Skip to main content

Advertisement

Log in

Wake-Promoting Pharmacotherapy for Psychiatric Disorders

  • Sleep Disorders (P Gehrman, Section Editor)
  • Published:
Current Psychiatry Reports Aims and scope Submit manuscript

Abstract

Medications promoting wakefulness are currently used in psychopharmacology in different contexts and with different objectives. In particular, they may be used for the treatment of syndromes that primarily show significant impairment in alertness/wakefulness (e.g., excessive sleepiness and other sleep disorders) as well as for the symptomatic treatment of different neuropsychiatric disorders that, in turn, are not exclusively characterized by sleep-wake disturbances (like mood disorders, for instance). In addition, several psychotropic compounds, including some antipsychotics, mood stabilizers, antidepressants, and anxiolytics have well-established sedating side effects that may go beyond the therapeutic target and require the symptomatic use of wake-promoting agents. Even though such a clinical scenario reflects millions of individuals affected (alterations of wakefulness have a prevalence rate of 20–43 % in the general population), relatively few pharmacotherapies are available, mainly including compounds with psychostimulating effects, such as methylphenidate, modafinil, and armodafinil and some amphetaminic agents. In light of their side effects and potential for abuse, such compounds have received FDA approval only for a limited number of psychiatric disorders. Nonetheless, their clinical application has recently become more widespread, including attention deficit hyperactivity disorder, narcolepsy, treatment-resistant depression, bipolar disorder, shift work sleep disorder, schizophrenia, and addictions. Wake-promoting agents have different mechanisms of action, peculiar clinical strengths and specific limitations, with novel drugs in the field under extensive investigation. The present review is aimed to provide an updated overview of the aforementioned compounds as well as investigational drugs in the field, in terms of mechanism of action, indications and use in clinical practice.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as:• Of importance

  1. Saraf G, Viswanath B, Narayanaswamy JC, Holla B, Math SB. Modafinil for the treatment of antipsychotic-induced excessive daytime sedation: does it exacerbate tics? J Neuropsychiatry Clin Neurosci. 2013;25:E35–6.

    Article  PubMed  Google Scholar 

  2. Hasler G, Buysse DJ, Gamma A, Ajdacic V, Eich D, Rössler W, et al. Excessive daytime sleepiness in young adults: a 20-year prospective community study. J Clin Psychiatry. 2005;66:521–9.

    Article  PubMed  Google Scholar 

  3. Boutrel B, Koob GF. What keeps us awake: the neuropharmacology of stimulants and wakefulness-promoting medications. Sleep. 2004;27(6):1181–94.

    PubMed  Google Scholar 

  4. Sheng P, Hou L, Wang X, Wang X, Huang C, Yu M, et al. Efficacy of modafinil on fatigue and excessive daytime sleepiness associated with neurological disorders: a systematic review and meta-analysis. PLoS One. 2013;8(12):e81802.

  5. Yeoh JW, Campbell EJ, James MH, Graham BA, Dayas CV. Orexin antagonists for neuropsychiatric disease: progress and potential pitfalls. Front Neurosci. 2014;8:36. This review illustrates possible future targets for the treatment of excessive sleepiness in psychiatric disorder, using molecules acting on orexin system.

    Article  PubMed Central  PubMed  Google Scholar 

  6. Sinita E, Coghill D. The use of stimulants medication for non-core aspects of ADHD and in other disorders. Neuropsychopharmacology. 2014; in press. The present article reviews the major applications of stimulant agents in psychiatric disorders and other medical conditions.

  7. Steriade M. Presynaptic dendrites of thalamic local-circuit neurons and sculpting inhibition during activated states. J Physiol. 2003;546(Pt 1):1.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Hiyoshi H, Terao A, Okamatsu-Ogura Y, Kimura K. Characteristics of sleep and wakefulness in wild-derived inbred mice. Exp Anim. 2014;63(2):205–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  9. Monti JM, Jantos H. The roles of dopamine and serotonin, and of their receptors, in regulating sleep and waking. Prog Brain Res. 2008;172:625–46.

