Advertisement

CNS Drugs

, Volume 7, Issue 6, pp 480–500 | Cite as

Sertraline

An Overview of its Pharmacological Properties and a Review of its Therapeutic Efficacy in Obsessive-Compulsive Disorder
Adis Drug Evaluation

Abstract

Synopsis

Sertraline, a selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) which was initially developed as an antidepressant, has also been shown to be an effective treatment for patients with obsessive-compulsive disorder (OCD).

Results of short and long term (≤ 2 years) clinical trials have shown that sertraline is an effective treatment for nondepressed adult and paediatric patients with OCD. In several placebo-controlled clinical trials conducted in patients with OCD, sertraline 50 to 200 mg/day produced significantly greater improvements than placebo on Yale-Brown Obsessive-Compulsive Scale and Clinical Global Impression Severity Scale and on various other OCD assessment scales. The efficacy of sertraline in OCD has not yet been directly compared with that of the SSRIs fluvoxamine, fluoxetine or paroxetine. However, findings of a single comparative trial indicate that sertraline is at least as effective as, and is better tolerated than, the tricyclic antidepressant (TCA) clomipramine in adults.

Sertraline, like other SSRIs, is generally well tolerated. It is not associated with the anticholinergic, sedative and cardiovascular adverse effects that are characteristic of the TCAs. Headache, insomnia, nausea and diarrhoea were reported as the most common adverse events in sertraline recipients who participated in a 12-week placebo-controlled trial; the incidences of these events (except headache) decreased in patients who received sertraline treatment in a 40-week extension of this trial. Like other SSRIs, sertraline has been reported to cause sexual dysfunction in some patients.

Because sertraline has a plasma elimination half-life of 25 to 26 hours, once-daily administration is sufficient to ensure adequate plasma sertraline concentrations are achieved in patients with normal renal function. The favourable drug interaction profile of sertraline as compared with other SSRIs used to treat OCD has been partly explained by its weak inhibitory effects on some hepatic cytochrome P450 isoenzymes.

In conclusion, sertraline is an effective primary treatment option for adults, adolescents and children with OCD and has broadened the range of available agents for this often disabling condition. In addition, it is better tolerated than clomipramine and thus may be preferred for the treatment of specific patient groups, particularly those susceptible to the adverse effects of TCAs.

Pharmacodynamic Properties

Sertraline, a naphthylamine derivative, is one of several selective serotonin (5-hydroxytryptamine; 5—HT) reuptake inhibitors (SSRIs) that have demonstrated efficacy in the treatment of obsessive-compulsive disorder (OCD). The cause of OCD has not yet been conclusively established, but a dysregulation of serotonergic functioning appears to be involved.

Sertraline is a potent and highly selective inhibitor of serotonin reuptake. The resultant effect is an increase in synaptic serotonin levels, enhanced serotonergic activity and subsequent downregulation of serotonergic subsystems. Although sertraline produces only minor inhibition of noradrenaline (norepinephrine) reuptake, biogenic amines other than serotonin may also be involved in mediating its therapeutic activity.

CNS σ1-receptors have been implicated in the pharmacological activity of sertraline and it has also been suggested that the drug may exert clinical effects via γ-aminobutyric acid neuronal pathways. Sertraline shows no marked affinity for 5-HT1A, 5-HT1B, 5-HT2, histamine H1, muscarinic or dopamine D2 receptors, or α1-, α2- or β-adrenoceptors in vitro.

Increased vigilance has been observed in healthy volunteers after single 100 to 400mg doses of the drug. Sertraline was also associated with improved cognitive performance and alertness in healthy volunteers aged 50 to 67 years.

Pharmacokinetic Properties

The pharmacokinetics of sertraline appear to be broadly similar in male and female healthy adults, in elderly individuals aged ≥65 years and in children and adolescents. Sertraline has a linear pharmacokinetic profile after single or multiple oral doses of 50 to 200mg. It is slowly absorbed after oral administration and steady-state plasma concentrations are reached approximately 1 week after treatment initiation. The volume of distribution of sertraline (<20 L/kg) indicates that it is extensively distributed in body tissues.

After absorption, sertraline undergoes substantial first-pass metabolism in the liver. Its primary metabolite is demethyl-sertraline, which subsequently undergoes oxidative deamination to produce conjugated and unconjugated metabolites. The metabolites of sertraline have been shown to have virtually no effects on serotonin reuptake. Sertraline is eliminated in approximately equal amounts in the urine and faeces. As the plasma elimination half-life of the drug is 25 to 26 hours, it is administered on a once-daily basis.

The pharmacokinetics of sertraline (administered as single or multiple oral doses) are not significantly altered in patients with mild, moderate or severe renal impairment, although clearance may be reduced in patients with end-stage renal disease. Because sertraline is metabolised in the liver, its clearance is reduced in patients with hepatic disease.

