Antipsychotic Hiatus Prolongs Recovery, Ups Relapse Risk

Daniel M. Keller, PhD

April 10, 2013

NICE, France — Interrupting antipsychotic medication following a first episode of psychosis is associated with a 5-fold increased risk for relapse and a longer time to recovery, new research shows.

The results of a prospective study led by Thomas Elanjithara, MBBS, MRCPsych, of the Institute of Psychiatry at Maudsley Hospital and King's College London in the United Kingdom, suggest that "antipsychotic treatment should be uninterrupted in the early stages of psychosis, and periods of even short breaks in treatment carry risk of adverse outcome, like longer time to recover, and high risk of immediate relapse."

The findings were presented here at EPA 2013: 21st European Congress of Psychiatry.

Interruption Common

According to investigators, discontinuation of antipsychotic medication is common and occurs in 40% to 55% of patients following a first episode of psychosis.

To examine the impact of brief periods of nonadherence (defined as a break in medication therapy for a period of at least 1 month) in antipsychotic treatment, the investigators studied 127 consecutive patients aged 18 to 35 years who had had a first episode of schizophreniform psychosis (nonaffective psychosis).

Patients with an organic psychosis or a primary drug or alcohol dependence were excluded from the study. Demographic and clinical information and treatment details were derived from a review of case notes.

Researchers interviewed patients using the Positive and Negative Syndrome Scale (PANSS) and the Calgary Scale for depression.

The study population was 73% male and was ethnically diverse. Diagnoses were schizophrenia (62%), nonorganic psychosis (27%), schizoaffective disorder (6%), delusional disorder (4%), and acute transient psychotic disorder (1%).

During the first month, patients took risperidone, olanzapine, or quetiapine, with a mean chlorpromazine equivalent dose at baseline of 140 mg. At 18 months, 74% took an antipsychotic medication.

"During 18 months, about 57% of patients stopped taking antipsychotics for a month" or longer against medical advice, said Dr. Elanjithara.

Most of the interruptions occurred after recovery from the first episode and typically more than 6 months later (mean days since recovery = 213).

Fifty percent (n = 36) of patients who stopped taking antipsychotics for longer than 1 month relapsed compared with 17% (n = 9) of patients who had no break in medication (P < .001).

"Forty percent of relapse happened within the first month...and about 60% of all relapses in the first 3 months," said Dr. Elanjithara. The mean time to recovery among the 14% (n = 16) who interrupted medication before recovery was 210 days vs 127 days if there was no break in antipsychotic treatment (P = .01).

A multivariate logistic regression analysis adjusting for ethnicity and adverse effects showed that the odds ratio for relapse if medication was interrupted was 5.0 (95% confidence interval, 2.1 - 11; P < .001).

Strong Link to Relapse

Session chair Pierre Michel Llorca, MD, PhD, professor and chairman of psychiatry at the University of Auverge in Clermont-Ferrand, France, who was not involved in the research, said that the study results are "confirmation of information that we all already have that patients with a first episode of schizophrenia very frequently interrupt the treatment after a short duration of treatment of the first episode and that interruption is closely related with relapse."

Whereas previous large datasets in this area were collected retrospectively, he said an interesting point of Dr. Elanjithara's study is its prospective nature, "and that's probably one of the strengths of what he presented."

However, Dr. Llorca pointed out a limitation of the results as presented here was a lack of more specific characterization of the patients and the forms of schizophrenia.

Also, the study dichotomized patients into categories of therapy interruption or not, so it was not possible to evaluate partial adherence, which may have affected the majority of patients, he suspected.

"Probably you have this kind of 'noise' in terms of signal related to this kind of patients." Furthermore, the possibility of substance use in the prospective period was not evaluated, which could affect relapse.

"In a methodological point of view, scientific point of view, it's a good response, and we know all the difficulties to do such prospective studies," Dr. Llorca noted. "It's important to underline the fact that it's a prospective study with a long period of evaluation."

Dr. Elanjithara reports no relevant financial relationships. Dr. Llorca reports that he is a speaker for Otsuka, Janssen, and Roche, and that he has received research support from Lundbeck.

EPA 2013: 21st European Congress of Psychiatry. Abstract 1414. Presented April 7, 2013.


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