    Article  CAS  PubMed  Google Scholar 

  10. Westfall TC, Westfall DP. In: Brunton LL, Lazo JS, Parker KL, editors. Adrenergic agonsists and antagonists, in Goodman & Gilman s The Pharmacological Basis of Therapeutics. 11th ed. New York: The McGraw-Hill Companies; 2006.

  11. Wood S, Sage JR, Shuman T, Anagnostaras SG. Psychostimulants and cognition: a continuum of behavioral and cognitive activation. Pharmacol Rev. 2013;66(1):193–221.

    Article  PubMed  Google Scholar 

  12. Ritalin®. Summary of product characteristics. Available at http://www.medicines.org.uk/emc/medicine/1316/SPC/ritalin/.

  13. Kimko HC1, Cross JT, Abernethy DR. Pharmacokinetics and clinical effectiveness of methylphenidate. Clin Pharmacokinet. 1999;37(6):457–70.

    Article  CAS  PubMed  Google Scholar 

  14. Ritalin SR ® prescribing information. http://www.pharma.us.novartis.com/product/pi/pdf/ritalin_ritalin-sr.pdf.

  15. Biphentin® product monograph. http://www.purdue.ca/files/Biphentin%Capsules%20PM%20EN.pdf.

  16. Daytrana ® prescribing information. http://www.daytrana.com/documents/daytrana-prescribing-information.pdf .

  17. Concerta XL® summary of product characteristics. http://www.medicines.org.uk/EMC/medicine/8382/SPC/Concerta+XL+18+mg+−+36+mg+prolonged+release+tablets/.

  18. Equasym XL® summary of product characteristics. http://www.medicines.org.uk/emc/medicine/15804/SPC/Equasym+XL+10+mg,+20+mg+or+30+mg+Capsules.

  19. Focalin XR ® prescribing information. http://www.pharma.us.novartis.com/product/pi/pdf/focalinXR.pdf.

  20. Medikinet XL® 5 Mg summary of product characteristics. http://www.medicines.org.uk/emc/medicine/24854/.

  21. Ritalin LA® prescribing information. http://www.pharma.us.novartis.com/product/pi/pdf/ritalin_la.pdf.

  22. Coghill D, Banaschewski T, Zuddas A, Pelaz A, Gagliano A, Doepfner M. Long-acting methylphenidate formulations in the treatment of attention-deficit/hyperactivity disorder: a systematic review of head-to-head studies. BMC Psychiatry. 2013;13:237.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Volkow ND, Fowler JS, Wang G, Ding Y, Gatley SJ. Mechanism of action of methylphenidate: insights from PET imaging studies. J Atten Disord. 2002;6 Suppl 1:S31–43.

    PubMed  Google Scholar 

  24. Stahl SM. The prescriber’s guide. Stahl’s essential psychopharmacology. 3rd Edition. Cambridge University Press. 2009. pp 77–81.

  25. Berridge CW, Devilbiss DM, Andrzejewski ME, Arnsten AF, Kelley AE, Schmeichel B, et al. Methylphenidate preferentially increases catecholamine neurotransmission within the prefrontal cortex at low doses that enhance cognitive function. Biol Psychiatry. 2006;60(10):1111–20.

    Article  CAS  PubMed  Google Scholar 

  26. Bolea-Alamanac B, Nutt DJ, Adamou M, Asherson P, Bazire S, Coghill D, et al. Evidence-based guidelines for the pharmacological management of attention deficit hyperactivity disorder: update on recommendations from the British Association for Psychopharmacology. J Psychopharmacol. 2014;28:179–203.

  27. Golubchik P, Kodesh A, Weizman A. Attention-deficit/hyperactivity disorder and comorbid subsyndromal depression: what is the impact of methylphenidate on mood? Clin Neuropharmacol. 2013;36(5):141–5.

