The Effect of Aripiprazole versus Risperidone on Prefrontal Brain Metabolite Levels and Brain Volume in Psychotic Disorders: An Exploratory Study

Abstract

ObjectiveGiven that aripiprazole acts as a partial agonist on the dopamine receptor, it may have unique effects on brain neuro-metabolism, specifically in the prefrontal cortex. In this exploratory study, we investigated the effect of aripiprazole compared to risperidone on prefrontal metabolite levels (Glx, NAA, Creatine, Choline and myo-Inositol) and changes in gray and white matter volume (GMV and WMV) in patients with a psychotic disorder. We hypothesized that patients treated with aripiprazole would show increased levels of Glx and NAA and preserved brain volumes, in contrast to risperidone. MethodsIn this randomized, single blind study, patients (n=24) treated with either risperidone or aripiprazole underwent magnetic resonance spectroscopy ( 1 H-MRS) and high-resolution anatomical scans (3T) at baseline and after 9 weeks. LC Model was used to determine the absolute spectral metabolite levels and SPM12 was to perform voxel based morphometry analyses. Both metabolite levels and brain volumes were compared between treatment groups. ResultsWe found a trend for a different effect of both antipsychotics on Glx levels, whereby risperidone reduced Glx levels compared to aripiprazole. Moreover, patients treated with aripiprazole showed a decreased GMV in the precentral gyrus, caudate and lateral frontal regions and increased WMV in the precentral gyrus and a non-significant but consistent pattern of prefrontal WM increases, in contrast to risperidone. ConclusionOur results point to possibility of different effects of aripiprazole on brain volume and metabolism compared to risperidone. Studies in larger samples are needed to shed more light on the robustness and nature of such differences.

Micro- and Macrostructural White Matter Integrity in Never-Treated and Currently Unmedicated Patients With Schizophrenia and Effects of Short-Term Antipsychotic Treatment

“…Another question that remains unanswered is if different antipsychotic medications affect white matter structure differentially. A recent exploratory study in a small sample of patients directly compared effects of risperidone and aripiprazole on gray matter and white matter volumes as well as neurometabolite levels and found a non-significant increase in prefrontal white matter volume in those treated with aripiprazole but not risperidone, suggesting that these drugs may have differential effects (55). However, these results need to be considered preliminary at this time, and larger scale studies making head to head comparisons of medication effects not only on macrostructural but also microstructural white matter integrity are direly needed in the field.…”

Efficacy and tolerability of aripiprazole versus D2 antagonists in the early course of schizophrenia: a systematic review and meta-analysis

“… ARI: 14.7 (4.7) PER ( N = 22) PER: 18.4 (11.6) Total ( N = 40) Nussbaum et al 18 (Romania) OL-RCT ARI ( N = 22) 104 wk (of 13, 26, 52, 78, 104 wk) 16.0 (2.5), 53.3% Schizophrenia or bipolar disorder (DSM-IV, K-SADS-PL) - only used schizophrenia; 135.3 (15.9) According to mean age: <18 y, doi:? No info RIS ( N = 22) Total ( N = 44) Pagsberg et al 19 ; related publication 31 (Denmark) DB-RCT ARI ( N = 58) 12 wk 15.8 (1.3), 30.1% Schizophrenia-spectrum disorder, delusional disorder, affective-spectrum psychotic disorder (ICD-10); 77.9 (12.3) According to authors’ definition (first episode), doi: 30 mo ARI: 13.0 (5.5) QUE ( N = 55) QUE: 426.4 (169.3) Total ( N = 113) Wang et al 20 (China) OL-RCT ARI ( N = 39) 6-8 wk 27.8 (8.3), 46.3% Schizophrenia (DSM-IV); ~99 According to authors’ definition (first episode, antipsychotic-naïve), doi: 8.5 (13.0) mo ARI: 25.7 (6.5) RIS ( N = 43) RIS: 5.0 (2.5) QUE ( N = 39) QUE: 634.5 (207.6) ZIP ( N = 19) ZIP: 102.9 (49.6) OLA ( N = 35) OLA: 17.6 (3.4) Total ( N = 175) Liemburg et al 21 (Netherlands) SB-RCT ARI ( N = 12) 9 wk 27.7 (10.0), 87.5% Schizophrenia or a related non-affective psychotic disorder (DSM-IV); 66.3 (10.6) …”

“…Of the 1072 records identified, 14 studies, involving a total of 2494 patients were included in our meta-analysis (Supplementary Fig. 1) [10][11][12][13][14][15][16][17][18][19][20][21][22][23] . Included studies are summarized in Table 1.…”