Skip to main content
Log in

A Risk-Benefit Assessment of Drugs Used in the Management of Obsessive-Compulsive Disorder

  • Review Article
  • Risk-Benefit Assessment
  • Published:
Drug Safety Aims and scope Submit manuscript

Summary

Established efficacy and tolerability in large multicentre controlled studies have made serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SRIs) the mainstay of monotherapy for adult obsessive-compulsive disorder (OCD). When compared with the selective serotonin reuptake inhibitors (SSRIs), the tricyclic compound clomipramine has a higher incidence of adverse effects but is well tolerated by most OCD patients and may confer the best overall antiobsessional effects.

Consideration of specific adverse effect profiles, special patient population characteristics, drug interactions and relative cost of the various agents may direct clinicians in choosing the most appropriate first-line drug. Alternative agents as monotherapies have been explored, but none has consistently proven effective to date.

Investigations of SRI augmentation with serotonin-enhancing agents have also failed to demonstrate substantial benefits for treatment-refractory OCD. Combination treatment with SRIs and dopamine receptor antagonist drugs appears to provide an improved response for the subpopulation of OCD patients who have comorbid ‘tic-spectrum’ disorders, though large-scale studies of the efficacy and tolerability of these regimens are not yet available.

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

  1. Insel TR, Mueller EA, Alterman A, et al. Obsessive-compulsive disorder and serotonin: is there a connection? Biol Psychiatry 1985; 20: 1174–88

    PubMed  CAS  Google Scholar 

  2. Flament MF, Rapoport JL, Murphy DL, et al. Biochemical changes during clomipramine treatment of childhood obsessive-compulsive disorder. Arch Gen Psychiatry 1987; 44: 219–25

    PubMed  CAS  Google Scholar 

  3. Rasmussen SA, Eisen JL, Pato MT. Current issues in the pharmacologic management of obsessive compulsive disorder. J Clin Psychiatry 1993; 54 (6 Suppl.): 4–9

    PubMed  Google Scholar 

  4. Montgomery SA. Clomipramine in obsessional neurosis: a placebo controlled trial. Pharm Med 1980; 1: 189–92

    Google Scholar 

  5. DeVeaugh-Geiss J, Landau P, Katz R. Preliminary results from a multicenter trial of clomipramine in obsessive-compulsive disorder. Psychopharm Bull 1989; 25: 36–40

    CAS  Google Scholar 

  6. Clomipramine Collaborative Study Group. Clomipramine in the treatment of patients with obsessive-compulsive disorder. Arch Gen Psychiatry 1991; 48: 730–8

    Google Scholar 

  7. Thorén PM, Åsberg M, Cronholm B, et al. Clomipramine treatment of obsessive-compulsive disorder, I: a controlled clinical trial. Arch Gen Psychiatry 1980; 37: 1281–5

    PubMed  Google Scholar 

  8. Jaskari MO. Observations on mianserin in the treatment of obsessive neurosis. Curr Med Res Opin 1980; 6: 128–31

    Google Scholar 

  9. Ananth J, Pecknold JC, Van Den Steen N, et al. Double-blind comparative study of clomipramine and amitriptyline in obsessive neurosis. Prog Neuro-Psychopharmacol Biol Psychiatry 1981; 5: 257–62

    CAS  Google Scholar 

  10. Volavka J, Neziroglu F, Yaryura-Tobias JA. Clomipramine and imipramine in obsessive compulsive disorder. Psychiatry Res 1985; 14: 83–91

    Google Scholar 

  11. Insel TR, Murphy DL, Cohen RM, et al. Obsessive-compulsive disorder: a double-blind trial of clomipramine and clorgyline. Arch Gen Psychiatry 1983; 40: 605–12

    PubMed  CAS  Google Scholar 

  12. Zohar J, Insel TR. Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment, and pathophysiology. Biol Psychiatry 1987; 22: 667–87

    PubMed  CAS  Google Scholar 

  13. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS): part I. Development, use, and reliability. Arch Gen Psychiatry 1989; 46: 1006–11

    PubMed  CAS  Google Scholar 

  14. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown Obsessive Compulsive Scale (Y-BOCS): part II. Validity. Arch Gen Psychiatry 1989; 46: 1012–6

    PubMed  CAS  Google Scholar 

  15. Price LH, Goodman WK, Charney DS, et al. Treatment of severe obsessive-compulsive disorder with fluvoxamine. Am J Psychiatry 1987; 144: 1059–61

    PubMed  CAS  Google Scholar 

  16. Jenike MA, Hyman S, Baer L, et al. A controlled trial of fluvoxamine in obsessive-compulsive disorder: implications for a serotonergic theory. Am J Psychiatry 1990; 147: 1209–15

    PubMed  CAS  Google Scholar 

  17. Goodman WK, Price LH, Rasmussen SA, et al. Efficacy of fluvoxamine in obsessive-compulsive disorder: A double-blind comparison with placebo. Arch Gen Psychiatry 1989; 46: 36–43

