Association of Aripiprazole With Reduced Hippocampal Atrophy During Maintenance Treatment of First-Episode Schizophrenia.

Adolescent Adult Antipsychotic Agents / administration & dosage Aripiprazole / administration & dosage Atrophy / prevention & control Brief Psychiatric Rating Scale Female Hippocampus / drug effects Humans Inflammation / drug therapy Male Oxidative Stress / drug effects Schizophrenia / drug therapy Treatment Outcome Young Adult

Journal

Journal of clinical psychopharmacology

ISSN: 1533-712X

Titre abrégé: J Clin Psychopharmacol

Pays: United States

ID NLM: 8109496

Informations de publication

Date de publication:

Historique:

pubmed: 6 4 2021

medline: 10 11 2021

entrez: 5 4 2021

Statut: ppublish

Résumé

Hippocampal volume loss in early schizophrenia has been linked with markers of inflammation and oxidative stress, and with less response of negative symptoms. Aripiprazole has been reported to preserve hippocampal volume and to reduce inflammation. Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2). Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES. These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.

Sections du résumé

PURPOSE/BACKGROUND OBJECTIVE

METHODS/PROCEDURES METHODS

Study 1 was a 12-month multicenter randomized placebo-controlled trial of citalopram added to clinician-determined second-generation antipsychotic medication in 95 patients with first-episode schizophrenia (FES), 19 of whom received aripiprazole. We compared participants taking aripiprazole with those on other antipsychotics to determine whether those on aripiprazole had less hippocampal volume loss. We also examined peripheral biomarker data from medication-naive patients with schizophrenia receiving 8 weeks of antipsychotic treatment (n = 24) to see whether markers of inflammation and oxidative stress that previously predicted hippocampal volume differed between aripiprazole (n = 9) and other antipsychotics (study 2).

FINDINGS/RESULTS RESULTS

Aripiprazole was associated with a mean increase in hippocampal volume of 0.35% (SD, 0.80%) compared with a 0.53% decrease (SD, 1.2%) with other antipsychotics during the first year of maintenance treatment in patients with FES. This difference was significant after adjusting for age, sex, citalopram treatment, and baseline Brief Psychiatric Rating Scale score (B = 0.0079, P = 0.03). Aripiprazole was also associated with reduced concentrations of the inflammatory cytokines interleukin-8 and tumor necrosis factor (P < 0.01) during the first 8 weeks of treatment in medication-naive patients with FES.

IMPLICATIONS/CONCLUSIONS CONCLUSIONS

These results suggest that aripiprazole may protect against hippocampal atrophy via an anti-inflammatory mechanism, but these results require replication in larger, randomized trials, and the clinical relevance of hippocampal volume loss is not established.

Identifiants

DOI: 10.1097/JCP.0000000000001391 PMID: 33814546

pubmed: 33814546

doi: 10.1097/JCP.0000000000001391

pii: 00004714-202105000-00004

doi:

Substances chimiques

Antipsychotic Agents 0

Aripiprazole 82VFR53I78

Banques de données

ClinicalTrials.gov

['NCT01041274']

Types de publication

Comparative Study Journal Article Multicenter Study Randomized Controlled Trial

Langues

eng

Sous-ensembles de citation

Pagination

244-249

Commentaires et corrections

Type : ErratumIn

Informations de copyright

Références

van Erp TGM, Hibar DP, Rasmussen JM, et al. Subcortical brain volume abnormalities in 2028 individuals with schizophrenia and 2540 healthy controls via the ENIGMA consortium. Mol Psychiatry. 2016;21:547–553.

Ho NF, Iglesias JE, Sum MY, et al. Progression from selective to general involvement of hippocampal subfields in schizophrenia. Mol Psychiatry. 2017;22:142–152.

Goff DC, Zeng B, Ardekani BA, et al. Association of hippocampal atrophy with duration of untreated psychosis and molecular biomarkers during initial antipsychotic treatment of first-episode psychosis. JAMA Psychiat. 2018;75:370–378.

Bodnar M, Malla AK, Makowski C, et al. The effect of second-generation antipsychotics on hippocampal volume in first episode of psychosis: longitudinal study. BJPsych Open. 2016;2:139–146.

