Drug Safety

, Volume 12, Issue 2, pp 146–153 | Cite as

Drug-Induced Mania

  • Malcolm Peet
  • Steve Peters
Review Article Pharmacoepidemiology


Mania can occur by chance association during drug treatment, particularly in patients predisposed to mood disorder. Single case reports are unreliable, and evidence must be sought from large series of treated patients, particularly those with a matched control group. Drugs with a definite propensity to cause manic symptoms include levodopa, corticosteroids and anabolic-androgenic steroids. Antidepressants of the tricyclic and monoamine oxidase inhibitor classes can induce mania in patients with pre-exisdng bipolar affective disorder. Drugs which are probably capable of inducing mania, but for which the evidence is less scientifically secure, include other dopaminergic anti-Parkinsonian drugs, thyroxine, iproniazid and isoniazid, sympathomimetic drugs, chloroquine, baclofen, alprazolam, captopril, amphetamine and phencyclidine. Other drugs may induce mania rarely and idiosyncratically.

Management involves discontinuation or dosage reduction of the suspected drug, if this is medically possible, and treatment of manic symptoms with anti-psychotic drugs or lithium.


Levodopa Mood Disorder Baclofen Manic Symptom Bipolar Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994: 317–91Google Scholar
  2. 2.
    Leff JP, Fischer M, Bertelsen A. A cross-national epidemiological study of mania. Br J Psychiatry 1976; 129: 428–42PubMedCrossRefGoogle Scholar
  3. 3.
    Sultzer DL, Cummings JL. Drug-induced mania-causative agents, clinical and characteristics and management. Med Toxicol Adverse Drug React 1989; 4: 127–43Google Scholar
  4. 4.
    Krauthammer C, Klerman GL. Secondary mania. Arch Gen Psychiatry 1978; 35: 1333–9PubMedCrossRefGoogle Scholar
  5. 5.
    Cotzias GC, van Woert MH, Schiffer LM. Aromatic amino acids and modification of Parkinsonism. N Engl J Med 1967; 276: 374PubMedCrossRefGoogle Scholar
  6. 6.
    Goodwin FK. Psychiatric side-effects of levodopa in man. JAMA 1971; 218: 1915–20PubMedCrossRefGoogle Scholar
  7. 7.
    Presthus J, Holmsen R. Appraisal of long-term levodopa treatment of parkinsonism with special reference to therapy-limiting factors. Acta Neurol Scand 1974; 50: 774–90PubMedCrossRefGoogle Scholar
  8. 8.
    Lin JT-Y, Zeigler D. Psychiatric symptoms with initiation of carbidopa-levodopa treatment. Neurology 1976; 26: 679–700CrossRefGoogle Scholar
  9. 9.
    Harsch HH, Miller M, Young LD. Induction of mania by 1-dopa in a nonbipolar patient. J Clin Psychopharmacol 1985; 5: 338–9PubMedGoogle Scholar
  10. 10.
    Mindham RHS. Psychiatric symptoms in Parkinsonism. J Neurol Neurosurg Psychiatry 1970; 33: 188–91PubMedCrossRefGoogle Scholar
  11. 11.
    Mindham RHS. Psychiatric aspects of Parkinson’s disease. Br J Hosp Med 1974; 11: 411–4Google Scholar
  12. 12.
    Van Woert MH, Ambani LM, Weintraub MI. Manic behaviour and levodopa. N Engl J Med 1971; 285: 1326CrossRefGoogle Scholar
  13. 13.
    Murphy DL, Brodie HKH, Goodwin FK, et al. Regular induction of hypomania by 1-dopa in bipolar manic-depressive patients. Nature 1971; 229: 135–6PubMedCrossRefGoogle Scholar
  14. 14.
