The acute effects of aerobic exercise on sleep in patients with unipolar depression: a randomized controlled trial

Study Objectives Insomnia increases the risk of negative disease trajectory, relapse, and suicide in patients with depression. We aimed at investigating the effects of a single bout of aerobic exercise, performed after 02:00 pm, on the subsequent night’s sleep in patients with depression. Methods The study was designed as a two-arm parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. Patients between 18 and 65 years of age with a primary diagnosis of unipolar depression were included. The intervention was a single 30-minute bout of moderate aerobic exercise. The control group sat and read for 30 minutes. The primary outcome was sleep efficiency measured by polysomnography. Secondary outcomes were other polysomnographic variables, subjective sleep quality, daytime sleepiness, mood states, and adverse events. Results Ninety-two patients were randomized to the exercise (N = 46) or control group (N = 46). There were no clinically relevant differences at baseline. Intent-to-treat analysis ANCOVA of follow-up sleep efficiency, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = −0.93, p = 0.59). There was no evidence for significant differences between both groups in any other objective or subjective sleep outcomes, daytime sleepiness, or adverse events. The intervention had an immediate positive effect on mood states, including depressiveness (β = −0.40, p = 0.003). Conclusions This is the first trial to study the effects of a single bout of aerobic exercise on sleep in patients with depression to the best of our knowledge. Aerobic exercise had no effect on sleep efficiency but had a strong beneficial effect on mood and did not increase adverse outcomes. These results add to the growing body of evidence that, contrary to sleep hygiene recommendations, exercise after 02:00 pm is not detrimental for sleep. Clinical Trial Registration Clinicaltrials.gov, https://clinicaltrials.gov/ct2/show/NCT03673397. Protocol registered on September 17, 2018

Wirkmechanismen körperlicher Aktivität auf den Schlaf bei Patienten mit Depression: Ein Narratives Review

Insomnie ist eines der Kardinalsymptome einer unipolaren Depression. Insomnie hat dabei einen negativen Einfluss auf den Krankheitsverlauf, ist eines der häufigsten Residualsymptome und ein Risikofaktor für ein Rezidiv. Im vorliegenden Überblick werden mögliche Wirkmechanismen von körperlichem Training auf den Schlaf bei Patienten mit Depression zusammengefasst. Die vorgestellten Mechanismen beruhen auf Daten aus In-vitro‑, Tier- und Humanstudien, welche die Effekte von Kraft‑, Ausdauer- und Mind-Body-Training untersuchen. Sowohl akutes Training als auch über mehrere Wochen regelmäßig absolviertes Training kann über verschiedene Signalwege positive Effekte auf den Schlaf bei Patienten mit Depression haben. Folgende Mechanismen sind dabei relevant: Zeitgebereffekte, Energiekonservierung, Regeration, Thermoregulation, psychophysiologische Effekte und „tissue–brain crosstalk“. Diese Befunde sind relevant, um die Therapie von nichtorganischen Schlafstörungen im Rahmen einer depressiven Episode besser zu verstehen, weiterzuentwickeln und auf individuelle Patienten anzupassen

The effects of exercise on sleep in unipolar depression: A systematic review and network meta-analysis

Insomnia predicts the onset, course, and reoccurrence of unipolar depression. However, systematic reviews of treatment options for insomnia in unipolar depression are lacking. After screening 7725 records, 17 trials comprising 1645 patients randomized to 13 treatments were included for quantitative synthesis. Network meta-analysis showed that compared to a passive control condition, all exercise interventions except moderate aerobic exercise alone resulted in significantly better sleep outcomes. Compared with treatment as usual, mind-body exercise plus treatment as usual (SMD: −0.46; 95% CI: −0.80, −0.12) and vigorous strength exercise (SMD: −0.61; 95% CI: −1.12, −0.10) were significantly more effective. Pairwise meta-analyses showed that mind-body exercise (SMD: −0.54; 95% CI: −0.85, −0.23) had beneficial effects compared to passive control. The network meta-analysis is statistically very robust with low heterogeneity, incoherence, and indirectness. However, confidence in the findings was moderate to very low, primarily due to within-study bias. This is the first network meta-analysis to assess exercise's efficacy to improve sleep quality in patients with depression. The findings confirm the benefits of exercise as an add-on treatment for depression. This consolidation of the current state of evidence can help clinicians make evidence-based decisions

Effects of exercise on sleep and nocturnal arousal in patients with unipolar depression

