Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents: Preliminary evidence from an open-label study

A. Irem Sonmez; M. Utku Kucuker; Charles P. Lewis; Bhanu Prakash Kolla; Deniz Doruk Camsari; Jennifer L. Vande Voort; Kathryn M. Schak; Simon Kung; Paul E. Croarkin

doi:10.1016/j.pnpbp.2019.109763

Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents: Preliminary evidence from an open-label study

A. Irem Sonmez, M. Utku Kucuker, Charles P. Lewis, Bhanu Prakash Kolla, Deniz Doruk Camsari, Jennifer L. Vande Voort, Kathryn M. Schak, Simon Kung, Paul E. Croarkin

Research output: Contribution to journal › Article › peer-review

21 Scopus citations

Abstract

Study objectives: Sleep disruption is a significant symptom of major depressive disorder (MDD). To our knowledge, no prior work has examined the impact of repetitive transcranial magnetic stimulation (rTMS) on sleep disturbances in adolescents with MDD. Methods: Seventeen adolescents with treatment-resistant depression received 30 daily sessions of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC). Clinical symptoms were assessed at baseline; after 10, 20, and 30 treatments; and at a 6-month follow-up visit. Insomnia was measured with a 3-item subscale of the Quick Inventory of Depressive Symptomatology – Adolescent (17 Item) – Self Report (QIDS-A₁₇-SR). Hypersomnia was measured with a single QIDS-A₁₇-SR item. Depression severity was rated with the Children's Depression Rating Scale, Revised (CDRS-R). The effect of rTMS on sleep was examined via linear mixed model analyses, with fixed effects of time (as a proxy of treatment), depression severity, age, and hypnotic medication use. Results: No significant main effect of time was observed on the insomnia subscale (F_4,43.442 = 1.078, p = 0 .379). However, there was a significant main effect of time on the QIDS-A₁₇-SR hypersomnia score (F_4,46.124 = 2.733, p = 0 .040), with significant improvement from baseline to treatment 10 (p_adj = 0.019) and from baseline to 6-month follow-up (p_adj = 0.044). In exploratory sensitivity analyses, response/nonresponse to rTMS for overall depressive symptoms had no significant effect on sleep outcomes. Conclusions: rTMS may have intrinsic effects on hypersomnia apart from its antidepressant effects in depressed adolescents. Future work should utilize sham controls and objective, quantitative measurements of sleep architecture to assess effects of rTMS in depressed adolescents. Clinical trial registry: Clinicaltrials.gov identifiers are NCT00587639, NCT01502033, NCT01804270.

Original language	English (US)
Article number	109763
Journal	Progress in Neuro-Psychopharmacology and Biological Psychiatry
Volume	97
DOIs	https://doi.org/10.1016/j.pnpbp.2019.109763
State	Published - Mar 8 2020
Externally published	Yes

Bibliographical note

Funding Information:
Research reported in this publication was supported by the National Institutes of Health under award R01 MH113700 (Dr. Croarkin). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Neuronetics, Inc. provided equipment support for the study. Role of the Sponsor: The supporters had no role in the design, analysis, interpretation, or publication of the study.Dr. Croarkin has received research grant support from Pfizer, Inc.; equipment support from Neuronetics, Inc.; and received supplies and genotyping services from Assurex Health, Inc. for investigator-initiated studies. He is the primary investigator for a multicenter study funded by Neuronetics, Inc. and a site primary investigator for a study funded by NeoSync, Inc. Dr. Croarkin is a paid consultant for Procter & Gamble Company. Dr. Lewis receives research support from the Brain and Behavior Research Foundation and has served as a site co-investigator on multicenter trials funded by Neuronetics, Inc. and NeoSync, Inc. The other authors have no disclosures or potential conflicts of interest to declare.

Funding Information:
Research reported in this publication was supported by the National Institutes of Health under award R01 MH113700 (Dr. Croarkin). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Neuronetics, Inc. provided equipment support for the study. Role of the Sponsor: The supporters had no role in the design, analysis, interpretation, or publication of the study.

