Objectives A sizable fraction of people with bipolar I disorder ( BDI ) experience a deteriorating clinical course with increasingly frequent mood episodes and chronic disability. This is believed to result from neurobiological illness progression, or neuroprogression. Excessive weight gain predicts neuroprogression across multiple brain illnesses, but no prospective studies have investigated this in BDI . The objective of this study was to determine whether BDI patients who experienced clinically significant weight gain ( CSWG ; gaining ≥7% of baseline weight) over 12 months had greater 12‐month brain volume loss in frontal and temporal regions important to BDI . Methods In 55 early‐stage BDI patients we measured (i) rates of CSWG , (ii) the number of days with mood symptoms, using NIMH LifeCharts, and (iii) baseline and 12‐month brain volumes, using 3T MRI . We quantified brain volumes using the longitudinal processing stream in FreeSurfer v6.0. We used general linear models for repeated measures to investigate whether CSWG predicted volume loss, adjusting for potentially confounding clinical and treatment variables. Results After correction for multiple comparisons, CSWG in patients predicted greater volume loss in the left orbitofrontal cortex (effect size [ ES ; Cohen's d ] = −1.01, P = 0.002), left cingulate gyrus ( ES = −1.31, P < 0.001), and left middle temporal gyrus ( ES = −0.96, P = 0.004). Middle temporal volume loss predicted more days with depression (β = −0.406, P = 0.010). Conclusions These are the first prospective data on weight gain and neuroprogression in BDI . CSWG predicted neuroprogression, and neuroprogression predicted a worse clinical illness course. Trials of weight loss interventions are needed to confirm the causal direction of the weight gain‐neuroprogression relationship, and to determine whether weight loss is a disease‐modifying treatment.
To determine the differences between escitalopram and citalopram in the treatment of patients with major depressive disorder across a range of baseline severity of depression using trend analysis.Data from the three placebo-controlled studies comparing escitalopram to citalopram were analyzed. The pre-specified primary outcome variable was MADRS total score; secondary outcomes included Clinical Global Impression-Severity (CGI-S) and -Improvement (CGI-I) scores. All analyses were based on an intent-to-treat (ITT) population and all direct comparisons were done by ANCOVA adjusting for baseline value and centre.Analyses of the pooled data (N=1203) show that, while the difference between citalopram and placebo was approximately constant across the range of baseline severity, the difference between escitalopram and placebo (p=0.0010 for no trend) and between escitalopram and citalopram (p=0.0012 for no trend) became greater, the more severely depressed the patients were at baseline. A similar pattern was apparent with the CGI-S and CGI-I results. There was a significant superiority of escitalopram over citalopram in response rate (defined as > or = 50% decrease in MADRS total score), and this difference increased with increasing baseline severity.These trend analyses thus indicate that the superiority of escitalopram over citalopram is more apparent as the baseline severity of depression increases.
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