Background Unipolar depression is a debilitating disease and one of the leading causes of global disease burden. Unipolar depression is bidirectionally associated with insomnia and attenuated heart rate variability. Insomnia has a negative effect on disease trajectory across all treatment phases in depression. Attenuated heart rate variability is one of the pathophysiological mechanisms explaining the increased risk of cardiovascular disease in patients with depression. Approximately one-third of the patients do not remit when treated with guideline therapies for depression, i.e., psychotherapy and pharmacotherapy. Moreover, insomnia is one of the most frequent residual symptoms in those who respond or remit. Lastly, guideline therapies do not seem to improve heart rate variability. Therefore, adjuvant therapies to improve depressive and insomnia symptoms and heart rate variability are need. Exercise is a promising auxiliary treatment based on previous research, but multiple knowledge gaps remain. Aims This Ph.D. project aimed to address important knowledge gaps. The first aim was to summarize the existing research concerning the effects of aerobic, resistance, and mind-body exercise on sleep quality in patients with unipolar depression. The second aim was to quantify the effect of a single bout of moderate-intensity aerobic exercise performed in the afternoon on sleep outcomes in patients with unipolar depression. The third aim was to quantify the effect of a single bout of moderate-intensity aerobic exercise performed in the afternoon on mood and adverse effects. The fourth and last aim was to quantify the effect of a single bout of moderate-intensity aerobic exercise performed in the afternoon on nocturnal and pre-sleep arousal. Methods A systematic review with network meta-analysis and a randomized controlled trial were conducted within this Ph.D. project. The systematic review (PROSPERO CRD42019115705) was conducted according to the PRISMA network meta-analysis extension and AMSTAR2 guidelines. A systematic search was conducted in multiple electronic bibliographic databases (PubMed, EMBASE, Cochrane Library, PsycINFO, Sportdiscus, CINHAL, OpenGrey, ProQuest Dissertations & Theses A&I, Clinicaltrials.gov, and WHO International Clinical Trials Registry) from their inception until February 12th, 2020. Randomized controlled trials investigating the effects of regular aerobic, resistance, or mind-body exercise on self- or observer-reported sleep quality in patients with depression were included. Network meta-analysis was conducted, and the network geometry, forest plots, and league tables were reported. The trial (NCT03673397) was a two-arm parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. It was conducted and reported in compliance with SPIRIT, GRAPH, FAIR, CONSORT, GCP, and GDPR guidelines and directives. The trial took place in the OBERWAID clinic. Patients between 18 and 65 years of age with a primary diagnosis of unipolar depression were included. The intervention was a single 30-minute bout of moderate aerobic exercise. The control group sat and read for 30 minutes. The primary outcome was sleep efficiency measured by polysomnography. Secondary outcomes were other polysomnographic variables, subjective sleep quality, daytime sleepiness, mood states, adverse events, pre-sleep arousal, as well as pre-sleep and nocturnal heart rate variability. Results Publication 1: The effects of aerobic, resistance, and meditative movement exercise on sleep in individuals with depression: protocol for a systematic review and network meta-analysis This publication provides a thorough account of the purpose and methodology of the systematic revie and network meta-analysis. The report adhered to the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) guideline. Publication 2: The effects of exercise on sleep in unipolar depression: a systematic review and network meta-analysis The network meta-analysis was based on 17 trials with N = 1645 patients randomized to 13 treatments yielding 35 comparisons. The confidence in the mixed (i.e., direct and indirect) evidence was moderate (43% of comparisons), low (39% of comparisons), or very low (18% of comparisons). All exercise types and intensity levels except moderate aerobic exercise improved sleep quality more than passive control. The effects of active control, mind-body exercise, treatment as usual, and vigorous aerobic exercise were similar. Vigorous strength exercise yielded a significantly larger effect on sleep quality than aerobic or mind-body exercise compared to passive control. None of the exercise modes or intensities was significantly less efficacious than treatment as usual. Adding moderate or vigorous aerobic exercise to treatment as usual resulted in slightly larger effect sizes, but these differences were not statistically significant. However, vigorous strength exercise alone or adding mind-body exercise to treatment as usual resulted in significantly larger effects than treatment as usual alone. Publication 3: The acute effects of aerobic exercise on sleep in patients with depression: study protocol for a randomized controlled trial This publication presents the rationale, hypothesis, and procedures of the randomized controlled trial in detail. The publication was written in accordance with the Standard Protocol Items Recommendations for Interventional Trials (SPIRIT) statement. Publication 4: The acute effects of aerobic exercise on sleep in patients with unipolar depression: a randomized controlled trial There was no evidence for an effect of allocation on polysomnographic sleep efficiency. This finding was confirmed in all sensitivity analyses (i.e., complete case and per-protocol analysis as well as excluding an influential data point). There was also no evidence that chronotype, expectancy, or credibility altered the effect of allocation. No evidence of a correlation between exercise intensity (i.e., rate of perceived exertion and percent of maximal age-predicted heart rate) and sleep efficiency at follow-up was found. Furthermore, there was no evidence for an effect of allocation on any of the secondary objective or subjective measures of sleep or daytime sleepiness. However, there was a strong effect of allocation on mood immediately post-exercise. This effect was consistent across all subscales, with the intervention group showing decreases in negative and increases in positive mood states. Although there was a trend toward lower symptom severity in the intervention group compared to the control group immediately post-exercise, this effect was non-significant. Publication 5: The acute effects of aerobic exercise on nocturnal and pre-sleep arousal in patients with unipolar depression: a randomized controlled trial There was no evidence for an effect of allocation on root mean square of successive differences of normal-to-normal intervals during the sleep period. All sensitivity analyses confirmed this finding (i.e., only using complete data, excluding patients who smoked, used either beta-blockers, any antidepressant, or only tricyclic antidepressants). Furthermore, no evidence suggested that allocation altered root mean square of successive differences of normal-to-normal intervals in any sleep stage (although N1 was not analyzed due to insufficient data). There was also no evidence to suggest that any of the other heart rate variability parameters were affected by allocation during the sleep period. Lastly, no evidence indicated that pre-sleep root mean square of successive differences of normal-tonormal intervals or pre-sleep somatic and cognitive arousal were altered by allocation. Conclusions The findings of the network meta-analysis confirm the salubrious effects of regular aerobic, resistance, and mind-body exercise for patients with depression. None of the investigated exercise types or intensities lowered subjective sleep quality. Vigorous resistance and mind-body exercise in combination with treatment as usual elicited the most substantial effects. Therefore, these exercise modes might be recommended to target sleep quality in patients with depression specifically. However, the confidence in these findings is low, and thus more research is needed. The results of publications 4 and 5 confirm previous findings, which found no evidence of an adverse effect of acute exercise after 02:00 pm on sleep-related outcomes. The absence of evidence was consistent across all outcomes of sleep, pre-sleep arousal, and heart rate variability. Thus, these findings question the validity of the exercise timing recommendations in sleep hygiene guidelines. Moreover, a single bout of moderate-intensity exercise lasting 30 minutes can be recommended to improve the mood of patients with depression. In summary, regular aerobic, resistance, and mind-body exercise can be recommended as an adjuvant treatment to improve mood and insomnia symptoms in patients with depression

