Attitude Toward Antipsychotic Medication as a Predictor of Antipsychotic Treatment Discontinuation in First-Episode Early-Onset Psychosis

Abstract Background Different effectiveness profiles among antipsychotics may be a key point to optimize treatment in patients suffering a first episode of psychosis to impact on long-term outcome. The aim of this study is to compare the clinical effectiveness of olanzapine, risperidone, haloperidol, aripiprazole, ziprasidone, and quetiapine in the treatment of first episode of psychosis at 3-year follow-up. Method From February 2001 to January 2011, 2 phases of a prospective, randomized, open-label study were undertaken. A total of 376 first-episode drug-naïve patients were randomly assigned to olanzapine (n = 55), risperidone (n = 63), haloperidol (n = 56), aripiprazole (n = 78), ziprasidone (n = 62), or quetiapine (n = 62) and followed up for 3 years. The primary effectiveness measure was all cause of treatment discontinuation. In addition, an analysis based on intention-to-treat principle was conducted in the analysis for clinical efficacy. Results The overall dropout rate at 3 years reached 20.75%. Treatment discontinuation rates were significantly different among treatment groups (olanzapine = 69.09, risperidone = 71.43, aripiprazole = 73.08%, ziprasidone = 79.03%, haloperidol = 89.28%, and quetiapine = 95.53%) (χ2 = 79.86; P = .000). Statistically significant differences in terms of lack of efficacy, adherence, and tolerability were observed among treatment groups along the 3-year follow-up, determining significant differences in time to all-cause discontinuation (log-rank = 92.240; P = .000). Significant differences between treatments were found in the categories of sleepiness/sedation, increased sleep duration, akinesia, weight gain, ejaculatory dysfunction, extrapyramidal-symptoms, and amenorrhea. Conclusions Olanzapine, risperidone, and aripiprazole presented advantages for the first-line treatment of first episode of psychosis in terms of effectiveness. Identifying different discontinuation patterns may contribute to optimize treatment selection after first episode of psychosis. ClinicalTrials.gov Identifier: NCT02526030 https://clinicaltrials.gov/show/NCT02526030

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Rates and predictors of one-year antipsychotic treatment discontinuation in first-episode schizophrenia: Results from an open-label, randomized, “real world” clinical trial

Psychiatry Research ◽

10.1016/j.psychres.2019.01.068 ◽

2019 ◽

Vol 273 ◽

pp. 631-640 ◽

Cited By ~ 4

Author(s):

Zhang Cheng ◽

Yanbo Yuan ◽

Xue Han ◽

Lei Yang ◽

Xin Zeng ◽

...

Keyword(s):

Clinical Trial ◽

Real World ◽

Treatment Discontinuation ◽

First Episode ◽

Antipsychotic Treatment ◽

Open Label ◽

One Year ◽

First Episode Schizophrenia

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Early striatal hypertrophy in first-episode psychosis within 3 weeks of initiating antipsychotic drug treatment

Psychological Medicine ◽

10.1017/s0033291708004212 ◽

2008 ◽

Vol 39 (5) ◽

pp. 793-800 ◽

Cited By ~ 37

Author(s):

S. E. Chua ◽

Y. Deng ◽

E. Y. H. Chen ◽

C. W. Law ◽

C. P. Y. Chiu ◽

...

Keyword(s):