    PubMed  CAS  Google Scholar 

  18. Perse TL, Greist JH, Jefferson JW, et al. Fluvoxamine treatment of obsessive compulsive disorder. Am J Psychiatry 1988; 144: 1543–8

    Google Scholar 

  19. Greist JH. Fluvoxamine in OCD: a multicenter parallel design double-blind placebo-controlled trial [poster]. 18th Collegium Internationale Neuro-Psychopharmacologicum; 1992 Jun; Nice

  20. Guy W. ECDEU Assessment Manual for Psychopharmacology. Washington, DC: National Institute of Mental Health, US Dept of Health, Education, and Welfare, 1976: 76–338

    Google Scholar 

  21. Turner SM, Jacob RG, Beidel DC, et al. Fluoxetine treatment of obsessive compulsive disorder. J Clin Psychopharmacol 1985; 5: 201–12

    Google Scholar 

  22. Pigott TA, Pato MT, Bernstein SE, et al. Controlled comparisons of clomipramine and fluoxetine in the treatment of obsessive-compulsive disorder: behavioral and biological results. Arch Gen Psychiatry 1990; 47: 926–93

    PubMed  CAS  Google Scholar 

  23. Montgomery SA, McIntyre A, Osterheider M, et al. A double-blind, placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive-compulsive disorder. Eur Neuro-psychopharmacol 1993; 3: 143–52

    CAS  Google Scholar 

  24. Tollefson GD, Rampey Jr AH, Potvin JH, et al. A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. Arch Gen Psychiatry 1994; 51: 559–67

    PubMed  CAS  Google Scholar 

  25. Koe BK, Weissman A, Welch WM, et al. Sertraline, 1S,4S-N-methyl-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-1 -napthyl-amine, a new uptake inhibitor with selectivity for serotonin. J Pharmacol Exp Ther 1983; 226: 686–700

    PubMed  CAS  Google Scholar 

  26. Jenike MA, Baer L, Summergrad P, et al. Sertraline in obsessive compulsive disorder: a double-blind comparison with placebo. Am J Psychiatry 1990; 147: 923–8

    PubMed  CAS  Google Scholar 

  27. Chouinard G, Goodman W, Greist J, et al. Results of a double-blind placebo-controlled trial of a new serotonin uptake inhibitor, sertraline, in the treatment of OCD. Psychopharmacol Bull 1990; 26: 279–84

    PubMed  CAS  Google Scholar 

  28. Greist J, Chouinard G, DuBoff E, et al. Double-blind parallel comparison of three dosages of sertraline and placebo in outpatients with obsessive-compulsive disorder. Arch Gen Psychiatry 1995; 52: 289–95

    PubMed  CAS  Google Scholar 

  29. Wheadon DE, Bushneil WD, Steiner M. A fixed-dose comparison of 20, 40, or 60mg paroxetine to placebo in the treatment of obsessive-compulsive disorder [poster]. 32nd Annual Meeting of the American College of Neuropsychopharmacology (ACNP): 1993 Dec; San Juan

  30. White K, Keck P, Lipinski J. Serotonin uptake inhibitors in OCD: a case report. Compr Psychiatry 1986; 27: 211–4

    PubMed  CAS  Google Scholar 

  31. Prasad A. A double blind study of imipramine versus zimeldine in treatment of obsessive compulsive neurosis. Pharmacopsychiatry 1984; 17: 61–2

    PubMed  CAS  Google Scholar 

  32. Kahn RS, Westenberg HGM, Jolies J. Zimeldine treatment of obsessive-compulsive disorder. Acta Psychiatr Scand 1984; 69: 259–61

    PubMed  CAS  Google Scholar 

  33. Fontaine R, Chouinard G, Iny L. An open clinical trial of zimeldine in the treatment of obsessive compulsive disorder. Curr Ther Res 1985; 37: 326–32

    Google Scholar 

  34. Fagius J, Osterman PO, Siden A, et al. Guillain-Barré syndrome following zimeldine treatment. J Neurol Neurosurg Psychiatr 1985; 48: 65–9

    PubMed  CAS  Google Scholar 

  35. US Food and Drug Administration. Prozac/fluoxetine hydrochloride safety and effectiveness for use in the treatment of obsessive-compulsive disorder. Psychopharmacologic Drugs Advisory Committee Meeting #40 on New Drug Application 20–187: 1993 Jul 20; Rockville, MD, USA

  36. Freeman CPL, Trimble MR, Deakin JFW, et al. Fluvoxamine versus clomipramine in the treatment of obsessive compulsive disorder: a multicenter, randomized double-blind, parallel group comparison. J Clin Psychiatry 1994; 55: 301–5

    PubMed  CAS  Google Scholar 

  37. Greist JH, Jefferson JW, Kobak KA, et al. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder. Arch Gen Psychiatry 1995; 52: 53–60