The favourable drug interaction profile of sertraline has been partly explained by its weak inhibitory effect on the hepatic cytochrome P450 (CYP) isoenzymes CYP2D6, CYP3A3/4, CYP2C19, CYP2C9/10 and CYP1A2. In contrast, the SSRIs fluoxetine and paroxetine have substantial inhibitory effects on CYP2D6, and fluvoxamine has marked inhibitory effects on CYP1A2 and CYP2C19. Thus, these SSRIs have a greater propensity than sertraline to interact with drugs metabolised by these enzymes. As sertraline is highly plasma protein bound, it has the potential to interact with other highly protein bound drugs. However, no reports of such interactions have yet been published.

Therapeutic Efficacy

Several placebo-controlled trials in nondepressed adults with OCD have demonstrated that sertraline 50 to 200 mg/day produces significantly greater improvements than placebo on the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Clinical Global Impression (CGI) Severity Scale and on various other OCD assessment scales. Sertraline has been shown to be effective both as short term treatment (≤16 weeks) and as longer term maintenance therapy over 1 to 2 years. In a 12-week placebo-controlled trial (n = 324 adults), 60.4 and 49% of sertraline and placebo recipients, respectively, responded to study medication. During a 40-week extension phase of this study, the clinical efficacy of sertraline was sustained, with improvements in Y-BOCS, National Institute of Mental Health Global Obsessional-Compulsive Scale (NIMH) and CGI Severity Scale scores indicating that sertraline was significantly more effective than placebo.

The only study that has compared sertraline 50 to 200 mg/day with clomipramine 50 to 200 mg/day demonstrated that both agents produced significant improvements on the Y-BOCS and several other OCD assessment scales. Sertraline and clomipramine showed equal efficacy among patients completing the trial. However, intention-to-treat analysis revealed a significant advantage for sertraline over clomipramine which was explained in part by the higher treatment discontinuation rate because of adverse events in the latter group.

A recent meta-analysis of data from large placebo-controlled trials revealed that sertraline, fluoxetine and fluvoxamine have similar efficacies in OCD; however, all 3 agents appeared to be significantly less effective than clomipramine. These results may be partly explained by inclusion of treatment-naive patients in earlier trials of clomipramine. In contrast, the more recent trials of SSRIs included a higher proportion of treatment-experienced patients who had not responded to previous treatment with clomipramine or with other SSRIs.

In noncomparative investigations that included patients with paraphilias (classified as OCD spectrum disorders), sertraline 50 to 200 mg/day produced marked improvements on most sexuality scales and significantly decreased obsession scores.

Sertraline, in dosages of 25 to 200 mg/day, has also demonstrated clinical efficacy in children and adolescents (aged 6 to 17 years) with OCD. Significant improvements in mean Children’s Y-BOCS, NIMH and CGI Severity Scale scores, compared with baseline values, were evident after 5 weeks’ sertraline treatment.

Tolerability

Sertraline 50 to 200 mg/day was generally well tolerated by adults and paediatric patients with OCD who participated in clinical trials. The incidence and severity of sertraline-related adverse events appeared to be dose related. In a placebo-controlled trial conducted in 324 nondepressed adults with OCD, the most common adverse events reported during 12 weeks’ sertraline treatment (50 to 200 mg/day) were headache, insomnia, nausea, diarrhoea, decreased libido and anorexia. These events occurred with an incidence ≥10% greater than with placebo. All of the sertraline-related adverse events (except headache) decreased in incidence during a 40-week extension of the 12-week trial. There was a significantly higher incidence of insomnia, nausea, agitation and tremor in children and adolescents with OCD receiving sertraline treatment than in similar patients who received placebo.

Unlike the tricyclic antidepressants (TCAs), sertraline is associated with minimal anticholinergic activity and is essentially devoid of cardiovascular effects. Moreover, in contrast to the sedative effects of the TCAs, sertraline does not generally appear to impair psychomotor performance. Results of a recent comparative study showed that there was a significantly higher treatment discontinuation rate because of adverse events in patients receiving clomipramine (25.6%) than in the sertraline treatment group (10.5%).

Sertraline has a wide therapeutic index and appears to be less harmful in overdosage than the TCAs.

Dosage and Administration

The optimal starting dosage of sertraline for treating adult and paediatric patients with OCD is 50 mg/day. Thereafter, the dosage may, if necessary, be increased in 50mg increments (over several weeks or months) to a maximum of 200 mg/day. Dosage modification is not usually required for patients with mild to moderate renal impairment, but dosage reduction is recommended for patients with hepatic disease.

