Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression | Depressive Disorders | JAMA Psychiatry | JAMA Network
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Goodyer  IMHerbert  JAltham  PMEPearson  JSecher  SMShiers  HM Adrenal secretion during major depression in 8- to 16-year-olds, I: altered diurnal rhythms in salivary cortisol and dehydroepiandrosterone (DHEA) at presentation.  Psychol Med 1996;26245- 256PubMedGoogle ScholarCrossref
Yaffe  KEttinger  BPressman  ASeeley  DWhooley  MSchaefer  CCummings  S Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study.  Biol Psychiatry 1998;43694- 700PubMedGoogle ScholarCrossref
Heuser  IDeuschle  MLuppa  PSchweiger  UStandhardt  HWeber  B Increased diurnal plasma concentrations of dehydroepiandrosterone in depressed patients.  J Clin Endocrinol Metab 1998;833130- 3133PubMedGoogle ScholarCrossref
Michael  AJenaway  APaykel  ESHerbert  J Altered salivary dehydroepiandrosterone levels in major depression in adults.  Biol Psychiatry 2000;48989- 995PubMedGoogle ScholarCrossref
Schmidt  PJMurphy  JHHaq  NDanaceau  MASimpson St Clair  L Basal plasma hormone levels in depressed perimenopausal women.  Psychoneuroendocrinology 2002;27907- 920PubMedGoogle ScholarCrossref
Berr  CLafton  SDebuire  BDartigues  JFBaulieu  EE Relationships of dehydroepiandrosterone sulfate in the elderly with functional, psychological, and mental status, and short-term mortality: a French community-based study.  Proc Natl Acad Sci U S A 1996;9313410- 13415PubMedGoogle ScholarCrossref
Morales  AJNolan  JJNelson  JCYen  SSC Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age.  J Clin Endocrinol Metab 1994;781360- 1367PubMedGoogle Scholar
Wolkowitz  OMReus  VIRoberts  EManfredi  FChan  TRaum  WJOrmiston  SJohnson  RCanick  JBrizendine  LWeingartner  H Dehydroepiandrosterone (DHEA) treatment of depression.  Biol Psychiatry 1997;41311- 318PubMedGoogle ScholarCrossref
Bloch  MSchmidt  PJDanaceau  MAAdams  LFRubinow  DR Dehydroepiandrosterone treatment of mid-life dysthymia.  Biol Psychiatry 1999;451533- 1541PubMedGoogle ScholarCrossref
Wolkowitz  OMReus  VIKeebler  ANelson  NFriedland  MBrizendine  LRoberts  E Double-blind treatment of major depression with dehydroepiandrosterone.  Am J Psychiatry 1999;156646- 649PubMedGoogle Scholar
Labrie  FBelanger  ACusan  LCandas  B Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology.  J Clin Endocrinol Metab 1997;822403- 2409PubMedGoogle ScholarCrossref
Rabkin  JGFerrando  SJWagner  GJRabkin  R DHEA treatment for HIV+ patients: effects on mood, androgenic and anabolic parameters.  Psychoneuroendocrinology 2000;2553- 68PubMedGoogle ScholarCrossref
Beck  ATWard  CHMendelson  MMock  JErbaugh  J An inventory for measuring depression.  Arch Gen Psychiatry 1961;4561- 571PubMedGoogle ScholarCrossref
Hamilton  M A rating scale for depression.  J Neurol Neurosurg Psychiatry 1960;2356- 62PubMedGoogle ScholarCrossref
Faries  DHerrera  JRayamajhi  JDeBrota  DDemitrack  MPotter  WZ The responsiveness of the Hamilton Depression Rating Scale.  J Psychiatr Res 2000;343- 10PubMedGoogle ScholarCrossref
Harlow  BLCohen  LSOtto  MWSpiegelman  DCramer  DW Prevalence and predictors of depressive symptoms in older premenopausal women: the Harvard Study of mood and cycles.  Arch Gen Psychiatry 1999;56418- 424PubMedGoogle ScholarCrossref
McKinlay  JBMcKinlay  SMBrambilla  D The relative contributions of endocrine changes and social circumstances to depression in mid-aged women.  J Health Soc Behav 1987;28345- 363PubMedGoogle ScholarCrossref
Harrington  RFudge  HRutter  MPickles  AHill  J Adult outcomes of childhood and adolescent depression, I: psychiatric status.  Arch Gen Psychiatry 1990;47465- 473PubMedGoogle ScholarCrossref
Bosworth  HBBastian  LAKuchibhatla  MNSteffens  DCMcBride  CMSkinner  CSRimer  BKSiegler  IC Depressive symptoms, menopausal status, and climacteric symptoms in women at midlife.  Psychosom Med 2001;63603- 608PubMedGoogle ScholarCrossref
