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  • The International Journal of Neuropsychopharmacology, Volume 15, Issue 5
  • June 2012, pp. 695-713

Rapid-acting antidepressant strategies: mechanisms of action

  • Blynn G. Bunney (a1) and William E. Bunney (a1)
  • DOI:
  • Published online: 07 July 2011

Current antidepressants are ineffective in many depressed patients. Thus there is an urgent need to develop treatment strategies which have significantly faster response, can be sustained and have minimal side-effects. This paper reviews clinical data, potential biomarkers, mechanisms of action and future research directions for two proven strategies that produce marked improvement in severe depressive symptoms within 48 h, ketamine and sleep deprivation therapy (SDT). These treatments provide unequivocal evidence that the depressive process can be rapidly reversed in a subgroup of patients. Seventeen ketamine studies in over 150 patients showed a rapid response. Low-dose intravenous ketamine produced mild psychotomimetic effects but response has not been effectively sustained. SDT has been investigated in over 60 studies with a 40–60% response rate within 48 h. Although SDT is often used in Europe to initiate a rapid response, it is less utilized within the USA, in part, because it has a short duration when administered alone. We review data concerning chronotherapeutic strategies of bright-light therapy (BLT) and sleep-phase advance (SPA) which successfully sustain the antidepressant efficacy of SDT. Evidence is further discussed that a significant group of mood disorders have abnormal circadian rhythms which are known to be controlled by clock genes. It is hypothesized that chronotherapeutic manipulations can reset clock genes and thus, abnormalities in circadian rhythms. Further findings are reviewed that ketamine, in addition to its role as an NMDA antagonist, can also alter circadian rhythms. Thus, ketamine may share a critical mechanism with SDT.

Corresponding author
Address for correspondence: Dr B. G. Bunney, Department of Psychiatry, Med Sci I, D438, School of Medicine, University of California Irvine, Irvine, CA 92697. Tel.: 949-824-4242Fax: 949-824-1787Email:
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M Abe , ED Herzog , GD Block (2000). Lithium lengthens the circadian period of individual suprachiasmatic nucleus neurons. Neuroreport 11, 32613264.

H Abe , B Rusak , HA Robertson (1992). NMDA and non-NMDA receptor antagonists inhibit photic induction of Fos protein in the hamster suprachiasmatic nucleus. Brain Research Bulletin 28, 831835.

M aan het Rot , KA Collins , JW Murrough , AM Perez , (2010). Safety and efficacy of repeated-dose intravenous ketamine for treatment-resistant depression. Biological Psychiatry 67, 139145.

A Alt , JM Witkin , D Bleakman (2005). AMPA receptor potentiators as novel antidepressants. Current Pharmaceutical Design 11, 15111527.

E Ampuero , FJ Rubio , R Falcon , M Sandoval , (2010). Chronic fluoxetine treatment induces structural plasticity and selective changes in glutamate receptor subunits in the rat cerebral cortex. Neuroscience 169, 98108.

DH Avery , SH Shah , DN Eder , G Wildschiodtz (1999). Nocturnal sweating and temperature in depression. Acta Psychiatrica Scandinavica 100, 295301.

LR Baxter (1985). Can lithium carbonate prolong the antidepressant effect of sleep deprivation? Archives of General Psychiatry 42, 635.

LR Baxter , EH Liston , JM Schwartz , LL Altshuler , (1986). Prolongation of the antidepressant response to partial sleep deprivation by lithium. Psychiatry Research 19, 1723.

R Benca , MJ Duncan , E Frank , C McClung , (2009). Biological rhythms, higher brain function, and behavior: gaps, opportunities, and challenges. Brain Research Reviews 62, 5770.

F Benedetti , B Barbini , A Bernasconi , MC Fulgosi , (2008). Lithium overcomes the influence of 5-HTTLPR gene polymorphism on antidepressant response to sleep deprivation. Journal of Clinical Psychopharmacology 28, 249251.

F Benedetti , B Barbini , E Campori , MC Fulgosi , (2001). Sleep phase advance and lithium to sustain the antidepressant effect of total sleep deprivation in bipolar depression: new findings supporting the internal coincidence model? Journal of Psychiatric Research 35, 323329.