Keywords

Adis International Limited Paroxetine Clomipramine Clinical Global Impression Mental Health Global 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Davis R, Wilde MI. Sertraline: a pharmacoeconomic evaluation of its use in depression. PharmacoEconomics 1996 Oct; 10: 409–31PubMedCrossRefGoogle Scholar
  2. 2.
    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: 36–44PubMedCrossRefGoogle Scholar
  3. 3.
    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: 577–85PubMedCrossRefGoogle Scholar
  4. 4.
    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(9): 1209–15PubMedGoogle Scholar
  5. 5.
    Wheadon DE, Bushnell WD, Steiner M. A fixed dose comparison of 20, 40, or 60 mg paroxetine to placebo in the treatment of obsessive-compulsive disorder [abstract]. Annual Meeting of the Americal College of Neuropsychopharmacology; 1993 Dec 13-17; HonoluluGoogle Scholar
  6. 6.
    Montgomery SA, McIntyre A, Osthereider M, et al. A double-blind placebo-controlled study of fluoxetine in patients with DSM-III-R obsessive compulsive disorder. Eur Neuropsychopharmacol 1993; 3: 143–52PubMedCrossRefGoogle Scholar
  7. 7.
    Tollefson GD, Rampey AH, Potvin JH, et al. A multicenter investigation of fixed-dose fluoxetine in the treatment of obsessive-compulsive disorder. Arch Gen Psychiatry 1994; 51: 559–67PubMedCrossRefGoogle Scholar
  8. 8.
    McDougle CJ, Goodman WK, Leckman JF, et al. The psychopharmacology of obsessive compulsive disorder: implications for treatment and pathogenesis. Psychiatr Clin North Am 1993; 16(4): 749–66PubMedGoogle Scholar
  9. 9.
    Murdoch D, McTavish D. Sertraline: a review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depression and obsessive-compulsive disorder. Drugs 1992 Oct; 44: 604–24PubMedCrossRefGoogle Scholar
  10. 10.
    Karno M, Golding JM, Sorenson SB, et al. The epidemiology of obsessive compulsive dsorder in five U.S. communities. Arch Gen Psychiatry 1988; 45: 1094–9PubMedCrossRefGoogle Scholar
  11. 11.
    Hollander E, Fay M, Cohen B, et al. Serotonergic and noradrenergic sensitivity in obsessive-compulsive disorder: behavioural findings. Am J Psychiatry 1988; 145: 1015–7PubMedGoogle Scholar
  12. 12.
    Zohar J, Insel TR. Obsessive-compulsive disorder: psychobiological approaches to diagnosis, treatment and pathophysiology. Biol Psychiatry 1987; 22: 677–87CrossRefGoogle Scholar
  13. 13.
    Pigott TA. OCD: where the serotonin selectivity story begins. J Clin Psychiatry 1996; 57Suppl. 6: 11–20PubMedGoogle Scholar
  14. 14.
    Barr LC, Goodman WK, Price LH. The serotonin hypothesis of obsessive compulsive disorder. Int Clin Psychopharmacol 1993 Nov; 8Suppl. 2: 79–82PubMedCrossRefGoogle Scholar
  15. 15.
    Dolberg OT, Iancu I, Sasson Y, et al. The pathogenesis and treatment of obsessive-compulsive disorder. Clin Neuropharmacol 1996 Apr; 19: 129–47PubMedCrossRefGoogle Scholar
  16. 16.
    Warneke L. Anxiety disorders. Focus on obsessive-compulsive disorder. Can Fam Phys 1993 Jul; 39: 1612–21Google Scholar
  17. 17.
    Zohar J, Mueller EA, Insel TR, et al. Serotonergic responsivity in obsessive-compulsive disorder: comparison of patients and healthy controls. Arch Gen Psychiatry 1987; 44: 946–51PubMedCrossRefGoogle Scholar
  18. 18.
    Murphy DL, Zohar J, Benkelfat C, et al. Obsessive-compulsive disorder as a 5-HT subsystem-related behavioural disorder. Br J Psychiatry 1989; 155Suppl. 8: 15–24Google Scholar
  19. 19.
    Goodwin GM. How do antidepressants affect serotonin receptors? The role of serotonin receptors in the therapeutic and side effect profile of the SSRIs. J Clin Psychiatry 1996; 57Suppl. 4: 9–13PubMedGoogle Scholar
  20. 20.
    Grimsley SR, Jann MW. Paroxetine, sertraline, and fluvoxamine: new selective serotonin reuptake inhibitors. Clin Pharm 1992; 11(11): 930–57PubMedGoogle Scholar
  21. 21.
    Hoffman BJ, Mezey E, Brownstein MJ. Cloning of a serotonin transporter affected by antidepressants. Science 1991; 254: 579–80PubMedCrossRefGoogle Scholar
