title: Mirtazapine provokes periodic leg movements during sleep in young healthy men.
abstract: OBJECTIVE
  Recent evidence suggests that certain antidepressants are associated with an increase of periodic leg movements (PLMS) that may disturb sleep. So far, this has been shown in patients clinically treated for depression and in cross-sectional studies for various substances, but not mirtazapine. It is unclear whether antidepressants induce the new onset of PLMS or only increase preexisting PLMS, and whether this is a general property of the antidepressant or only seen in depressed patients. We report here the effect of mirtazapine on PLMS in young healthy men.
  
  
  METHODS
  Open-labeled clinical trial (NCT00878540) including a 3-week preparatory phase with standardized food, physical activity, and sleep-wake behavior, and a 10-day experimental inpatient phase with an adaptation day, 2 baseline days, and 7 days with mirtazapine.
  
  
  METHODS
  Research institute.
  
  
  METHODS
  Twelve healthy young (20-25 years) men.
  
  
  METHODS
  Seven days of nightly intake (22:00) of 30 mg mirtazapine.
  
  
  RESULTS
  Sleep was recorded on 2 drug-free baseline nights, the first 2 drug nights, and the last 2 drug nights. Eight of the 12 subjects showed increased PLMS after the first dose of mirtazapine. Frequency of PLMS was highest on the first drug night and attenuated over the course of the next 6 days. Three subjects reported transient restless legs symptoms.
  