F Benedetti , B Barbini , C Colombo , E Smeraldi (2007 a). Chronotherapeutics in a psychiatric ward. Sleep Medicine Reviews 11, 509522.

F Benedetti , B Barbini , MC Fulgosi , C Colombo , (2005). Combined total sleep deprivation and light therapy in the treatment of drug-resistant bipolar depression: acute response and long-term remission rates. Journal of Clinical Psychiatry 66, 15351540.

F Benedetti , C Colombo , B Barbini , E Campori , (1999). Ongoing lithium treatment prevents relapse after total sleep deprivation. Journal of Clinical Psychopharmacology 19, 240245.

F Benedetti , S Dallaspezia , MC Fulgosi , B Barbini , (2007 b). Phase advance is an actimetric correlate of antidepressant response to sleep deprivation and light therapy in bipolar depression. Chronobiology International 24, 921937.

F Benedetti , A Serretti , C Colombo , R Lilli , (2003). Dopamine receptor D2 and D3 gene variants are not associated with the antidepressant effect of total sleep deprivation in bipolar depression. Psychiatry Research 118, 241247.

F Benedetti , A Lucca , F Brambilla , C Colombo , (2002). Interleukine-6 serum levels correlate with response to antidepressant sleep deprivation and sleep phase advance. Progress in Neuropsychopharmacology & Biological Psychiatry 26, 11671170.

RM Berman , A Cappiello , A Anand , DA Oren , (2000). Antidepressant effects of ketamine in depressed patients. Biological Psychiatry 47, 351354.

GM Bump , CF Reynolds 3rd, G Smith , BG Pollock , (1997). Accelerating response in geriatric depression: a pilot study combining sleep deprivation and paroxetine. Depression and Anxiety 6, 113118.

TM Buckley , AF Schatzberg (2010). A pilot study of the phase angle between cortisol and melatonin in major depression – a potential biomarker? Journal of Psychiatric Research 44, 6974.

JN Bunney , SG Potkin (2008). Circadian abnormalities, molecular clock genes and chronobiological treatments in depression. British Medical Bulletin 86, 2332.

WE Bunney , BG Bunney (2000). Molecular clock genes in man and lower animals: possible implications for circadian abnormalities in depression. Neuropsychopharmacology 22, 335345.

O Caliyurt , F Guducu (2005). Partial sleep deprivation therapy combined with sertraline induces more rapid improvements in quality of life items in major depressive disorder. Journal of Affective Disorders 88, 7578.

SS Campbell , JC Gillin , DF Kripke , DS Janowsky , (1989). Lithium delays circadian phase of temperature and REM sleep in a bipolar depressive: a case report. Psychiatry Research 27, 2329.

R Cao , B Lee , HY Cho , S Saklayen , (2008). Photic regulation of the mTOR signaling pathway in the suprachiasmatic circadian clock. Molecular Cell Neuroscience 38, 312324.

R Cao , A Li , HY Cho , B Lee , (2010). Mammalian target of rapamycin signaling modulates photic entrainment of the suprachiasmatic circadian clock. Journal of Neuroscience 30, 63026314.

WT Carpenter Jr., WE Bunney Jr. (1971). Adrenal cortical activity in depressive illness. American Journal of Psychiatry 128, 3140.

I Chambille (1999). Circadian rhythm of AMPA receptor GluR2/3 subunit-immunoreactivity in the suprachiasmatic nuclei of Syrian hamster and effect of a light-dark cycle. Brain Research 833, 2738.

D Chassard , F Duflo , M de Queiroz Siqueira , B Allaouchiche , (2007). Chronobiology and anaesthesia. Current Opinion in Anaesthesiology 20, 186190.

C Clark , R Dupont , S Golshan , JC Gillin , (2000). Preliminary evidence of an association between increased REM density and poor antidepressant response to partial sleep deprivation. Journal of Affective Disorders 59, 7783.

CP Clark , GG Brown , L Frank , L Thomas , (2006). Improved anatomic delineation of the antidepressant response to partial sleep deprivation in medial frontal cortex using perfusion-weighted functional MRI. Psychiatry Research 146, 213222.

