Advertisement

Double-blind placebo-controlled administration of fluoxetine in restricting- and restricting-purging-type anorexia nervosa

  • Walter H Kaye
    Correspondence
    Address reprint requests to Walter H. Kaye, M.D., University of Pittsburgh, Western Psychiatric Institute and Clinic, 3811 O’Hara Street, E-724, Pittsburgh PA 15213
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)
    Search for articles by this author
  • Toshihiko Nagata
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)

    Department of Neuropsychiatry, Osaka City University Medical School, Osaka, Japan (TN)
    Search for articles by this author
  • Theodore E Weltzin
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)

    Department of Psychiatry, University of Wisconsin, Madison, Wisconsin, USA (TEW)
    Search for articles by this author
  • L.K.George Hsu
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)

    Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts, USA (LKGH)
    Search for articles by this author
  • Mae S Sokol
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)

    Eating Disorders Program, Menninger Clinic, Topeka, Kansas, USA (MSS)
    Search for articles by this author
  • Claire McConaha
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)
    Search for articles by this author
  • Katherine H Plotnicov
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)
    Search for articles by this author
  • Jeff Weise
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)
    Search for articles by this author
  • Dianne Deep
    Affiliations
    Department of Psychiatry, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA (WHK, TN, TEW, LKGH, MSS, CM, KHP, JW, DD)
    Search for articles by this author

      Abstract

      Background: Anorexia nervosa is an often chronic disorder with high morbidity and mortality. Many people relapse after weight restoration. This study was designed to determine whether a selective serotonin reuptake inhibitor would improve outcome and reduce relapse after weight restoration by contributing to maintenance of a healthy normal weight and a reduction of symptoms.
      Methods: We administered a double-blind placebo-controlled trial of fluoxetine to 35 patients with restricting-type anorexia nervosa. Anorexics were randomly assigned to fluoxetine (n = 16) or a placebo (n = 19) after inpatient weight gain and then were observed as outpatients for 1 year.
      Results: Ten of 16 (63%) subjects remained on fluoxetine for a year, whereas only three of 19 (16%) remained on the placebo for a year (p = .006). Those subjects remaining on fluoxetine for a year had reduced relapse as determined by a significant increase in weight and reduction in symptoms.
      Conclusions: This study offers preliminary evidence that fluoxetine may be useful in improving outcome and preventing relapse of patients with anorexia nervosa after weight restoration.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Biological Psychiatry
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. American Psychiatric Association (1994): Diagnostic and Statistical Manual of Mental Disorders, 4th ed. Washington, DC: American Psychiatric Press.

        • Anderson I
        • Parry-Billings M
        • Newsholme E
        • Fairburn C
        • Cowen P
        Dieting reduces plasma tryptophan and alters brain serotonin function in women.
        J Psychol Med. 1990; 20: 785-791
        • Attia E
        • Haiman C
        • Walsh B.T
        • Flater S.R
        Does fluoxetine augment the inpatient treatment of anorexia nervosa?.
        Am J Psychiatry. 1998; 155: 548-551
        • Benfield P
        • Heel R
        • Lewis S
        Fluoxetine.
        Drugs. 1986; 32: 481-508
        • Biederman J
        • Herzog D
        • Rivinus T
        • Harper G
        • Gerber R
        • Rosenbauk J
        • et al.
        Amitriptyline in the treatment of anorexia nervosa.
        J Clin Psychopharmacol. 1985; 5: 10-16
        • Campbell D.A
        • Sundaramurthy D
        • Markham A.F
        • Pieri L.F
        Lack of association between 5-HT2A promoter polymorphism and susceptibility to anorexia nervosa.
        Lancet. 1998; 351: 499
        • Channon S
        • DeSilva W.P
        Psychological correlates of weight gain in patients with anorexia nervosa.
        J Psychiatr Res. 1985; 19: 267-271
        • Collier D.A
        • Arranz M.J
        • Li T
        • Mupita D
        • Brown N
        • Treasure J
        Association between 5-HT2A gene promoter polymorphism and anorexia nervosa.
        Lancet. 1997; 350: 412
      2. Cox D, Oakes D (1984): Analysis of Survival Data. London: Chapman & Hall.