    Article  CAS  PubMed  Google Scholar 

  28. Stoll AL, Pillay SS, Diamond L, Workum SB, Cole JO. Methylphenidate augmentation of serotonin selective reuptake inhibitors: a case series. J Clin Psychiatry. 1996;57:72–76.

  29. Ravindran AV, Kennedy SH, O'Donovan MC, Fallu A, Camacho F, Binder CE. Osmotic-release oral system methylphenidate augmentation of antidepressant monotherapy in major depressive disorder: results of a double-blind, randomized, placebo-controlled trial. J Clinical Psychiatry. 2008;69:87–94.

  30. El-Mallakh RS. An open study of methylphenidate in bipolar depression. Bipolar Disord. 2000;1:56–9.

    Article  Google Scholar 

  31. Dell′Osso B, Ketter TA, Cremaschi L, Spagnolin G, Altamura AC. Assessing the roles of stimulants/stimulant-like drugs and dopamine-agonists in the treatment of bipolar depression. Curr Psychiatry Rep. 2013;15(8):378.

    Article  PubMed  Google Scholar 

  32. Greenhill LL, Pliszka S, Dulcan MK, Bernet W, Arnold V, Beitchman J, et al. Practice parameter for the use of stimulant medications in the treatment of children, adolescents and adults. J Am Acad Child Adolesc Psychiatry. 2002;41(2 Suppl):26S–49S.

  33. Hesapcioglu ST, Gokerb Z, Bilginerc C, Kandilc S. Methylphenidate induced psychotic symptoms: two cases report. Journal of Medical Cases. 2013;4(2):106–8.

    Google Scholar 

  34. Schweickert LA, Strober M, Moskowitz A. Efficacy of methylphenidate in bulimia nervosa comorbid with attention-deficit hyperactivity disorder: a case report. Int J Eat Disord. 1997;21(3):299–301.

    Article  CAS  PubMed  Google Scholar 

  35. Sokol MS, Gray NS, Goldstein A, Kaye WH. Methylphenidate treatment for bulimia nervosa associated with a cluster B personality disorder. Int J Eat Disord. 1999;25(2):233–7.

    Article  CAS  PubMed  Google Scholar 

  36. Di Jeffrey E, Kelsey CB, Nemeroff D. Principles of psychopharmacology for mental health professionals. New Jersey: Wiley; 2006.

  37. Kurlan R. Tourette’s syndrome: are stimulants safe? Curr Neurol Neurosci Rep. 2003;3(4):285–8.

    Article  PubMed  Google Scholar 

  38. Bloch MH, Panza KE, Landeros-Weisenberger A, Leckman JF. Meta-analysis: treatment of attention-deficit/hyperactivity disorder in children with comorbid tic disorders. J Am Acad Child Adolesc Psychiatry. 2009;48:884–93. This meta-analysis focuses on the debate on the use of psychostimulants in ADHD patients with comorbid tics.

    Article  PubMed Central  PubMed  Google Scholar 

  39. Hardy SE. Methylphenidate for the treatment of depressive symptoms, including fatigue and apathy, in medically ill older adults and terminally ill adults. Am J Geriatr Pharmacother. 2009;7(1):34–59.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  40. Besag FM. ADHD treatment and pregnancy. Drug Saf. 2014;37(6):397–408.

    Article  CAS  PubMed  Google Scholar 

  41. Provigil A. ® (Modafinil) Tablets [C-IV] [Package Insert]. Frazer, PA: Cephalon, Inc; 2010.

  42. Wisor J. Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions. Front Neurol. 2013;4:139.

    Article  PubMed Central  PubMed  Google Scholar 

  43. Robertson Jr P, Hellriegel ET. Clinical pharmacokinetic profile of modafinil. Clin Pharmacokinet. 2003;42(2):123–37.

    Article  CAS  PubMed  Google Scholar 

  44. Robertson Jr P, Hellriegel ET, Arora S, Nelson M. Effect of modafinil at steady state on the single-dose pharmacokinetic profile of warfarin in healthy volunteers. J Clin Pharmacol. 2002;42(2):205–14.

