Effectiveness of chromium in atypical depression: a placebo-controlled trial

  • Jonathan R.T Davidson
    Address reprint requests to Jonathan R. T. Davidson, M.D., Anxiety and Traumatic Stress Progam, Duke University Medical Center, Department of Psychiatry and Behavioral Sciences, Trent Drive, Yellow Zone, 4th Floor, Room 4082B, Box 3812, Durham, NC 27710, USA.
    Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA (JRTD, KA, KMC)
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  • Kurian Abraham
    Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA (JRTD, KA, KMC)
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  • Kathryn M Connor
    Department of Psychiatry and Behavioral Sciences, Duke University Medical Center, Durham, North Carolina, USA (JRTD, KA, KMC)
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  • Malcolm N McLeod
    The Department of Psychiatry, University of North Carolina School of Medicine, Chapel Hill, North Carolina, USA (MNM)
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      Chromium picolinate (CP) has been reported to benefit patients with symptoms of atypical depression.


      A placebo-controlled, double-blind, pilot study of CP was conducted in 15 patients with DSM-IV major depressive disorder, atypical type. Patients received 600 μg of CP or matching placebo (PBO) for 8 weeks.


      Seven (70%) CP and zero (0%) PBO patients met responder criteria (p = .02). Other outcomes were consistent with greater effect of CP. Three patients on CP failed to show any improvement. Chromium picolinate was well tolerated.


      Chromium picolinate shows promising antidepressant effects in atypical depression. Its mechanism of action may relate to 5HT2A downregulation, increased insulin sensitivity, or to other effects.


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        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. 4th ed. American Psychiatric Association, Washington, DC1994
        • Anderson R.A.
        Chromium, glucose intolerance and diabetes.
        J Am Coll Nutrition. 1998; 17: 548-555
        • Anderson R.A.
        • Polansky M.M.
        • Bryden N.A.
        • Bhathena S.J.
        • Canary J.
        Effects of supplemental chromium on patients with symptoms of reactive hypoglycemia.
        Metabolism. 1987; 36: 351-355
        • Attenburrow M.-J.
        • Odontiadis J.
        • Murray B.J.
        • Cowen P.J.
        • Franklin M.
        Chromium treatment decreases the sensitivity of 5HT2A receptors.
        Psychopharmacology. 2002; 159: 432-436
        • Barnett S.D.
        • Tharwani H.M.
        • Hertzberg M.A.
        • Sutherland S.M.
        • Connor K.M.
        • Davidson J.R.T.
        Tolerability of fluoxetine in posttraumatic stress disorder.
        Prog Neuropsychopharmacol Biol Psychiatry. 2001; 26: 363-367
        • Cohen J.
        Statistical Power Analysis for the Behavioral Sciences. 2nd ed. Lawrence Erlbaum and Associates, Hillsdale, NJ1988
        • Connor K.M.
        • Davidson J.R.T.
        • Churchill E.
        Adverse effect profile of kava.
        CNS Spectrums. 2001; 6: 848-853
        • Davidson J.R.T.
        • Giller E.L.
        • Zisook S.
        • Overall J.E.
        An efficacy study of isocarboxazid and placebo in depression, and its relationship to depressive nosology.
        Arch Gen Psychiatry. 1988; 45: 120-127
        • Davidson J.R.T.
        • Miller R.D.
        • Turnbull C.D.
        • Sullivan J.L.
        Atypical depression.
        Arch Gen Psychiatry. 1982; 39: 527-534
        • Davidson J.R.T.
        • Woodbury M.A.
        • Zisook S.
        • Giller E.L.
        Classification of depression by grade of membership.
        Psychol Med. 1989; 19: 987-998
        • Davis C.M.
        • Vincent J.B.
        Chromium oligopeptide activates insulin receptor kinase activity.
        Biochemistry. 1997; 36: 4382-4385
        • Derogatis L.R.
        • Lipman R.S.
        • Covi L.
        Psychopharmacol Bull. 1973; 9: 13-28
        • Guy W.
        ECDEU Assessment Manual for Psychopharmacology. Department of Health and Human Services, Publication ADM, Washington, DC1976
        • Hamilton M.
        The effect of treatment on the melancholias (depressions).
        Br J Psychiatry. 1982; 140 (76–338): 223-230
        • Horacek J.
        • Kuzmiakova M.
        • Hoschl C.
        • Andel M.
        • Bahbonh R.
        The relationship between central serotonergic activity and insulin sensitivity in healthy volunteers.
        Psychoneuroendocrinology. 1999; 24: 785-787
        • Jarrett R.B.
        • Schaffer M.
        • McIntire D.
        • Witt-Browder A.
        • Kraft D.
        • Risser R.C.
        Treatment of atypical depression with cognitive therapy or phenelzine.
        Arch Gen Psychiatry. 1999; 56: 431-437
        • McCarthy M.F.
        Enhancing central and peripheral insulin activity as a strategy for treatment of endogenous depression—an adjuvant role for chromium picolinate.
        Med Hypotheses. 1994; 43: 247-252
        • McGrath P.J.
        • Stewart J.W.
        • Quitkin F.M.
        • Wager S.
        • Jenkins S.W.
        • Archibald D.G.
        • et al.
        Gepirone treatment of atypical depression.
        J Clin Psychopharmcol. 1994; 14: 347-352
        • McLeod M.N.
        • Gaynes B.N.
        • Golden R.N.
        Chromium potentiation of antidepressant pharmacotherapy for dysthymic disorder in five patients.
        J Clin Psychiatry. 1999; 60: 237-240
        • McLeod M.N.
        • Golden R.N.
        Chromium treatment of depression.
        Int J Neuropsychopharmacol. 2000; 3: 311-314
        • Pande A.C.
        • Birkett M.
        • Fechner-Bates S.
        • Haskett R.F.
        • Greden J.F.
        Fluoxetine versus phenelzine in atypical depression.
        Biol Psychiatry. 1996; 40: 1017-1020
        • Paykel E.S.
        Classification of depressed patients.
        Br J Psychiatry. 1972; 118: 275-288
        • Paykel E.S.
        • Mueller P.S.
        • de la Vergne P.M.
        Amitriptyline, weight gain and carbohydrate craving.
        Br J Psychiatry. 1973; 123: 501-508
        • Posternak M.A.
        • Zimmerman M.
        Partial validation of the atypical features subtype of major depressive disorder.
        Arch Gen Psychiatry. 2002; 59: 70-76
        • Quitkin F.M.
        • Stewart J.W.
        • McGrath P.J.
        • Tricamo E.
        • Rabkin J.G.
        • Ocepek-Welikson I.K.
        • et al.
        Columbia atypical depres-sion.
        Br J Psychiatry. 1993; 163: 30-34
        • Sheehan D.V.
        • Lecrubier Y.
        • Sheehan K.H.
        • Amorim P.
        • Janavs J.
        • Weiller E.
        • et al.
        The Mini-International Neuropsychiatric Interview (MINI).
        J Clin Psychiatry. 1998; 59: 22-33
        • Stewart J.W.
        • McGrath P.J.
        • Rabkin J.G.
        • Quitkin F.M.
        Atypical depression. A valid clinical entity?.
        Psychiatric Clin North Am. 1993; 16: 479-495
        • Thase M.
        • Fava M.
        • Halbreich U.
        • Kocsis J.H.
        • Koran L.
        • Davidson J.R.T.
        • Rosenbaum J.
        • Harrison W.
        A placebo-controlled, randomized clinical trial comparing sertraline and imipramine for the treatment of dysthymia.
        Arch Gen Psychiatry. 1996; 53: 777-784