Funding Information:
Dr. Croarkin has received research grant support from Pfizer, Inc.; equipment support from Neuronetics, Inc.; and received supplies and genotyping services from Assurex Health, Inc. for investigator-initiated studies. He is the primary investigator for a multicenter study funded by Neuronetics, Inc. and a site primary investigator for a study funded by NeoSync, Inc. Dr. Croarkin is a paid consultant for Procter & Gamble Company. Dr. Lewis receives research support from the Brain and Behavior Research Foundation and has served as a site co-investigator on multicenter trials funded by Neuronetics, Inc. and NeoSync, Inc. The other authors have no disclosures or potential conflicts of interest to declare.

Publisher Copyright:
© 2019 Elsevier Inc.

Keywords

Adolescent
Depression
Hypersomnia
Insomnia
Repetitive transcranial magnetic stimulation (rTMS)

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10.1016/j.pnpbp.2019.109763

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Sonmez, A. I., Kucuker, M. U., Lewis, C. P., Kolla, B. P., Doruk Camsari, D., Vande Voort, J. L., Schak, K. M., Kung, S., & Croarkin, P. E. (2020). Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents: Preliminary evidence from an open-label study. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 97, Article 109763. https://doi.org/10.1016/j.pnpbp.2019.109763

Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents: Preliminary evidence from an open-label study. / Sonmez, A. Irem; Kucuker, M. Utku; Lewis, Charles P. et al.
In: Progress in Neuro-Psychopharmacology and Biological Psychiatry, Vol. 97, 109763, 08.03.2020.

Research output: Contribution to journal › Article › peer-review

Sonmez, AI, Kucuker, MU, Lewis, CP, Kolla, BP, Doruk Camsari, D, Vande Voort, JL, Schak, KM, Kung, S & Croarkin, PE 2020, 'Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents: Preliminary evidence from an open-label study', Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 97, 109763. https://doi.org/10.1016/j.pnpbp.2019.109763

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abstract = "Study objectives: Sleep disruption is a significant symptom of major depressive disorder (MDD). To our knowledge, no prior work has examined the impact of repetitive transcranial magnetic stimulation (rTMS) on sleep disturbances in adolescents with MDD. Methods: Seventeen adolescents with treatment-resistant depression received 30 daily sessions of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC). Clinical symptoms were assessed at baseline; after 10, 20, and 30 treatments; and at a 6-month follow-up visit. Insomnia was measured with a 3-item subscale of the Quick Inventory of Depressive Symptomatology – Adolescent (17 Item) – Self Report (QIDS-A17-SR). Hypersomnia was measured with a single QIDS-A17-SR item. Depression severity was rated with the Children's Depression Rating Scale, Revised (CDRS-R). The effect of rTMS on sleep was examined via linear mixed model analyses, with fixed effects of time (as a proxy of treatment), depression severity, age, and hypnotic medication use. Results: No significant main effect of time was observed on the insomnia subscale (F4,43.442 = 1.078, p = 0 .379). However, there was a significant main effect of time on the QIDS-A17-SR hypersomnia score (F4,46.124 = 2.733, p = 0 .040), with significant improvement from baseline to treatment 10 (padj = 0.019) and from baseline to 6-month follow-up (padj = 0.044). In exploratory sensitivity analyses, response/nonresponse to rTMS for overall depressive symptoms had no significant effect on sleep outcomes. Conclusions: rTMS may have intrinsic effects on hypersomnia apart from its antidepressant effects in depressed adolescents. Future work should utilize sham controls and objective, quantitative measurements of sleep architecture to assess effects of rTMS in depressed adolescents. Clinical trial registry: Clinicaltrials.gov identifiers are NCT00587639, NCT01502033, NCT01804270.",

