Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial

Kahn, René S.; Fleischhacker, W. Wolfgang; Boter, Han; Davidson, Michael; Vergouwe, Yvonne; Keet, I. P. M.; Gheorghe, M.D.; Rybakowski, Janusz; Galderisi, Silvana; Libiger, Jan; Hummer, Martina; Dollfus, Sonia; López-Ibor, Juan J; Hranov, Luchezar; Gäebel, Wolfgang; Peuskens, Joseph; Lindefors, Nils; Riecher-Rössler, Anita; Grobbee, Diederick E.

doi:10.1016/s0140-6736(08)60486-9

Cited by 975 publications

(866 citation statements)

References 36 publications

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“…Another key feature of this study is that the age of inclusion is wider than in other previous works, including 23 subjects under 18-year old. Apart from this feature, clinical characteristics of the sample were similar to other studies with FEP in our context (Castro-Fornieles et al, 2008;Kahn et al, 2008). In addition, complex statistical analyses were conducted to limit biases in the results described.…”

Section: Discussionmentioning

confidence: 99%

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

Bioque

García‐Bueno

MacDowell

et al. 2013

Neuropsychopharmacol

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Several hypotheses involving alterations of the immune system have been proposed among etiological explanations for psychotic disorders. The endocannabinoid system (ECS) has a homeostatic role as an endogenous neuroprotective and anti-inflammatory system. Alterations of this system have been associated with psychosis. Cannabis use is a robust risk factor for these disorders that could alter the ECS signalling. In this study, 95 patients with a first episode of psychosis (FEP) and 90 healthy controls were recruited. Protein expression of cannabinoid receptor 2 (CB2), the protein levels of the main endocannabinoid synthesizing enzymes N-acyl phosphatidylethanolamine phospholipase (NAPE) and diacylglycerol lipase (DAGL), and of degradation enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL) were determined by western blot analysis in peripheral blood mononuclear cells (PBMCs). Patients with a FEP showed a decreased expression of CB2 and of both endocannabinoids synthesizing enzymes (NAPE and DAGL) in comparison to healthy controls. After controlling for age, gender, body mass index, and cannabis use, NAPE and DAGL expression remained significantly decreased, whereas FAAH and MAGL expression were increased. On the other hand, FEP subjects with history of severe cannabis use showed a larger ECS dysregulation compared with healthy controls. These results indicate an ECS dysregulation in PBMC of FEP patients. The alteration of the ECS presented at the initial phases of psychosis could be contributing to the pathophysiology of the disease and constitutes a possible biomarker of psychotic disorders and an interesting pharmacological target to take into account for therapeutic purposes.

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Section: Discussionmentioning

confidence: 99%

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

Bioque

García‐Bueno

MacDowell

et al. 2013

Neuropsychopharmacol

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“…In comparison to adult schizophrenia trials, these findings suggest that youth are less likely to maintain the same treatment over one year. [14][15][16][17] In addition, symptom response tended to plateau during maintenance therapy, such that most youth did not make significant improvements beyond what they had achieved at 8 weeks of acute treatment.…”

Section: Discussionmentioning

confidence: 99%

Double-Blind Maintenance Safety and Effectiveness Findings From the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

Findling

Johnson

McClellan

et al. 2010

Journal of the American Academy of Child & Adolescent Psych

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OBJECTIVE-To examine the long-term safety and efficacy of three antipsychotics in early-onset schizophrenia spectrum disorders (EOSS). (age 8-19 years) who had improved during an 8-week, randomized doubleblind acute trial of olanzapine, risperidone, or molindone (plus benztropine) were eligible to continue on the same medication for up to 44 additional weeks under double-blind conditions. Adjunctive medications were allowed following defined algorithms. Standardized symptom, safety, and functional assessments were conducted every 4 weeks. METHOD-PatientsRESULTS-Of the 116 youth randomized in the acute trial, 54 entered maintenance treatment (molindone, N=20; olanzapine, N=13; risperidone, N=21). Fourteen (26%) completed 44 weeks of treatment. Adverse effects (N=15), inadequate efficacy (N=14), or study non-adherence (N=8) were the most common reasons for discontinuation. The three treatment arms did not significantly differ in symptom reduction or time to discontinuation. Akathisia was more common with molindone and elevated prolactin concentrations more common with risperidone. Although weight gain and metabolic adverse events had occurred more often with olanzapine and risperidone during the acute trial, no significant between-drug differences emerged in most of these parameters during maintenance treatment.CONCLUSIONS-Only 12 % of youth with EOSS continued on their originally randomized treatment at 52 weeks. No agent demonstrated superior efficacy, and all were associated with side effects, including weight gain. Improved treatments are needed for EOSS.

