Actigraphy assessment of motor activity and sleep in patients with alcohol withdrawal syndrome and the effects of intranasal oxytocin

Katrine Melby, Ole B Fasmer, Tone E Henriksen, Rolf W Gråwe, Trond O Aamo, Olav Spigset, Katrine Melby, Ole B Fasmer, Tone E Henriksen, Rolf W Gråwe, Trond O Aamo, Olav Spigset

Abstract

Background and aims: The alcohol withdrawal syndrome increases autonomic activation and stress in patients during detoxification, leading to alterations in motor activity and sleep irregularities. Intranasal oxytocin has been proposed as a possible treatment of acute alcohol withdrawal. The aim of the present study was to explore whether actigraphy could be used as a tool to register symptoms during alcohol detoxification, whether oxytocin affected actigraphy variables related to motor activity and sleep compared to placebo during detoxification, and whether actigraphy-recorded motor function during detoxification was different from that in healthy controls.

Methods: This study was a part of a randomized, double blind, placebo-controlled trial in which 40 patients with alcohol use disorder admitted for acute detoxification were included. Of these, 20 received insufflations with intranasal oxytocin and 20 received placebo. Outcomes were actigraphy-recorded motor activity during 5-hour sequences following the insufflations and a full 24-hour period, as well as actigraphy-recorded sleep. Results were related to clinical variables of alcohol intake and withdrawal, including self-reported sleep. Finally, the actigraphy results were compared to those in a group of 34 healthy individuals.

Results: There were no significant differences between the oxytocin group and the placebo group for any of actigraphy variables registered. Neither were there any correlations between actigraphy-recorded motor function and clinical symptoms of alcohol withdrawal, but there was a significant association between self-reported and actigraphy-recorded sleep. Compared to healthy controls, motor activity during alcohol withdrawal was lower in the evenings and showed increased variability.

Conclusion: Intranasal oxytocin did not affect actigraphy-recorded motor activity nor sleep in patients with acute alcohol withdrawal. There were no findings indicating that actigraphy can be used to evaluate the degree of withdrawal symptoms during detoxification. However, patients undergoing acute alcohol withdrawal had a motor activity pattern different from than in healthy controls.

Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1. Flowchart of patients with alcohol…
Fig 1. Flowchart of patients with alcohol use disorder undergoing detoxification from alcohol included in the trial.
Fig 2. Actigram showing motor activity and…
Fig 2. Actigram showing motor activity and sleep during detoxification from alcohol.
The figure shows the actigram of one patient in the oxytocin group, with the activity counts in black, during three days of alcohol withdrawal. The height of a bar represents the motor activity during a time period. Grey areas indicate sleeping periods, as interpreted by the Actiware software.
Fig 3. Motor activity in 40 patients…
Fig 3. Motor activity in 40 patients with alcohol use disorder during a 3-day course of detoxification.
Actigraphy recordings took place in 5-hour sequences in the mornings (09:00 to 14:00) and in the evenings (18:00 to 23:00). Values are presented as means ± standard deviations. Total motor activity and activity in the most active periods in each sequence are compared to those in the previous sequence using paired t-tests. * p