    PubMed  CAS  Google Scholar 

  38. Jenike MA, Baer L, Greist JH. Clomipramine versus fluoxetine in obsessive-compulsive disorder: a retrospective comparison of side effects and efficacy. J Clin Psychopharmacol 1990; 10: 122–4

    PubMed  CAS  Google Scholar 

  39. Baer L, Jenike MA. Serotonergic antidepressants and obsessive-compulsive disorder. Dr Baer and Dr Jenike reply [letter]. Am J Psychiatry 1991; 148: 1416

    Google Scholar 

  40. Piccinelli M, Pini S, Bellantuono C, et al. Efficacy of drug treatment in obsessive-compulsive disorder: A meta-analytic review. Br J Psychiatry 1995; 166: 424–43

    PubMed  CAS  Google Scholar 

  41. Rasmussen SA, Goodman WK, Greist JH, et al. Fluvoxamine in the treatment of obsessive-compulsive disorder: a multicenter double-blind placebo-controlled study in outpatients. Am J Psychiatry. In press

  42. Goodman WK, McDougle CJ, Price H. Pharmacotherapy of obsessive compulsive disorder. J Clin Psychiatry 1992; 53 (4 Suppl.): 29–37

    PubMed  Google Scholar 

  43. Boyer WF, Feighner JP. Side-effects of the selective serotonin re-uptake inhibitors. In: Feighner JP, Boyer WF, editors. Perspectives in psychiatry, volume I. Selective serotonin reuptake inhibitors. Chichester: John Wiley & Sons, 1991: 133–52

    Google Scholar 

  44. Boyer WF, Feighner JP. Pharmacokinetics and drug interactions. In: Feighner JP, Boyer WF, editors. Selective serotonin reuptake inhibitors. Chichester: John Wiley & Sons, 1991: 81–8

    Google Scholar 

  45. von Moltke LL, Greenblatt DJ, Harmatz JS, et al. Cytochromes in psychopharmacology. J Clin Psychopharmacol 1994; 14(1): 1–4

    Google Scholar 

  46. Spina E, Perucca E. Newer and older antidepressants: a comparative review of drug interactions. CNS Drugs 1994; 2(6): 479–97

    Google Scholar 

  47. von Moltke LL, Greenblatt DJ, Court MH, et al. Inhibition of alprazolam and desipramine hydroxylation in vitro by paroxetine and fluvoxamine: comparison with other selective serotonin reuptake inhibitor antidepressants. J Clin Pharmacol 1995; 15: 125–31

    Google Scholar 

  48. Perucca E, Gatti G, Cipolla G, et al. Inhibition of diazepam metabolism by fluvoxamine: a pharmacokinetic study in normal volunteers. Clin Pharmacol Ther 1994; 56: 471–6

    PubMed  CAS  Google Scholar 

  49. Kivisto KT, Neuvonen PJ, Klotz U. Inhibition of terfenadine metabolism: Pharmacokinetic and pharmacodynamic consequences. Clin Pharmacokinet 1994; 27(1): 1–5

    PubMed  CAS  Google Scholar 

  50. Gelenberg AJ. The P450 Family. Biol Ther Psychiatry Newslett 1995; 18(8): 29–31

    Google Scholar 

  51. Ereschefsky L, Riesenman C, Lam YWF. Serotonin selective reuptake inhibitor drug interactions and the cytochrome P450 system. J Clin Psychiatry 1996; 57: 1–8

    Google Scholar 

  52. Mallya GK, White K, Waternaux C, et al. Short-and long-term treatment of obsessive-compulsive disorder with fluvoxamine. Ann Clin Psychiatry 1992; 4: 77–80

    Google Scholar 

  53. Holland R, Vardy A, Block BA. Long-term use of fluvoxamine in obsessive compulsive disorder (OCD): sustained efficacy and good tolerability [poster]. 18th Collegium Internationale Neuro-Psychopharmacologicum; 1992; Nice

  54. Pato MT, Zohar-Kadouch R, Zohar J, et al. Return of symptoms after discontinuation of clomipramine in patients with obsessivecompulsive disorder. Am J Psychiatry 1988; 145: 1521–5

    PubMed  CAS  Google Scholar 

  55. Leonard HL, Swedo SE, Lenane MC, et al. A double-blind desipramine substitution during long-term clomipramine treatment in children and adolescents with obsessive-compulsive disorder. Arch Gen Psychiatry 1991; 48: 922–7

    PubMed  CAS  Google Scholar 

  56. Fontaine R, Chouinard G. Fluoxetine in the long-term maintenance treatment of obsessive-compulsive disorder. Psychiatric Ann 1989; 19: 88–91

    Google Scholar 

  57. Prien RF, Kupfer DJ. Continuation drug therapy for major depressive disorders: how long should it be maintained? Am J Psychiatry 1986; 143: 18–23