    Jouvent R, Abensour P, Bonnet AM, et al. Antiparkinsonian and antidepressant effects of high doses of bromocriptine. J Affect Disord 1983; 5: 141–5PubMedCrossRefGoogle Scholar
  15. 15.
    Turner TH, Cookson JC, Wass JAH, et al. Psychotic reactions during treatment of pituitary tumours with dopamine agonists. BMJ 1984; 289: 1101–3PubMedCrossRefGoogle Scholar
  16. 16.
    Brook NM, Cookson IB. Bromocriptine-induced mania? BMJ 1978; 1: 790PubMedCrossRefGoogle Scholar
  17. 17.
    Vlissides DN, Gill D, Castelow J. Bromocriptine-induced mania? BMJ 1978; 1: 510PubMedCrossRefGoogle Scholar
  18. 18.
    Lake CR, Reid A, Martin C, et al. Cyclothymic disorder and bromocriptine: predisposing factors for postpartum mania? Can J Psychiatry 1987; 32: 693–4PubMedGoogle Scholar
  19. 19.
    Menza MA, Cölbe LI. Hypomania in a patient receiving deprenyl (selegiline) after adrenal-striatal transplantation of Parkinson’s disease. Clin Neuropharmacol 1988; 11: 549–50PubMedCrossRefGoogle Scholar
  20. 20.
    Kurlan R, Dimitsopoulos T. Selegiline and manic behaviour in Parkinson’s disease. Arch Neurol 1992; 49: 1231PubMedCrossRefGoogle Scholar
  21. 21.
    Suchowersky O, de Vries JD. Interaction of fluoxetine and selegiline. Can J Psychiatry 1990; 35: 571–2PubMedGoogle Scholar
  22. 22.
    Przedborski S, Liard A, Hildebrand J. Induction of mania by apomorphine in a depressed Parkinsonian patient. Mov Disord 1992; 7: 285–6PubMedCrossRefGoogle Scholar
  23. 23.
    Pearlman CA. Manic behaviour and levodopa. N Engl J Med 1971; 285: 1326PubMedCrossRefGoogle Scholar
  24. 24.
    Ryback RS, Schwab RS. Manic behaviour and levodopa. N Engl J Med 1971; 285: 788–9PubMedCrossRefGoogle Scholar
  25. 25.
    Jeffcoate WJ, Silverstone JT, Edwards CRW, et al. Psychiatric manifestations of Cushing’s syndrome: response to lowering of plasma cortisol. Q J Med 1979; 191: 465–72Google Scholar
  26. 26.
    Hall RCW, Popkin MK, Stickney SK, et al. Presentation of the steroid psychoses. J Nerv Ment Dis 1979; 167: 229–36PubMedCrossRefGoogle Scholar
  27. 27.
    Sergent JS, Lockshin MD, Klempner MS, et al. Central nervous system disease in systemic lupus erythematosus. Am J Med 1975; 58: 644–54PubMedCrossRefGoogle Scholar
  28. 28.
    Lewis DA, Smith RE. Steroid-induced psychiatric syndromes. J Affect Disord 1983; 5: 319–32PubMedCrossRefGoogle Scholar
  29. 29.
    Cade R, Spooner G, Schlein E, et al. Comparison of azathio-prine, prednisone and heparin alone or together in treating lupus nephritis. Nephron 1973; 10: 37–56PubMedCrossRefGoogle Scholar
  30. 30.
    Marx FW, Barker WF. Surgical results in patients with ulcerative colitis treated with and without corticosteroids. Am J Surg 1967; 113: 157–63PubMedCrossRefGoogle Scholar
  31. 31.
    Boston Collaborative Drug Surveillance Programme. Acute adverse reactions to prednisone in relation to dosage. Clin Pharmacol Ther 1972; 13: 694–8Google Scholar
  32. 32.
    Sharfstein SS, Sack DS, Fauci AS. Relationship between alternate-day corticosteroid therapy and behavioural abnormalities. JAMA 1982; 248: 2987–9PubMedCrossRefGoogle Scholar
  33. 33.
    Falk WE, Mahnke MW, Poskanzer DC. Lithium prophylaxis of corticotropin-induced psychosis. JAMA 1979; 242: 1011–2CrossRefGoogle Scholar
  34. 34.