References

    1. Jesse S, Brathen G, Ferrara M, Keindl M, Ben-Menachem E, Tanasescu R, et al. Alcohol withdrawal syndrome: mechanisms, manifestations, and management. Acta Neurol Scand. 2017;135(1):4–16. 10.1111/ane.12671
    1. Mirijello A, D'Angelo C, Ferrulli A, Vassallo G, Antonelli M, Caputo F, et al. Identification and management of alcohol withdrawal syndrome. Drugs. 2015;75(4):353–65. 10.1007/s40265-015-0358-1
    1. Amato L, Minozzi S, Davoli M. Efficacy and safety of pharmacological interventions for the treatment of the Alcohol Withdrawal Syndrome. Cochrane Database Syst Rev. 2011(6):CD008537 10.1002/14651858.CD008537.pub2
    1. Daeppen JB, Gache P, Landry U, Sekera E, Schweizer V, Gloor S, et al. Symptom-triggered vs fixed-schedule doses of benzodiazepine for alcohol withdrawal: a randomized treatment trial. Arch Intern Med. 2002;162(10):1117–21. 10.1001/archinte.162.10.1117
    1. Acheson D, Feifel D, de Wilde S, McKinney R, Lohr J, Risbrough V. The effect of intranasal oxytocin treatment on conditioned fear extinction and recall in a healthy human sample. Psychopharmacology (Berl). 2013;229(1):199–208.
    1. Bartz JA, Lydon JE, Kolevzon A, Zaki J, Hollander E, Ludwig N, et al. Differential Effects of Oxytocin on Agency and Communion for Anxiously and Avoidantly Attached Individuals. Psychol Sci. 2015;26(8):1177–86. 10.1177/0956797615580279
    1. De Cagna F, Fusar-Poli L, Damiani S, Rocchetti M, Giovanna G, Mori A, et al. The Role of Intranasal Oxytocin in Anxiety and Depressive Disorders: A Systematic Review of Randomized Controlled Trials. Clin Psychopharmacol Neurosci. 2019;17(1):1–11. 10.9758/cpn.2019.17.1.1
    1. Gottschalk MG, Domschke K. Oxytocin and Anxiety Disorders. Curr Top Behav Neurosci. 2018;35:467–98. 10.1007/7854_2017_25
    1. Kirsch P. Oxytocin in the socioemotional brain: implications for psychiatric disorders. Dialogues Clin Neurosci. 2015;17(4):463–76.
    1. Neumann ID, Slattery DA. Oxytocin in General Anxiety and Social Fear: A Translational Approach. Biol Psychiatry. 2016;79(3):213–21. 10.1016/j.biopsych.2015.06.004
    1. Jain V, Marbach J, Kimbro S, Andrade DC, Jain A, Capozzi E, et al. Benefits of oxytocin administration in obstructive sleep apnea. Am J Physiol Lung Cell Mol Physiol. 2017;313(5):L825–L33. 10.1152/ajplung.00206.2017
    1. MacDonald E, Dadds MR, Brennan JL, Williams K, Levy F, Cauchi AJ. A review of safety, side-effects and subjective reactions to intranasal oxytocin in human research. Psychoneuroendocrinology. 2011;36(8):1114–26. 10.1016/j.psyneuen.2011.02.015
    1. Hansson AC, Koopmann A, Uhrig S, Buhler S, Domi E, Kiessling E, et al. Oxytocin Reduces Alcohol Cue-Reactivity in Alcohol-Dependent Rats and Humans. Neuropsychopharmacology. 2018;43(6):1235–46. 10.1038/npp.2017.257
    1. Miller MA, Bershad A, King AC, Lee R, de Wit H. Intranasal oxytocin dampens cue-elicited cigarette craving in daily smokers: a pilot study. Behav Pharmacol. 2016;27(8):697–703. 10.1097/FBP.0000000000000260
    1. Mitchell JM, Arcuni PA, Weinstein D, Woolley JD. Intranasal Oxytocin Selectively Modulates Social Perception, Craving, and Approach Behavior in Subjects With Alcohol Use Disorder. J Addict Med. 2016;10(3):182–9. 10.1097/ADM.0000000000000213
    1. Stauffer CS, Musinipally V, Suen A, Lynch KL, Shapiro B, Woolley JD. A two-week pilot study of intranasal oxytocin for cocaine-dependent individuals receiving methadone maintenance treatment for opioid use disorder. Addict Res Theory. 2016;24(6):490–8. 10.3109/16066359.2016.1173682
    1. Woolley JD, Arcuni PA, Stauffer CS, Fulford D, Carson DS, Batki S, et al. The effects of intranasal oxytocin in opioid-dependent individuals and healthy control subjects: a pilot study. Psychopharmacology (Berl). 2016;233(13):2571–80.
    1. Pedersen CA, Smedley KL, Leserman J, Jarskog LF, Rau SW, Kampov-Polevoi A, et al. Intranasal oxytocin blocks alcohol withdrawal in human subjects. Alcohol Clin Exp Res. 2013;37(3):484–9. 10.1111/j.1530-0277.2012.01958.x
    1. Melby K, Grawe RW, Aamo TO, Salvesen O, Spigset O. Effect of intranasal oxytocin on alcohol withdrawal syndrome: A randomized placebo-controlled double-blind clinical trial. Drug Alcohol Depend. 2019;197:95–101. 10.1016/j.drugalcdep.2019.01.003
    1. Walum H, Waldman ID, Young LJ. Statistical and Methodological Considerations for the Interpretation of Intranasal Oxytocin Studies. Biol Psychiatry. 2016;79(3):251–7. 10.1016/j.biopsych.2015.06.016