        • Crisp A.H
        • Lacey J.H
        • Crutchfield M
        Clomipramine and “drive” in people with anorexia nervosa.
        Br J Psychiatry. 1987; 150: 355-358
        • Delgado P.L
        • Charney D.S
        • Price L.H
        • Aghajanian G.K
        • Landis H
        • Heninger G.R
        Serotonin function and the mechanism of antidepressant action.
        Arch Gen Psychiatry. 1990; 47: 411-418
        • Eckert E.D
        • Goldberg S.C
        • Halmi K.A
        • Casper R.C
        • Davis J.M
        Depression in anorexia nervosa.
        Psychol Med. 1982; 12: 115-122
        • Enoch M
        • Kaye W
        • Ozaki N
        • Mazzanti C
        • Rotondo A
        • Greenberg B
        • et al.
        Replication of an association between 5-HT2A promoter polymorphism −1438G/A and anorexia nervosa, and association with obsessive-compulsive disorder.
        Lancet. 1998; 351: 1785-1786
        • Ferguson C.P
        • La Via M.C
        • Crossan P.J
        • Kaye W.H
        Are SSRI’s effective in underweight anorexia nervosa?.
        Int J Eat Disord. 1999; 25: 11-18
        • Fink G
        • Summner B.E.H
        Oestrogen and mental state.
        Nature. 1996; 383: 306
        • Gibbons J
        • Barr G
        • Bridger W
        • Leibowitz S
        Manipulations of dietary tryptophan.
        Brain Res. 1979; 169: 139-153
        • Goodman W
        • Price L
        • Rasmussen S
        • Mazure C
        • Delgado P
        • Heninger G
        • et al.
        The Yale-Brown Obsessive Compulsive Scale (YBOCS).
        Arch Gen Psychiatry. 1989; 46: 1012-1016
        • Goodman W
        • Price L
        • Rasmussen S
        • Mazure C
        • Fleischmann R
        • Hill C
        • et al.
        The Yale-Brown Obsessive Compulsive Scale (YBOCS).
        Arch Gen Psychiatry. 1989; 46: 1006-1011
        • Gowers S
        • Norton K
        • Halek C
        • Crisp A.H
        Outcome of outpatient psychotherapy in a random allocation treatment study of anorexia nervosa.
        Int J Eat Disord. 1994; 15: 165-177
        • Gram L.F
        Fluoxetine.
        N Engl J Med. 1994; 331: 1354-1361
        • Gwirtsman H.E
        • Guze B.H
        • Yager J
        • Gainsley B
        Fluoxetine treatment of anorexia nervosa.
        J Clin Psychiatry. 1990; 51: 378-382
        • Hall A
        • Crisp A
        Brief psychotherapy in the treatment of anorexia nervosa.
        Br J Psychiatry. 1987; 151: 185-191
        • Halmi K
        • Eckert E
        • LaDu T
        • Cohen J
        anorexia nervosa.
        Arch Gen Psychiatry. 1986; 43: 177-181
        • Hamilton M
        The assessment of anxiety states by rating.
        Br J Med Psychol. 1959; 32: 50-55
        • Hamilton M
        A rating scale for depression.
        J Neurology Neurosurg Psychiatry. 1960; 23: 56-65
        • Herzog D
        • Keller M
        • Strober M
        • Yeh C
        • Pai S.-Y
        The current status of treatment for anorexia nervosa and bulimia nervosa.
        Int J Eat Disord. 1992; 12: 215-220
        • Hinney A
        • Barth N
        • Ziegler A
        • von Prittwitz S
        • Hamann A
        • Hennighausen K
        • et al.
        Serotonin transporter gene-linked polymorphic region.
        Life Sci. 1997; 61: 295-303
        • Hsu L
        The outcome of anorexia nervosa.
        Psychol Med. 1988; 18: 807-812
        • Hsu L.K.G
        Outcome of anorexia nervosa—a review of the literature (1954–1978).
        Arch Gen Psychiatry. 1980; 37: 1041-1045
      3. Kalbfleisch J, Prentice R (1980): The Statistical Analysis of Failure Time Data. New York: Wiley.

