ATLANTA – Adolescents with prodromal psychosis who were being treated with second-generation antipsychotic drugs had significantly higher rates of medication noncompliance than adolescents who had the same early symptoms and were taking antidepressants, according to early results from a naturalistic treatment study.

Preliminary findings from the ongoing Recognition and Prevention (RAP) program at the Zucker Hillside Hospital in Glen Oaks, N.Y., and Schneider Children's Hospital in New Hyde Park, N.Y., also showed that the medication-noncompliant adolescents were 10 times more likely to convert to full psychosis during a 5-year follow-up period than adolescents who remained on their prescribed regimen, Barbara Cornblatt, Ph.D., said at the annual meeting of the American Psychiatric Association.

“While the second-generation antipsychotics may have a positive effect in treating symptoms, if adolescents won't stay on them, the drugs cannot possibly be effective,” said Dr. Cornblatt, director of the RAP program.

“On the other hand, it seems that the antidepressants are more tolerated and have some kind of protective effect, though exactly what that may be is not yet clear,” she said.

The RAP program began in 1997 and typically serves adolescents between the ages of 12 and 18 who fall somewhere on the prodromal psychosis continuum and have been referred to the stand-alone RAP clinic for treatment.

The objective of the research arm of the RAP program is to gain insight into the natural history and developmental course of psychotic disorders, as well as to understand the effects of different medications at different phases of the illness using a naturalistic vs. randomized control format.

“Our researchers treat patients as they would if they were in private practice with respect to selecting drug and behavior therapy. We give them no input; there's no ideation of our hypotheses. When they prescribe medication, it's based on the symptoms being displayed, not the notion of prevention,” Dr. Cornblatt said.

To date, 152 patients at a mean age of 15 years have completed the baseline research procedures and have been divided into one of three subgroups:

▸ Clinical high-risk negative patients, who meet prodromal criteria but have only exhibited nonspecific negative symptoms, such as anhedonia and lack of affect.

▸ Clinical high-risk positive patients, who have attenuated positive prodromal symptoms (delusions and hallucinations, as well as disorganized thoughts and speech).

▸ Clinical high-risk “slip” patients, “who are just slipping into first-episode psychosis,” Dr. Cornblatt explained.

The adherence/conversion data come from a sample of 50 clinical high-risk positive patients who had at least 1 year of follow-up and available adherence rates. Although no significant differences were found in baseline symptoms, 22 of the patients were prescribed antidepressants, 11 received monotherapy with second-generation antipsychotics (either olanzapine or risperidone), and 17 received combination therapy of antidepressants and antipsychotics.

“For purposes of reporting outcome, the two groups that received antipsychotic medications were combined because we didn't find any difference between the baseline characteristics or outcome between combination [and] monotherapy,” Dr. Cornblatt said.

During the follow-up period, investigators found that 13 of the 50 patients developed psychoses. Of the 13 who converted, 12 were receiving antipsychotic medication.

“In other words, nearly half the patients being treated with antipsychotics converted, compared with 1 out of 22 patients on antidepressants,” Dr. Cornblatt noted.

The only major difference that was noted between these two groups, other than the class of medication they received, was noncompliance to medication. Approximately 64% of adolescents prescribed antipsychotics were noncompliant, compared with 18% of those prescribed antidepressants alone.

“In general, the females in the study were more compliant with medication, and the older boys were the least compliant, suggesting that the earlier therapy is introduced, the more successful it might be,” Dr. Cornblatt said.

The low conversion rate in this study among those adolescents who stayed on their antidepressant medication and the high conversion rate among those who were medication noncompliant generate several hypotheses.

“It's possible that the negative symptoms set up some sort of biologic vulnerability, and maybe going to antidepressants directly affects these underlying negative components,” Dr. Cornblatt said.

“It's also possible that, although noncompliance doesn't cause positive symptoms, it could act as a trigger that makes them worse or more likely to progress to psychosis,” she said.

Although the outcome data from this investigation are “obviously not the final word because the study was not randomized, it does make the case that treating prodromal individuals with antidepressants does not cause any damage and might have some kind of positive effect,” she said.

“And it also points to medication noncompliance as a possible stressor, and one that we might be able to deal with,” Dr. Cornblatt noted.

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'It seems that the antidepressants are more tolerated and have some kind of protective effect.' DR. CORNBLATT

Compliance Puts New Spin on Psychosis Treatment : Adolescents with prodromal psychosis had better outcomes with antidepressants than antipsychotics.