    PubMed  CAS  Google Scholar 

  58. Diamond BI, Borison RL, Katz R, et al. Rebound withdrawal reactions due to clomipramine. Psychopharmacol Bull 1989; 25: 209–12

    PubMed  CAS  Google Scholar 

  59. DeJonghe F, Swinkeis J, Tuynman-Qua H. Randomized double-blind study of fluvoxamine and maprotiline in treatment of depression. Pharmacopsychiatry 1991; 24: 21–7

    CAS  Google Scholar 

  60. Szabadi E. Fluvoxamine withdrawal syndrome [letter]. Br J Psychiatry 1992; 160: 283–4

    PubMed  CAS  Google Scholar 

  61. Pato MT, Hill JL, Murphy DL. A clomipramine dosage reduction in the course of long-term treatment of obsessive-compulsive disorder patients. Psychopharm Bull 1990; 26: 211–4

    CAS  Google Scholar 

  62. Monteiro WO, Noshirvani HF, Marks IM, et al. Anorgasmia from clomipramine in obsessive compulsive disorder. Br J Psychiatry 1987; 151: 107–12

    PubMed  CAS  Google Scholar 

  63. Drug topics red book pharmacy’s fundamental reference. Montvale. (NJ): Medical Economics Company, Inc., 1995

  64. Goodman WK, Price LH, Delgado PL, et al. Specificity of serotonin reuptake inhibitors in the treatment of obsessive compulsive disorder: comparison of fluvoxamine and desipramine. Arch Gen Psychiatry 1990; 47: 577–85

    PubMed  CAS  Google Scholar 

  65. Leonard HL, Swedo SE, Rapoport JL, et al. Treatment of obsessive-compulsive disorder with clomipramine and desipramine in children and adolescents: a double-blind crossover comparison. Arch Gen Psychiatry 1989; 46: 1088–92

    PubMed  CAS  Google Scholar 

  66. Marek GJ, McDougle CJ, Price LH, et al. A comparison of trazodone and fluoxetine: implications for a serotonergic mechanism of antidepressant action. Psychopharmacology 1992; 109: 2–11

    PubMed  CAS  Google Scholar 

  67. Haresh H, Aizenberg D, Munitz H. Trazodone in clomipramineresistant obsessive-compulsive disorder. Clin Neuropharmacol 1990; 13: 322–8

    Google Scholar 

  68. Baxter Jr LR, Thompson JM, Schwartz JM, et al. Trazodone treatment response in obsessive-compulsive disorder correlated with shifts in glucose metabolism in the caudate nuclei. Psychopathology 1987; 20 (1 Suppl.): 113–22

    Google Scholar 

  69. Kim SW. Trazodone in the treatment of obsessive-compulsive disorder: a case report. J Clin Psychopharmacol 1987; 7: 278–9

    PubMed  CAS  Google Scholar 

  70. Lydiard RB. Obsessive-compulsive disorder successfully treated with trazodone. Psychosomatics 1986; 27: 858–9

    PubMed  CAS  Google Scholar 

  71. Swerdlow NR, Andia AM. Trazodone-fluoxetine combination for treatment of obsessive-compulsive disorder [letter]. Am J Psychiatry 1989; 146: 1637

    PubMed  CAS  Google Scholar 

  72. Pigott TA, L’Heureux F, Rubenstein CS, et al. A double-blind, placebo controlled study of trazodone in patients with obsessive-compulsive disorder. J Clin Psychopharmacol 1992; 12: 156–62

    PubMed  CAS  Google Scholar 

  73. Jenike MA, Surman OS, Cassem NH, et al. Monoamine oxidase inhibitors in obsessive-compulsive disorder. J Clin Psychiatry 1983; 144: 131–2

    Google Scholar 

  74. Vallejo J, Olivares J, Marcos T, et al. Clomipramine versus phenelzine in obsessive-compulsive disorder. A controlled clinical trial. Br J Psychiatry 1992; 161: 665–70

    PubMed  CAS  Google Scholar 

  75. Altschuler M. Massive doses of trifluoperazine in the treatment of compulsive rituals. Clin Notes 1962; Oct: 367–8

    Google Scholar 

  76. O’Regan JB. Treatment of obsessive-compulsive neurosis with haloperidol. Can Med Assoc J 1970; 103: 167–8

    PubMed  Google Scholar 

  77. O’Regan JB. Treatment of obsessive compulsive neurosis [letter]. Can Med Assoc J 1970; 103: 650–1

    PubMed  Google Scholar 

  78. Rivers-Bulkeley N, Hollender MH. Successful treatment of obsessive-compulsive disorder with loxapine. Am J Psychiatry 1982; 139: 1345–6