    Minden SL, Orav J, Schildkraut JJ. Hypomanic reactions to ACTH and prednisone treatment for multiple sclerosis. Neurology 1988; 38: 1631–4PubMedCrossRefGoogle Scholar
  35. 35.
    Glaser GH. Psychotic reactions induced by corticotrophin (ACTH) and cortisone. Psychosom Med 1953; 15: 280–91PubMedGoogle Scholar
  36. 36.
    Phelan MC. Beclomethasone mania. Br J Psychiatry 1989; 155: 871–2PubMedCrossRefGoogle Scholar
  37. 37.
    Ling MHM, Perry PJ, Tsnang MT. Side effects of corticosteroid therapy — psychiatric aspects. Arch Gen Psychiatry 1981; 38: 471–7PubMedCrossRefGoogle Scholar
  38. 38.
    Griggs RC, Pandya S, Florence JM, et al. Randomised controlled trial of testosterone in myotonic dystrophy. Arch Gen Psychiatry 1989; 39: 375–82Google Scholar
  39. 39.
    Su TP, Pagliaro M, Ollo C, et al. Neuropsychiatric effects of anabolic steroids. JAMA 1993; 269: 2760–4PubMedCrossRefGoogle Scholar
  40. 40.
    Pope HG, Katz DL. Psychiatric and medical effects of anabolicandrogenic steroid use. Arch Gen Psychiatry 1994; 51: 375–82PubMedCrossRefGoogle Scholar
  41. 41.
    Bahrke MS, Wright JE, Strauss RH, et al. Psychological moods and subjectively perceived behavioural and somatic changes accompanying anabolic-androgenic steroid use. Am J Sports Med 1992; 20: 717–24PubMedCrossRefGoogle Scholar
  42. 42.
    Ball JRB, Kiloh LG. A controlled trial of imipramine in treatment of depressive states. BMJ 1959; 2: 1052–5PubMedCrossRefGoogle Scholar
  43. 43.
    Bunney WE. Psychopharmacology of the switch process in affective illness. In: Lipton MA, Kellam KF, editor. Psychopharmacology: a generation of progress. New York: Raven Press, 1978: 1249–59Google Scholar
  44. 44.
    Lewis JL, Winokur G. The induction of mania: a natural history study with controls. Arch Gen Psychiatry 1982; 39: 303–6PubMedCrossRefGoogle Scholar
  45. 45.
    Wehr TA, Goodwin FK. Can antidepressants cause mania and worsen the course of affective illness? Am J Psychiatry 1987; 144: 1403–11PubMedGoogle Scholar
  46. 46.
    Angst J, Angst K, Baruffol I, et al. ECT-induced and drug-induced hypomania. Convulsive Ther 1992; 8: 179–85Google Scholar
  47. 47.
    Peet M. Induction of mania with selective serotonin reuptake inhibitors and tricyclic antidepressants. Br J Psychiatry 1994; 164: 549–50PubMedCrossRefGoogle Scholar
  48. 48.
    Settle EC, Settle GP. Acase of mania associated with fluoxetine. Am J Psychiatry 1984; 141: 280–1PubMedGoogle Scholar
  49. 49.
    Lebuegue B. Mania precipitated by fluoxetine. Am J Psychiatry 1987; 144: 1620Google Scholar
  50. 50.
    Nakra BRS, Szwabo P, Grossberg GT. Mania induced by fluoxetine. Am J Psychiatry 1989; 146: 1515–6PubMedGoogle Scholar
  51. 51.
    Montgomery SA, Roberts A. SSRIs: well tolerated treatment for depression. Hum Psychopharmacol 1994; 9: S7–S10CrossRefGoogle Scholar
  52. 52.
    Jabeen S, Fischer CJ. Trazodone-induced transient hypomanic symptoms and their management. Br J Psychiatry 1991; 158: 275–8PubMedCrossRefGoogle Scholar
  53. 53.
    Terao T. Comparison of manic switch onset during fluoxetine and trazodone treatment. Biol Psychiatry 1993; 33: 477–8PubMedCrossRefGoogle Scholar
  54. 54.
    Fogelson DL, Bystritsky A, Pasnau R. Bupropion in the treatment of bipolar disorders: the same old story? J Clin Psychiatry 1992; 53: 443–6PubMedGoogle Scholar
  55. 55.