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“…All-cause discontinuation during the first year after medication initiation was defined with the following events (Lieberman et al, 2005;Kahn et al, 2008): a 460 days gap in the initial monotherapy medication; switch to new medication (in conjunction with a discontinuation of the initial medication); and all-cause mortality. The 60-day threshold for gap duration was chosen because we wanted to capture the majority of patients who continue on their initial medication after pausing therapy.…”

Section: Outcome Variablesmentioning

confidence: 99%

“…It was indexed by the prescriptionbased estimated proportion (%) of days when an AP medication was taken as compared to total the length of the baseline period (i.e., 6 month prior to the inclusion period). These variables used for the propensity score-based adjustment were previously associated with nonadherence in the treatment of schizophrenia (Sellwood and Tarrier, 1994;Klingberg et al, 2008;Lieberman et al, 2005;Kahn et al, 2008). We estimated the conditional probability of receiving a certain drug using a multinomial log-linear model.…”

Section: Analysis Modelsmentioning

confidence: 99%

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Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary

Bitter

Katona²,

Zámbori³

et al. 2013

European Neuropsychopharmacology

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We conducted a nationwide, full-population based investigation to evaluate the comparative effectiveness of all marketed second generation antipsychotic drugs (SGA) prescribed for outpatients with the diagnosis of schizophrenia in Hungary. Using the national central register, our observational follow-up study included all patients with schizophrenia or related disorder between 01/01/2006 and 30/06/2008. The study cohort comprised 9567 patients who started new SGA during the inclusion period (01/07/2007-30/06/2008). All-cause medication discontinuation of 8 SGAs (1 depot and 7 oral formulations) marketed during the inclusion period, and the time to all-cause discontinuation were the main outcomes. Statistical models included the Kaplan-Meier and the Cox proportional hazards models with propensity score adjustment. Patients treated with a depot formulation risperidone had the longest time to discontinuation with a median of 215 days (95%CI:181-242 days), which was statistically significantly different compared to patients treated with the rest of the medications: E-mail address: czobor.pal@med.semmelweis-univ.hu (P. Czobor). 1 Istvan Bitter MD, PhD and Lajos Katona MS are co-first authors contributed equally to the article. 2 At the time of beginning of the study he worked as a psychiatry expert for NHIF.European Neuropsychopharmacology (2013Neuropsychopharmacology ( ) 23, 1383Neuropsychopharmacology ( -1390 with patients who were discharged from their first hospitalization for schizophrenia (Tiihonen et al., 2006(Tiihonen et al., , 2011; namely the median times to all-cause medication discontinuation were o120 days for the majority of the oral SGA. In terms of medication differences, our data support the superior effectiveness of the depot formulation regarding all-cause discontinuation, followed by olanzapine at the efficacy rank order.

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Effectiveness of antipsychotic drugs in first-episode schizophrenia and schizophreniform disorder: an open randomised clinical trial

Abstract: SUMMARYBackground: A new generation of antipsychotics was introduced over a decade ago for the

Cited by 975 publications

References 36 publications

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

Peripheral Endocannabinoid System Dysregulation in First-Episode Psychosis

Double-Blind Maintenance Safety and Effectiveness Findings From the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) Study

Comparative effectiveness of depot and oral second generation antipsychotic drugs in schizophrenia: A nationwide study in Hungary

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