Late-Life Psychosis Mimics Schizophrenia

While examining these issues, Dr. Carpenter said it is important to keep in mind that schizophrenia is a syndrome. “Dr. Brian Kirkpatrick has summarized data (Arch. Gen. Psychiatry 2001;58:165-71) suggesting that relatives of deficit schizophrenia probands have a different morbid risk profile than relatives of non-deficit schizophrenia probands,” he said. “With the former, it tends to be schizophrenia and the negative [deficit] symptom form of the syndrome, while with the latter, it tends to be a range of psychiatric diagnoses. The deficit form of schizophrenia is uncommon in females and very rare if it occurs at all in late-age psychosis,” said Dr. Carpenter, who also directs the Maryland Psychiatric Research Center and is professor of psychiatry and psychopharmacology at the University of Maryland, Baltimore.

With regard to treatment, Dr. Howard noted that a Cochrane review concluded there is insufficient evidence to make any recommendations, a situation he finds appalling.

“It's extremely unsatisfactory that the treatment options we have for these patients at the moment are only those that have been extrapolated from data in young people. There's a tremendous paucity of data, because drug companies are not interested in psychosis in old people unless it's dementia,” the psychiatrist said.

When asked about Dr. Howard's assertions, Dr. Dilip V. Jeste, who was part of the international consensus conference and has worked with Dr. Howard several times over the years, agreed in an interview that psychotic disorders in older people have been largely ignored in diagnostic as well as therapeutic research.

“The usual tendency is to apply the same diagnostic criteria and the same treatment regimens for older people as for younger people, although the necessary research base is primarily derived from data in adults under age 65,” said Dr. Jeste, the Estelle and Edgar Levi Chair in Aging at the University of California, San Diego.

“This is unfortunate, because there are distinct clinical considerations in older age groups. This is well exemplified in the case of schizophrenia, which is often thought of as a disease more or less restricted to younger people.

“Yet, a number of studies all over the world have shown that schizophrenia can have onset after age 40 or 45. When the onset is much later, say, after 65, then schizophrenia becomes much less common. Yet, schizophrenia-like psychosis is not rare in older people,” said Dr. Jeste, who also serves as director of the Sam and Rose Stein Institute for Research on Aging at the university.

In an effort to help gather more data, Dr. Howard recently received funding from the U.K. Health Protection Agency to conduct a randomized, double-blind, placebo-controlled trial known as ATLAS (Antipsychotic Treatment of Very Late-Onset Schizophrenia-Like Psychosis).

Participants will be randomized to 100 mg/day of amisulpride or placebo for 12 weeks, with the primary outcomes being change in the Brief Psychiatric Rating Scale, a quality of life measure, and the Simpson-Angus Scale of Parkinsonian symptoms. At 12 weeks, the patients will be randomized again to determine whether another 24 weeks of amisulpride is of significant additional benefit. Enrollment in ATLAS will begin soon in the United Kingdom.

The impetus for the government-funded randomized trial was a small open-label Greek study; investigators concluded that 5 weeks of amisulpride at a mean dose of 101 mg/day brought significant improvements in the Brief Psychiatric Rating Scale and the Clinical Global Impression of Change Scale and was extremely well tolerated, with no safety issues (Int. J. Geriatr. Psychiatry 2009;24:518-22).

Anecdotally, Dr. Howard continued, he has observed that many patients with late-life psychosis appear to respond to depot fluphenazine decanoate at a mean dose of 14 mg every 2 weeks, or to risperidone at 1.5 mg/day or its equivalent.

“I rarely go above 1.5 mg of risperidone per day. If you're looking after a person with a new psychosis in late life and you're giving them more than that, you're not helping,” he said.

Dr. Jeste also emphasizes that older people with psychotic disorders are sensitive to side effects of antipsychotics and do not tolerate doses that are commonly recommended in younger adults. “Psychosocial interventions play a major role in their management,” said Dr. Jeste, who also is chair of the DSM-5 Neurocognitive Disorders Work Group. “Clearly, more research in this population is warranted.

“As baby boomers age, we are going to see a dramatic increase in the numbers of older people with various psychiatric, including psychotic, disorders. This is, therefore, a topic of growing public health significance and deserves greater attention by the mental health community,” Dr. Jeste said.