title: Antidepressant chronotherapeutics for bipolar depression.
abstract: Chronotherapeutics refers to treatments based on the principles of circadian rhythm organization and sleep physiology, which control the exposure to environmental stimuli that act on biological rhythms, in order to achieve therapeutic effects in the treatment of psychiatric conditions. It includes manipulations of the sleep-wake cycle such as sleep deprivation and sleep phase advance, and controlled exposure to light and dark. The antidepressant effects of chronotherapeutics are evident in difficult-to-treat conditions such as bipolar depression, which has been associated with extremely low success rates of antidepressant drugs in naturalistic settings and with stable antidepressant response to chronotherapeutics in more than half of the patients. Recent advances in the study of the effects of chronotherapeutics on neurotransmitter systems, and on the biological clock machinery, allow us to pinpoint its mechanism of action and to transform it from a neglected or "orphan" treatment to a powerful clinical instrument in everyday psychiatric practice.
authors: Department of Clinical Neurosciences, Scientific Institute and University Vita-Salute San Raffaele, Milan, Italy. benedetti.francesco@hsr.it
authors: Francesco
authors: F
authors: Benedetti
mesh_terms: D001714:Bipolar Disorder / Q000628:therapy*; D019454:Chronotherapy / Q000379:methods*; D006801:Humans
keywords: antidepressant; bipolar disorder; dawn simulation; dopamine; glutamate; light therapy; noradrenaline; serotonin; sleep deprivation; sleep phase advance
references: Arch Gen Psychiatry. 2001 Jan;58(1):69-75
references: 11146760
references: Neurosci Lett. 2004 Sep 23;368(2):123-6
references: 15351432
references: J Clin Psychiatry. 2012 Jul;73(7):924-30
references: 22480597
references: Psychiatry Res. 2000 Jul 24;95(1):43-53
references: 10904122
references: Biol Psychiatry. 2010 Sep 15;68(6):503-11
references: 20591414
references: Acta Psychiatr Scand. 2004 Mar;109(3):230-4
references: 14984396
references: J Clin Psychopharmacol. 2009 Aug;29(4):327-33
references: 19593170
references: Prog Neuropsychopharmacol Biol Psychiatry. 2008 Dec 12;32(8):1863-6
references: 18801406
references: Expert Opin Ther Targets. 2004 Feb;8(1):25-38
references: 14996616
references: Int Pharmacopsychiatry. 1980;15(2):81-5
references: 7440097
references: Neuropsychopharmacology. 2001 Nov;25(5 Suppl):S74-8
references: 11682278
references: Acta Psychiatr Scand. 2005 Aug;112(2):117-25
references: 15992393
references: Psychiatry Res. 2009 Sep 30;173(3):238-42
references: 19682864
references: Nat Neurosci. 2003 Oct;6(10):1086-90
references: 12958601
references: Sleep. 2010 Jan;33(1):97-106
references: 20120626
references: Nat Neurosci. 2008 Feb;11(2):200-8
references: 18204445
references: Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1333-8
references: 18212115
references: Eur Psychiatry. 2010 Dec;25(8):476-8
references: 20619611
references: J Clin Psychiatry. 1999 Nov;60(11):799-808; quiz 809
references: 10584776
references: J Affect Disord. 2010 Feb;121(1-2):68-72
references: 19520435
references: Nervenarzt. 1971 Mar;42(3):117-24
references: 5550102
references: J Clin Psychiatry. 2010 Sep;71(9):1176-86; quiz 1252-3
references: 20923622
references: Pharmacol Biochem Behav. 1983 Apr;18(4):501-7
references: 6602989
references: J Affect Disord. 2012 May;138(3):337-42
references: 22325712
references: Biol Psychiatry. 2002 Nov 15;52(10):921-6
references: 12437933
references: J Neurosci. 2005 May 11;25(19):4719-24