    PubMed  CAS  Google Scholar 

  79. Trethowan WH, Scott PAL. Chlorpromazine in obsessive-compulsive and allied disorders. Lancet 1955; I: 781–5

    Google Scholar 

  80. Cassano GB, Castrogiovanni P, Mauri M, et al. A multicenter controlled trial in phobic-obsessive psychoneurosis: the effect of chlorimipramine and of its combinations with haloperidol and diazepam. Prog Neuropsychopharmacol Biol Psychiatry 1981; 5: 129–38

    CAS  Google Scholar 

  81. Young CR, Bostic JQ, McDonald CL. Clozapine and refractory obsessive-compulsive disorder: a case report. J Clin Psychopharmacol 1994; 14: 209–10

    PubMed  CAS  Google Scholar 

  82. McDougle CJ, Barr LC, Goodman WK, et al. Lack of efficacy of clozapine monotherapy in refractory obsessive compulsive disorder. Am J Psychiatry 1995; 152: 1812–4

    PubMed  CAS  Google Scholar 

  83. Bacher NM. Clonazepam treatment of obsessive compulsive disorder [letter]. J Clin Psychiatry 1990; 51: 168–9

    PubMed  CAS  Google Scholar 

  84. Bodkin JA, White K. Clonazepam in the treatment of obsessive compulsive disorder associated with panic disorder in one patient. J Clin Psychiatry 1989; 50: 265–6

    PubMed  CAS  Google Scholar 

  85. Hewlett WA, Vinogradov S, Agras WS. Clonazepam treatment of obsessions and compulsions. J Clin Psychiatry 1990; 51: 158–61

    PubMed  CAS  Google Scholar 

  86. Tollefson G. Alprazolam in the treatment of obsessive symptoms. J Clin Psychopharmacol 1985; 5(1): 39–42

    PubMed  CAS  Google Scholar 

  87. Ross DC, Piggott LR. Clonazepam for OCD [letter]. J Am Acad Child Adolesc Psychiatry 1993; 32: 470

    PubMed  CAS  Google Scholar 

  88. Cohen LS, Rosenbaum JF. Clonazepam: new uses and potential problems. J Clin Psychiatry 1987; 48 (10 Suppl.): 50–5

    PubMed  Google Scholar 

  89. Pigott TA, L’Heureux F, Rubenstein CS, et al. A controlled trial of clonazepam augmentation in OCD patients treated with clomipramine or fluoxetine [abstract no. 144]. New Research Program and Abstracts of the 145th Annual Meeting of the American Psychiatric Association: 1992 May 4; Washington, DC, 82

  90. Leonard HL, Topol D, Bukstein O, et al. Clonazepam as an augmenting agent in the treatment of childhood-onset obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1994; 33(6): 792–4

    PubMed  CAS  Google Scholar 

  91. Hewlett WA, Vinogradov S, Agras WS. Clomipramine, clonazepam, and clonidine treatment of obsessive-compulsive disorder. J Clin Psychopharmacol 1992; 12: 420–30

    PubMed  CAS  Google Scholar 

  92. Hollander E, Fay M, Cohen B, et al. Serotonergic and noradrenergic sensitivity in obsessive-compulsive disorder: behavioral findings. Am J Psychiatry 1988; 145: 1015–7

    PubMed  CAS  Google Scholar 

  93. Knesevich JW. Successful treatment of obsessive-compulsive disorder with clonidine hydrochloride. Am J Psychiatry 1982; 139: 364–5

    PubMed  CAS  Google Scholar 

  94. Jacobsen LK, Chappell P, Woolston JL. Bupropion and compulsive behavior [letter]. J Am Acad Child Adolesc Psychiatry 1994; 33: 143–4

    PubMed  CAS  Google Scholar 

  95. Spencer T, Biederman J, Steingard R, et al. Bupropion exacerbates tics in children with attention-deficit hyperactivity disorder and Tourette’s syndrome. J Am Acad Child Adolesc Psychiatry 1993; 32: 211–4

    PubMed  CAS  Google Scholar 

  96. Zajecka JM, Fawcett J, Guy C. Coexisting major depression and obsessive-compulsive disorder treated with venlafaxine [letter]. J Clin Psychopharmacol 1990; 10(2): 152–3

    PubMed  CAS  Google Scholar 

  97. Rauch SL. Open treatment of obsessive-compulsive disorder with venlafaxine: a series of ten cases [letter]. J Clin Psychopharmacol 1996; 16(1): 81–3

    PubMed  CAS  Google Scholar 

  98. Anath J, Burgoyne K, Smith M, et al. Venlafaxine for treatment of obsessive-compulsive disorder [letter]. Am J Psychiatry 1995; 152(12): 1832

    Google Scholar 

  99. Yaryura-Tobias JA, Neziroglu FA. Venlafaxine in obsessive compulsive disorder [letter]. Arch Gen Psychiatry. In press

  100. Goodman WK, Rasmussen SA, Foa E, et al. Obsessive compulsive disorder. In: Prien RF, Robinson DS, editors. Clinical evaluation of psychotropic drugs: principles and guidelines. New York: Raven Press, 1994: 431–66