    Article  CAS  PubMed  Google Scholar 

  45. Kumar R. Approved and investigational uses of modafinil: an evidence-based review. Drugs. 2008;68(13):1803–39.

    Article  CAS  PubMed  Google Scholar 

  46. Goss AJ, Kaser M, Costafreda SG, Sahakian BJ, Fu CH. Modafinil augmentation therapy in unipolar and bipolar depression: a systematic review and meta-analysis of randomized controlled trials. J Clin Psychiatry. 2013;74(11):1101–7. This article reviews the effectiveness of augmentative Modafinil in reducing overall depressive scores, especially fatigue.

    Article  CAS  PubMed  Google Scholar 

  47. US Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. Ann Neurol. 1998;43(1):88–97.

    Article  Google Scholar 

  48. Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. US Modafinil in Narcolepsy Multicenter Study Group. Neurology. 2000;54(5):1166–75.

    Article  Google Scholar 

  49. Becker PM, Schwartz JR, Feldman NT, Hughes RJ. Effect of modafinil on fatigue, mood, and health-related quality of life in patients with narcolepsy. Psychopharmacology (Berl). 2004;171(2):133–9.

    Article  CAS  Google Scholar 

  50. Thorpy MJ. Managing the patient with shift-work disorder. J Fam Pract. 2010;59:S24–31.

    PubMed  Google Scholar 

  51. Roth T. Appropriate therapeutic selection for patients with shift work disorder. Sleep Med. 2012;13:335–41.

    Article  PubMed  Google Scholar 

  52. Czeisler CA, Walsh JK, Roth T, Hughes RJ, Wright KP, Kingsbury L, et al. U.S. Modafinil in Shift Work Sleep Disorder Study Group. Modafinil for excessive sleepiness associated with shift-work sleep disorder. N Engl J Med. 2005;353:476–86.

    Article  CAS  PubMed  Google Scholar 

  53. Grady S, Aeschbach D, Wright Jr KP, Czeisler CA. Effect of modafinil on impairments in neurobehavioral performance and learning associated with extended wakefulness and circadian misalignment. Neuropsychopharmacology. 2010;35(9):1910–20.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  54. Taylor FB, Russo J. Efficacy of modafinil compared to dextroamphetamine for the treatment of attention deficit hyperactivity disorder in adults. J Child Adolesc Psychopharmacol. 2000;10:311–20.

  55. Turner DC, Clark L, Dowson J, Robbins TW, Sahakian BJ. Modafinil improves cognition and response inhibition in adult attention-deficit/hyperactivity disorder. Biol Psychiatry. 2004;55:1031–40.

  56. Rugino T. A review of modafinil film-coated tablets for attention-deficit/hyperactivity disorder in children and adolescents. Neuropsychiatr Dis Treat. 2007;3(3):293–301.

    PubMed Central  CAS  PubMed  Google Scholar 

  57. Ravindran AV, Lam RW, Filteau MJ, Lespérance F, Kennedy SH, Parikh SV, et al. Canadian Network for Mood and Anxiety Treatments (CANMAT).Canadian Network for Mood and Anxiety Treatments (CANMAT) Clinical guidelines for the management of major depressive disorder in adults. V. Complementary and alternative medicine treatments. J Affect Disord. 2009;117 Suppl 1:S54–64. These guidelines represent an updated milestone for the treatment of Major Depressive and Anxiety Disorders in adults.

    Article  PubMed  Google Scholar 

  58. American Psychiatric Association practice guideline for the treatment of patients with major depressive disorder, 3rd edition. 2010. Available at: http://psychiatryonline.org/content.aspx?bookid=28&sectionid=1667485. These guidelines provide an helpful tool in managing the treatment of Major Depressive Disorder.