Antipsychotic Medication ◽

Grey Matter ◽

Economic Status ◽

Region Of Interest ◽

Brain Morphology ◽

Group Differences ◽

First Episode ◽

Antipsychotic Treatment ◽

Caudate Nuclei ◽

The Right

BackgroundWe and others have reported that patients experiencing their first episode of psychosis already have significant structural brain abnormalities. Antipsychotics seem to reverse subcortical volume deficits after months of treatment. However, the early impact of medication on brain morphology is not known.MethodForty-eight individuals in their first episode of psychosis underwent magnetic resonance imaging (MRI) brain scanning. Twenty-six were antipsychotic naive and 22 were newly treated with antipsychotic medication for a median period of 3 weeks. In each group, 80% of subjects received a diagnosis of schizophrenia. The two groups were balanced for age, sex, handedness, ethnicity, height, years of education, paternal socio-economic status (SES) and Positive and Negative Syndrome Scale (PANSS) score. Group differences in whole-brain grey matter were compared voxel by voxel, using Brain Activation and Morphological Mapping (BAMM) software. We also conducted testing of group differences with region-of-interest (ROI) measurements of the caudate nucleus.ResultsRelative to the untreated group, those receiving antipsychotic medication for 3–4 weeks had significantly greater grey-matter volumes in the bilateral caudate and cingulate gyri, extending to the left medial frontal gyrus. ROI analysis confirmed that, in treated patients, the right and left caudate nuclei were significantly larger by 10% (p<0.039, two-tailed) and 9% (p<0.048, two-tailed) respectively.ConclusionsEarly striatal grey-matter enlargement may occur within the first 3–4 weeks of antipsychotic treatment. Possible reasons for putative striatal hypertrophy and its implications are discussed.

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Changes in the cytokine profile in first episode, drug-naïve patients with psychosis after short-term antipsychotic treatment

European Psychiatry ◽

10.1016/j.eurpsy.2017.02.382 ◽

2017 ◽

Vol 41 (S1) ◽

pp. S371-S371

Author(s):

P. Petrikis ◽

P. Voulgari ◽

V. Boumba ◽

D. Archimandriti ◽

P. Skapinakis ◽

...

Keyword(s):

Antipsychotic Medication ◽

Transforming Growth Factor ◽

Serum Levels ◽

Psychotic Symptoms ◽

First Episode ◽

Enzyme Linked Immunosorbent Assay ◽

Antipsychotic Treatment ◽

Before And After ◽

Drug Naïve ◽

Competing Interest

IntroductionAn increasing body of evidence suggests that antipsychotic medication can cause immunological changes that could be attributed to the amelioration of psychotic symptoms or the metabolic side effects of the drugs. So far, the results of the studies remain controversial.ObjectiveOur aim was to compare the levels of interleukin (IL) IL-2, IL-6 and transforming growth factor-β2 (TGF-β2) in drug-naïve, first-episode patients with psychosis before and after six weeks of antipsychotic medication.MethodsThirty-nine first episode patients with psychosis were enrolled in the study. Serum levels of IL-2, IL-6 and TGF-β2 were measured by enzyme linked immunosorbent assay (ELISA) before and six weeks after the initiation of antipsychotic medication. In addition, clinical psychopathology was assessed using Positive and Negative Syndrome Scale (PANSS) before and after treatment.ResultsSerum levels of IL-2 were significantly higher in the study group six weeks after the initiation of antipsychotic treatment (P < 0.001) while TGF-β2 levels were decreased (P < 0.001) and IL-6 levels were slightly reduced (P < 0.004).ConclusionThe changes in cytokine levels may be attributed to the action of antipsychotic medication and the remission of psychopathology. The reduction in TGF-β2 levels is observed in all patients and with all antipsychotic medications used. TGF-β2 may be a marker of clinical efficacy.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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Functional deterioration from the premorbid period to 2 years after the first episode of psychosis in early-onset psychosis

European Child & Adolescent Psychiatry ◽

10.1007/s00787-015-0693-5 ◽

2015 ◽

Vol 24 (12) ◽

pp. 1447-1459 ◽

Cited By ~ 12

Author(s):

Ángel Del Rey-Mejías ◽

David Fraguas ◽

Covadonga M. Díaz-Caneja ◽

Laura Pina-Camacho ◽

Josefina Castro-Fornieles ◽

...

Keyword(s):

Early Onset ◽

First Episode ◽

Early Onset Psychosis ◽

Functional Deterioration

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Lipid alterations in adolescents with early-onset psychosis may be independent of antipsychotic medication

Schizophrenia Research ◽

10.1016/j.schres.2019.11.039 ◽

2020 ◽

Vol 216 ◽

pp. 295-301 ◽

Cited By ~ 1

Author(s):

Kirsten Wedervang-Resell ◽

Svein Friis ◽

Vera Lonning ◽

Runar E. Smelror ◽

Cecilie Johannessen ◽

...