references: 15888647
references: Am J Psychiatry. 1978 Mar;135(3):375-6
references: 626237
references: Psychol Med. 2006 Sep;36(9):1247-52
references: 16756691
references: Neurosci Lett. 2008 Nov 14;445(2):184-7
references: 18789374
references: Proc Natl Acad Sci U S A. 2006 May 9;103(19):7414-9
references: 16648247
references: Sleep Med Rev. 2006 Feb;10(1):49-62
references: 16376591
references: Arch Gen Psychiatry. 2010 Aug;67(8):793-802
references: 20679587
references: Chronobiol Int. 2007;24(5):921-37
references: 17994346
references: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Feb;29(2):297-303
references: 15694238
references: Bipolar Disord. 2008 Dec;10(8):907-15
references: 19594506
references: Neuropsychopharmacology. 2005 Jul;30(7):1223-37
references: 15827567
references: Cereb Cortex. 2013 Feb;23(2):332-8
references: 22314045
references: Curr Drug Targets. 2006 Nov;7(11):1377-88
references: 17100578
references: Neurosci Lett. 2005 Mar 7;376(1):51-5
references: 15694273
references: J Psychiatr Res. 1979;15(1):21-40
references: 219193
references: Arch Gen Psychiatry. 2007 Feb;64(2):179-87
references: 17283285
references: CNS Spectr. 2005 Aug;10(8):647-63; quiz 672
references: 16041296
references: J Clin Psychopharmacol. 2008 Apr;28(2):249-51
references: 18344745
references: Science. 2007 Sep 14;317(5844):1488-90
references: 17872420
references: Int Clin Psychopharmacol. 2006 Feb;21 Suppl 1:S11-5
references: 16436934
references: J Affect Disord. 1998 May;49(2):109-17
references: 9609674
references: Biol Psychiatry. 1994 Jun 1;35(11):880-5
references: 8054411
references: Pharmacology. 1978;16(2):98-105
references: 201949
references: Prog Neuropsychopharmacol Biol Psychiatry. 1993 Jan;17(1):113-23
references: 8416598
references: Brain Res Bull. 2003 Dec 15;62(2):143-50
references: 14638388
references: Prog Neuropsychopharmacol Biol Psychiatry. 2005 Jul;29(6):1074-84
references: 15939518
references: J Affect Disord. 1998 May;49(2):133-9
references: 9609677
references: J Biol Rhythms. 2010 Dec;25(6):410-20
references: 21135157
references: Biol Psychiatry. 1994 Dec 15;36(12):840-6
references: 7893848
references: J Affect Disord. 1993 Feb;27(2):107-16
references: 8440806
references: Pharmacol Biochem Behav. 1986 Apr;24(4):809-12
references: 3012593
references: Am J Psychiatry. 1990 Jan;147(1):14-21
references: 2403471
references: Brain Res Rev. 2009 Dec 11;62(1):57-70
references: 19766673
references: Br J Psychiatry. 1982 Mar;140:231-5
references: 7093591
references: Am J Psychiatry. 1997 Jun;154(6):870-2
references: 9167521
references: Biol Psychiatry. 2007 Dec 1;62(11):1295-302
references: 17628506
references: Arch Gen Psychiatry. 1975 Sep;32(9):1121-5
references: 1101846
references: Am J Psychiatry. 2006 Dec;163(12):2126-33
references: 17151164
references: Int Clin Psychopharmacol. 2011 Mar;26(2):96-106
references: 21178634
references: Genes Brain Behav. 2008 Feb;7(1):20-5
references: 17428266
references: J Physiol. 2003 Jun 15;549(Pt 3):945-52
references: 12717008
references: Bipolar Disord. 2007 Aug;9(5):531-5
references: 17680925
references: Psychiatry Res. 1999 Jun 30;86(3):267-70
references: 10482346
references: Prog Neuropsychopharmacol Biol Psychiatry. 1990;14(1):37-47
references: 2405456
references: Annu Rev Pharmacol Toxicol. 2009;49:327-47
references: 18928402
references: Acta Psychiatr Scand. 1993 Jul;88(1):16-20
references: 8396844
references: Sleep Med Rev. 2007 Dec;11(6):509-22
references: 17689120
references: Am J Psychiatry. 1992 Feb;149(2):159-68
references: 1734735
