Current evidence indicates that low-dose antipsychotic treatment during the FEP is associated with symptomatic and functional improvement. “We have a variety of drugs that have one common feature: They sit on dopamine receptors in the limbic system and they protect them from storm,” Dr. McEvoy said. “If we give [patients] too much of these drugs, they get side effects they don’t need. First-episode psychosis patients are discriminating consumers. If you give them drugs that jack up their prolactin or make them sleep 18 hours a day, they’re unhappy.” He favors a “succeed first” strategy with very lose dose first-generation antipsychotics such as haloperidol, perphenazine, or loxapine. “Selection of antipsychotic medications that do not produce extrapyramidal side effects, weight gain/metabolic side effects, sedation, or sexual dysfunction at reasonable doses is now possible,” he said.
According to results from up to 10 years of follow-up in patients who experienced FEP, 60%-70% will achieve remission (defined as key positive and negative features rated mild or less) at some point, but the numbers for sustained remission are substantially lower. In addition, 10%-20% of patients will achieve recovery (defined as good social and occupational functioning in the community) at some point, but the numbers for sustained recovery are lower. Relapse rates are high, even with continued treatment. For example, among patients enrolled in an FEP program in Spain, 21% relapsed by the end of year 1, 41% by the end of year 2, and 65% by the end of year 3 (J Psychiatr Res. 2012;46[8]:1099-1105). And in an FEP program in New York, 5 years after initial recovery, the cumulative first relapse rate was 82%. Discontinuing antipsychotic drug therapy increased the risk of relapse by almost fivefold (Arch Gen Psychiatry 1999;56[3]:241-7).
A novel study led by Jean Addington, Ph.D., of the University of Calgary (Alta.), underscores the importance of early treatment of FEP patients. The researchers enrolled 404 individuals with FEP who presented for treatment at 34 nonacademic medical centers in 21 states (Psychiatr Serv. 2015;66[7]:753-6). The mean duration of untreated psychosis was 74 weeks. “This is like someone coming to you a year-and-a-half after developing untreated hypertension, with changes in the vascular system, the kidneys, and the heart,” said Dr. McEvoy, who was not involved with the study. “You can’t reverse some of these changes.”
Correlates of longer duration of untreated psychosis included earlier age at first psychotic symptoms, substance use disorder, positive and general symptom severity, poorer functioning, and referral from outpatient treatment settings.
Dr. McEvoy disclosed that he has received research grants from Alkermes, Avanir Pharmaceuticals, Ameritox, Auspex Pharmaceuticals, and Otsuka Pharmaceutical. He also is a member of the advisory boards for FORUM Pharmaceuticals, Otsuka, and Lundbeck.