  22. 22.
    Koe BK. Preclinical pharmacology of sertraline: a potent and specific inhibitor of serotonin reuptake. J Clin Psychiatry 1990 Dec; 51Suppl. B: 13–7PubMedGoogle Scholar
  23. 23.
    Sprouse J, Clarke T, Reynolds L, et al. Comparison of the effects of sertraline and its metabolite desmethylsertraline on blockade of central 5-HT reuptake in vivo. Neuropsychopharmacology 1996 Apr; 14: 225–31PubMedCrossRefGoogle Scholar
  24. 24.
    Artigas F. 5-HT and antidepressants: new views from microdialysis studies. Trends Pharmacol Sci 1993 Jul; 14: 262PubMedCrossRefGoogle Scholar
  25. 25.
    Doogan DP, Caillard V. Sertraline: a new antidepressant. J Clin Psychiatry 1988; 49(Suppl.): 46–51PubMedGoogle Scholar
  26. 26.
    Kovachich GB, Aronson CE, Brunswick DJ. Effect of repeated administration of antidepressants on serotonin uptake sites in limbic and neocortical structures of rat brain determined by quantitative autoradiography. Neuropsychopharmacology 1992 Dec; 7: 317–24PubMedGoogle Scholar
  27. 27.
    O’Donnell JM, Grealy M. Neuroendocrine response to clonidine and 8-OH-DPAT in rats following chronic administration of desipramine or sertraline. Br J Pharmacol 1992 Apr; 105: 863–8PubMedCrossRefGoogle Scholar
  28. 28.
    Kovachich GB, Frazer A, Aronson CE. Effect of chronic administration of antidepressants on α2-adrenoceptors in the locus coeruleus and its projection fields in rat brain determined by quantitative autoradiography. Neuropsychopharmacology 1993 Jan; 8: 57–65PubMedGoogle Scholar
  29. 29.
    Hyttel J. Pharmacological characterization of selective serotonin reuptake inhibitors (SSRIs). Int Clin Psychopharmacol 1994 Mar; 9Suppl. 1: 19–26PubMedCrossRefGoogle Scholar
  30. 30.
    Narita N, Hashimoto K, Tomitaka S-I, et al. Interactions of selective serotonin reuptake inhibitors with subtypes of δ receptors in rat brain. Eur J Pharmacol 1996 Jun 20; 307: 117–9PubMedCrossRefGoogle Scholar
  31. 31.
    Lightowler S, Kennett GA, Tulloch IF, et al. An investigation of the acute effects of sertraline in a rat social interaction test [abstract]. Eur Neuropsychopharmacol 1995 Sep; 5 Spec, issue: 277Google Scholar
  32. 32.
    Walker JM, Bowen WD, Walker FO, et al. Sigma receptors: biology and function. Pharmacol Rev 1990; 42(4): 355–402PubMedGoogle Scholar
  33. 33.
    Bergeron R, Debonnel G, De Montigny C. Modification of the N-methyl-D-aspartate response by antidepressant a receptor ligands. Eur J Pharmacol 1993 Aug 24; 240: 319–23PubMedCrossRefGoogle Scholar
  34. 34.
    Giardino L, Zanni M, Velardo A, et al. Effect of sertraline treatment on benzodiazepine receptors in the rat brain. J Neural Transm 1993; 94(1): 31–41CrossRefGoogle Scholar
  35. 35.
    Giardino L, Zanni M, Bettelli C, et al. Regulation of glutamic acid decarboxylase mRNA expression in rat brain after sertraline treatment. Eur J Pharmacol 1996; 312: 183–7PubMedCrossRefGoogle Scholar
  36. 36.
    Hindmarch I, Bhatti JZ. Psychopharmacological effects of sertraline in normal healthy volunteers. Eur J Clin Pharmacol 1988; 35: 221–3PubMedCrossRefGoogle Scholar
  37. 37.
    Hindmarch I, Shillingford J, Shillingford C. The effects of sertraline on psychomotor performance in elderly volunteers. J Clin Psychiatry 1990 Dec; 51Suppl. B: 34–6PubMedGoogle Scholar
  38. 38.
    Saletu B, Grünberger J. Drug profiling by computed electroencephalography and brain maps, with special consideration of sertraline and its psychometric effects. J Clin Psychiatry 1988; 49Suppl.: 59–71PubMedGoogle Scholar
  39. 39.
    Mattila MJ, Saarialho-Kere U, Mattila M. Acute effects of sertraline, amitriptyline and placebo on the psychomotor performance of healthy subjects over 50 years of age. J Clin Psychiatry 1988; 49Suppl.: 52–8PubMedGoogle Scholar
  40. 40.
    Lane RM. Withdrawal symptoms after discontinuation of selective serotonin reuptake inhibitors (SSRIs). J Serotonin Res 1996; 3: 75–83Google Scholar