Radloff  LS The CES-D Scale: a self-report depression scale for research in the general population.  Appl Psychol Meas 1977;1385- 401Google ScholarCrossref
Mason  BJKocsis  JHLeon  ACThompson  SFrances  AJMorgan  ROParides  MK Measurement of severity and treatment response in dysthymia.  Psychiatr Ann 1993;23625- 631Google ScholarCrossref
Derogatis  LR The Derogatis Interview for Sexual Functioning (DISF/DISF-SR): an introductory report.  J Sex Marital Ther 1997;23291- 304PubMedGoogle ScholarCrossref
Bech  PGram  LFDein  EJacobsen  OVitger  JBolwig  TG Quantitative rating of depressive states.  Acta Psychiatr Scand 1975;51161- 170PubMedGoogle ScholarCrossref
Strous  RDMaayan  RLapidus  RStryjer  RLustig  MKotler  MWeizman  A Dehydroepiandrosterone augmentation in the management of negative, depressive, and anxiety symptoms in schizophrenia.  Arch Gen Psychiatry 2003;60133- 141PubMedGoogle ScholarCrossref
Soules  MRSherman  SParrott  ERebar  RSantoro  NUtian  WWoods  N Stages of Reproductive Aging Workshop (STRAW).  J Womens Health Gend Based Med 2001;10843- 848PubMedGoogle ScholarCrossref
Spitzer  RLWilliams  JBGibbon  MFirst  MB Structured Clinical Interview for DSM-III-R, Patient Edition.  New York Biometrics Research Dept, New York State Psychiatric Institute1990;
Spitzer  RLEndicott  J Schedule for Affective Disorders and Schizophrenia– Lifetime Version.  New York Biometrics Research Dept, New York State Psychiatric Institute1979;
American Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.  Washington, DC American Psychiatric Association1994;
Morris  CAAvorn  J Internet marketing of herbal products.  JAMA 2003;2901505- 1509PubMedGoogle ScholarCrossref
Fava  MKendler  KS Major depressive disorder.  Neuron 2000;28335- 341PubMedGoogle ScholarCrossref
Mortola  JFYen  SSC The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women.  J Clin Endocrinol Metab 1990;71696- 704PubMedGoogle ScholarCrossref
Arlt  WCallies  Fvan Vlijmen  JCKoehler  IReincke  MBidlingmaier  MHuebler  DOettel  MErnst  MSchulte  HMAllolio  B Dehydroepiandrosterone replacement in women with adrenal insufficiency.  N Engl J Med 1999;3411013- 1020PubMedGoogle ScholarCrossref
Hunt  PJGurnell  EMHuppert  FARichards  CPrevost  ATWass  JAHHerbert  JChatterjee  VKK Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial.  J Clin Endocrinol Metab 2000;854650- 4656PubMedGoogle Scholar
Lovas  KGebre-Medhin  GTrovik  TSFougner  KJUhlving  SNedrebo  BGMyking  OLKampe  LHusebye  ES Replacement of dehydroepiandrosterone in adrenal failure: no benefit for subjective health status and sexuality in a 9-month, randomized, parallel group clinical trial.  J Clin Endocrinol Metab 2003;881112- 1118PubMedGoogle ScholarCrossref
Barnhart  KTFreeman  EGrisso  JARader  DJSammel  MKapoor  SNestler  JE The effect of dehydroepiandrosterone supplementation to symptomatic perimenopausal women on serum endocrine profiles, lipid parameters, and health-related quality of life.  J Clin Endocrinol Metab 1999;843896- 3902PubMedGoogle Scholar
Arlt  WCallies  FKoehler  Ivan Vlijmen  JCFassnacht  MStrasburger  CJSeibel  MJHuebler  DErnst  MOettel  MReincke  MSchulte  HMAllolio  B Dehydroepiandrosterone supplementation in healthy men with an age-related decline of dehydroepiandrosterone secretion.  J Clin Endocrinol Metab 2001;864686- 4692PubMedGoogle ScholarCrossref
Morales  AJHaubricht  RHHwang  JYAsakura  HYen  SSC The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women.  Clin Endocrinol (Oxf) 1998;49421- 432PubMedGoogle ScholarCrossref
Wolf  OTNeumann  OHellhammer  DHGeiben  ACStrasburger  CJDressendorfer  RAPirke  KMKirschbaum  C Effects of a two-week physiological dehydroepiandrosterone substitution on cognitive performance and well-being in healthy elderly women and men.  J Clin Endocrinol Metab 1997;822363- 2367PubMedGoogle Scholar