references: J Clin Psychopharmacol. 1999 Jun;19(3):240-5
references: 10350030
references: Dialogues Clin Neurosci. 2007;9(3):237-55
references: 17969862
references: J Clin Psychiatry. 2003 Jun;64(6):648-53
references: 12823078
references: Psychiatry Res. 1998 Jun 2;79(1):43-50
references: 9676825
references: Psychiatry Res. 1981 Aug;5(1):67-76
references: 6116257
references: J Psychiatr Res. 1994 Jul-Aug;28(4):381-99
references: 7877117
references: Science. 1979 Nov 9;206(4419):710-3
references: 227056
references: Eur Arch Psychiatry Clin Neurosci. 1997;247(2):100-3
references: 9177956
references: Acta Psychiatr Scand. 1985 Aug;72(2):161-5
references: 4050508
references: Biol Psychiatry. 2003 Oct 1;54(7):687-92
references: 14512208
references: Am J Med Genet B Neuropsychiatr Genet. 2007 Jul 5;144B(5):631-5
references: 17221848
references: Am J Psychiatry. 2010 Jun;167(6):708-15
references: 20231325
references: Brain Res Mol Brain Res. 1998 Jun 15;57(2):235-40
references: 9675421
references: Brain Res. 1973 May 17;54:372-5
references: 4709153
references: Neuroscience. 2011 Dec 1;197:8-16
references: 21963350
references: Eur Arch Psychiatry Clin Neurosci. 2003 Apr;253(2):68-72
references: 12799743
references: J Clin Psychiatry. 1989 Dec;50 Suppl:8-16; discussion 45-7
references: 2689437
references: Brain Res. 1988 Nov;472(3):213-33
references: 3066435
references: Psychopharmacology (Berl). 2009 Mar;203(1):155-60
references: 18989660
references: Cell Mol Life Sci. 2007 Aug;64(15):1930-44
references: 17530463
references: Am J Psychiatry. 2005 Apr;162(4):656-62
references: 15800134
references: FASEB J. 2006 Mar;20(3):530-2
references: 16507766
references: Neuroscience. 2003;121(2):523-30
references: 14522011
references: Compr Psychiatry. 1995 May-Jun;36(3):224-8
references: 7648847
references: Trends Neurosci. 2012 Jan;35(1):36-46
references: 22217451
references: Psychiatry Res. 1983 Oct;10(2):105-12
references: 6581487
references: Eur Psychiatry. 2011 Apr;26(3):138-40
references: 21316201
references: Am J Psychiatry. 1985 Jun;142(6):725-7
references: 4003592
references: Biol Psychiatry. 1996 Nov 15;40(10):1000-7
references: 8915559
references: J Affect Disord. 1987 Jan-Feb;12(1):41-6
references: 2952693
references: Dialogues Clin Neurosci. 2007;9(3):257-72
references: 17969863
references: Arch Gen Psychiatry. 2001 Dec;58(12):1108-14
references: 11735838
references: Prog Neurobiol. 2001 Nov;65(4):391-426
references: 11527574
references: Dialogues Clin Neurosci. 2003 Dec;5(4):315-25
references: 22033593
references: J Clin Psychiatry. 2005 Dec;66(12):1535-40
references: 16401154
references: Neuropsychopharmacology. 1999 Apr;20(4):380-5
references: 10088139
references: Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2010 Dec;154(4):355-61
references: 21293548
references: Eur Neuropsychopharmacol. 1995;5 Suppl:89-93
references: 8775765
references: Biol Psychiatry. 1988 Oct;24(6):631-41
references: 3167147
references: Depress Anxiety. 2001;14(1):37-49
references: 11568981
references: Pharmacol Biochem Behav. 1981 Jul;15(1):149-51
references: 7197363
references: Am J Psychiatry. 2009 Feb;166(2):164-72
references: 19015231
references: J Affect Disord. 2001 May;64(2-3):257-60
references: 11313092
references: Am J Psychiatry. 1982 Nov;139(11):1496-8
references: 7137404
references: J Biol Chem. 2005 Aug 19;280(33):29397-402
references: 15972822
references: Neuropsychobiology. 1977;3(1):23-9
references: 895995
references: Lancet. 2002 Dec 7;360(9348):1840-2
references: 12480364
references: Neurosci Lett. 1995 Sep 22;198(1):21-4
references: 8570087
