Dose Reduction Discontinuation Research Articles

Reprint of: Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy

BackgroundIn first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. MethodsWe performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. OutcomesBNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. InterpretationBNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients.

Negative symptoms predict high relapse rates and both predict less favorable functional outcome in first episode psychosis, independent of treatment strategy

BackgroundIn first episode psychosis (FEP) baseline negative symptoms (BNS) and relapse both predict less favorable functional outcome. Relapse-prevention is one of the most important goals of treatment. Apart from discontinuation of antipsychotics, natural causes of relapse are unexplained. We hypothesized that BNS, apart from predicting worse functional outcome, might also increase relapse risk. MethodsWe performed a post-hoc analysis of 7-year follow-up data of a FEP cohort (n = 103) involved in a dose-reduction/discontinuation (DR) vs. maintenance treatment (MT) trial. We examined: 1) what predicted relapse, 2) what predicted functional outcome, and 3) if BNS predicted relapse, whether MT reduced relapse rates compared to DR. After remission patients were randomly assigned to DR or MT for 18 months. Thereafter, treatment was uncontrolled. OutcomesBNS and duration of untreated psychosis (DUP) predicted relapse. Number of relapses, BNS, and treatment strategy predicted functional outcome. BNS was the strongest predictor of relapse, while number of relapses was the strongest predictor of functional outcome above BNS and treatment strategy. Overall and within MT, but not within DR, more severe BNS predicted significantly higher relapse rates. Treatment strategies did not make a difference in relapse rates, regardless of BNS severity. InterpretationBNS not only predicted worse functional outcome, but also relapses during follow-up. Since current low dose maintenance treatment strategies did not prevent relapse proneness in patients with more severe BNS, resources should be deployed to find optimal treatment strategies for this particular group of patients.

Discontinuation vs. continuation treatment with neuroleptics for a better long-term outcome

BackgroundLong-term functional outcome of dose-reduction/discontinuation strategies in first-episode psychosis (FEP) has not been studied before. The present study compared 7-year outcome of an early antipsychotic dose-reduction/discontinuation (DR) strategy with maintenance treatment (MT). Primary outcome was (symptomatic and functional) recovery; relapse rates, functional and symptomatic remission were secondary outcomes.MethodsFEP patients (n = 128) symptomatically remitted for 6 m during their first treatment year who completed an 18 months trial comparing MT and DR were followed-up at 7 years. Symptomatic remission criteria were adopted from Andreasen et al., functional remission criteria were based on a functioning scale. Recovery was defined as meeting both criteria sets. MT or DR strategy, and baseline parameters were entered in a logistic regression analysis with symptom and functional remission and recovery at 7-years follow-up as dependent variables.ResultsOne hundred and three patients consented to participate. DR-patients showed twice the recovery-rate of MT-patients (40% against 18%), odds ratio 3.5 (P = .014). Symptomatic remission-rates were equal (69% and 67%). Better DR recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR. Predictors of recovery were DR, baseline living together and less severe negative symptoms. During the last 2 years of follow-up the mean daily dose in haloperidol equivalents was 2.20 mg in DR vs. 3.60 mg in MT (P = .031).Relapse rates were initially higher in DR but leveled at 3 years; 61.5% relapsed in DR and 68.6% in MT in 7 years.ConclusionDR of antipsychotics during early stages of remitted FEP significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment. Though initially relapse rates in GD were higher, these equalled those in MT from 3 years to the end of the study. While the necessity of immediate antipsychotic treatment in FEP and positive symptoms relapse is robustly demonstrated in a great number of studies, this study suggests that we are faced with a dilemma concerning the drawbacks of long-term maintenance antipsychotic treatment on functional capacity. Though antipsychotic discontinuation appears only feasible without relapse in a substantial minority of patients, guided dose-reduction as far as positive symptoms remain subsided and allow it, appears a feasible strategy in view of functional recovery, doing justice to both sides of the dilemma.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Long Term Recovery Rates in Schizophrenia After Early Antipsychotic Dose Reduction

Long-term recovery rates in schizophrenia after early antipsychotic dose reduction Objective Comparing 7-year outcome of early antipsychotic dose-reduction/discontinuation (DR) with maintenance treatment (MT) on remission, relapse and recovery in remitted first episode psychosis (FEP). Method FEP patients (N=128) symptomatically remitted for 6m during their first treatment year who completed an 18 months trial comparing MT and DR were followed-up at 7 years. Symptomatic remission criteria were adopted from Andreasen et al., functional remission criteria were based on a functioning scale. Recovery was defined as meeting both criteria sets. MT or DR strategy, and baseline parameters were entered in a logistic regression analysis with symptom and functional remission and recovery at 7-years follow-up as dependent variables. Results 103 patients consented to participate. DR-patients showed twice the recovery-rate of MT-patients (40% against 18%), odds ratio 3.5 ( P =.014). Symptomatic remission-rates were equal (69% and 67%). Better DR recovery-rates were attributable to higher functional remission-rates (46% vs. 20%) in DR. Predictors of recovery were DR, baseline living together and less severe negative symptoms. During the last 2 years of follow-up the mean daily dose in haloperidol equivalents was 2.20mg in DR vs. 3.60mg in MT ( P =.031). Relapse-rates were initially higher in DR but leveled at 3 years; 61.5% relapsed in DR and 68.6% in MT in 7 years. Conclusion DR of antipsychotics during early stages of remitted FEP significantly improved 7-years outcome in terms of recovery and functional remission compared to maintenance treatment. Though initially relapse-rates in GD were higher, these equaled those in MT from 3 years to the end of the study.

Recovery in Remitted First-Episode Psychosis at 7 Years of Follow-up of an Early Dose Reduction/Discontinuation or Maintenance Treatment Strategy

Short-term outcome studies of antipsychotic dose-reduction/discontinuation strategies in patients with remitted first-episode psychosis (FEP) showed higher relapse rates but no other disadvantages compared with maintenance treatment; however, long-term effects on recovery have not been studied before. To compare rates of recovery in patients with remitted FEP after 7 years of follow-up of a dose reduction/discontinuation (DR) vs maintenance treatment (MT) trial. Seven-year follow-up of a 2-year open randomized clinical trial comparing MT and DR. One hundred twenty-eight patients participating in the original trial were recruited from 257 patients with FEP referred from October 2001 to December 2002 to 7 mental health care services in a 3.2 million-population catchment area. Of these, 111 patients refused to participate and 18 patients did not experience remission. PARTICIPANTS After 7 years, 103 patients (80.5%) of 128 patients who were included in the original trial were located and consented to follow-up assessment. After 6 months of remission, patients were randomly assigned to DR strategy or MT for 18 months. After the trial, treatment was at the discretion of the clinician. Primary outcome was rate of recovery, defined as meeting the criteria of symptomatic and functional remission. Determinants of recovery were examined using logistic regression analysis; the treatment strategy (MT or DR) was controlled for baseline parameters. The DR patients experienced twice the recovery rate of the MT patients (40.4% vs 17.6%). Logistic regression showed an odds ratio of 3.49 (P = .01). Better DR recovery rates were related to higher functional remission rates in the DR group but were not related to symptomatic remission rates. Dose reduction/discontinuation of antipsychotics during the early stages of remitted FEP shows superior long-term recovery rates compared with the rates achieved with MT. To our knowledge, this is the first study showing long-term gains of an early-course DR strategy in patients with remitted FEP. Additional studies are necessary before these results are incorporated into general practice. isrctn.org Identifier: ISRCTN16228411.