Keyword(s):

Antipsychotic Medication ◽

Early Onset ◽

Early Onset Psychosis

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Treatment Discontinuation Impact on Long-Term (10-Year) Weight Gain and Lipid Metabolism in First-Episode Psychosis: Results From the PAFIP-10 Cohort

The International Journal of Neuropsychopharmacology ◽

10.1093/ijnp/pyaa066 ◽

2020 ◽

Author(s):

Javier Vázquez-Bourgon ◽

Jaqueline Mayoral-van Son ◽

Marcos Gómez-Revuelta ◽

María Juncal-Ruiz ◽

Víctor Ortiz-García de la Foz ◽

...

Keyword(s):

Positive Impact ◽

Metabolic Changes ◽

Treatment Discontinuation ◽

First Episode ◽

Antipsychotic Treatment ◽

Metabolic Parameter ◽

Metabolic Disturbances ◽

Anthropometric Measures ◽

Complete Reversal

Abstract Background Patients with a first episode of psychosis (FEP) are at higher risk of gaining weight and presenting metabolic disturbances, partly related to antipsychotic exposure. Previous studies suggest that treatment discontinuation might have a positive impact on weight in schizophrenia. The aim of this study was to evaluate the effect of treatment discontinuation on weight and metabolic changes in a FEP cohort. Methods A total of 209 FEP patients and 57 healthy controls were evaluated at study entry and prospectively at 10-year follow-up. Anthropometric measures and, clinical, metabolic, and sociodemographic data were collected. Results Patients discontinuing antipsychotic treatment presented a significantly lower increase in weight and better metabolic parameter results than those still on antipsychotic treatment at 10-year follow-up. Conclusions Treatment discontinuation had a positive effect on the weight and metabolic changes observed in FEP patients; however, this effect was not sufficient to reaching a complete reversal to normal levels.

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Antipsychotic treatment of first-episode or early-onset schizophrenia

Current Psychiatry Reports ◽

10.1007/s11920-009-0050-9 ◽

2009 ◽

Vol 11 (4) ◽

pp. 261-263 ◽

Cited By ~ 2

Author(s):

Trina Webb ◽

Rajiv Tandon

Keyword(s):

Early Onset ◽

First Episode ◽

Antipsychotic Treatment ◽

Early Onset Schizophrenia

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Psychosocial Intervention With or Without Antipsychotic Medication for First-Episode Psychosis: A Randomized Noninferiority Clinical Trial

Schizophrenia Bulletin Open ◽

10.1093/schizbullopen/sgaa015 ◽

2020 ◽

Vol 1 (1) ◽

Cited By ~ 5

Author(s):

Shona M Francey ◽

Brian O’Donoghue ◽

Barnaby Nelson ◽

Jessica Graham ◽

Lara Baldwin ◽

...

Keyword(s):

Early Intervention ◽

Antipsychotic Medication ◽

Psychosocial Intervention ◽

First Episode Psychosis ◽

Functional Improvement ◽

First Episode ◽

Antipsychotic Treatment ◽

Free Treatment ◽

Intervention Service ◽

Episode Psychosis

Abstract This triple-blind (participants, clinicians, and researchers) randomized controlled noninferiority trial examined whether intensive psychosocial intervention (cognitive-behavioral case management, CBCM) for first-episode psychosis (FEP) in 15–25 year-olds managed in a specialized early intervention for psychosis service was noninferior to usual treatment of antipsychotic medication plus CBCM delivered during the first 6 months of treatment. To maximize safety, participants were required to have low levels of suicidality and aggression, a duration of untreated psychosis (DUP) of less than 6 months, and be living in stable accommodation with social support. The primary outcome was level of functioning as assessed by the Social and Occupational Functioning Scale (SOFAS) at 6 months. Ninety young people were randomized by computer, 46 to placebo, and 44 antipsychotic medication and 33% of those who commenced trial medication completed the entire 6-month trial period. On the SOFAS, both groups improved, and group differences were small and clinically trivial, indicating that treatment with placebo medication was no less effective than conventional antipsychotic treatment (mean difference = −0.2, 2-sided 95% confidence interval = −7.5 to 7.0, t = 0.060, P = .95). Within the context of a specialized early intervention service, and with a short DUP, the immediate introduction of antipsychotic medication may not be required for all cases of FEP in order to see functional improvement. However, this finding can only be generalized to a very small proportion of FEP cases at this stage, and a larger trial is required to clarify whether antipsychotic-free treatment can be recommended for specific subgroups of those with FEP. Trial Registration: ACTRN12607000608460 (www.anzctr.org.au).

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