  59. Turner DC, Clark L, Pomarol-Clotet E, McKenna P, Robbins TW, Sahakian BJ. Modafinil improves cognition and attentional set shifting in patients with chronic schizophrenia. Neuropsychopharmacology. 2004;29:1363–73.

  60. Makela EH, Miller K, Cutlip 2nd WD. Three case reports of modafinil use in treating sedation induced by antipsychotic medications. J Clinical Psychiatry. 2003;64:485–86.

  61. Anderson AL, Reid MS, Li SH, Holmes T, Shemanski L, Slee A, et al. Modafinil for the treatment of cocaine dependence. Drug Alcohol Depend. 2009;104(1–2):133–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  62. Haervig KB, Mortensen LH, Hansen AV, Strandberg-Larsen K. Use of ADHD medication during pregnancy from 1999 to 2010: a Danish register-based study. Pharmacoepidemiol Drug Saf. 2014;23(5):526–33.

    Article  CAS  PubMed  Google Scholar 

  63. Nuvigil A. ® (Armodafinil) Tablets [C-IV] [Package Insert]. Frazer, PA: Cephalon, Inc; (2010).

  64. Wong YN, Simcoe D, Hartman LN, Laughton WB, King SP, McCormick GC, et al. A double-blind, placebo-controlled, ascending-dose evaluation of the pharmacokinetics and tolerability of modafinil tablets in healthy male volunteers. J Clin Pharmacol. 1999;39:30–40.

    Article  CAS  PubMed  Google Scholar 

  65. Garnock-Jones KP, Dhillon S, Scott LJ. Armodafinil. CNS drugs. 2009;23:793–803.

    Article  CAS  PubMed  Google Scholar 

  66. Beuming T, Kniazeff J, Bergmann ML, Shi L, Gracia L, Raniszewska K, et al. The binding sites for cocaine and dopamine in the dopamine transporter overlap. Nat Neurosci. 2008;11(7):780–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  67. Loland CJ, Mereu M, Okunola OM, Cao J, Prisinzano TE, Mazier S, et al. R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry. 2012;72(5):405–13.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  68. De la Herrán-Arita AK, García-García F. Current and emerging options for the drug treatment of narcolepsy. Drugs. 2013;73(16):1771–81.

    Article  PubMed  Google Scholar 

  69. Calabrese JR, Frye MA, Yang R, Ketter TA; for the Armodafinil Treatment Trial Study Network. Efficacy and safety of adjunctive armodafinil in adults with major depressive episodes associated with bipolar I disorder: a randomized, double-blind, placebo-controlled, multicenter trial. J Clin Psychiatry. 2014 [Epub ahead of print].

  70. Krystal AD, Harsh JR, Yang R, Rippon GA, Lankford DA. A double-blind, placebo-controlled study of armodafinil for excessive sleepiness in patients with treated obstructive sleep apnea and comorbid depression. J Clin Psychiatry. 2010;71(1):32–40.

    Article  CAS  PubMed  Google Scholar 

  71. Karch SB, Drummer O. Karch’s pathology of drug abuse, fourth edition. 2008. CRC Press.

  72. Heal DJ, Smith SL, Gosden J, Nutt DJ. Amphetamine, past and present—a pharmacological and clinical perspective. J Psychopharmacol. 2013;27:479–96.

  73. Stiefel G, Besag FM. Cardiovascular effects of methylphenidate, amphetamines and atomoxetine in the treatment of attention-deficit hyperactivity disorder. Drug Saf. 2010;33(10):821–42.

    Article  CAS  PubMed  Google Scholar 

  74. Rasmussen N. America’s first amphetamine epidemic 1929–1971. Am J Public Heatlh. 2008;98(6):974–85.

    Article  Google Scholar 

  75. Parker G, Brotchie H, McClure G, Fletcher K. Psychostimulants for managing unipolar and bipolar treatment-resistant melancholic depression: a medium-term evaluation of cost benefits. J Affect Disord. 2013;151(1):360–4.

