Clinical response of quetiapine in rapid cycling manic bipolar patients and lactate level changes in proton magnetic resonance spectroscopy

Abstract

The aim of the current study was to evaluate the relationship between quetiapine's effect on the improvement of mood symptoms in bipolar patients and brain metabolite level changes as measured by proton magnetic resonance spectroscopy ((1)H-MRS). Rapid cycling bipolar patients in the manic state were recruited and treated with quetiapine for 12 weeks. Clinical assessment was performed using the Young Mania Rating Scale (YMRS), the 17-item Hamilton Depression Rating Scale (HDRS) and the Clinical Global Impression-Severity scale (CGI-S) at baseline and weekly intervals during the 12-week period. In order to evaluate metabolite level changes over time, (1)H-MRS scans were acquired at baseline and week 12. There were significant reductions in YMRS scores (by 43.0%), HDRS scores (by 27.5%) and CGI-S score (by 44.6%) over the 12 week-period. Lactate levels significantly decreased over the 12-week study period (22.4%). This change in lactate levels was more prominent in quetiapine responders than in non-responders. Additionally, there was a positive correlation between changes in lactate levels and those in YMRS scores (r=0.52, p=0.003). Our findings suggest that quetiapine's antimanic and antidepressant efficacy in patients with rapid cycling bipolar disorder may potentially be related to decreased lactate levels in frontal regions of the brain.

Figure 1. Midfrontal voxel-of-interest

Figure 2. Reduction of YMRS scores and HDRS scores over the 12-week period in rapid cycling bipolar patients with quetiapine treatment

Footnote: Results of repeated measures ANOVA for YMRS and HDRS [F(12, 444)=27.7, p<0.001 and F(12, 444)=23.9, p<0.001, respectively] were presented. Pattern of CGI-S changes is similar to those of YMRS and HDRS, although data are not shown in this figure. Plot indicates observed cases means. Error bar means 95% confidence interval and box means standard errors. Abbreviations: ANOVA, analysis of variance; YMRS, Young Mania Rating Scale; HDRS, Hamilton Depression Rating Scale; CGI-S, Clinical Global Impression-Severity scale

Figure 3. Midfrontal lactate level changes in rapid cycling bipolar patients with quetiapine treatment

Pane A: Comparison of lactate level changes between baseline and week 12 Pane B: Comparison of lactate level changes between non-responders and responders Footnotes: There were significant differences in the lactate level in the midfrontal gray matter at baseline and week 12 [t(29)=15.4, p<0.001](Pane A). Lactate level changes of responders following the quetiapine treatment were greater than that of non-responders (z=−2.08, p=0.037)(Pane B). Plot indicates observed cases means. Error bar means 95% confidence interval and box means standard errors.

Figure 3. Midfrontal lactate level changes in rapid cycling bipolar patients with quetiapine treatment

Pane A: Comparison of lactate level changes between baseline and week 12 Pane B: Comparison of lactate level changes between non-responders and responders Footnotes: There were significant differences in the lactate level in the midfrontal gray matter at baseline and week 12 [t(29)=15.4, p<0.001](Pane A). Lactate level changes of responders following the quetiapine treatment were greater than that of non-responders (z=−2.08, p=0.037)(Pane B). Plot indicates observed cases means. Error bar means 95% confidence interval and box means standard errors.