A Randomized Controlled Trial of Desvenlafaxine-Induced Structural Brain Changes in the Treatment of Persistent Depressive Disorder

Elsevier

Available online 24 March 2023, 111634

Psychiatry Research: NeuroimagingAuthor links open overlay panel, , , , Abstract

The anatomical changes that antidepressant medications induce in the brain and through which they exert their therapeutic effects remain largely unknown. We randomized 61 patients with Persistent Depressive Disorder (PDD) to receive either desvenlafaxine or placebo in a 12-week trial and acquired anatomical MRI scans in 42 of those patients at baseline before randomization and immediately at the end of the trial. We also acquired MRIs once in 39 age- and sex-matched healthy controls. We assessed whether the serotonin-norepinephrine reuptake inhibitor, desvenlafaxine, differentially changed cortical thickness during the trial compared with placebo. Patients relative to controls at baseline had thinner cortices across the brain. Although baseline thickness was not associated with symptom severity, thicker baseline cortices predicted greater reduction in symptom severity in those treated with desvenlafaxine but not placebo. We did not detect significant treatment-by-time effects on cortical thickness. These findings suggest that baseline thickness may serve as predictive biomarkers for treatment response to desvenlafaxine. The absence of treatment-by-time effects may be attributable either to use of insufficient desvenlafaxine dosing, a lack of desvenlafaxine efficacy in treating PDD, or the short trial duration.

Section snippetsINTRODUCTION

Persistent Depressive Disorder (PDD), or dysthymia, is a chronic, non-episodic form (Pillay et al., 1998) of depression that lasts longer than 2 years (Li et al., 2022; Qiu et al., 2020). PDD has a lifetime prevalence of approximately 6% (Murphy and Byrne, 2012; Satyanarayana et al., 2009; Vakili et al., 2000; Weissman et al., 1988) and a 12-month incidence rate of 1.5% in the general population (Blanco et al., 2010). Randomized controlled trials (RCTs) of Selective Serotonin Reuptake

Study Participants

This was an investigator-initiated trial funded by Pfizer, Inc, and registered with ClinicalTrials.gov (identifier: NCT01537068). Study procedures were approved by the Institutional Review Board of the New York State Psychiatric Institute (NYSPI). The study was advertised at local clinics, psychiatric listservs, hospital bulletin boards, newspapers, and craigslist. The study started recruiting participants in February 2012 and was completed by December 2016. Participants provided written,

Preliminary Analyses of Medication Effects on Symptoms

Symptom severity declined significantly and similarly in both groups over the 12-week duration of the clinical trial (p<0.0001), so that at the end of the trial, symptom severity in the DVLX group (HDRS-17=6.4±4.2) and in the PBO group (HDRS-17=8.0±5.6) did not differ significantly (p=0.29). Furthermore, the decline in symptom severity did not differ by treatment group (i.e., treatment-by-time effect was not significant [p=0.54]). These findings in our MRI subgroup mirror those in the larger

DISCUSSION

Findings confirmed one of our a priori hypotheses, that baseline cortical thickness predicts reduction in symptom severity in patients treated with DVLX (Fig. 3, left panel). Baseline cortical thickness, however, did not significantly associate inversely with symptom severity (Fig. 2, middle panel), and cortical thickness did not change differentially in DVLX- relative to placebo-treated patients (not shown), thereby failing to support our other two a priori hypotheses.

The absence of

Uncited References

Mazziotta et al., 2001, Shrout and Fleiss, 1979

Declaration of Competing Interest

This study was supported by Pfizer Pharmaceuticals via investigator-initiated funding (desvenlafaxine vs. placebo clinical trial and open-label continuation treatment) received by Drs. Hellerstein and Peterson. Pfizer Pharmaceuticals or its employees did not contribute to patient enrollment, data collection, data processing, and writing of this paper. Dr. Hellerstein has received research grants (through the Research Foundation for Mental Hygiene) from: Compass Pathways, Relmada, Marinus,

ACKNOWLEDGEMENTS

The study was also supported by funding from an anonymous donor, Patrice and Mike Harmon, and the Robert Coury family. The research was made possible by the provision of data by New York State Psychiatric Institute and Columbia University.

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