CNS Drugs

, Volume 21, Issue 3, pp 239–257 | Cite as

Psychostimulants in the Treatment of Depression

A Review of the Evidence
Review Article

Abstract

Psychostimulants have euphoric and alerting properties that suggest their usefulness in treating depressive disorders; however, problems with tolerance and dependence with some drugs militate against their widespread therapeutic use where more acceptable licensed alternatives are available. The introduction of modafinil, a stimulant not associated with tolerance and dependence, has re-awakened interest in psychostimulants as antidepressants. The available literature, while containing somewhat inconsistent data of rather poor quality, does suggest that psychostimulants have useful antidepressant properties and are usually well tolerated. They may be useful as adjuncts to standard antidepressants in refractory depression, but have particular utility in conditions where a prompt therapeutic effect is desired and where tolerance and dependence are less of a concern. Such conditions include the treatment of depression in terminal illness and in extreme old age.

Psychostimulants, although now largely discarded as treatment options for depression, deserve careful consideration as potential therapeutic agents in specific patient subgroups.

Notes

Acknowledgements

No sources of funding were used to assist in the preparation of this review. Dr Taylor has acted as a consultant to Servier Laboratories and Lundbeck Plc; received honoraria from Eli Lilly & Co., Lundbeck Plc and Wyeth; and received grants from Lundbeck Plc. Ms Orr has no conflicts of interest that are directly relevant to the content of this review.

