APA: Atypical Antipsychotics: Effective or Efficacious?

SAN DIEGO, May 30 -- When talking about antipsychotic agents for schizophrenia, it's important to distinguish efficacy from effectiveness.

Efficacy is the ability of a specific intervention, such as a drug or surgical procedure, to produce a desired beneficial effect under controlled conditions, said John Lauriello, M.D., of the University of New Mexico at Albuquerque.

In contrast, effectiveness of an antipsychotic agent is a combination of efficacy, tolerability, adherence, and ease of use, Dr. Lauriello said at an industry-sponsored satellite symposium held in conjunction with the American Psychiatric Association meeting here.

In schizophrenia, he said, effective treatment includes prevention of relapse-defined as rehospitalization, significant worsening of symptoms, and prevention of violent outbursts.

Ideally, Dr. Lauriello said, effective treatment should also include a focus on improving cognitive deficits, which in turn will have an effect on functional outcomes, including work, social situations, independent living, and skills acquisition.

Noting the importance of work to self-worth, Dr. Lauriello commented that he'd "rather have a patient hearing voices with a job than to have a patient who's just lying in his bed all day."

Adherence, or the lack of it, is also an important factor in determining effectiveness of treatment, Dr. Lauriello noted, citing a review of California Medicaid data. The study suggested that the odds of a patient's hospitalization go from 6.4% when a prescription for an antipsychotic agent is filled immediately after it's written, to more than 21% when there is a gap of a month or more before it's filled.

Failure to stick to an antipsychotic regimen may be caused by patient and family perceptions about the illness and its severity, substance abuse, a poor therapeutic alliance (e.g., a lack of trust between patients and clinicians) medication-specific side effects, cost, or complexity of the regimen, or by a lack of social support, Dr. Lauriello said.

Interventions that can help improve compliance, he said, include pillboxes or other memory aids, behavioral reinforcement and therapy, psycho-education and skills training, pharmacologic delivery, and family therapy.

"Many studies have shown that if you can get families to buy into treatment, the rate of relapse drops dramatically," Dr. Lauriello said.

He also discussed lessons from the CATIE (Clinical Antipsychotic Trials of Intervention Effectiveness) study.

"Even with atypical antipsychotics, the treatment response in schizophrenia is still unsatisfactory," he said.

In the CATIE trial, which compared five different agents, the overall rate of discontinuation of therapy was 74% before 18 months, and the median time to discontinuation was six months.

CATIE also showed that all atypicals pose therapeutic challenges in terms of balancing efficacy and tolerability, that hospitalization rates were high compared with the short time that patients stayed on the drug, that quality of life was modestly improved on the drugs, but also that the study experience may not accurately affect the experience in the clinic.

Dr. Lauriello concluded with a preview of the in-progress PROACTIVE study, a National Institute of Mental Health supported trial looking at the effectiveness of a long-acting formulation of risperidone (Risperdal) vs. other first-line oral atypicals at preventing relapse.