  
  CONCLUSIONS
  Mirtazapine provoked PLMS in 67% of young healthy males. The effect was most pronounced in the first days. The possible role of serotonergic, noradrenergic and histaminergic mechanisms in mirtazapine-induced PLMS is discussed.
authors: Max Planck Institute of Psychiatry, Munich, Germany. stephany.fulda@gmail.com
authors: Stephany
authors: S
authors: Fulda
authors: Stefan
authors: S
authors: Kloiber
authors: Tatjana
authors: T
authors: Dose
authors: Susanne
authors: S
authors: Lucae
authors: Florian
authors: F
authors: Holsboer
authors: Ludwig
authors: L
authors: Schaaf
authors: Johannes
authors: J
authors: Hennings
mesh_terms: D000328:Adult; D000367:Age Factors; D000929:Antidepressive Agents, Tricyclic / Q000009:adverse effects*; D015992:Body Mass Index; D015331:Cohort Studies; D004334:Drug Administration Schedule; D006304:Health Status; D006801:Humans; D008297:Male; D008803:Mianserin / Q000009:adverse effects / Q000031:analogs & derivatives*; D000078785:Mirtazapine; D020189:Nocturnal Myoclonus Syndrome / Q000139:chemically induced*; D012307:Risk Factors; D012737:Sex Factors; D055815:Young Adult
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine
keywords: Mirtazapine; periodic leg movements; restless legs syndrome; sleep
references: Sleep Med. 2002 Nov;3(6):489-95
references: 14592143
references: Sleep. 1999 Aug 1;22(5):575-80
references: 10450592
references: Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58
references: 9537821
references: Psychiatry Clin Neurosci. 2004 Dec;58(6):669-70
references: 15601394
references: Psychiatry Clin Neurosci. 2011 Apr;65(3):246-53
references: 21507131
references: Sleep Breath. 2008 Aug;12(3):281-5
references: 18369672
references: Neuropsychopharmacology. 2006 Apr;31(4):832-44
references: 16237393
references: J Clin Psychiatry. 2000 Nov;61(11):858-62
references: 11105739
references: Sleep Med Rev. 2006 Jun;10(3):169-77
references: 16762807
references: Hum Psychopharmacol. 2005 Dec;20(8):533-59
references: 16229049
references: Metab Brain Dis. 2012 Jun;27(2):151-8
references: 22350963
references: J Clin Psychiatry. 1997 Aug;58(8):348-50
references: 9515972
references: Eur J Neurosci. 2000 Mar;12(3):1079-95
references: 10762339
references: J Clin Sleep Med. 2007 Feb 15;3(1):15-7
references: 17557447
references: Psychiatry Res. 1989 May;28(2):193-213
references: 2748771
references: Neuropsychopharmacology. 2003 Feb;28(2):413-20
references: 12589396
references: Sleep. 2007 Jun;30(6):755-66
references: 17580597
references: Biol Psychiatry. 2005 Sep 15;58(6):510-4
references: 16005440
references: Sleep Med. 2003 Mar;4(2):101-19
references: 14592341
references: Hum Psychopharmacol. 2008 Oct;23(7):615-20
references: 18756499
references: Can J Psychiatry. 2006 Jan;51(1):27-34
references: 16491981
references: Sleep. 1991 Apr;14(2):163-5
references: 1866530
references: Sleep Med Rev. 2012 Aug;16(4):283-95
references: 21795081
references: Clin Neurophysiol. 2004 Oct;115(10):2236-46
references: 15351364
references: Sleep. 2008 Jun;31(6):824-31
references: 18548827
references: Sleep. 1991 Dec;14(6):496-500
references: 1798881
references: J Mol Neurosci. 2002 Feb-Apr;18(1-2):143-9
references: 11931344
references: Drugs. 2005;65(7):927-47
references: 15892588
references: Sleep. 2007 Jan;30(1):35-41
references: 17310863
references: J Psychiatr Res. 2008 Nov;43(1):70-5
references: 18468624
references: Nat Genet. 2007 Aug;39(8):1000-6
references: 17637780
references: N Engl J Med. 2007 Aug 16;357(7):639-47
references: 17634447
references: Schweiz Med Wochenschr. 1989 Feb 11;119(6):184-6
references: 2928741
references: Therapie. 2000 Sep-Oct;55(5):655-6
references: 11201984
references: Sleep Med Rev. 2006 Jun;10(3):153-67
references: 16762806
references: Clin Neurophysiol. 2002 Jun;113(6):883-91
references: 12048047
references: Psychopharmacologia. 1975 Sep 17;43(3):279-84
references: 171695
references: Prog Neuropsychopharmacol Biol Psychiatry. 2006 Mar;30(2):316-8
references: 16309808
references: J Clin Psychiatry. 2003 Aug;64(8):883-9
references: 12927002
references: Pharmacopsychiatry. 2002 Nov;35(6):220-5
references: 12518269
references: Res Commun Chem Pathol Pharmacol. 1982 Apr;36(1):129-40
references: 7079579
references: Ann Neurol. 2012 Jun;71(6):834-44
references: 22718547
references: Sleep Med. 2011 Jan;12(1):47-55
references: 20851046
references: Biol Psychiatry. 2000 Jul 1;48(1):75-8
references: 10913511
references: J Clin Sleep Med. 2007 Feb 15;3(1):12-4
references: 17557446
references: J Clin Sleep Med. 2010 Feb 15;6(1):79-83
references: 20191944
references: Clin Neurophysiol. 2003 Nov;114(11):2188-95
references: 14580618
references: Int Rev Psychiatry. 2005 Aug;17(4):237-45
references: 16194795
references: Expert Opin Pharmacother. 2005 Apr;6(4):631-41
references: 15934889
references: Sleep. 2008 Sep;31(9):1221-7
references: 18788647
references: Brain Res Bull. 2002 Sep 30;58(6):601-5
references: 12372565
references: Neuropharmacology. 1988 Apr;27(4):399-408
references: 3419539
references: Neurology. 2007 Apr 10;68(15):1213-8
references: 17420405
references: Ann Pharmacother. 1994 Jul-Aug;28(7-8):878-81
references: 7949505
references: Brain Res Bull. 2004 Apr 30;63(3):237-41
references: 15145142
references: Psychiatry Clin Neurosci. 2002 Apr;56(2):209-10
references: 11952928
references: J Clin Psychiatry. 2003 Oct;64(10):1224-9
references: 14658972
references: J Sleep Res. 2007 Sep;16(3):333-9
references: 17716283
references: Sleep Med. 2006 Mar;7(2):175-83
references: 16459136
references: Sleep. 1988 Apr;11(2):182-6
references: 2898166
references: CNS Spectr. 2005 Sep;10(9):732-47
references: 16142213
references: Nat Rev Neurol. 2010 Jun;6(6):337-46
references: 20531433
references: Neurology. 2002 Dec 24;59(12):1889-94
references: 12499479
references: Int J Chronobiol. 1976;4(2):97-110
references: 1027738
references: Sleep. 2006 Jun;29(6):759-69
references: 16796214
references: J Clin Psychopharmacol. 2002 Oct;22(5):511-5
references: 12352276
references: Sleep. 1991 Dec;14(6):540-5
references: 1798888
references: J Clin Psychiatry. 2002 Dec;63(12):1179
references: 12530413
references: Brain. 2000 Feb;123 ( Pt 2):331-9
references: 10648440
references: Biol Psychiatry. 2000 Mar 1;47(5):468-70
references: 10704958
references: Sleep. 2006 Dec;29(12):1587-94
references: 17252889
references: Neurology. 1999 Mar 10;52(4):786-91
references: 10078729
references: Neuropharmacology. 1994 Mar-Apr;33(3-4):467-71
references: 7984285
references: Eur Neuropsychopharmacol. 2005 Oct;15(5):521-4
references: 16139170
references: Pharmacol Toxicol. 1987 Nov;61(5):278-81
references: 2894022
references: Sleep. 1996 Jan;19(1):52-8
references: 8650464
references: Sleep. 2002 Sep 15;25(6):677-9
references: 12224847
references: Clin Neurophysiol. 2007 Sep;118(9):1923-30
references: 17588809
references: Eur J Clin Pharmacol. 1990;38(6):551-4
references: 2373128
references: Neuropsychobiology. 2002;46(4):197-201
references: 12566938
references: Sleep. 2005 Jul;28(7):891-8
references: 16124671
references: J Clin Psychopharmacol. 2000 Oct;20(5):531-7
references: 11001237
references: Clin Neurophysiol. 2007 Feb;118(2):438-48
references: 17140849