    Article  CAS  PubMed  Google Scholar 

  76. Lasser RA, Dirks B, Nasrallah H, Kirsch C, Gao J, Pucci ML, et al. Adjunctive lisdexamfetamine dimesylate therapy in adult outpatients with predominant negative symptoms of schizophrenia: open-label and randomized-withdrawal phases. Neuropsychopharmacology. 2013;38:2140–149.

  77. Castellanos FX, Giedd JN, Elia J, Marsh WL, Ritchie GF, Hamburger SD, et al. Controlled stimulant treatment of ADHD and comorbid Tourette’s syndrome: effects of stimulant and dose. J Am Acad Child Adolesc Psychiatry. 1997;36(5):589–96.

    Article  CAS  PubMed  Google Scholar 

  78. European Medicines Agency. (2010). Available from: http://www.ema.europa.eu/docs/en_GB/document_library/Other/2010/08/WC500095687.pdf.

  79. Cortese S, Holtmann M, Banaschewski T, Buitelaar J, Coghill D, Danckaerts M, et al. on behalf of the European ADHD Guidelines Group Practitioner Review: current best practice in the management of adverse events during treatment with ADHD medications in children and adolescents. J Child Psychol Psychiatry. 2013;54(3):227–46.

    Article  PubMed  Google Scholar 

  80. Westover AN, Halm EA. Do prescription stimulants increase the risk of adverse cardiovascular events?: A systematic review. BMC Cardiovasc Disord. 2012;12:41.

    Article  PubMed Central  PubMed  Google Scholar 

  81. Hodgkins P, Shaw M, Coghill D, Hechtman L. Amfetamine and methylphenidate medications for attention-deficit/hyperactivity disorder: complementary treatment options. Eur Child Adolesc Psychiatry. 2012;21(9):477–92.

    Article  PubMed Central  PubMed  Google Scholar 

  82. Weiner CP, Buhimschi C. Drugs for pregnant and lactating women. 2009. Elsevier Health Sciences, 2nd edition.

  83. Lloyd JT, Walker DR. Death after combined dexamphetamine and phenelzine. Br Med J. 1965;2(5454):168–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  84. Feinberg SS. Combining stimulants with monoamine oxidase inhibitors: a review of uses and one possible additional indication. J Clin Psychiatry. 2004;65(11):1520–4.

    Article  CAS  PubMed  Google Scholar 

  85. Dexedrine. Prescribing information. Available at: http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=a37b6ef9-78b4-4b18-8797ecb583502500.

  86. Galloway GP, Buscemi R, Coyle JR, Flower K, Siegrist JD, Fiske LA, et al. A randomized, placebo-controlled trial of sustained-release dextroamphetamine for treatment of methamphetamine addiction. Clin Pharmacol Ther. 2011;89(2):276–82.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  87. Green WH. Child and Adolescent Clinical Psychopharmacology. 2007. Ed Lippincott Williams and Wilkins, 4th edition.

  88. Fitzgerald KT, Bronstein AC. Adderall® (amphetamine-dextroamphetamine) toxicity. Top Companion Anim Med. 2013;28(1):2–7.

    Article  PubMed  Google Scholar 

  89. Taylor D, Paton C, Kapur S. Psychostimulants in depression. Maudsley Prescr. Guidel. Psychiatry. 2012. p. 239.

  90. Kitanaka J, Kitanaka N, Takemura M. Neurochemical consequences of dysphoric state during amphetamine withdrawal in animal models: a review. Neurochem Res. 2008;33(1):204–19.

    Article  CAS  PubMed  Google Scholar 

  91. Boellner SW, Stark JG, Krishnan S, Zhang Y. Pharmacokinetics of lisdexamfetamine dimesylate and its active metabolite, d-amphetamine, with increasing oral doses of lisdexamfetamine dimesylate in children with attention-deficit/hyperactivity disorder: a single-dose, randomized, open-label, crossover study. Clin Ther. 2010;32:252–64.