    Masand P, Stern TA. Bupropion and secondary mania: is there a relationship? Ann Clin Psychiatry 1993; 5: 271–4PubMedCrossRefGoogle Scholar
  56. 56.
    Mirin SM, Schatzberg AF, Creasey DE. Hypomania and mania after withdrawal of tricyclic antidepressants. Am J Psychiatry 1981; 138: 87–9PubMedGoogle Scholar
  57. 57.
    McGrath PJ, Stewart JW, Tricamo E, et al. Paradoxical shifts to euthymia or hypomania upon withdrawal of antidepressant drugs. J Clin Psychopharmacol 1993; 13: 224–5PubMedGoogle Scholar
  58. 58.
    Mander AJ, Loudon JB. Rapid recurrence of mania following abrupt discontinuation of lithium. Lancet 1988; 2: 15–7PubMedCrossRefGoogle Scholar
  59. 59.
    Suppes T, Baldessarini RJ, Faedda GL, et al. Risk of recurrence following discontinuation of lithium treatment in bipolar disorder. Arch Gen Psychiatry 1991; 48: 1082–8PubMedCrossRefGoogle Scholar
  60. 60.
    Faedda GL, Tondo L, Baldessarini RJ, et al. Outcome after rapid vs gradual discontinuation of lithium treatment in bipolar disorders. Arch Gen Psychiatry 1993; 50: 448–55PubMedCrossRefGoogle Scholar
  61. 61.
    Quitkin FM, Kane J, Rifkin A, et al. Prophylactic lithium carbonate with and without imipramine for bipolar patients: a double-blind study. Arch Gen Psychiatry 1981; 38: 902–7PubMedCrossRefGoogle Scholar
  62. 62.
    Prien RF, Kupfer DJ, Mansky PA, et al. Arch Gen Psychiatry 1984; 41: 1096–104PubMedCrossRefGoogle Scholar
  63. 63.
    Akhtar S, Mukherjee S. Chloroquine induced mania. Int J Psychiatry Med 1993; 23: 349–56PubMedCrossRefGoogle Scholar
  64. 64.
    Bhatia MS, Singhal PK, Dhar NK. Psychiatric complications of chloroquine. Ann Nat Acad Med Sci (India) 1988; 24: 223–8Google Scholar
  65. 65.
    Lovestone S. Chloroquine-induced mania. Br J Psychiatry 1991; 159: 164–5PubMedCrossRefGoogle Scholar
  66. 66.
    Josephson AM, Mackenzie TB. Thyroid-induced mania in hypothyroid patients. Br J Psychiatry 1980; 137: 222–8PubMedCrossRefGoogle Scholar
  67. 67.
    Evans DL, Strawn SK, Haggerty JJ, et al. Appearance of mania in drug-resistant bipolar depressed patients after treatment with 1-triiodothyronine. J Clin Psychiatry 1986; 47: 521–2PubMedGoogle Scholar
  68. 68.
    Bloch RC, Dooneief AS, Buchberg AS, et al. The clinical effects of isoniazid and iproniazid in the treatment of pulmonary tuberculosis. Ann Intern Med 1954; 40: 881–900PubMedGoogle Scholar
  69. 69.
    Crane GE. The psychiatric side-effects of iproniazid. Am J Psychiatry 1956; 112: 494–501PubMedGoogle Scholar
  70. 70.
    Wood KA. Nasal decongestant and psychiatric disturbance. Br J Psychiatry 1994; 164: 566–7PubMedCrossRefGoogle Scholar
  71. 71.
    Lake CR. Manic psychosis after coffee and phenylpropanolamine. Biol Psychiatry 1991; 30: 401–4PubMedCrossRefGoogle Scholar
  72. 72.
    Lake CR, Gallant S, Masson E, et al. Adverse drug effects attributed to phenylpropanolamine: a review of 142 case reports. Am J Med 1990; 89: 195–208PubMedCrossRefGoogle Scholar
  73. 73.
    Lake CR, Tenglin R, Chernow B, et al. Psychomotor stimulant-induced mania in a genetically predisposed patient a review of the literature and report of a case. J Clin Psychopharmacol 1983; 3: 97–100PubMedGoogle Scholar
  74. 74.
    Roxanas MG, Spalding J. Ephedrine abuse psychosis. Med J Aust 1977; 2: 639–40PubMedGoogle Scholar