  41. 41.
    Louie AK, Lannon RA, Ajari LJ. Withdrawal reaction after sertraline discontinuation. Am J Psychiatry 1994 Mar; 151: 450–1PubMedGoogle Scholar
  42. 42.
    Kent LSW, Laidlaw JDD. Suspected congenital sertraline dependence. Br J Psychiatry 1995 Sep; 167: 412–3PubMedCrossRefGoogle Scholar
  43. 43.
    Fava GA, Grandi S. Withdrawal syndromes after paroxetine and sertraline discontinuation. J Clin Psychopharmacol 1995 Oct; 15: 374–5PubMedCrossRefGoogle Scholar
  44. 44.
    Van Harten J. Clinical pharmacokinetics of selective serotonin reuptake inhibitors. Clin Pharmacokinet 1993 Mar; 24: 203–20PubMedCrossRefGoogle Scholar
  45. 45.
    Catterson ML, Preskorn SH. Pharmacokinetics of selective serotonin reuptake inhibitors: clinical relevance. Pharmacol Toxicol 1996 Apr; 78: 203–8PubMedCrossRefGoogle Scholar
  46. 46.
    Warrington SJ. Clinical implications of the pharmacology of sertraline. Int Clin Psychopharmacol 1991 Dec; 6Suppl. 2: 11–21PubMedCrossRefGoogle Scholar
  47. 47.
    Alderman J, Wolkow R, Johnston H, et al. Sertraline treatment in children and adolescents: tolerability, efficacy and pharmacokinetics [abstract]. Eur Neuropsychopharmacol 1996 Jun; 6Suppl. 3: 11CrossRefGoogle Scholar
  48. 48.
    Greist J, Chouinard G, DuBoff E, et al. Double-blind parallel comparison of three dosages of sertraline and placebo in out-patients with obsessive-compulsive disorder. Arch Gen Psychiatry 1995 Apr; 52: 289–95PubMedCrossRefGoogle Scholar
  49. 49.
    Ronfeld RA, Wilner KD, Baris BA. Sertraline: chronopharmacokinetics and the effect of coadministration with food. Clin Pharmacokinet 1997; 32Suppl. 1: 50–5PubMedCrossRefGoogle Scholar
  50. 50.
    Ronfeld RA, Tremaine LM, Wilner KD. Pharmacokinetics of sertraline and its N-demethyl metabolite in elderly and young male and female volunteers. Clin Pharmacokinet 1997; 32Suppl. 1: 22–30PubMedCrossRefGoogle Scholar
  51. 51.
    Altshuler LL, Burt VK, McMullen M, et al. Breastfeeding and sertraline: a 24-hour analysis. J Clin Psychiatry 1995 Jun; 56: 243–5PubMedGoogle Scholar
  52. 52.
    Baum AL, Misri S. Selective serotonin-reuptake inhibitors in pregnancy and lactation. Harvard Rev Psychiatry 1996 Sep-Oct; 4: 117–25CrossRefGoogle Scholar
  53. 53.
    Harvey A, Preskorn S, Lane R, et al. Sertraline and P4503A3/4 [abstract]. Eur Neuropsychopharmacol 1996 Jun; 6Suppl. 3: 40CrossRefGoogle Scholar
  54. 54.
    Hamelin BA, Turgeon J, Vallée F, et al. The disposition of fluoxetine but not sertraline is altered in poor metabolizers of debrisoquin. Clin Pharmacol Ther 1996; 60(5): 512–21PubMedCrossRefGoogle Scholar
  55. 55.
    LeBel M, Turgeon J, Vallée F, et al. Genetic determinant of sertraline (S) and fluoxetine (F) disposition in 20 healthy volunteers [abstract]. Pharm Res 1995 Sep; 12Suppl.: S374Google Scholar
  56. 56.
    Wilner KD, Baris BA, Foulds GH, et al. Multiple dose pharmacokinetics of sertraline in subjects with varying degrees of renal impairment [abstract]. Eur Neuropsychopharmacol 1996 Jun; 6Suppl. 3: 41CrossRefGoogle Scholar
  57. 57.
    Schwenk MH, Verga MA, Wagner JD. Hemodialyzability of sertraline. Clin Nephrol 1995 Aug; 44: 121–4PubMedGoogle Scholar
  58. 58.
    Tremaine LM, Joerg EA. Automated gas chromatographic-electron-capture assay for the selective serotonin uptake blocker sertraline. J Chromatogr 1989 Nov 24; 496: 423–9PubMedCrossRefGoogle Scholar
  59. 59.
    Démolis J-L, Angebaud P, Grangé J-D, et al. Influence of liver cirrhosis on sertraline pharmacokinetics. Br J Clin Pharmacol 1996 Sep; 42: 394–7PubMedCrossRefGoogle Scholar
  60. 60.
    Wilner KD, Everson G, Foulds GH, et al. Multiple dose pharmacokinetics of sertraline in subjects with varying degrees of hepatic impairment [abstract]. Eur Neuropsychopharmacol 1996 Jun; 6Suppl. 3: 40–1CrossRefGoogle Scholar
  61. 61.
