Med-Psych.com

Preface: This information is provided for educational purposes and should not be viewed as any recommendation for treatment. While I am a doctor, I am not YOUR doctor and you should follow the recommendations of YOUR doctor when it comes to making decisions about your treatment.

Asenapine is a new antipsychotic medication, now available in the United States. Asenapine is the generic name, and Saphris is the trade name. The FDA approved asenapine for use in the United States on August 13, 2009, for use in both schizophrenia as well as bipolar disorder.

There is always some initial excitement when a new medication is approved for schizophrenia as there are many people who only have partial improvement with their current treatments and most people suffer with problematic side effects at the same time. Newer medications tend to be designed with the goals of better symptom control as well as fewer side effects. In recent years, there have been some improvements in medications that are possibly better at controlling symptoms but have more tolerable side effects. Instead of the side effects of the older medications with muscle stiffness and tremors, the newer medications instead tend to cause weight gain and increased risks for diabetes.

Many of the newest medications came with promise of less weight gain than the newer medications along with less tremors of the older medications, while still providing improvement in shizophrenia symptoms. Unfortunately, the results have been underwhelming.

So, what does asenapine / Saphris have to offer? In this FDA file on asenapine, you can see the clinical trial data they referenced. It is fairly technical, but on page 34 you can see the clinical trial data to which they refer. In gaining approval for schizophrenia, they reviewed 3 different trials that were 6 weeks each, comparing asenapine to either placebo or an active drug such as risperidone or olanzapine. In two fo the three trials, asenapine was better than placebo. In the third trial, asenapine was no better than placebo, but one of the other active drugs was better than placebo. This third trial raises a few concerns in my mind as to the results people are going to find with asenapine (although time will tell, as it always does). This third trial suggests that our current treatments are better than asenapine. We'll need to wait and see as trials can often be misleading (both positively and negatively - although the ones that get published are almost always in favor of a positive result for the treatment being tested).

In the first trial, asenapine was tested at 5mg twice a day and compared to placebo. Asenapine was better than placebo.

In the second trial, asenapine was tested at 5mg twice a day and compared to asenapine at 10mg twice a day, both of which were compared to placebo. Interestingly, the 5mg twice a day was statistically better than placebo, but the 10mg twice a day dose was statistically no better than placebo. (I mention statistically, because in medical research studies, one treatment may be better than another, but if you haven't tested it in enough people, you will get misleading results, which is why you want someone very good at mathematical statistics to analyze any studies.) I'm not sure why the 10mg twice a day would be less effective than the 5mg twice a day dose. As a result of these study, though, it seems that the recommended dose in schizophrenia is 5mg twice a day, as the evidence seems to suggest that a higher dose is no better and may actually be worse (based on how I interpret what the referenced FDA file says).

I couldn't find anything in the referenced FDA file in regards to the third trial. Although, in this article on Saphris, the authors say it was olanzapine that was superior to placebo, while asenapinen was not better than placebo.

There were also two studies in bipolar mania, but these were only 3 week long studies. Patients were started at 10mg twice a day and the dose could be lowered to 5mg twice a day if necessary to reduce side effects. Most (90%) of patients stayed at the 10mg twice a day dose. The referenced articles mention that asenapine was better than placebo, but there is no mention whether asenapine was better than olanzapine (to which asenapine was also compared in those trials).

The other unique thing about asenapine is that it needs to be taken by disolving it under your tongue. If you swallow it, only 5% gets into your body. You have to let it disolve, and not eat or drink anything immediately after taking the asenapine for 10 minutes.

The most common adverse reactions (≥5% and at least twice the rate on placebo) in schizophrenia were akathisia (inner restlessness), oral hypoesthesia (reduced sensation in the mouth), and somnolence (being tired).

The most common adverse reactions (≥5% and at least twice the rate on placebo) in bipolar disorder were somnolence, dizziness, extrapyramidal symptoms (muscle stiffness or tremors typically) other than akathisia, and weight increased.

It does look like there is some weight gain associated with asenapine, but it isn't clear from the referenced articles as to how much weight gain.

Based on the referenced articles, it doesn't seem to be that asenapine is going to be a wonder drug and time will tell where asenapine fits into the current treatment options for schizophrenia and bipolar disorder.

Please note that this information is being provided here for educational purposes and should not be interpreted as medical advice.

On 9/14/09 Shering-Plough issued a press release with information about their long term relapse prevention study. I don't think that the data has been published in a peer reviewed journal yet, but it was presented at European psychiatry conference in Istanbul, Turkey. It also appears that this trial was sponsored by the drug manufacturer.

The main findings are that there was a higher rate of relapse in the placebo group (47%) compared to the asenapine group (12%). They also found that people stayed on the active medication longer than they stayed on placebo.

Nothing that has been presented so far seems to be a major breakthrough. It seems the biggest promoted advantage thus far is less weight gain than other currently available options. Time will tell how much less weight gain patients will see, and also we'll see how effective the medication will be.