CP Clark , LR Frank , GG Brown (2001). Sleep deprivation, EEG, and functional MRI in depression: preliminary results. Neuropsychopharmacology 25 (Suppl. 5), S79S84.

JA Clements , WS Nimmo (1981). Pharmacokinetics and analgesic effect of ketamine in man. British Journal of Anaesthesiology 53, 2730.

C Colombo , F Benedetti , B Barbini , E Campori , (1999). Rate of switch from depression into mania after therapeutic sleep deprivation in bipolar depression. Psychiatry Research 86, 267270.

C Colombo , A Lucca , F Benedetti , B Barbini , (2000). Total sleep deprivation combined with lithium and light therapy in the treatment of bipolar depression: replication of main effects and interaction. Psychiatry Research 95, 4353.

N Diazgranados , L Ibrahim , NE Brutsche , A Newberg , (2010 a). A randomized add-on trial of an N-methyl-D-aspartate antagonist in treatment-resistant bipolar depression. Archives of General Psychiatry 67, 793802.

N Diazgranados , LA Ibrahim , NE Brutsche , R Ameli , (2010 b). Rapid resolution of suicidal ideation after a single infusion of an N-methyl-D-aspartate antagonist in patients with treatment-resistant major depressive disorder. Journal of Clinical Psychiatry 71, 16051611.

GE Correll , GE Futter (2006). Two case studies of patients with major depressive disorder given low-dose (subanesthetic) ketamine infusions. Pain Medicine 7, 9295.

CS Colwell , M Menaker (1992). NMDA as well as non-NMDA receptor antagonists can prevent the phase-shifting effects of light on the circadian system of the golden hamster. Journal of Biological Rhythms 7, 125136.

WC Drevets , ML Furey (2010). Replication of scopolamine's antidepressant efficacy in major depressive disorder: a randomized, placebo-controlled clinical trial. Biological Psychiatry 67, 432438.

WC Duncan Jr. (1996). Circadian rhythms and the pharmacology of affective illness. Pharmacology and Therapeutics 71, 253312.

K Dzirasa , L Coque , MM Sidor , S Kumar , (2010). Lithium ameliorates nucleus accumbens phase-signaling dysfunction in a genetic mouse model of mania. Journal of Neuroscience 30, 1631416323.

D Ebert , H Feistel , A Barocka (1991). Effects of sleep deprivation on the limbic system and the frontal lobes in affective disorders: a study with Tc-99 m-HMPAO SPECT. Psychiatry Research 40, 247251.

EJ Eide , H Kang , S Crapo , M Gallego , (2005). Casein kinase I in the mammalian circadian clock. Methods in Enzymology 393, 408418.

S Elsenga , RH van den Hoofdakker (1982). Clinical effects of sleep deprivation and clomipramine in endogenous depression. Journal of Psychiatric Research 17, 361374.

S Elsenga , RH Van den Hoofdakker (1987). Response to total sleep deprivation and clomipramine in endogenous depression. Journal of Psychiatric Research 21, 151161.

J Emens , A Lewy , JM Kinzie , D Arntz , (2009). Circadian misalignment in major depressive disorder. Psychiatry Research 168, 259261.

M Fritzsche , R Heller , H Hill , H Kick (2001). Sleep deprivation as a predictor of response to light therapy in major depression. Journal of Affective Disorders 62, 207215.

JJ Fleming , PM England (2010). AMPA receptors and synaptic plasticity: a chemist's perspective. Nature Chemical Biology 6, 8997.

ML Furey , WC Drevets (2006). Antidepressant efficacy of the antimuscarinic drug scopolamine: a randomized, placebo-controlled clinical trial. Archives of General Psychiatry 63, 11211129.

P Galecki , J Szemraj , G Bartosz , M Bienkiewicz , (2010). Single-nucleotide polymorphisms and mRNA expression for melatonin synthesis rate-limiting enzyme in recurrent depressive disorder. Journal of Pineal Research 48, 311317.

AJ Gelenberg , CL Chesen (2000). How fast are antidepressants? Journal of Clinical Psychiatry 61, 712721.

H Giedke , F Schwarzler (2002). Therapeutic use of sleep deprivation in depression. Sleep Medicine Reviews 6, 361377.