    Wilner KD, Everson G, Foulds GH, et al. Multiple dose pharmacokinetics of sertraline in subjects with varying degrees of hepatic impairment [poster]. XXth Collegium Internationale Neuro-Psychopharmacologicum; 1996 Jun 23-27; MelbourneGoogle Scholar
  62. 62.
    Harvey AT, Preskorn SH. Cytochrome P450 enzymes: interpretation of their interactions with selective serotonin reuptake inhibitors. Part II. J Clin Psychopharmacol 1996 Oct; 16: 345–55PubMedCrossRefGoogle Scholar
  63. 63.
    Salzman C. Heterogeneity of SSRI response. Harv Rev Psychiatry 1996 (4): 215–7PubMedCrossRefGoogle Scholar
  64. 64.
    Sproule BA, Otton SV, Cheung SW, et al. Does sertraline inhibit CYP2D6 after chronic dosing? [abstract]. Clin Pharmacol Ther 1995 Feb; 57: 151Google Scholar
  65. 65.
    Lane RM. Pharmacokinetics drug interaction potential of selective serotonin reuptake inhibitors. Int Clin Psychopharmacol 1996; 11Suppl. 5: 31–61PubMedCrossRefGoogle Scholar
  66. 66.
    Gardner MJ, Baris BA, Wilner KD, et al. Effect of sertraline on the pharmacokinetics and protein binding of diazepam in healthy volunteers. Clin Pharmacokinet 1997; 32Suppl. 1: 43–9PubMedCrossRefGoogle Scholar
  67. 67.
    Tremaine LM, Wilner KD, Preskorn SH. A study of the potential effect of sertraline on the pharmacokinetics and protein binding of tolbutamide. Clin Pharmacokinet 1997; 32Suppl. 1: 31–6PubMedCrossRefGoogle Scholar
  68. 68.
    March JS, Leonard HL, Swedo SE. Pharmacotherapy of obsessive-compulsive disorder. Child Adolesc Psychiatr Clin North Am 1995; 4(1): 217–36Google Scholar
  69. 69.
    Finley PR. Selective serotonin reuptake inhibitors: pharmacologic profiles and potential therapeutic distinctions. Ann Pharmacother 1994 Dec; 28: 1359–69PubMedGoogle Scholar
  70. 70.
    Rapeport WG, Muirhead DC, Williams SA, et al. Absence of effect of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin. J Clin Psychiatry 1996; 57Suppl. 1: 24–8PubMedGoogle Scholar
  71. 71.
    Apseloff G, Wilner KD, Gerber N, et al. Effect of sertraline on protein binding of warfarin. Clin Pharmacokinet 1997; 32Suppl. 1: 37–42PubMedCrossRefGoogle Scholar
  72. 72.
    MacKay ES, Carson SW, Grimsley S, et al. Effects of sertraline on steady-state serum concentrations of imipramine and its metabolites [abstract]. Pharmacotherapy 1994 May-Jun; 14: 368Google Scholar
  73. 73.
    Rapeport WG, Coates PE, Dewland PM. Absence of a sertraline-mediated effect on digoxin pharmacokinetics and electrocardiographic findings. J Clin Psychiatry 1996; 57Suppl. 1: 16–9PubMedGoogle Scholar
  74. 74.
    Apseloff G, Wilner KD, von Deutsch DA, et al. Sertraline does not alter steady-state concentrations or renal clearance of lithium in healthy volunteers. J Clin Pharmacol 1992; 32: 643–6PubMedGoogle Scholar
  75. 75.
    Ziegler MG, Wilner KD. Sertraline does not alter the β-adrenergic blocking activity of atenolol in healthy male volunteers. J Clin Psychiatry 1996; 57Suppl. 1: 12–5PubMedGoogle Scholar
  76. 76.
    Zohar J, Zohar-Kadouch RC, Kindler S. Current concepts in the pharmacological treatment of obsessive-compulsive disorder. Drugs 1992 Feb; 43: 210–8PubMedCrossRefGoogle Scholar
  77. 77.
    Lydiard RB. Obsessive-compulsive disorder: a new perspective in diagnosis and treatment. Int Clin Psychopharmacol 1994 Jun; 9Suppl. 3: 33–7PubMedCrossRefGoogle Scholar
  78. 78.
    McTavish D, Benfield P. Clomipramine: an overview of its pharmacological properties and a review of its therapeutic use in obsessive compulsive disorder and panic disorder. Drugs 1990 Jan; 39: 136–53PubMedCrossRefGoogle Scholar
  79. 79.
    Goodman WK, Price LH, Rasmusson SA, et al. The Yale-Brown Obsessive Compulsive Scale II. Validity. Arch Gen Psychiatry 1989 Nov; 46: 1012–6PubMedCrossRefGoogle Scholar
  80. 80.
    Goodman WK, Price LH, Rasmusson SA, et al. The Yale-Brown Obsessive Compulsive Scale. I. Development, use and reliability. Arch Gen Psychiatry 1989 Nov; 46: 1006–11PubMedCrossRefGoogle Scholar
  81. 81.