    Google Scholar 

  101. Goodman WK, McDougle CJ, Barr LC, et al. Biological approaches to treatment-resistant obsessive compulsive disorder. J Clin Psychiatry 1993; 54 (6 Suppl.): 16–26

    PubMed  Google Scholar 

  102. Rasmussen SA. Lithium and tryptophan augmentation in clomipramine-resistant obsessive-compulsive disorder. Am J Psychiatry 1984; 141: 1283–5

    PubMed  CAS  Google Scholar 

  103. Mattes JA. A pilot study of combined trazodone and tryptophan in obsessive compulsive disorder. Int Clin Psychopharmacol 1986; 1: 170–3

    PubMed  CAS  Google Scholar 

  104. Hertzman PA, Blevins WL, Mayer J, et al. Association of the eosinophilia-myalgia syndrome with the ingestion of tryptophan. N Engl J Med 1990; 322: 869–73

    PubMed  CAS  Google Scholar 

  105. Judd FK, Chua P, Lynch C, et al. Fenfluramine augmentation of clomipramine treatment of obsessive compulsive disorder. Aust NZ J Psychiatry 1991; 25: 412–4

    CAS  Google Scholar 

  106. Hollander E, DeCaria CM, Schneier FR, et al. Fenfluramine augmentation of serotonin reuptake blockade antiobsessional treatment. J Clin Psychiatry 1990; 51: 119–23

    PubMed  CAS  Google Scholar 

  107. Kleven MS, Seiden LS. d-, 1-and dl-Fenfluramine cause long-lasting depletions of serotonin in rat brain. Brain Res 1989; 505: 351–3

    PubMed  CAS  Google Scholar 

  108. Price LH, Ricaurte GA, Krystal JH, et al. Neuroendocrine and mood responses to I.V. L-tryptophan in 3,4-methylenedioxymethamphetamine (MDMA) users: preliminary findings. Arch Gen Psychiatry 1989; 46: 20–2

    PubMed  CAS  Google Scholar 

  109. Clineschmidt BV, Zacchei AG, Totaro JA, et al. Fenfluramine and brain serotonin. Ann NY Acad Sci 1978; 305: 222–41

    PubMed  CAS  Google Scholar 

  110. Heninger GR, Charney DS, Sternberg DE. Lithium carbonate augmentation of antidepressant treatment: an effective prescription for treatment-refractory depression. Arch Gen Psychiatry 1983; 40: 1335–42

    PubMed  CAS  Google Scholar 

  111. Blier P, de Montigny C. Lack of efficacy of lithium augmentation in obsessive-compulsive disorder: the perspective of different regional effects of lithium on serotonin release in the central nervous system [letter]. J Clin Psychopharmacol 1992; 12: 65–6

    PubMed  CAS  Google Scholar 

  112. Stern TA, Jenike MA. Treatment of obsessive-compulsive disorder with lithium carbonate. Psychosomatics 1983; 24: 671–3

    PubMed  CAS  Google Scholar 

  113. Golden RN, Morris JE, Sack DA. Combined lithium-tricyclic treatment of obsessive-compulsive disorder. Biol Psychiatry 1988; 23: 181–5

    PubMed  CAS  Google Scholar 

  114. Feder R. Lithium augmentation of clomipramine. J Clin Psychiatry 1988; 49: 458

    PubMed  CAS  Google Scholar 

  115. Ruegg RG, Evans DL, Comer WS, et al. Lithium plus fluoxetine treatment of obsessive compulsive disorder [New Research Abstract no.92]. American Psychiatric Association 143rd Annual Meeting; 1990; New York: 81

  116. Pigott TA, Pato MT, L’Heureux F, et al. A controlled comparison of adjuvant lithium carbonate or thyroid hormone in clomipramine-treated patients with obsessive-compulsive disorder. J Clin Psychopharmacol 1991; 11: 242–8

    PubMed  CAS  Google Scholar 

  117. McDougle CJ, Price LH, Goodman WK, et al. A controlled trial of lithium augmentation in fluvoxamine-refractory obsessive compulsive disorder: lack of efficacy. J Clin Psychopharmacol 1991; 11: 175–84

    PubMed  CAS  Google Scholar 

  118. Jenike MA, Baer L. An open trial of buspirone in obsessive-compulsive disorder. Am J Psychiatry 1988; 145: 1285–6

    PubMed  CAS  Google Scholar 

  119. Pato MT, Pigott TA, Hill JL, et al. Controlled comparison of buspirone and clomipramine in obsessive-compulsive disorder. Am J Psychiatry 1991; 148: 127–9

    PubMed  CAS  Google Scholar 

  120. Markovitz PJ, Stagno SJ, Calabrese JR. Buspirone augmentation of fluoxetine in obsessive-compulsive disorder. Am J Psychiatry 1990; 147: 798–800

