Gralnick Award Lecturer Emphasizes Importance of First-Episode Treatment

Early identification and appropriate engagement of patients experiencing symptoms of schizophrenia remain a major public health challenge, said John Kane, M.D., winner of the American Psychiatric Association Foundation’s 2016 Alexander Gralnick Award for Research in Schizophrenia. He was presented the award last month at this year’s IPS: The Mental Health Services Conference in Washington, D.C.

Kane said he believes new technology is the cutting edge in improving treatment and preventing relapse and rehospitalization, as well as in reaching out to young people who may be at risk for psychosis. He has experimented with the use of smartphone applications to help patients remember to take medications and—an especially novel approach—the use of a digital health feedback system (DHFS), a device that is embedded in the medication itself and that provides feedback to a clinician confirming that the pill has been ingested (Psychiatric News, December 18, 2015).

The pill is embedded with a tiny sensing device that emits a signal when it comes into contact with gastric contents after being swallowed. The signal is picked up by a receiver in a patch worn by the patient, which in turn transmits the signal to caregivers and clinicians indicating that the medication has been ingested.

Kane and colleagues at Zucker Hillside Hospital and Massachusetts General Hospital partnered with Proteus Digital Health Inc. (which manufactures a DHFS) to characterize the feasibility and safety of the system in patients with bipolar disorder and schizophrenia. In a paper published in the June 2013 Journal of Clinical Psychiatry, Kane and colleagues reported that the results of using the DHFS in 12 patients with bipolar disorder and 16 patients with schizophrenia were positive. No subjects experienced worsening of psychosis due to use of the DHFS. Of the 27 patients who completed the study, 19 found the DHFS concept easy to understand, and 24 said they believed it would be useful.

“Social media and the Internet should be utilized in the effort to improve early identification and effective treatment of first-episode psychosis [FEP],” Kane said. “New technologies, such as smartphones and other monitoring tools, should be systematically developed, tested, and applied.”

The bulk of Kane’s lecture was devoted to emphasizing the importance of early identification and effective treatment of FEP, the results of the RAISE (Recovery After an Initial Schizophrenia Episode) study, showing the critical nature of duration of untreated psychosis in determining response to treatment and what he termed the unrealized potential of long-acting injectable medications.

“The first episode is when it all begins, and it sets the stage for what happens later,” Kane said. “Hospitalization for a first episode of psychosis can be extraordinarily stressful and traumatic. So we have to make sure our initial treatment is as effective as possible.”

Kane noted that cognitive dysfunction and other impairments may begin long before acute psychosis sets in, and many patients with active psychosis go long periods without treatment. In the RAISE study, the median duration-of-untreated-psychosis (DUP) was a year and a half.

The RAISE study compared usual care with a comprehensive, team-based approach to FEP called NAVIGATE.

The study found that NAVIGATE was significantly better at keeping patients engaged in treatment. However, the study did not find significantly better rates of hospitalization. Kane suggested, however, that the finding may be because of the unusually good care provided in the control group.

“Our control group was highly selected and committed to being a part of this project. I can’t prove this, but I would propose that the patients in the usual care group were receiving better care than we would have seen with a random selection [of providers in the community].”

He emphasized also that DUP was among the most important predictors of initial response to treatment in the study.

When it comes to relapse, Kane also said the single most important factor is nonadherence to medication—a difficult issue and one that he said is not confined to people with serious mental illness. “I think we need to destigmatize nonadherence,” he said. “It’s human nature to not want to take medicine.”

But there are special factors that make adherence to medication among those with schizophrenia especially difficult. Patients and family members alike may see termination of medication as a goal to be achieved. And once patients begin to respond, they may be inclined to dismiss the psychotic episode as a one-time occurrence, related only to stressful life events.

Kane has been an advocate of long-acting injectable antipsychotics (LAIs) as a response to nonadherence. Although the literature on LAIs has been mixed, Kane said he believes that randomized, controlled trials—typically regarded as the “gold standard”—are not as good for studying the effectiveness of LAIs as “mirror studies” and cohort studies that follow groups over time.

“I think we do have enough data to show that this is a very effective option that we are not taking advantage of,” Kane said. ■