    American Psychiatric Association. DSM-III: diagnostic and statistical manual of mental disorders. 3rd ed. Washington, DC: American Psychiatric Association, 1980Google Scholar
  82. 82.
    American Psychiatric Association. DSM-III-R: diagnostic and statistical manual of mental disorders. 3rd ed. rev. Washington, DC: American Psychiatric Association, 1987Google Scholar
  83. 83.
    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 obsessive-compulsive disorder. Psychopharmacol Bull 1990; 26(3): 279–84PubMedGoogle Scholar
  84. 84.
    Kronig MH, Apter J, Asnis G, et al. A multicenter trial of sertraline for obsessive-compulsive disorder [poster]. 33rd American College of Neuropsycholopharmacology; 1995 Dec 12-16; San Juan, 38–9Google Scholar
  85. 85.
    Greist JH, Jefferson JW, Kobak KA, et al. A 1 year double-blind placebo-controlled fixed dose study of sertraline in the treatment of obsessive-compulsive disorder. Int Clin Psychopharmacol 1995 Jun; 10: 57–65PubMedCrossRefGoogle Scholar
  86. 86.
    Rasmussen S, Hackett E, DuBoff E, et al. Long-term sertraline treatment of obsessive compulsive disorder: a 2 year study [abstract]. Eur Neuropsychopharmacol 1995 Sep; 5 Spec, issue: 373Google Scholar
  87. 87.
    Bisserbe J-C, Lane RM, Flament M, et al. A double-blind comparison of sertraline and clomipramine in out-patients with obsessive-compulsive disorder. Eur Psychiatry 1997; 12: 82–97PubMedCrossRefGoogle Scholar
  88. 88.
    The Clomipramine Collaborative Study Group. Clomipramine in the treatment of patients with obsessive-compulsive disorder. Arch Gen Psychiatry 1991; 48: 730–8Google Scholar
  89. 89.
    Rasmussen S, Hackett E, DuBoff J, et al. A two-year study of sertraline in the treatment of obsessive compulsive disorder. Pfizer Inc. New York, NY, USA 1996. (Data on file)Google Scholar
  90. 90.
    Greist JH, Jefferson JW, Kobak KA, et al. Efficacy and tolerability of serotonin transport inhibitors in obsessive-compulsive disorder: a meta-analysis. Arch Gen Psychiatry 1995 Jan; 52: 53–60PubMedCrossRefGoogle Scholar
  91. 91.
    Piccinelli M, Pini S, Bellantuono C, et al. Efficacy of drug treatment in obsessive-compulsive disorder: a meta-analytic review. Br J Psychiatry 1995 Apr; 166: 424–43PubMedCrossRefGoogle Scholar
  92. 92.
    Stein DJ, Spadaccini E, Hollander E. Meta-analysis of pharmacotherapy trials for obsessive-compulsive disorder. Int Clin Psychopharmacol 1995 Mar; 10: 11–8PubMedCrossRefGoogle Scholar
  93. 93.
    Rasmussen S, Baer L, Shera D. Previous SRI treatment and efficacy of sertraline for OCD: combined analysis of 4 multicenter trials. Pfizer Inc. New York, NY, USA, 1997. (Data on file)Google Scholar
  94. 94.
    Bradford JM, Greenberg D, Gojer J, et al. Sertraline in the treatment of pedophilia: an open label study [poster]. 148th American Psychiatric Association; 1995 May 20-25; MiamiGoogle Scholar
  95. 95.
    American Psychiatric Association. Paraphilias. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994Google Scholar
  96. 96.
    Kafka MP. Sertraline pharmacotherapy for paraphilias and paraphilia-related disorders: an open trial. Ann Clin Psychiatry 1994; 6(3): 189–95PubMedCrossRefGoogle Scholar
  97. 97.
    Stein DJ, Hollander E, Josephson SC. Serotonin reuptake blockers for the treatment of obsessional jealousy. J Clin Psychiatry 1994 Jan; 55: 30–3PubMedGoogle Scholar
  98. 98.
    Roberts JM, Lydiard RB. Sertraline in the treatment of bulimia nervosa [letter]. Am J Psychiatry 1993 (150): 1753Google Scholar
  99. 99.
    Frankenburg FR, Kando JC. Sertraline treatment of attention deficit hyperactivity disorder and Tourette’s syndrome. J Clin Psychopharmacology 1994; 14(5): 359–60CrossRefGoogle Scholar
  100. 100.
    Bradford JM, Gratzer TG. A treatment for impulse control disorders and paraphilia: a case report. Can J Psychiatry 1995 Feb; 40: 4–5PubMedGoogle Scholar
  101. 101.