        • Kaye W.H
        • Ebert M.H
        • Raleigh M
        • Lake R
        Abnormalities in CNS monoamine metabolism in anorexia nervosa.
        Arch Gen Psychiatry. 1984; 41: 350-355
        • Kaye W.H
        • Greeno C.G
        • Moss H
        • Fernstrom J
        • Fernstrom M
        • Lilenfeld L.R
        • et al.
        Alterations in serotonin activity and psychiatric symptomatology after recovery from bulimia nervosa.
        Arch Gen Psychiatry. 1998; 55: 927-935
        • Kaye W.H
        • Gwirtsman H.E
        • George D.T
        • Jimerson D.C
        • Ebert M.H
        CSF 5-HIAA concentrations in anorexia nervosa.
        Biol Psychiatry. 1988; 23: 102-105
        • Kaye W.H
        • Weltzin T.E
        • Hsu L.K
        • Bulik C.M
        An open trial of fluoxetine in patients with anorexia nervosa.
        J Clin Psychiatry. 1991; 52: 464-471
        • Kendler K.S
        • MacLean C
        • Neale M
        • Kessler R
        • Health A
        • Eaves L
        The genetic epidemiology of bulimia nervosa.
        Am J Psychiatry. 1991; 148: 1627-1636
      4. Lacey JH, Crisp AH (1980): Hunger, food intake and weight: The impact of clomipramine on refeeding anorexia nervosa population. Postgrad Med J 56(suppl 1):79–85.

        • Laessle R.G
        • Schweiger U
        • Pirke K.M
        Depression as a correlate of starvation in patients with eating disorders.
        Biol Psychiatry. 1988; 23: 719-725
        • Lilenfeld L.R
        • Kaye W.H
        • Greeno C.G
        • Plotnicov K.H
        • Pollice C.P
        • Rao R
        • et al.
        A controlled family study of anorexia and bulimia nervosa.
        Arch Gen Psychiatry. 1998; 55: 603-610
        • McKenzie J.M
        • Joyce P.R
        Hospitalization for anorexia nervosa.
        Int J Eat Disord. 1992; 11: 235-241
        • McQueen J.K
        • Wilson H
        • Dow R.C
        • Fink G.J
        Oestradiol-17 Beta increases serotonin transporter (SERT) binding sites and SERT mRNA expression in discrete regions of female rat brain.
        J Physiol (Lond). 1996; 495: 114
        • Messing R
        • Fisher L
        • Phebus L
        • Lytle L
        Interaction of diet and drugs in the regulation of brain 5-hydroxy indoles and the response to painful electric shock.
        Life Sci. 1976; 18: 707-714
      5. Metropolitan Life Insurance Company (1959): New weight standards for men and women. Stat Bull Metrop Insur Co 40:1–11.