Robinson DG, Gallego JA, John M, et al. A randomized comparison of aripiprazole and risperidone for the acute treatment of first-episode schizophrenia and related disorders: 3-month outcomes. Schizophr Bull. 2015;41:1227–1236.

Shapiro DA, Renock S, Arrington E, et al. Aripiprazole, a novel atypical antipsychotic drug with a unique and robust pharmacology. Neuropsychopharmacology. 2003;28:1400–1411.

Sonnenschein SF, Gill KM, Grace AA. State-dependent effects of the D(2) partial agonist aripiprazole on dopamine neuron activity in the MAM neurodevelopmental model of schizophrenia. Neuropsychopharmacology. 2019;44:572–580.

Rocchetti J, Isingrini E, Dal Bo G, et al. Presynaptic D2 dopamine receptors control long-term depression expression and memory processes in the temporal hippocampus. Biol Psychiatry. 2015;77:513–525.

Grima G, Benz B, Parpura V, et al. Dopamine-induced oxidative stress in neurons with glutathione deficit: implication for schizophrenia. Schizophr Res. 2003;62:213–224.

Sharifi H, Mohajjel Nayebi A, Farajnia S. 8-OH-DPAT (5-HT1A agonist) attenuates 6-hydroxy-dopamine–induced catalepsy and modulates inflammatory cytokines in rats. Iran J Basic Med Sci. 2013;16:1270–1275.

Valvassori S, Stertz L, Andreazza A, et al. Lack of effect of antipsychotics on BNDF and NGF levels in hippocampus of Wistar rats. Metab Brain Dis. 2008;23:213–219.

Nowakowska E, Kus K, Ratajczak P, et al. The influence of aripiprazole, olanzapine and enriched environment on depressant-like behavior, spatial memory dysfunction and hippocampal level of BDNF in prenatally stressed rats. Pharmacol Rep. 2014;66:404–411.

Goff DC, Freudenreich O, Cather C, et al. Citalopram in first episode schizophrenia: the DECIFER trial. Schizophr Res. 2019;208:331–337.

Addington J, Shah H, Liu L, et al. Reliability and validity of the Calgary Depression Scale for Schizophrenia (CDSS) in youth at clinical high risk for psychosis. Schizophr Res. 2014;153:64–67.

Lindenmayer JP, Czobor P, Alphs L, et al. The InterSePT scale for suicidal thinking reliability and validity. Schizophr Res. 2003;63:161–170.

Ardekani BA, Bermudez E, Mubeen AM, et al. Prediction of incipient Alzheimer's disease dementia in patients with mild cognitive impairment. J Alzheimers Dis. 2017;55:269–281.

Andreasen NC. The Scale for the Assessment of Negative Symptoms (SANS): conceptual and theoretical foundations. Br J Psychiatry Suppl. 1989;155:49–58.

Overall JE, Gorham DR. The Brief Psychiatric Rating Scale. 1962;10:799–812.

Nuechterlein KH, Green MF, Kern RS, et al. The MATRICS Consensus Cognitive Battery, part 1: test selection, reliability, and validity. Am J Psychiatry. 2008;165:203–213.

Ishima T, Iyo M, Hashimoto K. Neurite outgrowth mediated by the heat shock protein Hsp90α: a novel target for the antipsychotic drug aripiprazole. Transl Psychiatry. 2012;2:e170–e170.

Stapel B, Sieve I, Falk CS, et al. Second generation atypical antipsychotics olanzapine and aripiprazole reduce expression and secretion of inflammatory cytokines in human immune cells. J Psychiatr Res. 2018;105:95–102.

Sato-Kasai M, Kato TA, Ohgidani M, et al. Aripiprazole inhibits polyI:C-induced microglial activation possibly via TRPM7. Schizophr Res. 2016;178:35–43.

Grace AA, Bunney BS. Induction of depolarization block in midbrain dopamine neurons by repeated administration of haloperidol: analysis using in vivo intracellular recording. J Pharmacol Exp Ther. 1986;238:1092–1100.