References

  1. 1.
    Connell PH. Amphetamine dependence. Proc Roy Soc Med 1968; 61(2): 170–81Google Scholar
  2. 2.
    Connell PH. Amphetamine psychosis. In: Maudsley Monographs no. 5. London: Oxford University Press, 1958Google Scholar
  3. 3.
    Janowsky DS, El-Yousef MK, Davis JM, et al. Provocation of schizophrenic symptoms by intravenous administration of methylphenidate. Arch Gen Psychiatry 1973; 28: 185–91PubMedCrossRefGoogle Scholar
  4. 4.
    McClellan KJ, Spencer CM. Modafinil: a review of its pharmacology and clinical efficacy in the management of narcolepsy. CNS Drugs 1998; 9(4): 311–24CrossRefGoogle Scholar
  5. 5.
    Biederman J, Swanson JM, Wigal SB, et al. A comparison of once-daily and divided doses of modafinil in children with attention-deficit/hyperactivity disorder: a randomized, double-blind, and placebo-controlled study. J Clin Psychiatry 2006; 67(5): 727–35PubMedCrossRefGoogle Scholar
  6. 6.
    Mattes JA. Methylphenidate in mild depression: a double-blind controlled trial. J Clin Psychiatry 1985; 46(12): 525–7PubMedGoogle Scholar
  7. 7.
    Little KY. d-Amphetamine versus methylphenidate effects in depressed inpatients. J Clin Psychiatry 1993; 54(9): 349–55PubMedGoogle Scholar
  8. 8.
    Rickels K, Gingrich RL, McLaughlin FW, et al. Methylphenidate in mildly depressed outpatients. Clin Pharmacol Ther 1972; 13(4): 595–601PubMedGoogle Scholar
  9. 9.
    O’Donnell M. Dexamphetamine compared with an inactive placebo in depression. Practitioner 1964; 192: 151–4PubMedGoogle Scholar
  10. 10.
    Robin AA, Wiseberg S. A controlled trial of methylphenidate (ritalin) in the treatment of depressive states. J Neurol Neurosurg Psychiatry 1958; 21: 55–7PubMedCrossRefGoogle Scholar
  11. 11.
    Rickels K, Gordon PE, Gansman DH, et al. Pemoline and methylphenidate in mildly depressed outpatients. Clin Pharmacol Ther 1970; 11(5): 698–710PubMedGoogle Scholar
  12. 12.
    Hare EH, Dominian J, Sharpe L. Phenelzine and dexamphetamine in depressive illness; a comparative trial. BMJ 1962; 5270: 9–12CrossRefGoogle Scholar
  13. 13.
    Rudolf GDEM. The treatment of depression with desoxyephedrine (methedrine). J Ment Sci 1949; 95: 920–9Google Scholar
  14. 14.
    Wilbur DL, MacLean AR, Allen EV. Clinical observation on the effect of benzedrine sulphate: a study of patients with states of chronic exhaustion, depression and psychoneurosis. JAMA 1937; 109(8): 549–54CrossRefGoogle Scholar
  15. 15.
    Wagner GJ, Rabkin R. Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial. J Clin Psychiatry 2000; 61(6): 436–40PubMedCrossRefGoogle Scholar
  16. 16.
    Kaplitz SE. Withdrawn, apathetic geriatric patients responsive to methylphenidate. J Am Geriatr Soc 1975; 23(6): 271–6PubMedGoogle Scholar
  17. 17.
    DeBattista C, Lembke A, Solvason HB, et al. A prospective trial of modafinil as an adjunctive treatment of major depression. J Clin Psychopharmacol 2004; 24(1): 87–90PubMedCrossRefGoogle Scholar
  18. 18.
    Gwirtsman HE, Szuba MP, Toren L, et al. The antidepressant response to tricyclics in major depressives is accelerated with adjunctive use of methylphenidate. Psychopharmacol Bull 1994; 30(2): 157–64PubMedGoogle Scholar
  19. 19.
    Rasmussen NA, Schroder P, Olsen LR, et al. Modafinil augmentation in depressed patients with partial response to antidepressants: a pilot study on self-reported symptoms covered by the major depression inventory (MDI) and the symptom checklist (SCL-92). Nord J Psychiatry 2005; 59(3): 173–8PubMedCrossRefGoogle Scholar
  20. 20.
    Fava M, Thase ME, DeBattista C. A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry 2005; 66(1): 85–93PubMedCrossRefGoogle Scholar
  21. 21.
    DeBattista C, Doghramji K, Menza MA, et al. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. J Clin Psychiatry 2003; 64(9): 1057–64PubMedCrossRefGoogle Scholar
  22. 22.
    Schwartz TL, Azhar N, Cole K, et al. An open-label study of adjunctive modafinil in patients with sedation related to serotonergic antidepressant therapy. J Clin Psychiatry 2004; 65(9): 1223–7PubMedCrossRefGoogle Scholar