  92. Pennick M. Absorption of lisdexamfetamine dimesylate and its enzymatic conversion to d-amphetamine. Neuropsychiatr Dis Treat. 2010;6:317–27.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  93. Sharma A, Couture J. A review of the pathophysiology, etiology, and treatment of attention-deficit hyperactivity disorder (ADHD). Ann Pharmacother. 2014;48(2):209–25.

    Article  PubMed  Google Scholar 

  94. Mattingly G. Lisdexamfetamine dimesylate: a prodrug stimulant for the treatment of ADHD in children and adults. CNS Spectr. 2010;15(5):315–25.

    PubMed  Google Scholar 

  95. Trivedi MH, Cutler AJ, Richards C, Lasser R, Geibel BB, Gao J, et al. A randomized controlled trial of the efficacy and safety of lisdexamfetamine dimesylate as augmentation therapy in adults with residual symptoms of major depressive disorder after treatment with escitalopram. J Clin Psychiatry. 2013;74(8):802–9.

    Article  CAS  PubMed  Google Scholar 

  96. McIntyre RS, Alsuwaidan M, Soczynska JK, Szpindel I, Bilkey TS, Almagor D, et al. The effect of lisdexamfetamine dimesylate on body weight, metabolic parameters, and attention deficit hyperactivity disorder symptomatology in adults with bipolar I/II disorder. Hum Psychopharmacol. 2013;28(5):421–7.

    Article  CAS  PubMed  Google Scholar 

  97. Hoyer D, Jacobson LH. Orexin in sleep, addiction and more: is the perfect insomnia drug at hand? Neuropeptides. 2013;47(6):477–88.

    Article  CAS  PubMed  Google Scholar 

  98. De Lecea L, Kilduff TS, Peyron C, Gao X, Foye PE, Danielson PE, et al. The hypocretins: hypothalamus-specific peptides with neuroexcitatory activity. Proc Natl Acad Sci U S A. 1998;95(1):322–7.

    Article  PubMed Central  PubMed  Google Scholar 

  99. Dugovic C, Shelton JE, Yun S, Bonaventure P, Shireman BT, Lovenberg TW. Orexin-1 receptor blockade dysregulates REM sleep in the presence of orexin-2 receptor antagonism. Front Neurosci. 2014;8:28.

    Article  PubMed Central  PubMed  Google Scholar 

  100. Mieda M, Hasegawa E, Kisanuki YY, Sinton CM, Yanagisawa M, Sakurai T. Differential roles of orexin receptor-1 and -2 in the regulation of non-REM and REM sleep. J Neurosci. 2011;31(17):6518–26.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  101. Mignot E, Lammers GJ, Ripley B, Okun M, Nevsimalova S, Overeem S, et al. The role of cerebrospinal fluid hypocretin measurement in the diagnosis of narcolepsy and other hypersomnias. Arch Neurol. 2002;59(10):1553–62.

    Article  PubMed  Google Scholar 

  102. Crocker A, España RA, Papadopoulou M, Saper CB, Faraco J, Sakurai T, et al. Concomitant loss of dynorphin, NARP and orexin in narcolepsy. Neurology. 2005;65(8):1184–8.

  103. Mieda M, Sakurai T. Orexin (hypocretin) receptor agonists and antagonists for treatment of sleep disorders. Rationale for development and current status CNS Drugs. 2013;27(2):83–90.

    Article  CAS  Google Scholar 

  104. Mieda M, Willie JT, Hara J, Sinton CM, Sakurai T, Yanagisawa M. Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice. Proc Natl Acad Sci U S A. 2004;101(13):4649–54.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  105. Schwartz TL, Azhar N, Cole K, Hopkins G, Nihalani N, Simionescu M, et al. An open-label study of adjunctive modafinil in patients with sedation related to serotonergic antidepressant therapy. J Clin Psychiatry. 2004;65(9):1223–7.