  75. 75.
    Waters BG, Lapierre YD. Secondary mania associated with sympathomimetic drug use. Am J Psychiatry 1981; 138: 837–8PubMedGoogle Scholar
  76. 76.
    Jones RF, Lance JW. Baclofen in the long-term management of spasticity. Med J Aust 1976; 1: 654–7PubMedGoogle Scholar
  77. 77.
    Wolf ME, Almy G, Toll M, et al. Mania associated with the use of baclofen. Biol Psychiatry 1982; 17: 757–9PubMedGoogle Scholar
  78. 78.
    Yassa RY, Iskandar HL. Baclofen-induced psychosis: two cases and a review. J Clin Psychiatry 1988; 49: 318–20PubMedGoogle Scholar
  79. 79.
    Stewart JT. A case of mania associated with high-dose baclofen therapy. J Clin Psychopharmacol 1992; 12: 215–7PubMedCrossRefGoogle Scholar
  80. 80.
    Arnold ES, Rudd SM, Kirshner H. Manic psychosis following rapid withdrawal from baclofen. Am J Psychiatry 1980; 137: 1466–7PubMedGoogle Scholar
  81. 81.
    Rottanburg D, Ben-Arie O, Robins AH, et al. Cannabis-associated psychosis with hypomanic features. Lancet 1982; 2: 1364–6PubMedCrossRefGoogle Scholar
  82. 82.
    McGuire P, Jones P, Murray R. Psychiatric symptoms in cannabis users. Br J Psychiatry 1993; 163: 698PubMedCrossRefGoogle Scholar
  83. 83.
    Thomas H. Psychiatric symptoms in cannabis users. Br J Psychiatry 1993; 163: 141–9PubMedCrossRefGoogle Scholar
  84. 84.
    Jacobs D, Silverstone T. Dextroamphetamine induced arousal in human subjects as a model for mania. Psychol Med 1986; 16: 323–9PubMedCrossRefGoogle Scholar
  85. 85.
    Gerner RM, Post RM, Bunney WE. A dopaminergic mechanism in mania. Am J Psychiatry 1976; 113: 1177–80Google Scholar
  86. 86.
    Van Kammen DP, Murphy DL. Attenuation of the euphoriant effect and activating effects of d- and d-amphetamine by lithium carbonate treatment. Psychopharmacology 1975; 44: 215–24CrossRefGoogle Scholar
  87. 87.
    Slavney PR, Rich GB, Pearlson GD, et al. Phencyclidine abuse and symptomatic mania. Biol Psychiatry 1977; 12: 697–9PubMedGoogle Scholar
  88. 88.
    Rosen A. Case report: symptomatic mania and phencyclidine abuse. Am J Psychiatry 1979; 136: 118–9PubMedGoogle Scholar
  89. 89.
    Cole JO, Kando JC. Adverse behavioural events reported in patients taking alprazolam and other benzodiazepines. J Clin Psychiatry 1993; 54 Suppl.: 49–61PubMedGoogle Scholar
  90. 90.
    Gajula RP, Berlin RM. Captopril-induced mania. Am J Psychiatry 1993; 150: 1429–30PubMedGoogle Scholar
  91. 91.
    Patten SB, Brager N, Sander S. Manic symptoms associated with the use of captopril. Can J Psychiatry 1991; 36: 314–5PubMedGoogle Scholar
  92. 92.
    McMahon T. Bipolar affective symptoms associated with use of captopril and abrupt withdrawal of pargyline and propranolol. Am J Psychiatry 1985; 142: 759–60PubMedGoogle Scholar
  93. 93.
    Post RM. Effectiveness of carbamazepine in the treatment of bipolar affective disorder. In: McElroy SL, Pope HG. editors. Use of anticonvulsants in psychiatry. Clifton, NJ: Oxford Health Care, 1988: 1–24Google Scholar

Copyright information

© Adis International Limited 1995

Authors and Affiliations

  • Malcolm Peet
    • 1
  • Steve Peters
    • 1
  1. 1.The University Department of PsychiatryNorthern General HospitalSheffieldEngland

Personalised recommendations