  23. 23.
    Fawcett J, Kravitz HM, Zajecka JM, et al. CNS stimulant potentiation of monoamine oxidase inhibitors in treatment refractory depression. J Clin Psychopharmacol 1991; 11(2): 127–32PubMedCrossRefGoogle Scholar
  24. 24.
    Postolache TT, Rosenthal RN, Hellerstein DJ, et al. Early augmentation of sertraline with methylphenidate. J Clin Psychiatry 1999; 60(2): 123–4PubMedCrossRefGoogle Scholar
  25. 25.
    Markovitz PJ, Wagner S. An open-label trial of modafinil augmentation in patients with partial response to antidepressant therapy. J Clin Psychopharmacol 2003; 23(2): 207–9PubMedCrossRefGoogle Scholar
  26. 26.
    Macleod AD. Methylphenidate in terminal depression. J Pain Symptom Manage 1998; 16(3): 193–8PubMedCrossRefGoogle Scholar
  27. 27.
    Homsi J, Nelson KA, Sarhill N, et al. A phase II study of methylphenidate for depression in advanced cancer. Am J Hosp Palliat Care 2001; 18(6): 403–7PubMedCrossRefGoogle Scholar
  28. 28.
    Olin J, Masand P. Psychostimulants for depression in hospitalized cancer patients. Psychosomatics 1996; 37(1): 57–62PubMedCrossRefGoogle Scholar
  29. 29.
    Fernandez F, Adams F, Holmes VF, et al. Methylphenidate for depressive disorders in cancer patients. Psychosomatics 1987; 28(9): 455–61PubMedCrossRefGoogle Scholar
  30. 30.
    Meyers CA, Weitzner MA, Valentine AD, et al. Methylphenidate therapy improves cognition, mood and function of brain tumor patients. J Clin Oncol 1998; 16(7): 2522–7PubMedGoogle Scholar
  31. 31.
    Grade C, Redford B, Chrostowski J, et al. Methylphenidate in early poststroke recovery: a double-blind, placebo-controlled study. Arch Phys Med Rehabil 1998; 79: 1047–50PubMedCrossRefGoogle Scholar
  32. 32.
    Lazarus LW, Winemiller DR, Lingam VR, et al. Efficacy and side effects of methylphenidate for poststroke depression. J Clin Psychiatry 1992; 53(12): 447–9PubMedGoogle Scholar
  33. 33.
    Masand P, Pickett P, Murray GB. Psychostimulants in post-stroke depression. J Neuropsychiatry Clin Neurosci 1991; 3(1): 23–7PubMedGoogle Scholar
  34. 34.
    Lingam VR, Lazarus LW, Groves L, et al. Methylphenidate in treating poststroke depression. J Clin Psychiatry 1988; 49(4): 151–3PubMedGoogle Scholar
  35. 35.
    Wagner GJ, Rabkin R, Rabkin JG. Dexamphetamine as a treatment for depression and low energy in AIDS patients: a pilot study. J Psychosom Res 1997; 42(4): 407–11PubMedCrossRefGoogle Scholar
  36. 36.
    Reynolds III CF, Frank E, Dew MA, et al. Treatment of 70 (+)-year-olds with recurrent major depression: excellent short-term but brittle long-term response. Am J Geriatr Psychiatry 1999; 7(1): 64–9PubMedGoogle Scholar
  37. 37.
    Paykel ES, Ramana R, Cooper Z, et al. Residual symptoms after partial remission: an important outcome in depression. Psychol Med 1995; 25(6): 1171–80PubMedCrossRefGoogle Scholar
  38. 38.
    Lebowitz BD, Pearson JL, Schneider LS, et al. Diagnosis and treatment of depression in late life: consensus statement update. JAMA 1997; 278(14): 1186–90PubMedCrossRefGoogle Scholar
  39. 39.
    Geerlings SW, Beekman AT, Deeg DJ, et al. The longitudinal effect of depression on functional limitations and disability in older adults: an eight-wave prospective community-based study. Psychol Med 2001; 31(8): 1361–71PubMedCrossRefGoogle Scholar
  40. 40.
    Wallace AE, Kofoed LL, West AN. Double-blind, placebo-controlled trial of methylphenidate in older, depressed, medically ill patients. Am J Psychiatry 1995; 152(6): 929–31PubMedGoogle Scholar
  41. 41.
    Lavretsky H, Kim MD, Kumar A, et al. Combined treatment with methylphenidate and citalopram for accelerated response in the elderly: an open trial. J Clin Psychiatry 2003; 64(12): 1410–4PubMedCrossRefGoogle Scholar
  42. 42.
    Lavretsky H, Kumar A. Methylphenidate augmentation of citalopram in elderly depressed patients. Am J Geriatr Psychiatry 2001; 9(3): 298–303PubMedGoogle Scholar
  43. 43.
    Jacobson A. The use of ritalin in psychotherapy of depression of the aged. Psychiatr Q 1958; 32: 474–83PubMedCrossRefGoogle Scholar
  44. 44.