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author = "Sonmez, {A. Irem} and Kucuker, {M. Utku} and Lewis, {Charles P.} and Kolla, {Bhanu Prakash} and {Doruk Camsari}, Deniz and {Vande Voort}, {Jennifer L.} and Schak, {Kathryn M.} and Simon Kung and Croarkin, {Paul E.}",

note = "Funding Information: Research reported in this publication was supported by the National Institutes of Health under award R01 MH113700 (Dr. Croarkin). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Neuronetics, Inc. provided equipment support for the study. Role of the Sponsor: The supporters had no role in the design, analysis, interpretation, or publication of the study.Dr. Croarkin has received research grant support from Pfizer, Inc.; equipment support from Neuronetics, Inc.; and received supplies and genotyping services from Assurex Health, Inc. for investigator-initiated studies. He is the primary investigator for a multicenter study funded by Neuronetics, Inc. and a site primary investigator for a study funded by NeoSync, Inc. Dr. Croarkin is a paid consultant for Procter & Gamble Company. Dr. Lewis receives research support from the Brain and Behavior Research Foundation and has served as a site co-investigator on multicenter trials funded by Neuronetics, Inc. and NeoSync, Inc. The other authors have no disclosures or potential conflicts of interest to declare. Funding Information: Research reported in this publication was supported by the National Institutes of Health under award R01 MH113700 (Dr. Croarkin). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Neuronetics, Inc. provided equipment support for the study. Role of the Sponsor: The supporters had no role in the design, analysis, interpretation, or publication of the study. Funding Information: Dr. Croarkin has received research grant support from Pfizer, Inc.; equipment support from Neuronetics, Inc.; and received supplies and genotyping services from Assurex Health, Inc. for investigator-initiated studies. He is the primary investigator for a multicenter study funded by Neuronetics, Inc. and a site primary investigator for a study funded by NeoSync, Inc. Dr. Croarkin is a paid consultant for Procter & Gamble Company. Dr. Lewis receives research support from the Brain and Behavior Research Foundation and has served as a site co-investigator on multicenter trials funded by Neuronetics, Inc. and NeoSync, Inc. The other authors have no disclosures or potential conflicts of interest to declare. Publisher Copyright: {\textcopyright} 2019 Elsevier Inc.",

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doi = "10.1016/j.pnpbp.2019.109763",

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T1 - Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents

T2 - Preliminary evidence from an open-label study

AU - Sonmez, A. Irem

AU - Kucuker, M. Utku

AU - Lewis, Charles P.

AU - Kolla, Bhanu Prakash

AU - Doruk Camsari, Deniz

AU - Vande Voort, Jennifer L.

AU - Schak, Kathryn M.

AU - Kung, Simon

AU - Croarkin, Paul E.

N1 - Funding Information: Research reported in this publication was supported by the National Institutes of Health under award R01 MH113700 (Dr. Croarkin). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Neuronetics, Inc. provided equipment support for the study. Role of the Sponsor: The supporters had no role in the design, analysis, interpretation, or publication of the study.Dr. Croarkin has received research grant support from Pfizer, Inc.; equipment support from Neuronetics, Inc.; and received supplies and genotyping services from Assurex Health, Inc. for investigator-initiated studies. He is the primary investigator for a multicenter study funded by Neuronetics, Inc. and a site primary investigator for a study funded by NeoSync, Inc. Dr. Croarkin is a paid consultant for Procter & Gamble Company. Dr. Lewis receives research support from the Brain and Behavior Research Foundation and has served as a site co-investigator on multicenter trials funded by Neuronetics, Inc. and NeoSync, Inc. The other authors have no disclosures or potential conflicts of interest to declare. Funding Information: Research reported in this publication was supported by the National Institutes of Health under award R01 MH113700 (Dr. Croarkin). The content of this publication is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Neuronetics, Inc. provided equipment support for the study. Role of the Sponsor: The supporters had no role in the design, analysis, interpretation, or publication of the study. Funding Information: Dr. Croarkin has received research grant support from Pfizer, Inc.; equipment support from Neuronetics, Inc.; and received supplies and genotyping services from Assurex Health, Inc. for investigator-initiated studies. He is the primary investigator for a multicenter study funded by Neuronetics, Inc. and a site primary investigator for a study funded by NeoSync, Inc. Dr. Croarkin is a paid consultant for Procter & Gamble Company. Dr. Lewis receives research support from the Brain and Behavior Research Foundation and has served as a site co-investigator on multicenter trials funded by Neuronetics, Inc. and NeoSync, Inc. The other authors have no disclosures or potential conflicts of interest to declare. Publisher Copyright: © 2019 Elsevier Inc.