    1. Zik JB, Roberts DL. The many faces of oxytocin: implications for psychiatry. Psychiatry Res. 2015;226(1):31–7. 10.1016/j.psychres.2014.11.048
    1. Ancoli-Israel S, Cole R, Alessi C, Chambers M, Moorcroft W, Pollak CP. The role of actigraphy in the study of sleep and circadian rhythms. Sleep. 2003;26(3):342–92. 10.1093/sleep/26.3.342
    1. Acebo C, LeBourgeois MK. Actigraphy. Respir Care Clin N Am. 2006;12(1):23–30, viii. 10.1016/j.rcc.2005.11.010
    1. Hodges CJ, Ogeil RP, Lubman DI. The effects of acute alcohol withdrawal on sleep. Hum Psychopharmacol. 2018:e2657 10.1002/hup.2657
    1. Sullivan JT, Sykora K, Schneiderman J, Naranjo CA, Sellers EM. Assessment of alcohol withdrawal: the revised clinical institute withdrawal assessment for alcohol scale (CIWA-Ar). Br J Addict. 1989;84(11):1353–7. 10.1111/j.1360-0443.1989.tb00737.x
    1. Guastella AJ, Hickie IB, McGuinness MM, Otis M, Woods EA, Disinger HM, et al. Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research. Psychoneuroendocrinology. 2013;38(5):612–25. 10.1016/j.psyneuen.2012.11.019
    1. Krane-Gartiser K, Henriksen TE, Morken G, Vaaler A, Fasmer OB. Actigraphic assessment of motor activity in acutely admitted inpatients with bipolar disorder. PLoS One. 2014;9(2):e89574 10.1371/journal.pone.0089574
    1. Krane-Gartiser K, Vaaler AE, Fasmer OB, Sorensen K, Morken G, Scott J. Variability of activity patterns across mood disorders and time of day. BMC Psychiatry. 2017;17(1):404 10.1186/s12888-017-1574-x
    1. Kaplan KA, Talbot LS, Gruber J, Harvey AG. Evaluating sleep in bipolar disorder: comparison between actigraphy, polysomnography, and sleep diary. Bipolar Disord. 2012;14(8):870–9. 10.1111/bdi.12021
    1. Paquet J, Kawinska A, Carrier J. Wake detection capacity of actigraphy during sleep. Sleep. 2007;30(10):1362–9. 10.1093/sleep/30.10.1362
    1. Corp I. IBM Corp. Released 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk In: Corp. NI, editor. 2017.
    1. Henriksen TE, Skrede S, Fasmer OB, Schoeyen H, Leskauskaite I, Bjorke-Bertheussen J, et al. Blue-blocking glasses as additive treatment for mania: a randomized placebo-controlled trial. Bipolar Disord. 2016;18(3):221–32. 10.1111/bdi.12390
    1. Krane-Gartiser K, Henriksen TE, Vaaler AE, Fasmer OB, Morken G. Actigraphically assessed activity in unipolar depression: a comparison of inpatients with and without motor retardation. J Clin Psychiatry. 2015;76(9):1181–7. 10.4088/JCP.14m09106
    1. Wood AC, Asherson P, Rijsdijk F, Kuntsi J. Is overactivity a core feature in ADHD? Familial and receiver operating characteristic curve analysis of mechanically assessed activity level. J Am Acad Child Adolesc Psychiatry. 2009;48(10):1023–30. 10.1097/CHI.0b013e3181b54612
    1. Lichstein KL, Stone KC, Donaldson J, Nau SD, Soeffing JP, Murray D, et al. Actigraphy validation with insomnia. Sleep. 2006;29(2):232–9.
    1. Kushida CA, Chang A, Gadkary C, Guilleminault C, Carrillo O, Dement WC. Comparison of actigraphic, polysomnographic, and subjective assessment of sleep parameters in sleep-disordered patients. Sleep Med. 2001;2(5):389–96. 10.1016/s1389-9457(00)00098-8
    1. Smith MT, McCrae CS, Cheung J, Martin JL, Harrod CG, Heald JL, et al. Use of Actigraphy for the Evaluation of Sleep Disorders and Circadian Rhythm Sleep-Wake Disorders: An American Academy of Sleep Medicine Systematic Review, Meta-Analysis, and GRADE Assessment. J Clin Sleep Med. 2018;14(7):1209–30. 10.5664/jcsm.7228
    1. Gavriloff D, Sheaves B, Juss A, Espie CA, Miller CB, Kyle SD. Sham sleep feedback delivered via actigraphy biases daytime symptom reports in people with insomnia: Implications for insomnia disorder and wearable devices. J Sleep Res. 2018:e12726 10.1111/jsr.12726
    1. Natale V, Plazzi G, Martoni M. Actigraphy in the assessment of insomnia: a quantitative approach. Sleep. 2009;32(6):767–71. 10.1093/sleep/32.6.767
    1. Lahti T, Methuen T, Roine R, Seppa KL, Sinclair D, Partinen M, et al. The impacts of nitrous oxide gas on sleep quality during alcohol withdrawal. BMC Res Notes. 2011;4:108 10.1186/1756-0500-4-108
    1. Clark I, Landolt HP. Coffee, caffeine, and sleep: A systematic review of epidemiological studies and randomized controlled trials. Sleep Med Rev. 2017;31:70–8. 10.1016/j.smrv.2016.01.006
    1. Littner M, Kushida CA, Anderson WM, Bailey D, Berry RB, Davila DG, et al. Practice parameters for the role of actigraphy in the study of sleep and circadian rhythms: an update for 2002. Sleep. 2003;26(3):337–41. 10.1093/sleep/26.3.337

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