        • Mitchell J.E
        • Raymond N
        • Specker S
        A review of the controlled trials of pharmacotherapy and psychotherapy in the treatment of bulimia nervosa.
        Int J Eat Disord. 1993; 14: 229-247
        • Patton G.C
        Mortality in eating disorders.
        Psychol Med. 1988; 18: 947-951
        • Piccinelli M
        • Pini S
        • Bellantuono C
        • Wilkinson G
        Efficacy of drug treatment in obsessive-compulsive disorder.
        Br J Psychiatry. 1995; 166: 424-443
        • Pollice C
        • Kaye W.H
        • Greeno C.G
        • Weltzin T.E
        Relationship of depression, anxiety, and obsessionality to state of illness in anorexia nervosa.
        Int J Eat Disord. 1997; 21: 367-376
        • Russell G.F
        • Szmukler G.I
        • Dare C
        • Eisler I
        An evaluation of family therapy in anorexia nervosa and bulimia nervosa.
        Arch Gen Psychiatry. 1987; 44: 1047-1056
        • Schweiger V
        • Warnoff M
        • Pahl J
        • Pirke K
        Effects of carbohydrate and protein meals on plasma large neutral amino acids, glucose and insulin plasma levels of anorectic patients.
        Metabolism. 1986; 35: 938-943
        • Sorbi S
        • Nacmias B
        • Tedde A
        • Ricca V
        • Mezzani B
        • Rotella C.M
        5-HT2A promoter polymorphism in anorexia nervosa.
        Lancet. 1998; 351: 1785
        • Srinivasagam N.M
        • Plotnicov K.H
        • Greeno C
        • Weltzin T.E
        • Rao R
        • Kaye W.H
        Persistent perfectionism, symmetry, and exactness in anorexia nervosa after long-term recovery.
        Am J Psychiatry. 1995; 152: 1630-1634
        • Stonehill E
        • Crisp A.H
        Psychoneurotic characteristics of patients with anorexia nervosa before and after treatment and at 4–7 year follow-up.
        J Psychosom Res. 1977; 21: 189-193
        • Strober M
        • Freeman R
        • DeAntonio M
        • Lampert C
        • Diamond J
        Does adjunctive fluoxetine influence the post-hospital course of restrictor-type anorexia nervosa? A 24-month prospective, longitudinal followup and comparison with historical controls.
        Psychopharmacol Bull. 1997; 33: 425-431
      6. Strober M, Katz JL (1988): Depression in the eating disorders: A review and analysis of descriptive, family, and biological findings. In: Garner DM, Garfinkel PE, editors. Diagnostic Issues in Anorexia Nervosa and Bulimia Nervosa, Vol 2. New York: Brunner/Mazel, 80–111.

        • Sullivan P.F
        Mortality in anorexia nervosa.
        Am J Psychiatry. 1995; 152: 1073-1074
        • Sunday S.R
        • Halmi K.A
        • Einhorn A
        The Yale-Brown-Cornell Eating Disorder Scale.
        Int J Eat Disord. 1995; 18: 237-245
      7. Theander S (1983): Long-term prognosis of anorexia nervosa: A preliminary report. In: Darby PL, editor. Anorexia Nervosa: Recent Developments in Research. New York: A.R. Liss, pp 441–442.

        • Thiel A
        • Broocks A
        • Ohlmeier M
        • Jacoby G.E
        • Schüßler G
        Obsessive-compulsive disorder among patients with anorexia nervosa and bulimia nervosa.
        Am J Psychiatry. 1995; 152: 72-75
      8. Tollefson GD (1995): Selective serotonin reuptake inhibitors. In: Schatzberg AF, Memeroff CB, editors. Textbook of Psychopharmacology. Washington, DC: American Psychiatric Press, pp 161–182.

        • Treasure J
        • Todd G
        • Brolly M
        • Tiller J
        • Nehmed A
        • Denman F
        A pilot study of a randomized trial of cognitive analytical therapy vs educational behavioral therapy for adult anorexia nervosa.
        Behav Res Ther. 1995; 33: 363-367
        • Vandereycken W
        Neuroleptics in the short-term treatment of anorexia nervosa.
        Br J Psychiatry. 1984; 144: 288-292
        • Vandereycken W
        • Pierloot R
        Pimozide combined with behavior therapy in the short-term treatment of anorexia nervosa.
        Acta Psychiatr Scand. 1982; 66: 445-450
      9. Walsh BT (1995): Pharmacotherapy of eating disorders. In: Brownell KD, Fairburn CG, editors. Eating Disorders and Obesity: A Comprehensive Handbook. New York: Guilford, pp 329–340.

      10. Winer BJ (1971): Statistical Principles in Experimental Design, 2nd ed. New York: McGraw Hill.

        • Yates M
        • Leake A
        • Candy J.M
        • Fairbairn A.F
        • McKeith I.G
        • Ferrier I.N
        5-HT2 receptor changes in major depression.
        Biol Psychiatry. 1990; 27: 489-496