HW Goforth , T Holsinger (2007). Rapid relief of severe major depressive disorder by use of preoperative ketamine and electroconvulsive therapy. Journal of ECT 23, 2325.

JP Gouin , J Connors , JK Kiecolt-Glaser , R Glaser , (2010). Altered expression of circadian rhythm genes among individuals with a history of depression. Journal of Affective Disorders 126, 161166.

BP Hasler , DJ Buysse , DJ Kupfer , A Germain (2010). Phase relationships between core body temperature, melatonin, and sleep are associated with depression severity: further evidence for circadian misalignment in non-seasonal depression. Psychiatry Research 178, 205207.

HJ Haug (1992). Prediction of sleep deprivation outcome by diurnal variation of mood. Biological Psychiatry 31, 271278.

PB Hedlund , S Huitron-Resendiz , SJ Henriksen , JG Sutcliffe (2005). 5-HT7 receptor inhibition and inactivation induce antidepressant-like behavior and sleep pattern. Biological Psychiatry 58, 831837.

G Hempelmann , DF Kuhn (1997). Clinical significance of S-(+)-ketamine. Anaesthesist 46 (Suppl. 1), S3S7.

E Holsboer-Trachsler , U Hemmeter , M Hatzinger , E Seifritz (1994). Sleep deprivation and bright light as potential augmenters of antidepressant drug treatment – neurobiological and psychometric assessment of course. Journal of Psychiatric Research 28, 381399.

VA Holthoff , B Beuthien-Baumann , U Pietrzyk , J Pinkert , (1999). Changes in regional cerebral perfusion in depression. SPECT monitoring of response to treatment. Nervenarzt 70, 620626.

PE Holtzheimer III, WM McDonald , M Mufti , ME Kelley , (2010). Accelerated repetitive transcranial magnetic stimulation for treatment-resistant depression. Depression & Anxiety 27, 960963.

TR Insel , EM Scolnick (2006). Cure therapeutics and strategic prevention: raising the bar for mental health research. Molecular Psychiatry 11, 1117.

N Ishida , M Matsui , Y Mitsui , M Mishina (1994). Circadian expression of NMDA receptor mRNAs, epsilon 3 and zeta 1, in the suprachiasmatic nucleus of rat brain. Neuroscience Letters 166, 211215.

DB Jarrett , JM Miewald , DJ Kupfer (1988). Acute changes in sleep-related hormone secretion of depressed patients following oral imipramine. Biological Psychiatry 24, 541554.

H Jick , JA Kaye , SS Jick (2004). Antidepressants and the risk of suicidal behaviors. Journal of the American Medical Association 292, 338343.

LL Judd , HS Akiskal , PJ Schettler , J Endicott , (2002). The long-term natural history of the weekly symptomatic status of bipolar I disorder. Archives of General Psychiatry 59, 530537.

SA Kaladchibachi , B Doble , N Anthopoulos , JR Woodgett , (2007). Glycogen synthase kinase 3, circadian rhythms, and bipolar disorder: a molecular link in the therapeutic action of lithium. Journal of Circadian Rhythms 5, 3.

S Kasper , H Kick , G Voll , A Vieira (1991). Therapeutic sleep deprivation and antidepressant medication in patients with major depression. European Neuropsychopharmacology 1, 107111.

S Kasper , G Voll , A Vieira , H Kick (1990). Response to total sleep deprivation before and during treatment with fluvoxamine or maprotiline in patients with major depression – results of a double-blind study. Pharmacopsychiatry 23, 135142.

DJ Kennaway (2010). Clock genes at the heart of depression. Journal of Psychopharmacology 24 (Suppl. 2), 514.

SH Kennedy , KR Evans , S Kruger , HS Mayberg , (2001). Changes in regional brain glucose metabolism measured with positron emission tomography after paroxetine treatment of major depression. American Journal of Psychiatry 158, 899905.

RJ Knapp , R Goldenberg , C Shuck , A Cecil , (2002). Antidepressant activity of memory-enhancing drugs in the reduction of submissive behavior model. European Journal of Pharmacology 440, 2735.

HW Koenigsberg , MH Teicher , V Mitropoulou , C Navalta , (2004). 24-h Monitoring of plasma norepinephrine, MHPG, cortisol, growth hormone and prolactin in depression. Journal of Psychiatry Research 38, 503511.

