Early versus late wake therapy improves mood more in antepartum versus postpartum depression by differentially altering melatonin-sleep timing disturbances - PubMed (original) (raw)

Randomized Controlled Trial

. 2019 Feb 15:245:608-616.

doi: 10.1016/j.jad.2018.11.064. Epub 2018 Nov 5.

Affiliations

Randomized Controlled Trial

Early versus late wake therapy improves mood more in antepartum versus postpartum depression by differentially altering melatonin-sleep timing disturbances

Barbara L Parry et al. J Affect Disord. 2019.

Abstract

Background: Peripartum major depression (MD) disables mothers and impairs emotional and neurocognitive development of offspring. We tested the hypothesis that critically-timed wake therapy (WT) relieves peripartum MD by altering melatonin and sleep timing, differentially, in antepartum vs. postpartum depressed patients (DP).

Methods: In a university clinical research center, we initially randomized 50 women - 26 antepartum (17 healthy comparison-HC, 9 DP) and 24 postpartum (8 HC, 16 DP) - to a cross-over trial of one night of early-night wake therapy (EWT: sleep 3:00-7:00 am) vs. late-night wake therapy (LWT: sleep 9:00 pm-01:00 am). Ultimately, we obtained mood, overnight plasma melatonin and polysomnography for: 15 antepartum women receiving EWT, 18 receiving LWT; 15 postpartum women receiving EWT, 14 receiving LWT.

Results: EWT improved mood more in antepartum vs. postpartum DP in conjunction with reduced (normalized) melatonin-sleep phase-angle differences (PADs) due to delayed melatonin onsets and advanced sleep onsets, and increased (from baseline) total sleep times (TST). LWT improved mood more in postpartum vs. antepartum DP in conjunction with increased TST.

Limitations: Small samples potentially rendered the study underpowered to detect group differences, making confirmation with larger samples essential. Sufficient follow-up data were not available in most women to document the duration of the mood response to wake therapy.

Conclusions: EWT benefitted antepartum DP more by realigning melatonin and sleep timing, whereas LWT benefitted postpartum DP more by increasing TST. Thus, consistent with precision medicine aims, maximum mood benefits accrue from timing sleep/wake interventions to specific peripartum circadian pathophysiologies.

Keywords: Chronobiology; Melatonin; Peripartum depression; Phase-angle differences; Sleep; Wake therapy.

Copyright © 2018. Published by Elsevier B.V.

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Conflict of interest statement

Declarations of Interest: none

Figures

Fig. 1.

Fig. 1.

Conceptual Model: At baseline, antepartum depressed patients (DP) vs. healthy comparison (HC) participants have phase-advanced Dim Light Melatonin Onset (DLMO) time plus phase-delayed Sleep Onset Time (SOT). After Early Wake Therapy, DLMO is delayed while SOT is advanced, thereby normalizing the DLMO_SOT phase angle difference (PAD) in association with improved mood in DP.

Fig. 2.

Fig. 2.

Melatonin-Sleep Timing Changes after Early Wake Therapy in Antepartum Depressed (DP) vs. Healthy Comparison (HC) women. Values represent means ± SEMs for antepartum healthy comparison (HC; N = 7) and depressed participants (DP; N = 5) at baseline, and after Early Wake therapy (EWT). By convention, phase-advances are listed as positive values, phase-delays as negative values. (Delta scores represent changes from baseline after EWT) (A): Dim Light Melatonin Onset (DLMO) in HC vs. DP at baseline (BSL) and after Early Wake Therapy (@EWT); (B) Sleep Onset Time (SOT) in HC vs. DP, at baseline and after EWT; (C) DLMO_SOT Phase Angle Difference in HC vs. DP, at baseline and after EWT.

Fig. 3.

Fig. 3.

Changes in Total Sleep Time (TST) after Wake Therapy in Antepartum and Postpartum Depressed women. Significant positive correlations occurred between change in mood (Hamilton Rating Scale for Depression; HRSD) and change in TST in (A) Antepartum depressed women after Early Wake Therapy (EWT; closed circles) and in (B) postpartum depressed women after Late Wake Therapy (LWT; open squares).

Fig. 4.

Fig. 4.

Percent Change/Improvement in HRSD scaled score vs. change in phase angle difference (PAD; scaled score) of Dim Light Melatonin Onset time (DLMO) - Sleep Onset Time (SOT) (DLMO_SOT PAD) after Early Wake Therapy (EWT) in antepartum and postpartum depressed patients (DP). Partial regression (controlling for baseline day length) showed a significant association between percent change/improvement in scaled scores on Hamilton Rating Scale for Depression (HRSD) and change in DLMO_SOT PAD in the combined antepartum and postpartum DP (r(partial) = −.749, p=.013). Reduction in DLMO_SOT PAD after EWT, evident more often in antepartum DP, was associated with greater mood improvement, while increase in DLMO_SOT PAD, evident more often in postpartum DP, was associated with smaller mood improvement.

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