PY - 2020/3/8

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N2 - Study objectives: Sleep disruption is a significant symptom of major depressive disorder (MDD). To our knowledge, no prior work has examined the impact of repetitive transcranial magnetic stimulation (rTMS) on sleep disturbances in adolescents with MDD. Methods: Seventeen adolescents with treatment-resistant depression received 30 daily sessions of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC). Clinical symptoms were assessed at baseline; after 10, 20, and 30 treatments; and at a 6-month follow-up visit. Insomnia was measured with a 3-item subscale of the Quick Inventory of Depressive Symptomatology – Adolescent (17 Item) – Self Report (QIDS-A17-SR). Hypersomnia was measured with a single QIDS-A17-SR item. Depression severity was rated with the Children's Depression Rating Scale, Revised (CDRS-R). The effect of rTMS on sleep was examined via linear mixed model analyses, with fixed effects of time (as a proxy of treatment), depression severity, age, and hypnotic medication use. Results: No significant main effect of time was observed on the insomnia subscale (F4,43.442 = 1.078, p = 0 .379). However, there was a significant main effect of time on the QIDS-A17-SR hypersomnia score (F4,46.124 = 2.733, p = 0 .040), with significant improvement from baseline to treatment 10 (padj = 0.019) and from baseline to 6-month follow-up (padj = 0.044). In exploratory sensitivity analyses, response/nonresponse to rTMS for overall depressive symptoms had no significant effect on sleep outcomes. Conclusions: rTMS may have intrinsic effects on hypersomnia apart from its antidepressant effects in depressed adolescents. Future work should utilize sham controls and objective, quantitative measurements of sleep architecture to assess effects of rTMS in depressed adolescents. Clinical trial registry: Clinicaltrials.gov identifiers are NCT00587639, NCT01502033, NCT01804270.

AB - Study objectives: Sleep disruption is a significant symptom of major depressive disorder (MDD). To our knowledge, no prior work has examined the impact of repetitive transcranial magnetic stimulation (rTMS) on sleep disturbances in adolescents with MDD. Methods: Seventeen adolescents with treatment-resistant depression received 30 daily sessions of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC). Clinical symptoms were assessed at baseline; after 10, 20, and 30 treatments; and at a 6-month follow-up visit. Insomnia was measured with a 3-item subscale of the Quick Inventory of Depressive Symptomatology – Adolescent (17 Item) – Self Report (QIDS-A17-SR). Hypersomnia was measured with a single QIDS-A17-SR item. Depression severity was rated with the Children's Depression Rating Scale, Revised (CDRS-R). The effect of rTMS on sleep was examined via linear mixed model analyses, with fixed effects of time (as a proxy of treatment), depression severity, age, and hypnotic medication use. Results: No significant main effect of time was observed on the insomnia subscale (F4,43.442 = 1.078, p = 0 .379). However, there was a significant main effect of time on the QIDS-A17-SR hypersomnia score (F4,46.124 = 2.733, p = 0 .040), with significant improvement from baseline to treatment 10 (padj = 0.019) and from baseline to 6-month follow-up (padj = 0.044). In exploratory sensitivity analyses, response/nonresponse to rTMS for overall depressive symptoms had no significant effect on sleep outcomes. Conclusions: rTMS may have intrinsic effects on hypersomnia apart from its antidepressant effects in depressed adolescents. Future work should utilize sham controls and objective, quantitative measurements of sleep architecture to assess effects of rTMS in depressed adolescents. Clinical trial registry: Clinicaltrials.gov identifiers are NCT00587639, NCT01502033, NCT01804270.

KW - Adolescent

KW - Depression

KW - Hypersomnia

KW - Insomnia

KW - Repetitive transcranial magnetic stimulation (rTMS)

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Improvement in hypersomnia with high frequency repetitive transcranial magnetic stimulation in depressed adolescents: Preliminary evidence from an open-label study

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