Transcription
Hello friends. If you or someone you love is struggling with depression, you may be frustrated with the many medications and therapies that have been thrown at you. But there has been some progress with a new medication, a new mechanism of action that was FDA approved in 2020. It's called Ovality. I wanted to go over it with you in case this could be helpful for you or anyone you love.
So first of all, remember this is not medical advice. This is just education and entertainment. So Ovality offers a new mechanism of action. And what that means is the way the drug works is working in a way that is not just serotonin reuptake inhibitor or something along the same lines.
So Ovality, as I mentioned, was FDA approved in 2022, and it combines two active ingredients which have a synergistic effect. One of these medications you may have heard of before. It's called Wellbutrin, also known by its formal name bupropion. Now, Wellbutrin works by blocking the reuptake of dopamine and norepinephrine. That's not serotonin. Those are two different neurotransmitters, and those increase in the brain when you take bupropion or Wellbutrin. So you have that in Ovality, and it combines that with something called dextromethorphan. Which is because when you combine bupropion with dextromethorphan, the bupropion increases the amount of dextromethorphan that's in your bloodstream and getting into your body. So they work synergistically to help each other.
And the dextromethorphan, which is also found in other medications you may have taken, but is unique because it's combined with what it does is it works on this neurotransmitter system called NMDA, and that works by glutamate. And by the way, ketamine, you may have heard of ketamine, it also works by NMDA and glutamate, but that's a totally different mechanism than this. So dextromethorphan also is unique because it works by two, what's called Sigma 1 receptors, which are also related to glutamate. And dextromethorphan also increases the amount of serotonin and norepinephrine by inhibiting reuptake. So it's got all these different mechanisms acting at once, and it's combined with bupropion, which is pretty interesting.
So one question you may have is, can you take dextromethorphan separately? No. And the reason is because it's rapidly metabolized. When you take it, the blood levels remain low, and you have to take it with bupropion to get those levels high enough.
So here's a study that first established that this Ovality is better than placebo. And you always want to compare a drug to placebo because anytime you take anything that you think is going to help you, you're going to benefit by placebo, both by the ritualistic action of taking the medication and the expectation of benefits. Here we see a significant change after six weeks with Ovality. And this was published in a pretty good journal, the Journal of Clinical Psychiatry.
Now, a second study that was important was showing that Ovality is actually better than taking bupropion by itself. Because you might think, why would I want to take this Ovality thing if I could just take bupropion by itself? It turns out that after six weeks, you get higher rates of remission, meaning going into having no depression symptoms or below a certain threshold that it's minimal depression symptoms. 46% remission with Ovality versus only 16% remission with Wellbutrin after six weeks. So that's a significant difference, and also published in a pretty good journal, the American Journal of Psychiatry. So those are two pretty good studies.
Now, why is this something that you may want to consider with your doctor? A lot of the time, people who are depressed have to wait a long time for medicines to kick in, sometimes up to six to eight weeks with a serotonin medicine. But here we see a more rapid onset of action. Some report improvements as early as week one. There's also a new mechanism, as I mentioned, we're going by NMDA and glutamate, which differs from serotonin or norepinephrine reuptake inhibitors. There was lower sexual dysfunction compared to serotonin medicines. That's often a very common, difficult side effect of having antidepressant medicines based on serotonin. People get sexual dysfunction, low libido, etc.
And because this NMDA mechanism has some relationship to cognitive dysfunction, it could be improving cognitive dysfunction as well, because we see a lot of cognitive dysfunction in depression, low concentration, difficulty with memory, etc. So those are some of the benefits.
What are some of the side effects? Because nothing that's efficacious or effective comes without side effects. So here are side effects that were pretty common, meaning more than 5% of people had them: insomnia. That could be from the Wellbutrin because it has a mild stimulating effect. Dizziness, headache, nausea, dry mouth. Also maybe the norepinephrine is causing the dry mouth. Less common were anxiety and agitation. So the bupropion can do that because it is increasing norepinephrine, increase blood pressure. Again, norepinephrine will do that. Fatigue and hyperhydrosis, excessive sweating. That can be from the sympathetic nervous system being activated or the fight and flight nervous system.
There's also contraindications you want to consider because you don't want to be taking this medicine in certain situations. So if you have a seizure disorder, we know that bupropion lowers your seizure threshold, and you have a higher risk of having a seizure. Use of certain medicines called MAO inhibitors, which is very uncommon usage these days. Eating disorders like anorexia and bulimia. Those things will increase your risk of having a seizure on their own. And so when you combine that risk with taking Ovality, specifically bupropion, you can have a higher risk of a seizure. Also, if you discontinue alcohol or benzodiazepines like Ativan or Klonopin, that can increase your seizure risk as well. And if you add that to the seizure risk of taking Wellbutrin or bupropion, that can be a contraindication. So it's better to avoid alcohol in general.
Severe hepatic impairment can be a contraindication. If your liver is not working, this drug can accumulate in your body to dangerous levels. So you want to always have your liver function checked before taking this. And pregnancy and breastfeeding are also relative contraindications. They're not necessarily contraindicated, but you want to make that decision with your clinician.
Other warnings and precautions. Now, if you're taking this medicine, you don't have a seizure disorder, you could still have a seizure if you have a very high dose or if you have certain predispositions like even chronic insomnia will increase your risk of having a seizure. So that's something to think about, as well as alcohol use, as well as other medications. High blood pressure, hypertension. So the bupropion component can increase your blood pressure, so you want to monitor that. Glaucoma. That can also be triggered by this medicine, specifically the interaction between dextromethorphan as well as bupropion on its own. So you want to make sure you don't have glaucoma. And also if you have any eye pain or any ocular symptoms, you want to stop the medicine and contact your clinician.
Mania and hypomania. So the norepinephrine, maybe they're going to get people activated, and sometimes people can get too activated and become manic or hypomanic. So if you have bipolar disorder, you wouldn't want this medicine anyway, because bipolar depression is not something that's been studied for Ovality or really even Wellbutrin. This is more non-bipolar depression called unipolar depression.
And serotonin syndrome is when you have too much serotonin from so many medications that are increasing serotonin in your body, which can be life-threatening. So if you're on a Prozac or Zoloft, an SSRI, or like duloxetine or Cymbalta, or you're taking triptans, which are migraine headache medications, or other medications, you have to make sure that you don't take too much serotonin into your body because that can be life-threatening.
There's also liver metabolism of these drugs, so they can interact with other things. So if you're on tamoxifen or antipsychotics, tamoxifen or breast cancer medication and antipsychotic medications can interact. So you want to make sure you talk about these things with your clinician. And we want to monitor suicidal ideation, particularly in young people, because those can sometimes get worse as people start medicines. You've got to carefully monitor that.
So this is not a simple solution here, as you can see. There's a lot of side effects. There's a lot of warnings and precautions. But that being said, this is not exactly like 90% of people people have these effects. And hopefully, these beneficial things can be something that will help people.
So if you found this helpful, just check out this other video here and feel free to join my free newsletter. Thanks so much. Take care.