    Article  PubMed  Google Scholar 

  106. Sudhakar TP, Prasada Rao G, Lakshmi Prasuna P, John Vijay Sagar K. Study of effects of modafinil add-on therapy on excessive day time drowsiness and weight gain in patients on atypical antipsychotics. Indian J Psychol Med. 2008;301:24–31.

    Article  Google Scholar 

  107. Saavedra-Velez C, Yusim A, Anbarasan D, Lindenmayer JP. Modafinil as an adjunctive treatment of sedation, negative symptoms, and cognition in schizophrenia: a critical review. J Clin Psychiatry. 2009;70(1):104–12.

    Article  CAS  PubMed  Google Scholar 

  108. Carlson PJ, Merlock MC, Suppes T. Adjunctive stimulant use in patients with bipolar disorder: treatment of residual depression and sedation. Bipolar Disord. 2004;6(5):416–20.

    Article  PubMed  Google Scholar 

  109. Mintzer MZ, Griffiths RR. Triazolam-amphetamine interaction: dissociation of effects on memory versus arousal. J Psychopharmacol. 2003;17(1):17–29.

    Article  CAS  PubMed  Google Scholar 

  110. Penzner JB, Dudas M, Saito E, Olshanskiy V, Parikh UH, Kapoor S, et al. Lack of effect of stimulant combination with second-generation antipsychotics on weight gain, metabolic changes, prolactin levels, and sedation in youth with clinically relevant aggression or oppositionality. J Child Adolesc Psychopharmacol. 2009;19(5):563–73.

    Article  PubMed Central  PubMed  Google Scholar 

  111. National Institute on Drug Abuse. 2011. Prescription drug abuse. Available at: http://www.drugabuse.gov/publications/research-reports/prescription-drugs.

  112. Carvalho M, Carmo H, Costa VM, Capela JP, Pontes H, Remião F, et al. Toxicity of amphetamines: an update. Arch Toxicol. 2012;86(8):1167–231.

    Article  CAS  PubMed  Google Scholar 

  113. Busto U, Sellers EM. Pharmacokinetics determinants of drug abuse and dependence. A conceptual perspective Clin Pharmacokinet. 1986;11(2):144–53.

    Article  CAS  Google Scholar 

  114. Abreu ME, Bigelow GE, Fleisher L, Walsh SL. Effect of intravenous injection speed on responses to cocaine and hydromorphone in humans. Psychopharmacology (Berl). 2001;154(1):76–84.

    Article  CAS  Google Scholar 

  115. Romach MK, Schoedel KA, Sellers EM. Human abuse liability evaluation of CNS stimulant drugs. Neuropharmacology. 2014. [Epub ahead of print]. This article highlights the clinical and biological aspects of the assessment of stimulants’ abuse potential.

  116. Launois SH, Tamisier R, Lévy P, Pépin JL. On treatment but still sleepy: cause and management of residual sleepiness in obstructive sleep apnea. Curr Opin Pulm Med. 2013;19(6):601–8.

    Article  CAS  PubMed  Google Scholar 

Download references

Compliance With Ethics Guidelines

Conflict of Interest

Cristina Dobrea, Laura Cremaschi and Chiara Arici declare that they have no conflict of interest.

Bernardo Dell’Osso has been part of the Speaker Bureau of Astra Zeneca, Bristol Myers Squibb, Janssen-Cilag, Eli Lilly, Pfizer, Glaxo Smith Kline, Lundbeck, Cyberonics and Italfarmaco.

A. Carlo Altamura is a consultant for Roche, Merck, Astra Zeneca, Bristol Myers Squibb, Janssen-Cilag, Lundbeck, Sanofi, Eli Lilly and Pfizer.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bernardo Dell’Osso.

Additional information

This article is part of the Topical Collection on Sleep Disorders

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Dell’Osso, B., Dobrea, C., Cremaschi, L. et al. Wake-Promoting Pharmacotherapy for Psychiatric Disorders. Curr Psychiatry Rep 16, 524 (2014). https://doi.org/10.1007/s11920-014-0524-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11920-014-0524-2

Keywords

Navigation