    Pickett P, Masand P, Murray GB. Psychostimulant treatment of geriatric depressive disorders secondary to medical illness. J Geriatr Psychiatry Neurol 1990; 3(3): 146–51PubMedCrossRefGoogle Scholar
  45. 45.
    Woods SW, Tesar GE, Murray GB, et al. Psychostimulant treatment of depressive disorders secondary to medical illness. J Clin Psychiatry 1986; 47(1): 12–5PubMedGoogle Scholar
  46. 46.
    Masand P, Pickett P, Murray GB. Psychostimulants for secondary depression in medical illness. Psychosomatics 1991; 32(2): 203–8PubMedCrossRefGoogle Scholar
  47. 47.
    Rosenberg PB, Ahmed I, Hurwitz S. Methylphenidate in depressed medically ill patients. J Clin Psychiatry 1991; 52(6): 263–7PubMedGoogle Scholar
  48. 48.
    Rothenhausler HB, Ehrentraut S, Degenfeld GV, et al. Treatment of depression with methylphenidate in patients difficult to wean from mechanical ventilation in the intensive care unit. J Clin Psychiatry 2000; 61(10): 750–5PubMedCrossRefGoogle Scholar
  49. 49.
    Landman ME, Preisig R, Perlman M. A practical mood stimulant. J Med Soc N J 1958; 55(2): 55–8PubMedGoogle Scholar
  50. 50.
    Hornig-Rohan M, Amsterdam JD. Venlafaxine versus stimulant therapy in patients with dual diagnosis ADD and depression. Prog Neuropsychopharmacol Biol Psychiatry 2002; 26: 585–9PubMedCrossRefGoogle Scholar
  51. 51.
    Lundt L. Modafinil treatment in patients with measonal affective disorder/ winter depression: an open-label pilot study. J Affect Disord 2004; 81: 173–8PubMedCrossRefGoogle Scholar
  52. 52.
    El-Mallakh RS. An open study of methylphenidate in bipolar depression. Bipolar Disord 2000; 2: 56–9PubMedCrossRefGoogle Scholar
  53. 53.
    Jonas AD. The adjunctive use of an intravenous amphetamine in psychotherapy. J Nerv Ment Dis 1954; 119: 135–47PubMedCrossRefGoogle Scholar
  54. 54.
    Linet LS. Treatment refractory depression with a combination of fluoxetine and dexamphetamine. Am J Psychiatry 1989; 146(6): 803–4PubMedGoogle Scholar
  55. 55.
    Menza MA, Kaufman KR, Castellanos A. Modafinil augmentation of antidepressant treatment in depression. J Clin Psychiatry 2000; 61(5): 378–81PubMedCrossRefGoogle Scholar
  56. 56.
    Xiong GL, Christopher EJ, Goebel J. Modafinil as an alternative to methylphenidate as augmentation for depression treatment. Psychosomatics 2005; 46(6): 578–9PubMedCrossRefGoogle Scholar
  57. 57.
    Schwartz TL, Leso L, Beale M, et al. Modafinil in the treatment of depression with severe comorbid medical illness. Psychosomatics 2002; 43(3): 336–7PubMedCrossRefGoogle Scholar
  58. 58.
    Ward NG, Lampe TH. A trial of dextroamphetamine in patients with involutional agitated depression. J Clin Psychiatry 1982; 43(1): 35–6PubMedGoogle Scholar
  59. 59.
    Kaufman KR, Menza MA, Fitzsimmons A. Modafinil monotherapy in depression. Eur Psychiatry 2002; 17(3): 167–9PubMedCrossRefGoogle Scholar
  60. 60.
    Stiebel VG. Methylphenidate plasma levels in depressed patients with renal failure. Psychosomatics 1994; 35(5): 498–500PubMedCrossRefGoogle Scholar
  61. 61.
    Holmes TF, Sabaawi M, Fragala MR. Psychostimulant suppository treatment for depression in the gravely ill. J Clin Psychiatry 1994; 55(6): 265–6PubMedGoogle Scholar
  62. 62.
    Kaufmann MW, Cassem NH, Murray GB, et al. Use of psychostimulants in medically ill patients with neurological disease and major depression. Can J Psychiatry 1984; 29(1): 46–9PubMedGoogle Scholar
  63. 63.
    Kaufmann MW, Cassem NH, Murray GB, et al. The use of methylphenidate in depressed patients after cardiac surgery. J Clin Psychiatry 1984; 45(2): 82–4PubMedGoogle Scholar
  64. 64.
    Kaufmann MW, Murray GB. The use of d-amphetamine in medically ill depressed patients. J Clin Psychiatry 1982; 43(11): 463–4PubMedGoogle Scholar
  65. 65.
    Kaufmann MW, Murray GB, Cassem NH. Use of psychostimulants in medically ill depressed patients. Psychosomatics 1982; 23(8): 817–9PubMedGoogle Scholar
  66. 66.
    Block SD. Assessing and managing depression in the terminally ill patient. Ann Intern Med 2000; 132: 209–18PubMedGoogle Scholar
  67. 67.