R Kohrs , ME Durieux (1998). Ketamine: teaching an old drug new tricks. Anesthesiology & Analgesia 87, 11861193.

DF Kripke (1984). Critical interval hypotheses for depression. Chronobiology International 1, 7380.

DF Kripke , CM Nievergelt , E Joo , T Shekhtman , (2009). Circadian polymorphisms associated with affective disorders. Journal of Circadian Rhythms 7, 2.

H Kuhs , D Farber , S Borgstadt , S Mrosek , (1996). Amitriptyline in combination with repeated late sleep deprivation versus amitriptyline alone in major depression. A randomised study. Journal of Affective Disorders 37, 3141.

H Kuhs , B Kemper , U Lippe-Neubauer , J Meyer-Dunker , (1998). Repeated sleep deprivation once versus twice a week in combination with amitriptyline. Journal of Affective Disorders 47, 97103.

EC Landsness , MR Goldstein , MJ Peterson , G Tononi , (2011). Antidepressant effects of selective slow wave sleep deprivation in major depression: a high-density EEG investigation. Journal of Psychiatric Research. Published online 3 March 2011. doi:10.1016/j.jpsychires.2011.02.003.

C Lavebratt , LK Sjoholm , P Soronen , T Paunio , (2010 b). CRY2 is associated with depression. PLoS One 5, e9407.

E Leibenluft , DE Moul , PJ Schwartz , PA Madden , (1993). A clinical trial of sleep deprivation in combination with antidepressant medication. Psychiatry Research 46, 213227.

AJ Lewy (2010). Depressive disorders may more commonly be related to circadian phase delays rather than advances: time will tell. Sleep Medicine 11, 117118.

AJ Lewy , NL Cutler , RL Sack (1999). The endogenous melatonin profile as a marker for circadian phase position. Journal of Biological Rhythms 14, 227236.

N Li , B Lee , RJ Liu , M Banasr , (2010). mTOR-dependent synapse formation underlies the rapid antidepressant effects of NMDA antagonists. Science 329, 959964.

M Liebrenz , R Stohler , A Borgeat (2009). Repeated intravenous ketamine therapy in a patient with treatment-resistant major depression. World Journal of Biological Psychiatry 10, 640643.

RT Loving , DF Kripke , SR Shuchter (2002). Bright light augments antidepressant effects of medication and wake therapy. Depression and Anxiety 16, 13.

RT Loving , DF Kripke , NC Knickerbocker , MA Grandner (2005). Bright green light treatment of depression for older adults [ISRCTN69400161]. BMC Psychiatry 5, 42.

G Lucas , J Du , T Romeas , O Mnie-Filali , (2010). Selective serotonin reuptake inhibitors potentiate the rapid antidepressant-like effects of serotonin4 receptor agonists in the rat. PLoS One 5, e9253.

R Machado-Vieira , P Yuan , N Brutsche , N DiazGranados , (2009). Brain-derived neurotrophic factor and initial antidepressant response to an N-methyl-D-aspartate antagonist. Journal of Clinical Psychiatry 70, 16621666.

G Lucas , VV Rymar , J Du , O Mnie-Filali , (2007). Serotonin. (5-HT). receptor agonists are putative antidepressants with a rapid onset of action. Neuron 55, 712725.

R Machado-Vieira , G Salvadore , DA Luckenbaugh , HK Manji , (2008). Rapid onset of antidepressant action: a new paradigm in the research and treatment of major depressive disorder. Journal of Clinical Psychiatry 69, 946958.

AK Malhotra , DA Pinals , CM Adler , I Elman , (1997). Ketamine-induced exacerbation of psychotic symptoms and cognitive impairment in neuroleptic-free schizophrenics. Neuropsychopharmacology 17, 141150.

SJ Mathew , HK Manji , DS Charney (2008). Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology 33, 20802092.

SJ Mathew , JW Murrough , M aan het Rot , KA Collis , (2010). Riluzole for relapse prevention following intravenous ketamine in treatment-resistant depression: a pilot randomized, placebo-controlled continuation trial. International Journal of Neuropsychopharmacology 13, 7182.