    PubMed  CAS  Google Scholar 

  121. Jenike MA, Baer L, Buttolph L. Buspirone augmentation of fluoxetine in patients with obsessive compulsive disorder. J Clin Psychiatry 1991; 52: 13–4

    PubMed  CAS  Google Scholar 

  122. Pigott TA, L’Heureux F, Hill JL, et al. A double-blind study of adjuvant buspirone hydrochloride in clomipramine-treated patients with obsessive-compulsive disorder. J Clin Psychopharmacol 1992; 12: 11–8

    PubMed  CAS  Google Scholar 

  123. McDougle CJ, Goodman WK, Leckman JF, et al. Limited therapeutic effect of addition of buspirone in fluvoxamine-refractory obsessive compulsive disorder. Am J Psychiatry 1993; 150: 647–9

    PubMed  CAS  Google Scholar 

  124. Grady TA, Pigott TA, L’Heureux F, et al. Double-blind study of adjuvant buspirone for fluoxetine-treated patients with obsessive-compulsive disorder. Am J Psychiatry 1993; 150: 819–21

    PubMed  CAS  Google Scholar 

  125. Crespi F, Martin KF, Marsden CA. Simultaneous in vivo voltametric measurement of striatal extracellular DOPAC and 5-HIAA levels: effect of electrical stimulation of dopamine and 5-HT neuronal pathways. Neurosci Lett 1988; 90: 285–91

    PubMed  CAS  Google Scholar 

  126. Eilam D, Golani I, Szechtman H. D2-agonist quinpirole induces perseveration of routes and hyperactivity but no perseveration of movements. Brain Res 1989; 490: 255–67

    PubMed  CAS  Google Scholar 

  127. Pauls DL, Leckman JF. The inheritance of Gilles de la Tourette’s syndrome and associated behaviors: Evidence for autosomal dominant transmission. N Engl J Med 1986; 315: 993–7

    PubMed  CAS  Google Scholar 

  128. Pauls DL, Towbin KE, Leckman JF, et al. Gilles de la Tourette’s syndrome and obsessive-compulsive disorder. Arch Gen Psychiatry 1986; 43: 1180–2

    PubMed  CAS  Google Scholar 

  129. Goodman WK, McDougle CJ, Price LH, et al. Beyond the serotonin hypothesis: a role for dopamine in some forms of obsessive compulsive disorder? J Clin Psychiatry 1990; 51: 36–43

    PubMed  Google Scholar 

  130. McDougle CJ, Goodman WK, Price LH. Dopamine antagonists in tic-related and psychotic spectrum OCD. J Clin Psychiatry 1994; 55 (3 Suppl.): 24–31

    PubMed  Google Scholar 

  131. Butler IJ, Koslow SH, Seifert Jr WE, et al. Biogenic amine metabolism in Tourette syndrome. Ann Neurol 1979; 6: 37–9

    PubMed  CAS  Google Scholar 

  132. Cohen DJ, Shaywitz BA, Young JG, et al. Central biogenic amine metabolism in children with the syndrome of chronic multiple tics of Gilles de la Tourette: Norepinephrine, serotonin, and dopamine. J Am Acad Child Psychiatry 1979; 18: 320–41

    PubMed  CAS  Google Scholar 

  133. Malison RT, McDougle CJ, van Dyck CH, et al. [123I]B-CIT SPECT imaging demonstrates increased striatal dopamine transporter binding in Tourette’s syndrome. Am J Psychiatry 1995; 152: 1359–61

    PubMed  CAS  Google Scholar 

  134. McDougle CJ, Goodman WK, Leckman JF, et al. The efficacy of fluvoxamine in obsessive-compulsive disorder: effects of comorbid chronic tic disorder. J Clin Psychopharmacol 1993; 13: 354–8

    PubMed  CAS  Google Scholar 

  135. Riddle MA, Leckman JF, Hardin MT, et al. Fluoxetine treatment of obsessions and compulsions in patients with Tourette’s syndrome. Am J Psychiatry 1988; 145: 1173–4

    PubMed  CAS  Google Scholar 

  136. Delgado PL, Goodman WK, Price LH, et al. Fluvoxamine/ pimozide treatment of concurrent Tourette’s and obsessive compulsive disorder. Br J Psychiatry 1990; 157: 762–5

    PubMed  CAS  Google Scholar 

  137. McDougle CJ, Goodman WK, Price LH, et al. Neuroleptic addition in fluvoxamine-refractory obsessive-compulsive disorder. Am J Psychiatry 1990; 147: 652–4

    PubMed  CAS  Google Scholar 

  138. McDougle CJ, Goodman WK, Leckman JF, et al. Haloperidol addition in fluvoxamine-refractory obsessive compulsive disorder: a double-blind, placebo-controlled study in patients with and without tics. Arch Gen Psychiatry 1994; 51: 302–8