    Sugden SG, Bourgeois JA. Modafinil monotherapy in post-stroke depression. Psychosomatics 2004; 45(1): 80–1PubMedCrossRefGoogle Scholar
  68. 68.
    Homsi J, Walsh D, Nelson KA, et al. Methylphenidate for depression in hospice practice. Am J Hosp Palliat Care 2000; 17(6): 393–8PubMedCrossRefGoogle Scholar
  69. 69.
    Sarhill N, Walsh D, Nelson KA, et al. Methylphenidate for fatigue in advanced cancer: a prospective open-label pilot study. Am J Hosp Palliat Care 2001; 18(3): 187–92PubMedCrossRefGoogle Scholar
  70. 70.
    Burns MM, Eisendrath SJ. Dextroamphetamine treatment for depression in terminally ill patients. Psychosomatics 1994; 35(1): 80–3PubMedCrossRefGoogle Scholar
  71. 71.
    Frye CB. Methylphenidate for depression in the elderly, medically ill patient. Am J Health Syst Pharm 1997; 54(21): 2510–1PubMedGoogle Scholar
  72. 72.
    Gurian B, Rosowsky E. Low-dose methylphenidate in the very old. J Geriatr Psychiatry Neurol 1990; 3(3): 152–4PubMedCrossRefGoogle Scholar
  73. 73.
    Anderson IM, Nutt DJ, Deakin JF. Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 1993 British Association for Psychopharmacology guidelines. British Association for Psychopharmacology. J Psychopharmacol 2000; 14(1): 3–20Google Scholar
  74. 74.
    Fava GA. Can long-term treatment with antidepressant drugs worsen the course of depression? J Clin Psychiatry 2003; 64(2): 123–33PubMedCrossRefGoogle Scholar
  75. 75.
    Summary of product characteristics (SPC) for Provigil® 100 and 200mg tablets (modafinil) [online]. Available from URL: http://www.medicines.org.uk [Accessed 2006 Dec 27]
  76. 76.
    Summary of product characteristics (SPC) for Dexedrine® 5mg (dexamphetamine) [online]. Available from URL: http://www.medicines.org.uk [Accessed 2006 Dec 27]
  77. 77.
    Summary of product characteristics (SPC) for Equasym® 5, 10 and 20mg tablets (methylphenidate) [online]. Available from URL: http://www.medicines.org.uk [Accessed 2006 Dec 27]
  78. 78.
    Micromedex® healthcare series. Modafinil Drugdex® evaluation [online]. Available from URL: http://healthcare.micromedex.com [Accessed 2006 Feb 7]
  79. 79.
    Micromedex® healthcare series. Dexamphetmaine Drugdex® evaluation [online]. Available from URL: http://healthcare.micromedex.com [Accessed 2006 Feb 7]
  80. 80.
    Micromedex® healthcare series. Methylphenidate Drugdex® evaluation [online]. Available from URL: http://healthcare.micromedex.com [Accessed 2006 Feb 7]
  81. 81.
    Markowitz PJ, Wagner S. An open-label trial of modafinil augmentation in patients with partial response to antidepressant therapy. J Clin Psychopharmacol 2003; 23(2): 207–8CrossRefGoogle Scholar
  82. 82.
    Ross RG. Psychotic and manic-like symptoms during stimulant treatment of attention deficit hyperactivity disorder. Am J Psychiatry 2006; 163(7): 1149–52PubMedCrossRefGoogle Scholar
  83. 83.
    Koehler-Troy C, Strober M, Malenbaum R. Methylphenidate-induced mania in a prepubertal child. J Clin Psychiatry 1986; 47(11): 566–7PubMedGoogle Scholar
  84. 84.
    Vorspan F, Warot D, Consoli A, et al. Mania in a boy treated with modafinil for narcolepsy. Am J Psychiatry 2005; 162(4): 813–4PubMedCrossRefGoogle Scholar
  85. 85.
    Food and Drug Administration. Drug Safety and Risk Management Advisory Committee meeting, 9–10 February 2006: table of contents [online]. Available from URL: http://www.fda.gov/ohrms/dockets/ac/06/briefing/2006-4202_00_TOC.htm) [Accessed 2006 Apr 18]
  86. 86.
    Nissen SE. ADHD drugs and cardiovascular risk. N Engl J Med 2006; 354(14): 1445–8PubMedCrossRefGoogle Scholar
  87. 87.
    Bennett IL, Walker WE. Cardiac arrhythmias following the use of large doses of central nervous system stimulants. Am Heart J 1952; 44: 428PubMedCrossRefGoogle Scholar
  88. 88.
    Anders T, Sharfstein S. ADHD drugs and cardiovascular risk [letter]. N Engl J Med 2006; 354(21): 2296–8PubMedCrossRefGoogle Scholar

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© Adis Data Information BV 2007

Authors and Affiliations

  1. 1.Pharmacy DepartmentMaudsley HospitalLondonUK

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