HS Mayberg , SK Brannan , RK Mahurin , PA Jerabek , (1997). Cingulate function in depression: a potential predictor of treatment response. Neuroreport 8, 10571061.

CA McClung (2007). Circadian genes, rhythms and the biology of mood disorders. Pharmacology & Therapeutics 114, 222232.

J Mendlewicz (2009 a). Disruption of the circadian timing systems: molecular mechanisms in mood disorders. CNS Drugs 23 (Suppl. 2), 1526.

J Mendlewicz (2009 b). Sleep disturbances: core symptoms of major depressive disorder rather than associated or comorbid disorders. World Journal of Biological Psychiatry 10, 269275.

M Messer , IV Haller , P Larson , Pattison-Crisostomo (2010). The use of a series of ketamine infusions in two patients with treatment-resistant depression. Journal of Neuropsychiatry & Clinical Neuroscience 22, 442444.

O Mnie-Filali , C Faure , L Lambas-Senas , ME Mansari , (2011). Pharmacological blockade of 5-HT. receptors as a putative fast acting antidepressant strategy. Neuropsychopharmacology 36, 12751288.

DW Morris , MH Trivedi , M Fava , SR Wisniewski , (2009). Diurnal mood variation in outpatients with major depressive disorder. Depression and Anxiety 26, 851863.

L Moscovici , M Kotler (2009). A multistage chronobiologic intervention for the treatment of depression: a pilot study. Journal of Affective Disorders 116, 201207.

S Mukherjee , L Coque , JL Cao , J Kumar , (2010). Knockdown of Clock in the ventral tegmental area through RNA interference results in a mixed state of mania and depression-like behavior. Biological Psychiatry 68, 503511.

H Nagayama (1996). Chronic administration of imipramine and lithium changes the phase-angle relationship between the activity and core body temperature circadian rhythms in rats. Chronobiology International 13, 251259.

NP Nair , N Hariharasubramanian , C Pilapil (1984). Circadian rhythm of plasma melatonin in endogenous depression. Progress in Neuropsychopharmacology & Biological Psychiatry 8, 715718.

PJ Nathan , GD Burrows , TR Norman (1999). Melatonin sensitivity to dim white light in affective disorders. Neuropsychopharmacology 21, 408413.

A Neumeister , R Goessler , M Lucht , T Kapitany , (1996). Bright light therapy stabilizes the antidepressant effect of partial sleep deprivation. Biological Psychiatry 39, 1621.

S Ohdo (2010). Chronopharmaceutics: pharmaceutics focused on biological rhythm. Biological & Pharmacological Bulletin 33, 159167.

G Paslakis , M Gilles , A Meyer-Lindenberg , M Deuschle (2010). Oral administration of the NMDA receptor antagonist S-ketamine as add-on therapy of depression: a case series. Pharmacopsychiatry 43, 3335.

KN Paul , C Fukuhara , M Karom , G Tosini , (2005). AMPA/kainate receptor antagonist DNQX blocks the acute increase of Per2 mRNA levels in most but not all areas of the SCN. Brain Research. Molecular Brain Research 139, 129136.

KN Paul , C Fukuhara , G Tosini , HE Albers (2003). Transduction of light in the suprachiasmatic nucleus: evidence for two different neurochemical cascades regulating the levels of Per1 mRNA and pineal melatonin. Neuroscience 119, 137144.

R Paul , N Schaaff , F Padberg , HJ Moller , (2009). Comparison of racemic ketamine and S-ketamine in treatment-resistant major depression: report of two cases. World Journal of Biological Psychiatry 10, 241244.

P Popik , T Kos , M Sowa-Kucma , G Nowak (2008). Lack of persistent effects of ketamine in rodent models of depression. Psychopharmacology (Berlin) 198, 421430.

MA Posternak , M Zimmerman (2005). Is there a delay in the antidepressant effect? A meta-analysis. Journal of Clinical Psychiatry 66, 148158.

P Pouget , N Wattiez , S Rivaud-Pechoux , B Gaymard (2010). Rapid development of tolerance to sub-anaesthetic dose of ketamine: an oculomotor study in macaque monkeys. Psychopharmacology (Berlin) 209, 313318.