references: J Affect Disord. 2001 Feb;62(3):221-3
references: 11223110
references: Neuropsychopharmacology. 1997 Aug;17(2):72-81
references: 9252982
references: Am J Med Genet B Neuropsychiatr Genet. 2003 Nov 15;123B(1):23-6
references: 14582141
references: Biol Psychiatry. 2005 Feb 15;57(4):430-2
references: 15705360
references: Brain Res. 1970 Jul 29;21(3):391-403
references: 4318998
references: Biol Psychiatry. 1989 Apr 1;25(7):966-70
references: 2720008
references: Psychiatry Res. 2012 Mar 30;196(1):57-61
references: 22424890
references: Am J Physiol. 1997 Apr;272(4 Pt 2):R1178-88
references: 9140018
references: Am J Psychiatry. 1999 Sep;156(9):1450-2
references: 10484962
references: Biol Psychiatry. 1990 Oct 1;28(7):569-87
references: 2171684
references: Arch Gen Psychiatry. 1980 Mar;37(3):267-71
references: 7189111
references: Neurosci Lett. 2004 Jan 23;355(1-2):37-40
references: 14729229
references: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9377-81
references: 15967985
references: Eur Neuropsychopharmacol. 2008 Jan;18(1):14-23
references: 17582745
references: Biol Psychiatry. 2006 Oct 15;60(8):896-9
references: 16631132
references: Arch Gen Psychiatry. 1993 Dec;50(12):929-37
references: 8250678
references: Psychiatry Res. 2001 Nov 30;104(3):239-46
references: 11728613
references: Neuropsychobiology. 2011;64(3):141-51
references: 21811084
references: Mol Psychiatry. 2000 Nov;5(6):578-93
references: 11126389
references: Sleep Med Rev. 2007 Dec;11(6):497-507
references: 17964200
references: Am J Psychiatry. 2003 Jul;160(7):1252-62
references: 12832239
references: Psychol Med. 2008 Jul;38(7):1069-71
references: 18377675
references: Brain Res Mol Brain Res. 2001 Feb 19;87(1):92-9
references: 11223163
references: J Affect Disord. 1991 Dec;23(4):231-7
references: 1791269
references: Annu Rev Physiol. 2010;72:517-49
references: 20148687
references: J Neurosci. 2009 Jan 21;29(3):620-9
references: 19158289
references: Science. 2005 Sep 30;309(5744):2228-32
references: 16195466
references: J Clin Psychiatry. 2011 Jul;72(7):986-93
references: 21535997
references: Psychol Med. 2005 Jul;35(7):939-44
references: 16045060
references: Acta Psychiatr Scand. 1981 May;63(5):453-62
references: 7032222
references: Psychother Psychosom. 2006;75(4):244-8
references: 16785774
references: Handb Clin Neurol. 2012;106:697-713
references: 22608653
references: J Psychiatr Res. 2001 Nov-Dec;35(6):323-9
references: 11684139
references: J Physiol. 2012 Jul 1;590(13):3035-45
references: 22547633
references: Neuropsychopharmacology. 1996 Oct;15(4):332-9
references: 8887987
references: J Psychiatr Res. 2009 Apr;43(7):711-20
references: 18930473
references: Sleep Med Rev. 2002 Oct;6(5):341-51
references: 12531125
references: Eur Neuropsychopharmacol. 2011 Sep;21 Suppl 4:S683-93
references: 21835596
references: Int Pharmacopsychiatry. 1971;6(3):187-96
references: 4950570
references: Dialogues Clin Neurosci. 2003 Dec;5(4):353-65
references: 22033495
references: Bibl Psychiatr. 1981;(160):56-61
references: 7458886
references: Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6406-11
references: 17379666
references: Dialogues Clin Neurosci. 2003 Dec;5(4):366-9
references: 22033748
references: Arch Gen Psychiatry. 2002 Jul;59(7):597-604
references: 12090812
references: J Affect Disord. 2012 Feb;136(3):514-9
references: 22119086
references: Biol Psychiatry. 2009 Aug 1;66(3):298-301
references: 19358978
references: Pharmacol Ther. 2006 May;110(2):135-370
references: 16522330
references: Cochrane Database Syst Rev. 2004;(2):CD004050
references: 15106233