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Low-dose amisulpride effective for late-onset psychosis

Robert Howard

Researchers found low-dose amisulpride was an effective and well-tolerated treatment for older patients with very late-onset schizophrenia-like psychosis.

Furthermore, these benefits persisted after 12 weeks with prolonged treatment, according to data published in The Lancet Psychiatry.

“We thought it was important to do [this] trial because there was no quality evidence base to guide the treatment of patients with this diagnosis,” Robert Howard, MD, professor in the department of psychiatry at University College London, told Healio Psychiatry. “Previously, clinicians would either have had to extrapolate from the results of studies in younger people with schizophrenia or people with Alzheimer’s disease who also have psychosis.”

Researchers conducted a double-blind controlled trial that enrolled cognitively normal participants aged 60 years or older with very late-onset schizophrenia-like psychosis from the United Kingdom. They compared 100-mg daily amisulpride with placebo for reducing psychosis symptoms over 12 weeks and to determine whether any benefit was maintained by continuing treatment after the 12-week period. They also examined the adverse effects and serious adverse events related to treatment with amisulpride.

In this two-stage trial, Howard and colleagues randomly assigned participants (1:1:1) to receive either amisulpride in stage 1 and 2 (group A), amisulpride followed by placebo (group B) or placebo followed by amisulpride (group C). Patients received treatment for 12 weeks in stage 1 and 12 weeks in stage 2.

The investigators measured psychosis symptoms using the Brief Psychiatric Rating Scale (BPRS) at weeks 4, 12 and 24, or 36 weeks, and assessed trial treatment discontinuation for nonefficacy.

Of 92 patients who took the trial medication, 59 completed stage 1 of treatment and 34 of these 59 completed stage 2. At 12 weeks, patients taking amisulpride showed a 7.7-point higher improvement in BPRS scores compared with placebo (95% CI, 3.8–11.5). Analysis also showed that BPRS scores improved 1.1 points on average in stage 2 between week 12 and the final assessment at 36 weeks in patients who continued amisulpride, but these scores dropped by 5.2 points in those who switched from amisulpride to placebo (difference = 6.3 points; 95% CI, 0.9– 11.7).

In the first and second stage, fewer participants receiving amisulpride stopped treatment due to nonefficacy than those receiving placebo (P = .01 and P = .031); however, patients receiving amisulpride also reported more frequent serious adverse events in both stages (P = .057 and P = .19) The most common adverse events included infection (five patients in the amisulpride group vs. three in the placebo group) and extrapyrimidal side effects (three vs. 0); no deaths were related to treatment.

“The trial results showed good efficacy with a large-sized treatment effect and a side effect profile that could be managed in clinical practice by dose reduction,” Howard told Healio Psychiatry. “At present, most people with this diagnosis remain untreated — largely because their doctors don’t have evidence that allows evaluation of the benefits and risks of antipsychotics. We hope that the trial results will change this.”

Though these findings are encouraging, they should not be viewed as permanent, Carl I. Cohen, MD, professor in the department of psychiatry and director of geriatric psychiatry at SUNY Downstate Medical Center, wrote in a related comment.

“Mortality rates are higher in this group of patients than in older adults with early-onset schizophrenia, and the effect of physical comorbidities on symptoms in very late-onset schizophrenia-like psychosis should be elaborated,” Cohen wrote. “A final concern is that the precise age of onset of the disorder is difficult to determine and a diagnosis of very late-onset schizophrenia-like psychosis might be based on age at clinical contact rather than onset age.” – by Savannah Demko

Disclosures: Howard reports receiving grants from the Health Technology Assessment Program and serves as a member of the Health Technology Assessment Commissioning Board. Please see the study for all other authors’ relevant financial disclosures. Cohen reports no relevant disclosures.