RB Price , MK Nock , DS Charney , SJ Mathew (2009). Effects of intravenous ketamine on explicit and implicit measures of suicidality in treatment-resistant depression. Biological Psychiatry 66, 522526.

JR Redman , B Guardiola-Lemaitre , M Brown , P Delagrange , (1995). Dose dependent effects of S-20098, a melatonin agonist, on direction of re-entrainment of rat circadian activity rhythms. Psychopharmacology 118, 385390.

JC Raeder , LB Stenseth (2000). Ketamine: a new look at an old drug. Current Opinion in Anaesthesiology 13, 463468.

D Riemann , M Berger , U Voderholzer (2001). Sleep and depression–results from psychobiological studies: an overview. Biological Psychology 57, 67103.

D Riemann , A Konig , F Hohagen , A Kiemen , (1999). How to preserve the antidepressive effect of sleep deprivation: a comparison of sleep phase advance and sleep phase delay. European Archives of Psychiatry and Clinical Neuroscience 249, 231237.

K Roybal , D Theobold , A Graham , JA DiNieri , (2007). Mania-like behavior induced by disruption of CLOCK. Proceedings of the National Academy of Sciences USA 104, 64066411.

AJ Rush , M Trivedi , M Fava (2003). Depression, IV: STAR*D treatment trial for depression. American Journal of Psychiatry 160, 237.

G Salvadore , BR Cornwell , V Colon-Rosario , R Coppola , (2009). Increased anterior cingulate cortical activity in response to fearful faces: a neurophysiological biomarker that predicts rapid antidepressant response to ketamine. Biological Psychiatry 65, 289295.

G Salvadore , BR Cornwell , F Sambataro , D Latov , (2010). Anterior cingulate desynchronization and functional connectivity with the amygdala during a working memory task predict rapid antidepressant response to ketamine. Neuropsychopharmacology 35, 14151422.

G Sanacora , CA Zarate , JH Krystal , HK Manji (2008). Targeting the glutamatergic system to develop novel, improved therapeutics for mood disorders. Nature Reviews Drug Discovery 7, 426437.

B Scharnholz , F Lederbogen , A Feuerhack , A Bach , (2010). Does night-time cortisol excretion normalize in the long-term course of depression? Pharmacopsychiatry 43, 161165.

J Seggie (1988). Lithium and the retina. Progress in Neuropsychopharmacology & Biological Psychiatry 12, 241253.

J Seggie , C Canny , F Mai , E McCrank , (1989). Antidepressant medication reverses increased sensitivity to light in depression: preliminary report. Prog Neuropsychopharmacology & Biological Psychiatry 13, 537541.

RC Shelton , PT Loosen (1993). Sleep deprivation accelerates the response to nortriptyline. Progress in Neuro-psychopharmacology & Biological Psychiatry 17, 113123.

K Shimomura , PL Lowrey , MH Vitaterna , ED Buhr , (2010). Genetic suppression of the circadian Clock mutation by the melatonin biosynthesis pathway. Proceedings of the National Academy of Sciences USA 107, 83998403.

LK Sjoholm , L Backlund , EH Cheteh , IR Ek , (2010). CRY2 is associated with rapid cycling in bipolar disorder patients. PLoS One 5, e12632.

DJ Skene , CJ Bojkowski , J Arendt (1994). Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans. British Journal of Clinical Pharmacology 37, 181186.

E Smeraldi , F Benedetti , B Barbini , E Campori , (1999). Sustained antidepressant effect of sleep deprivation combined with pindolol in bipolar depression. A placebo-controlled trial. Neuropsychopharmacology 20, 380385.

GS Smith , CF Reynolds III, PR Houck , MA Dew , (2002). Glucose metabolic response to total sleep deprivation, recovery sleep, and acute antidepressant treatment as functional neuroanatomic correlates of treatment outcome in geriatric depression. American Journal Geriatric Psychiatry 10, 561567.

KN Sokolski , C Reist , CC Chen , EM DeMet (1995). Antidepressant responses and changes in visual adaptation after sleep deprivation. Psychiatry Research 57, 197207.

E Souetre , E Salvati , D Pringuey , Y Plasse , (1987). Antidepressant effects of the sleep/wake cycle phase advance. Preliminary report. Journal of Affective Disorders 12, 4146.