    Rahman MA, Gregory R. Trichotillomania associated with HIV infection and response to sertraline. Psychosomatics 1995 Jul-Aug; 36: 417–8PubMedCrossRefGoogle Scholar
  102. 102.
    Bisserbe JC, Lane R. Sertraline in obsessive-compulsive spectrum disorders: a case study series [abstract]. Eur Neuropsychopharmacol 1996 Jun; 6Suppl. 3: 112Google Scholar
  103. 103.
    Wolkow R, Alderman J, Johnston H, et al. Sertraline treatment of children and adolescents with obsessive compulsive disorder or depression [poster]. World Congress of Psychiatry; 1996 Aug 23-28; MadridGoogle Scholar
  104. 104.
    Wolkow R, Marach J, Safferman A, et al. A placebo-controlled trial of sertraline treatment for pediatric obsessive compulsive disorder. Pfizer Inc. New York, NY, USA. (Data on file)Google Scholar
  105. 105.
    Fulton B, McTavish D. Fluoxetine: an overview of its pharmacodynamic and pharmacokinetic properties and review of its therapeutic efficacy in obsessive-compulsive disorder. CNS Drugs 1995 Apr; 3: 305–22CrossRefGoogle Scholar
  106. 106.
    Veivia AJ, Levin GM, Powell HS. Buspirone and sertraline in the treatment of a patient with refractory obsessive-compulsive disorder. J Pharm Technol 1995 Mar-Apr; 11: 50–2Google Scholar
  107. 107.
    Menkes DB. Buspirone augmentation of sertraline. Br J Psychiatry 1995 Jun; 166: 823–4PubMedGoogle Scholar
  108. 108.
    Doogan DP. Toleration and safety of sertraline: experience worldwide. Int Clin Psychopharmacol 1991 Dec; 6Suppl. 2: 47–56PubMedCrossRefGoogle Scholar
  109. 109.
    Lane RM. A critical review of selective serotonin reuptake inhibitor-related sexual dysfunction; incidence, possible aetiology and implications for management. J Psychopharmacol 1997; 11(1): 89–99CrossRefGoogle Scholar
  110. 110.
    Lane R, Sweeney M, Henry JA. Pharmacotherapy of the depressed patient with cardiovascular or cerebrovascular illness. Br J Clin Pract 1994; 48: 256–62PubMedGoogle Scholar
  111. 111.
    Lane R, Baldwin D, Preskorn S. The SSRIs: advantages, disadvantages and differences. J Psychopharmacol 1995; 9(2 Suppl. 1) 163–78PubMedGoogle Scholar
  112. 112.
    Fisch C, Knoebel SB. Electrocardiographic findings in sertraline depression trials. Drug Invest 1992; 4(4): 305–12CrossRefGoogle Scholar
  113. 113.
    Murdoch D, McTavish D. Sertraline. Curr Ther 1994 Jul; 35: 23–5Google Scholar
  114. 114.
    Lau GT, Horowitz BZ. Sertraline overdose. Acad Emerg Med 1996 Feb; 3: 132–6PubMedCrossRefGoogle Scholar
  115. 115.
    Myers LB, Dean BS, Krenzelok EP. Sertraline (Zoloft®): overdose assessment of a new antidepressant [abstract]. Vet Hum Toxicol 1993; 35: 341Google Scholar
  116. 116.
    Corkeron MA. Serotonin syndrome - a potentially fatal complication of antidepressant therapy. Med J Aust 1995 Nov 6; 163: 481–2PubMedGoogle Scholar
  117. 117.
    Sternbach H. The serotonin syndrome. Am J Psychiatry 1991; 148: 705–13PubMedGoogle Scholar
  118. 118.
    Braitberg G. Serotonin syndrome [letter]. Med J Aust 1994; 160: 527–8PubMedGoogle Scholar
  119. 119.
    Nierenberg DW, Semprebon M. The central nervous serotonin syndrome. Clin Pharmacol Ther 1993; 53: 84–8PubMedCrossRefGoogle Scholar
  120. 120.
    Klein-Schwartz W, Anderson B. Analysis of sertraline-only overdoses. Am J Emerg Med 1996; 14(5): 456–8PubMedCrossRefGoogle Scholar
  121. 121.
    Bhatara VS, Bandettini FC. Possible interaction between sertraline and tranylcypromine. Clin Pharm 1993 Mar; 12: 222–5PubMedGoogle Scholar
  122. 122.
    Sasson Y, Zohar J. New developments in obsessive-compulsive disorder research: implications for clinical management. Int Clin Psychopharmacol 1996; 11Suppl. 5: 3–12PubMedCrossRefGoogle Scholar
  123. 123.
    Anon. Inhibition of serotonin reuptake is the key to treating obsessive-compulsive disorder. Drug Ther Perspect 1993 Aug 30; 2 (4): 8–10Google Scholar

Copyright information

© Adis International Limited 1997

Authors and Affiliations

  1. 1.Adis International LimitedAuckland 10New Zealand

Personalised recommendations