for drug interactions with cariprazine. We were disappointed that the FDA did not require the company to do more research on this potential problem. Based on our understanding of metabolism and interactions, people should avoid drugs like butabarbital, codeine, doxylamine, enzalutamide, hydrocodone, levodopa, pentobarbital, perphenazine, phenytoin, propofol (during anesthesia), secobarbital and zolpidem.
This is only a partial list of potential drug interactions. Never add another medicine to cariprazine without having both the physician and pharmacist check for incompatibilities.
How Effective Is Vraylar for Bipolar Disorder?
We were surprised to discover that:
“The efficacy of VRAYLAR in the acute treatment of bipolar mania was established in three, 3-week placebo-controlled trials…”
It seems to us that one might want longer clinical trials to establish both safety and effectiveness. That’s especially true for patients with bipolar disorder, which generally lasts for years, if not indefinitely. Health professionals are likely to encourage patients to take this drug for long periods of time. Wouldn’t it have been nice to assess the long-term benefits and risks of this medicine?
Determining effectiveness in psychological trials is challenging. Psychiatrists develop “scales” to determine how sick someone is. In this case the drug company relied upon the Young Mania Rating Scale (YMRS). A patient can score from 0 (no problem) to 60 (severe bipolar disorder).
At baseline, before taking any medicine, the average score on the YMRS was roughly between 32-33. After three weeks, the improvement (over placebo) was right around 6 points on the scale. In the third trial the improvement was only 4.3 points (over placebo). That’s something, but hardly a cure of bipolar disorder. Remember, all the FDA requires is that the active drug be better than placebo.
The People’s Pharmacy Perspective:
The commercials for Vraylar are slick. If you would like to view them, here are some links:
Remember to close your eyes when the announcer starts to describe all the potential side effects!
Bipolar disorder is hard on families and patients. We desperately need breakthroughs in its treatment. We would define a breakthrough as a far safer and more effective medication.
We would love to see a clinical trial comparing cariprazine with lithium or some other treatment for bipolar disorder. Since the FDA rarely requires such comparative studies, we have no good way of determining which treatment is more effective or safer. Lithium has its own problems. You can learn more at this link.
If you have had been prescribed Vraylar, we would love to learn more about your experience. Please share your story in the comment section below.