V Soria , E Martinez-Amoros , G Escaramis , J Valero , (2010 b). Differential association of circadian genes with mood disorders: CRY1 and NPAS2 are associated with unipolar major depression and CLOCK and VIP with bipolar disorder. Neuropsychopharmacology 35, 12791289.

J Sprouse , J Braselton , L Reynolds (2006). Fluoxetine modulates the circadian biological clock via phase advances of suprachiasmatic nucleus neuronal firing. Biological Psychiatry 60, 896899.

MP Szuba , LR Baxter Jr., LL Altshuler , EM Allen , (1994). Lithium sustains the acute antidepressant effects of sleep deprivation: preliminary findings from a controlled study. Psychiatry Research 51, 283295.

JS Takahashi (2004). Finding new clock components: past and future. Journal of Biological Rhythms 19, 339347.

MH Trivedi , AJ Rush , SR Wisniewski , AA Nierenberg , (2006). Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. American Journal of Psychiatry 163, 2840.

R Uher , W Maier , J Hauser , A Marusic , (2009). Differential efficacy of escitalopram and nortriptyline on dimensional measures of depression. British Journal of Psychiatry 194, 252259.

SJ Utge , P Soronen , A Loukola , E Kronholm , (2010). Systematic analysis of circadian genes in a population-based sample reveals association of TIMELESS with depression and sleep disturbance. PLoS One 5, e9259.

W van den Burg , AL Bouhuys , RH van den Hoofdakker , DG Beersma (1990). Sleep deprivation in bright and dim light: antidepressant effects on major depressive disorder. Journal of Affective Disorders 19, 109117.

GW Vogel (1975). A review of REM sleep deprivation. Archives of General Psychiatry 32, 749761.

S Volk , SH Kaendler , R Weber , K Georgi , (1992). Evaluation of the effects of total sleep deprivation on cerebral blood flow using single photon emission computerized tomography. Acta Psychiatrica Scandinavica 86, 478483.

TA Wehr , NE Rosenthal , DA Sack , JC Gillin (1985). Antidepressant effects of sleep deprivation in bright and dim light. Acta Psychiatrica Scandinavica 72, 161165.

Y Wang , MF Barbaro , SC Baraban (2006). A role for the mTOR pathway in surface expression of AMPA receptors. Neuroscience Letters 401, 3539.

TA Wehr , A Wirz-Justice , FK Goodwin , W Duncan , (1979). Phase advance of the circadian sleep-wake cycle as an antidepressant. Science 206, 710713.

A Wirz-Justice (2006). Biological rhythm disturbances in mood disorders. International Clinical Psychopharmacology 21 (Suppl. 1), S11S15.

A Wirz-Justice , F Benedetti , M Terman (2009). Chronotherapeutics for Affective Disorders: A Clinician's Manual for Light and Wake Therapy. Basel: Karger.

A Wirz-Justice , RH Van den Hoofdakker (1999). Sleep deprivation in depression: what do we know, where do we go? Biological Psychiatry 46, 445453.

JC Wu , JC Gillin , MS Buchsbaum , C Schachat (2008). Sleep deprivation PET correlations of Hamilton symptom improvement ratings with changes in relative glucose metabolism in patients with depression. Journal of Affective Disorders 107, 181186.

JC Wu , JR Kelsoe , C Schachat , BG Bunney , (2009). Rapid and sustained antidepressant response with sleep deprivation and chronotherapy in bipolar disorder. Biological Psychiatry 66, 298301.

L Yin , J Wang , PS Klein , MA Lazar (2006). Nuclear receptor Rev-erbalpha is a critical lithium-sensitive component of the circadian clock. Science 311, 10021005.

C Zarate Jr., R Machado-Vieira , I Henter , L Ibrahim , (2010). Glutamatergic modulators: the future of treating mood disorders? Harvard Review of Psychiatry 18, 293303.

CA Zarate Jr., JB Singh , PJ Carlson , (2006). A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Archives of General of Psychiatry 63, 856864.

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The International Journal of Neuropsychopharmacology
  • ISSN: 1461-1457
  • EISSN: 1469-5111
  • URL: /core/journals/the-international-journal-of-neuropsychopharmacology
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