    PubMed  CAS  Google Scholar 

  139. McDougle CJ, Fleischmann RL, Epperson CN, et al. Risperidone addition in fluvoxamine-refractory obsessive compulsive disorder: three cases. J Clin Psychiatry 1995; 56: 526–8

    PubMed  CAS  Google Scholar 

  140. Rasmussen SA, Tsuang MT. Clinical characteristics and family history in DSM-III obsessive-compulsive disorder. Am J Psychiatry 1986; 143: 317–22

    PubMed  CAS  Google Scholar 

  141. Baer L, Jenike MA, Black DW, et al. Effect of Axis II diagnoses on treatment outcome with clomipramine in 55 patients with obsessive compulsive disorder. Arch Gen Psychiatry 1992; 49: 862–6

    PubMed  CAS  Google Scholar 

  142. Jenike MA, Baer L, Minichiello WE, et al. Concomitant obsessive-compulsive disorder and schizotypal personality disorder. Am J Psychiatry 1986; 143: 530–2

    PubMed  CAS  Google Scholar 

  143. Rapoport JL, Swedo SE, Leonard HL. Childhood obsessive-compulsive disorder. J Clin Psychiatry 1992; 53: 11–6

    PubMed  Google Scholar 

  144. Flament M, Rapoport JL. Childhood obsessive-compulsive disorder. In: Insel TR. New findings in obsessive-compulsive disorder. Washington, DC: American Psychiatric Press, 1984: 24–43

    Google Scholar 

  145. Flament MF, Rapoport JL, Berg CJ, et al. Clomipramine treatment of childhood obsessive compulsive disorder: a double-blind controlled study. Arch Gen Psychiatry 1985; 42: 977–83

    PubMed  CAS  Google Scholar 

  146. DeVeaugh-Geiss J, Moroz G, Biederman J, et al. Clomipramine hydrochloride in childhood and adolescent obsessive-compulsive disorder: a multicenter trial. J Am Acad Child Adolesc Psychiatry 1992; 31(2): 45–9

    PubMed  CAS  Google Scholar 

  147. Riddle MA, Geller B, Ryan N. Another sudden death in a child treated with desipramine. J Am Acad Child Adolesc Psychiatry 1993; 32(4): 792–7

    PubMed  CAS  Google Scholar 

  148. Leonard HL, Meyer MC, Swedo SE et al. Electrocardiographic changes during desipramine and clomipramine treatment in children and adolescents. J Am Acad Child Adolesc Psychiatry 1995; 34(11): 1460–8

    PubMed  CAS  Google Scholar 

  149. Oesterhelp J. TCA cardiotoxicity: the latest [letter]. J Am Acad Child Adolesc Psychiatry 1996; 35(6): 701–2

    Google Scholar 

  150. Riddle MA, Scahill L, King RA, et al. Double-blind, crossover trial of fluoxetine and placebo in children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1992; 31: 1062–9

    PubMed  CAS  Google Scholar 

  151. Riddle MA, Hardin MT, King R, et al. Fluoxetine treatment of children and adolescents with Tourette’s and obsessive compulsive disorders: preliminary clinical experience. J Am Acad Child Adolesc Psychiatry 1990; 29: 45–8

    PubMed  CAS  Google Scholar 

  152. Liebowitz MR, Hollander E, Fairbanks J, et al. Fluoxetine for adolescents with obsessive compulsive disorder. Am J Psychiatry 1990; 147: 370–1

    PubMed  CAS  Google Scholar 

  153. Como PG, Kurlan R. An open-label trial of fluoxetine for obsessive-compulsive disorders in Gilles de la Tourette’s syndrome. Neurology 1991; 41: 872–4

    PubMed  CAS  Google Scholar 

  154. Rapoport JL, Leonard HL, Swedo E, et al. Obsessive compulsive disorder in children and adolescents: Issues in Management. J Clin Psychiatry 1993; 54 (6 Suppl.): 27–9

    PubMed  Google Scholar 

  155. Geller DA, Biederman J, Reed ED, et al. Similarities in response to fluoxetine in the treatment of children and adolescents with obsessive-compulsive disorder. J Am Acad Child Adolesc Psychiatry 1995; 34(1): 36–44

    PubMed  CAS  Google Scholar 

  156. Apter A, Ratzoni G, King RA, et al. Fluvoxamine open-label treatment of adolescent inpatients with obsessive-compulsive disorder or depression. J Am Acad Child Adolesc 1994; 33(3): 342–8

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Christopher J. McDougle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carpenter, L.L., McDougle, C.J., Epperson, C.N. et al. A Risk-Benefit Assessment of Drugs Used in the Management of Obsessive-Compulsive Disorder. Drug-Safety 15, 116–134 (1996). https://doi.org/10.2165/00002018-199615020-00004

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00002018-199615020-00004

Keywords

Navigation