Effects of Noninvasive Neurostimulation on Sleep Quality and Symptoms in Depression

Konstiantyn Zapylaie/AdobeStock

Case Vignette

“Mr Bickle” is a 33 year-old Caucasian man with a history of major depressive disorder (MDD), recurrent, severe, without psychosis. The onset of his depression was in early adolescence. Mr Bickle previously failed trials of selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, bupropion, tricyclic antidepressants, lithium, thyroid hormone, and atypical antipsychotics.He declined electroconvulsive therapy due to a family history of significant adverse cognitive effects from the procedure. His current regimen includes fluoxetine 80 mg daily and amphetamine-dextroamphetamine extended-release 20 mg daily, to which he has had a partial response. At his most recent outpatient clinic visit, he asks about the potential benefits of transcranial magnetic stimulation (TMS) on his symptoms, including sleep. As his psychiatrist, how would you respond?

Sleep disturbance is common in patients with MDD.¹ Subjective sleep quality correlates with depressive symptom severity.^2,3 Improvements in objectively-measured sleep parameters, including sleep efficiency and duration, are associated with improvement in depressive symptoms.^4,5 There is meta-analytic evidence for noninvasive neurostimulation, including repetitive TMS (rTMS), transcranial direct current stimulation (tDCS), and bright light therapy (BLT) in the treatment of depression.^3,6,7 However, the effect of these techniques of sleep in MDD has not clearly been explicated.

The Current Study

Qiao et al performed a meta-analysis of randomized controls trials (RCTs) of noninvasive neurostimulation on sleep quality, efficiency, and duration in patients with MDD, and their association with changes in depressive symptoms.⁸ The authors searched PubMed, Cochrane Library, Web of Science, EMBASE, Wanfang, and China National Knowledge Infrastructure for relevant RCTs. Inclusion criteria were adults with MDD (either DSM or ICD); interventions of rTMS, tDCS, or BLT, with or without antidepressant medications; comparison between neurostimulation and sham/no neurostimulation; primary outcomes of sleep quality and disturbance based on validated self-report tools (eg, Pittsburgh Sleep Quality Index [PSQI]) or objective sleep measures (eg, polysomnography or actigraphy); and second outcomes of changes in depressive symptoms based on validated scales. Studies that simultaneously assessed multiple interventions or that did not have adequate data on outcomes were excluded. Studies were assessed for Risk of Bias using the Cochrane Risk of Bias tool. Methodologic quality was assessed using the Jadad scale.

For each study, standardized mean differences (SMD) between neurostimulation and control groups were calculated for sleep and depressive symptom outcomes. Aggregated data were analyzed using random-effects meta-analysis. Subgroup analyses were performed based on the presence or absence of improved sleep. Sensitivity analyses were also performed. Potential publication bias was analyzed using Egger’s test and Begg’s rank correlation.

Fifteen RCTs, comprising 1348 patients, met the inclusion/exclusion criteria (BLT n=7, TMS n=7, tDCS n=1). The median sample size was 40 patients per group. Median duration of neurostimulation was 4 weeks. Over half of patients (58%) received concomitant antidepressant medication. In controls, 64% received sham neurostimulation. Thirteen of the 15 studies showed high or unclear risk of bias in at least 1 assessed domain. However, all RCTs were of high methodological quality based on the Jadad scale.

Ten RCTs assessed sleep quality using the PSQI or the Hamilton Depression Scale. Neurostimulation was associated with significantly improved sleep quality with a medium-to-large effect size (SMD=0.74). There was no evidence of publication bias. Five RCTs objectively evaluated sleep efficiency, which was significantly improved with neurostimulation with a small-to-medium effect size (SMD=0.35). There was no evidence of publication bias. Seven RCTs assessed objective sleep duration. Neurostimulation was not associated with significantly longer or shorter sleep (SMD=0.07).

In subgroup analyses, rTMS (SMD=0.84), but not BLT was associated with significantly better sleep quality. There was inadequate data for subgroup analyses with sleep efficiency and duration, as well as tDCS (1 study). Moderator analysis comparing rTMS and BLT did not identify any factors affecting depressive symptoms.

Study Conclusions

The authors found evidence that noninvasive neurostimulation can significantly improve sleep quality and efficiency in patients with MDD, while also alleviating the severity of depressive symptoms. Findings were robust to sensitivity analyses and there was no evidence of publication bias. The authors hypothesized that these techniques may affect sleep by acting on the dorsolateral prefrontal cortex. A notable study strength was the large cumulative sample size. Study limitations included divergent outcomes in studies assessing both sleep efficiency and duration, and only 1 study of tDCS.

The Bottom Line

Noninvasive neurostimulation can significantly improve sleep in patients with MDD, in addition to improvements in other depressive symptoms. Findings are relevant to patients for whom pharmacologic options may be limited (eg, pregnancy or the elderly). Findings also raise the possibility of noninvasive neurostimulation as an alternative approach to the treatment of sleep disturbance in patients with MDD.

Dr Miller is professor in the Department of Psychiatry and Health Behavior, Augusta University, Augusta, Georgia. He is on the Editorial Board and serves as the schizophrenia section chief for Psychiatric Times. The author reports that he receives research support from Augusta University, the National Institute of Mental Health, and the Stanley Medical Research Institute.

References

1. Pandi-Perumal SR, Monti JM, Burman D, et al. Clarifying the role of sleep in depression: a narrative review. Psychiatry Res. 2020;291:113239.

2. Urrila AS, Paunio T, Palomäki E, et al. Sleep in adolescent depression: physiological perspectives. Acta Physiol (Oxf). 2015;213(4):758-777.

3. Zhang R, Lam CLM, Peng X, et al. Efficacy and acceptability of transcranial direct current stimulation for treating depression: a meta-analysis of randomized controlled trials. Neurosci Biobehav Rev. 2021;126:481-490.

4. Perlman CA, Johnson SL, Mellman TA. The prospective impact of sleep duration on depression and mania. Bipolar Disord. 2006;8(3):271-274.

5. Difrancesco S, Lamers F, Riese H, et al. Sleep, circadian rhythm, and physical activity patterns in depressive and anxiety disorders: a 2-week ambulatory assessment study. Depress Anxiety. 2019;36(10):975-986.

6. De Risio L, Borgi M, Pettorruso M, et al. Recovering from depression with repetitive transcranial magnetic stimulation (rTMS): a systematic review and meta-analysis of preclinical studies. Transl Psychiatry. 2020;10(1):393.

7. Geoffroy PA, Schroder CM, Reynaud E, et al. Efficacy of light therapy versus antidepressant drugs, and of the combination versus monotherapy, in major depressive episodes: a systematic review and meta-analysis. Sleep Med Rev. 2019;48:101213.

8. Qiao M-X, Yu H, Li T. Non-invasive neurostimulation to improve sleep quality and depressive symptoms in patients with major depressive disorder: a meta-analysis of randomized controlled trials. J Psychiatr Res. 2024;176:282-292.