Maintenance treatment with quetiapine versus discontinuation after one year of treatment in patients with remitted first episode psychosis: randomised controlled trial

Abstract

Objective To study rates of relapse in remitted patients with first episode psychosis who either continued or discontinued antipsychotic drugs after at least one year of maintenance treatment.Design 12 month randomised, double blind, placebo controlled trial.Setting Early psychosis outpatient clinics in Hong Kong.Participants 178 patients with first episode psychosis who had received at least one year of antipsychotic drug treatment between September 2003 and July 2006 and had no positive symptoms of psychosis.Interventions Patients received either maintenance treatment with quetiapine (400 mg/day) or placebo and were followed up for the next 12 months or until a relapse occurred.Main outcome measure Relapse assessed monthly and defined as re-emergence of psychotic symptoms (delusions, conceptual disorganisation, hallucinations, suspiciousness, and unusual thought content) according to predefined thresholds.Results 178 patients were randomised (89 to quetiapine and 89 to placebo). The Kaplan-Meier estimate of the risk of relapse at 12 months was 41% (95% confidence interval 29% to 53%) for the quetiapine group and 79% (68% to 90%) for the placebo group (P<0.001). Although quetiapine was generally well tolerated, the rate of discontinuation due to adverse or serious adverse events was greater in the quetiapine group (18%; 16/89) than in the placebo group (8%; 7/89) (relative risk 2.29, 95% confidence interval 0.99 to 5.28; χ 2 =3.20, df=1; P=0.07).Conclusion In a group of asymptomatic patients with first episode psychosis and at least one year of previous antipsychotic drug treatment, maintenance treatment with quetiapine compared with placebo resulted in a substantially lower rate of relapse during the following year.Trial registration Clinical trials NCT00334035. INTRODUCTIONPrevention of relapse is an important target in the treatment of schizophrenia and related psychotic conditions.1 In first episode psychosis, more than 80% of patients treated achieve a full response in psychotic symptoms, 2 yet as many as 80% have a relapse within five years.3 Relapse compromises the outcome of psychotic disorders and is associated with substantial risks and costs. 4 With each relapse, the response of symptoms to treatment seems to take approximately 50% longer and is increasingly difficult to reestablish.5 Prevention of relapse is particularly important in the early course of illness, when symptoms and disabilities may be less entrenched. Strategies to improve adherence and minimise early relapses are major focuses in treatment programmes and clinical research.1 For chronic psychotic illness, maintenance antipsychotic drug treatment is efficacious for preventing relapse. The rate of relapse after discontinuation of drug treatment in chronic schizophrenia is approximately 53% compared with 16% for patients maintained on antipsychotic drugs.6 Atypical antipsychotic drugs may have some benefits compared with typical antipsychotics in preventing relapse in chronic illness.7 8 The biological mechanism underlying relaps...

Withdrawal Confounding in Randomized Controlled Trials of Antipsychotic, Antidepressant, and Stimulant Drugs, 2000–2017

“…One study controlled for a potential withdrawal confound statistically [22], while another study compared patterns of potential withdrawal symptoms in discontinuation and maintenance groups [2]. In 1 of 3 studies employing mean scores [23], analyses were inconclusive as mean, upper, and lower 95% CI scores for maintenance and placebo groups “crossed” each other between the DCT and study endpoint.…”

Perinatal psychosis in mothers with a history of major depressive disorder

“…While Di Florio et al used stringent clinical diagnostic criteria to determine the presence of psychosis, we applied the PANSS. The PANSS is not a diagnostic instrument, but specific cut-off scores for five of its items have previously been used (in the context of evaluating relapse rates in patients with a history of first episode psychosis) to assess presence of psychosis (Hui et al 2013, Chen et al 2010. Though each cut off is anchored on the identification of clearly defined symptoms that have been deemed to be clinically significant (see Table 2), they have not been specifically validated to assess psychosis in women with a history of MDD, and it is important to consider whether they could potentially be confounded by the perinatal period.…”

“…When we removed the item conceptual disorganization, the percentage of women above threshold for symptoms of psychosis on the PANSS decreased to 15% (9/60) in the perinatal period (Table 3), and the most frequently occurring symptom became delusions (which was the most frequently occurring symptom of psychosis in a population of individuals with preexisting psychotic illness, Chen et al, 2010). Removing the conceptual disorganization item had no effect on the frequency of symptoms of psychosis during the perinatal period among participants with a history of single episode MDD, but decreased the frequency of symptoms of psychosis among women with a history of recurrent MDD (Table 3).…”

“…Five of the PANSS items can be used to assess the presence and severity of psychosis, using specific cut off scores for each of these items (delusions ≥ 3, conceptual disorganization ≥ 4, hallucinations ≥ 3, suspiciousness ≥ 5, unusual thought content ≥ 4). This approach was used to establish the presence of relapse of psychosis in a randomized clinical trial of relapse prevention in first episode psychosis (Hui et al 2013Chen et al 2010 All PANSS raters participated in training and underwent inter-rater reliability testing throughout the course of the study. Krippendorf's alpha for inter-rater reliability was calculated for each of the five PANSS items (delusions, conceptual disorganization, hallucinations, suspiciousness, and unusual thought content).…”

First episode psychosis with extrapyramidal signs prior to antipsychotic drug treatment

“…The Hong Kong sample was nearly equally split between males and females, while the Halifax sample was only one-quarter female. The origin of the gender differences is unclear, other studies from the Hong Kong EASY program also are gender balanced [74], and studies from Halifax as well as other Vancouver, Canada are male predominant [75,76]. Different clinical instruments were used between sites for assessment of several key clinical features of illness.…”