Modern Healthcare reported that Proteus Digital Health, a California company, is partnering with Otusuka Pharmaceuticals to approve an Abilify “smart pill.” When a medication embedded with a sensor reaches the stomach, it sends a signal to a wearable sensor patch. The patch records and time-stamps the information and other information such as rest and activity patterns. Then the information can be relayed to patients on their phones or other Bluetooth-enabled devices; or it can be forwarded to physicians or caregivers.

It was just in July of 2015 that Proteus announced that the FDA had expanded the Indications for Use statement for its Ingestible Sensor technology to be used as an aid in measuring medication adherence. At this point in time, it seems to be the only device with an FDA-sanctioned claim for measuring medication compliance. Proteus and Modern Healthcare pointed to findings from a 2014 article in Risk Management and Healthcare Policy that estimated avoidable healthcare costs from poor medication adherence as between $100 to $300 billion annually in the U.S. That represents 3% to 10% of total U.S. healthcare costs.

Dr. George Savage, the co-founder and chief medical officer of Proteus, said the company hopes to give patients feedback on their adherence so they can improve their health and avoid adverse medication events. Dr. William Carson, the president and CEO of Otsuka Pharmaceuticals said: “We believe this new digital medicine could revolutionize the way adherence is measured and fulfill a serious unmet medical need in this population.” They expect a response from the FDA by April of 2016.

There is reportedly a widespread problem of with non-adherence to taking medications as prescribed, especially with individuals with mental illness. So the FDA suggested to Proteus that the need for an ingestible sensor was most needed by mental health patients. It seems to have been rushed through the approval process, with about nine months from the FDA approved expansion of the Indications for Use statement for Proteus’s Ingestible Sensor to the expected response by the FDA approving the Abiliy “smart pill.” So there are two questions to ask about this. Why the rush? Why is the greatest need for a smart pill with antipsychotics like Abilify?

Abilify went off of patent in October of 2014 and was made available as a generic in April of 2015. The Abilify smart pill would probably be a new molecular entity (NME) and thus eligible for a new patent. While aripiprazole (Abilify) will be available as a generic, only Otsuka and Proteus will be able to sell the smart pill version. Otsuka and its former distribution partner, Bristol-Myers Squibb, grossed $5.5 billion in Abilify sales for 2014.

The pressing need for a smart pill with psychiatric medications to help counter non-adherence issues is because there are serious, and sometimes debilitating side effects from taking them. Here is a link to an advertisement for Abilify as an add-on medication with antidepressants to treat depression. Most of the audio in the 90-second commercial is describing the potential side effects.

The side effects from antipsychotics can include: weight gain, diabetes, pancreatitis, gynecomastia (abnormal breast tissue growth), hypotension, akathesia (a feeling of inner restlessness), cardiac arrhythmias, seizures, sexual dysfuntion, tardive dyskinesia, anticholinergic effects (constipation, dry mouth, blurred vision, urinary retention and at times cognitive impairment). Read more about these and other side effects at: “Side Effect of Atypical Antipsychotics: A Brief Overview”;  “Antipsychotic Drugs, Their Adverse Effects”; “Adverse Effects of Antipsychotic Medications”; and “An Overview of Side Effects Caused by Typical Antipsychotics.”

The website RxISK described some of the reports and first-hand accounts about individuals who had used Abilify in: “Abilify From the Inside Out.” Out of 34 who had used Abilify, only five had taken it for a “psychotic” diagnosis. Fourteen were taking it for depression. Six used it for bipolar disorder; three for other diagnoses; two for “stress”; and three for unknown reasons. Fifteen individuals were taking Abilify in conjunction with antidepressants.

Most patients were on more than one medication, so they could not be sure that if Abilify alone caused these adverse effects. Nevertheless, there were three confirmed suicides and several episodes of severe emotional stress or physical misery. Eight people reported akathisia and six reported unusual anger or aggression. Two of the aggression episodes were violent physical attacks on family members. One woman assaulted her husband when she had “bizarre and frightening thoughts.”

At the other extreme, 14 people reported over-sedation and cognitive slowing, with memory, concentration and word-finding problems.  About half felt a profound emotional numbing, an inability to feel pleasure or care about anything. One man regretted this state, but felt it was better than his prior severe depression.  For the rest, however, it brought new or worse depression.  Three felt trapped at home by “total lack of interest in life” along with anxious depression; loss of the ability to pursue, or even care about, formerly cherished goals was painful for others.  Most reported suicidal thoughts of varying intensity.

Three people had tremors, but of these cases cleared up when they stopped the drug. Four others had tardive dyskinesia. Their symptoms started after using Abilify for at least a year; and they continued despite stopping the drug. “They found their condition painful, debilitating, disfiguring and socially isolating.” Four men reported sexual dysfunction. One man had a gambling problem that began two months after starting Abilify. “Eight people had their worst problems on stopping Abilify.”

Johanna Ryan, who wrote the article on RxISK, said that most antidepressants are metabolized in the liver by the same enzymes that process Abilify. So the resulting “traffic jam” will effectively raise the level of Abilify in your blood. Some SSRIs have also a stronger effect than others on this issue. “Your actual Abilify levels might be 150% to 300% of your official dose.” Side effects such as agitation, anxiety, insomnia and nervousness commonly occur with antidepressants and can increase your chances of akathisia with Abilify.

In other words, the “little baby dose” was an illusion.  Even 2 mg was bigger than it seemed – and doses over 5 mg could put you on a par with patients taking Abilify for psychosis.  (Those patients may be taking excessive doses as well: Two patients with psychotic symptoms in the RxISK group found they did better on half the dose their doctor initially prescribed.)

In “Dodging Abilify” on RxISK, Johanna Ryan related how a psychiatrist had tried to convince her once to try Abilify for her depression.  He told her “these drugs” (referring to Abilify) weren’t really antipsychotics since they were used to treat several kinds of things. “’Oh, come on,’ he coaxed.  ‘We’re talking about little baby doses here, just a fraction what they give people for schizophrenia.’”  Like other antipsychotics, it blocks certain dopamine receptors. Unlike them, it is a “partial agonist,” meaning it activates others.

Now let’s go back to the cute Abilify commercials. This one includes a woman and her umbrella. Listen to see if Abilify is ever referred to as an antipsychotic or neuroleptic. As a matter of fact, it wasn’t. The same is true for the link to the commercial above. Admittedly, these commercials were pushing Abilify as an add-on to antidepressants. But now download the FDA Medication Guide for Abilify, and search through it. You won’t find the word “antipsychotic.” The word “neuroleptic” appears once within the listing of a side effect: neuroleptic malignant syndrome. Abilify is described and presented as an “antidepressant medicine” throughout the medication guide. There were other antipsychotics that seemed to also minimize using these two words (neuroleptic and antipsychotic) in referring to their drug, but not to the same extent as noted for Abilify. My thought is Otusuka decided that referring to Abilify as an antipsychotic or neuroleptic was bad for business.

So Abilify is a neuroleptic that apparently wants to be known as an antidepressant and absolutely HATES to be referred to as an antipsychotic. Yet it has the same kinds of adverse side effects as other neuroleptics. (If it walks like a duck and talks like a duck …) And of all the current antipsychotics on the market, Proteus partnered with Otsuka first to create an Abilify smart pill to facilitate medication compliance with its drug. To borrow a phrase from addiction recovery, it sounds like Abilify is in denial about being an antipsychotic.