The acute effect of aerobic exercise on sleep in patients with depression: a randomized controlled trial

This dataset will enable sharing of data collected within the EASED trial. BACKGROUND Unipolar depression is one of the most relevant mental disorders. Insomnia is a symptom of cardinal importance in depression. It increases the risk to develop depression, negatively affects disease trajectory, is the most common symptom after remission, increases the risk of relapse, and is associated with higher suicide rates. Existing therapies for insomnia in depression have limitations. Further adjuvant therapies are therefore needed. Acute aerobic exercise has been shown to have beneficial effects on sleep in healthy individuals and patients with insomnia. We therefore hypothesize that a single bout of aerobic exercise has positive effects on sleep in patients with unipolar depression. The aim of this trial is to investigate the effects of a single bout of aerobic exercise on sleep in patients with depression. METHODS This will be a two-arm parallel group, randomized, outcome assessor blinded, controlled, superiority trial. Patients between 18 and 65 years of age with a primary diagnosis of unipolar depression (without a psychotic episode) will be included. Exclusion criteria are regular use of hypnotic agents, opioids, and certain beta-blockers, presence of factors precluding exercise, history of epilepsy, restless legs syndrome, moderate obstructive sleep apnea and a BMI >40. The intervention is a single bout of aerobic exercise. Exercise will be performed for 30 minutes on a bicycle ergometer at 70% individual anaerobic threshold. The control group will sit and read magazines. The primary outcome is sleep efficiency measured by polysomnography. Secondary outcomes include further polysomnographic variables, subjective pre-sleep arousal, nocturnal cardiovascular autonomic tone, subjective sleep quality, daytime sleepiness, and adverse events. According to sample size calculation a total of 92 patients will be randomized using minimization. DISCUSSION This trial will add new information to the body of knowledge concerning the treatment of insomnia in patients with depression. Thereby, the trial will inform decision makers on the utility of acute aerobic exercise

The acute effects of aerobic exercise on sleep in patients with depression: study protocol for a randomized controlled trial

Background: Unipolar depression is one of the most important mental disorders. Insomnia is a symptom of cardinal importance in depression. It increases the risk to develop depression, negatively affects disease trajectory, is the most common symptom after remission, increases the risk of relapse, and is associated with higher suicide rates. Existing therapies for insomnia in depression have limitations. Further adjuvant therapies are therefore needed. Acute aerobic exercise has been shown to have beneficial effects on sleep in healthy individuals and patients with insomnia. We therefore hypothesize that a single session of aerobic exercise has a positive impact on sleep in patients with unipolar depression. This trial aims to investigate the effects of a single bout of aerobic exercise on the subsequent night's sleep in patients with depression. Methods/design: This is a two-arm parallel group, randomized, outcome assessor blinded, controlled, superiority trial. Patients between 18 and 65 years of age with a primary diagnosis of unipolar depression (without a psychotic episode) are included. Exclusion criteria are regular use of hypnotic agents, opioids, and certain beta-blockers, as well as the presence of factors precluding exercise, history of epilepsy, restless legs syndrome, moderate obstructive sleep apnea, and a BMI > 40. The intervention is a single bout of aerobic exercise, performed for 30 min on a bicycle ergometer at 80% individual anaerobic threshold. The control group sits and reads for 30 min. The primary outcome is sleep efficiency measured by polysomnography. Secondary outcomes include further polysomnographic variables, subjective pre-sleep arousal, nocturnal cardiovascular autonomic modulation, subjective sleep quality, daytime sleepiness, and adverse events. According to the sample size calculation, a total of 92 patients will be randomized using minimization. Discussion: This trial will add new information to the body of knowledge concerning the treatment of insomnia in patients with depression. Thereby, the results will inform decision makers on the utility of acute aerobic exercise. Trial registration: Clinicaltrials.gov, NCT03673397 . Protocol version 1 registered on 17 September 2018

The Acute Effects of Aerobic Exercise on Nocturnal and Pre-Sleep Arousal in Patients with Unipolar Depression: Preplanned Secondary Analysis of a Randomized Controlled Trial

Unipolar depression is associated with insomnia and autonomic arousal. The aim of this study was to quantify the effect of a single bout of aerobic exercise on nocturnal heart rate variability and pre-sleep arousal in patients with depression. This study was designed as a two-arm, parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. Patients with a primary diagnosis of unipolar depression aged 18–65 years were included. The intervention consisted of a single 30 min moderate-intensity aerobic exercise bout. The control group sat and read for 30 min. The primary outcome of interest was RMSSD during the sleep period assessed with polysomnography. Secondary outcomes were additional heart rate variability outcomes during the sleep and pre-sleep period as well as subjective pre-sleep arousal. A total of 92 patients were randomized to either the exercise (N = 46) or the control (N = 46) group. Intent-to-treat analysis ANCOVA of follow-up sleep period RMSSD, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = 0.12, p = 0.94). There was no evidence for significant differences between both groups in any other heart rate variability measure nor in measures of cognitive or somatic pre-sleep arousal. As this is the first trial of its kind in this population, the findings need to be confirmed in further studies. Patients with depression should be encouraged to exercise regularly in order to profit from the known benefits on sleep and depressive symptoms, which are supported by extensive literature

The Acute Effects of Aerobic Exercise on Nocturnal and Pre-Sleep Arousal in Patients with Unipolar Depression: Preplanned Secondary Analysis of a Randomized Controlled Trial

Unipolar depression is associated with insomnia and autonomic arousal. The aim of this study was to quantify the effect of a single bout of aerobic exercise on nocturnal heart rate variability and pre-sleep arousal in patients with depression. This study was designed as a two-arm, parallel-group, randomized, outcome assessor-blinded, controlled, superiority trial. Patients with a primary diagnosis of unipolar depression aged 18–65 years were included. The intervention consisted of a single 30 min moderate-intensity aerobic exercise bout. The control group sat and read for 30 min. The primary outcome of interest was RMSSD during the sleep period assessed with polysomnography. Secondary outcomes were additional heart rate variability outcomes during the sleep and pre-sleep period as well as subjective pre-sleep arousal. A total of 92 patients were randomized to either the exercise (N = 46) or the control (N = 46) group. Intent-to-treat analysis ANCOVA of follow-up sleep period RMSSD, adjusted for baseline levels and minimization factors, did not detect a significant effect of the allocation (β = 0.12, p = 0.94). There was no evidence for significant differences between both groups in any other heart rate variability measure nor in measures of cognitive or somatic pre-sleep arousal. As this is the first trial of its kind in this population, the findings need to be confirmed in further studies. Patients with depression should be encouraged to exercise regularly in order to profit from the known benefits on sleep and depressive symptoms, which are supported by extensive literature