Arlt  WJustl  HGCallies  FReincke  MHubler  DOettel  MErnst  MSchulte  HMAllolio  B Oral dehydroepiandrosterone for adrenal androgen replacement: pharmacokinetics and peripheral conversion to androgens and estrogens in young healthy females after dexamethasone suppression.  J Clin Endocrinol Metab 1998;831928- 1934PubMedGoogle ScholarCrossref
Johannsson  GBurman  PWiren  LEngstrom  BENilsson  AGOttosson  MJonsson  BBengtsson  BAKarlsson  FA Low dose dehydroepiandrosterone affects behavior in hypopituitary androgen-deficient women: a placebo-controlled trial.  J Clin Endocrinol Metab 2002;872046- 2052PubMedGoogle ScholarCrossref
Young  JCouzinet  BNahoul  KBrailly  SChanson  PBaulieu  EESchaison  G Panhypopituitarism as a model to study the metabolism of dehydroepiandrosterone (DHEA) in humans.  J Clin Endocrinol Metab 1997;822578- 2585PubMedGoogle Scholar
Arlt  WHaas  JCallies  FReincke  MHubler  DOettel  MErnst  MSchulte  HMAllolio  B Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens.  J Clin Endocrinol Metab 1999;842170- 2176PubMedGoogle ScholarCrossref
Flynn  MAWeaver-Osterholtz  DSharpe-Timms  KLAllen  SKrause  G Dehydroepiandrosterone replacement in aging humans.  J Clin Endocrinol Metab 1999;841527- 1533PubMedGoogle Scholar
Fabian  TJDew  MAPollock  BGReynolds  CF  IIIMulsant  BHButters  MAZmuda  MDLinares  AMTrottini  MKroboth  PD Endogenous concentrations of DHEA and DHEA-S decrease with remission of depression in older adults.  Biol Psychiatry 2001;50767- 774PubMedGoogle ScholarCrossref
Majewska  MD Neurosteroids: endogenous bimodal modulators of the GABAA receptor: mechanism of action and physiological significance.  Prog Neurobiol 1992;38379- 395PubMedGoogle ScholarCrossref
Lu  SFMo  QHu  SGarippa  CSimon  NG Dehydroepiandrosterone upregulates neural androgen receptor level and transcriptional activity.  J Neurobiol 2003;57163- 171PubMedGoogle ScholarCrossref
Sherwin  BBGelfand  MM Sex steroids and affect in the surgical menopause: a double-blind, cross-over study.  Psychoneuroendocrinology 1985;10325- 335PubMedGoogle ScholarCrossref
Klaiber  ELBroverman  DMGogel  WAbraham  GECone  FL Effects of infused testosterone on mental performances and serum LH.  J Clin Endocrinol Metab 1971;32341- 349PubMedGoogle ScholarCrossref
Anderson  RABancroft  JWu  FCW The effects of exogenous testosterone on sexuality and mood of normal men.  J Clin Endocrinol Metab 1992;751503- 1507PubMedGoogle Scholar
Cherrier  MMAsthana  SPlymate  SBaker  LMatsumoto  AMPeskind  ERaskind  MABrodkin  KBremner  WPetrova  ALaTendresse  SCraft  S Testosterone supplementation improves spatial and verbal memory in healthy older men.  Neurology 2001;5780- 88PubMedGoogle ScholarCrossref
Moffat  SDZonderman  ABMetter  EJBlackman  MRHarman  SMResnick  SM Longitudinal assessment of serum free testosterone concentration predicts memory performance and cognitive status in elderly men.  J Clin Endocrinol Metab 2002;875001- 5007PubMedGoogle ScholarCrossref
Yaffe  KLui  LYZmuda  JCauley  J Sex hormones and cognitive function in older men.  J Am Geriatr Soc 2002;50707- 712PubMedGoogle ScholarCrossref
Shifren  JLBraunstein  GDSimon  JACasson  PRBuster  JERedmond  GPBurki  REGinsburg  ESRosen  RCLeiblum  SRCaramelli  KEMazer  NA Transdermal testosterone treatment in women with impaired sexual function after oophorectomy.  N Engl J Med 2000;343682- 688PubMedGoogle ScholarCrossref
Weihua  ZLathe  RWarner  MGustafsson  JA An endocrine pathway in the prostate, ERβ, AR, 5α-androstane-3β, 17β-diol, and CYP7B1, regulates prostate growth.  Proc Natl Acad Sci U S A 2002;9913589- 13594PubMedGoogle ScholarCrossref
Park-Chung  MMalayev  APurdy  RHGibbs  TTFarb  DH Sulfated and unsulfated steroids modulate γ-aminobutyric acidA receptor function through distinct sites.  Brain Res 1999;83072- 87PubMedGoogle ScholarCrossref
Majewska  MD Neuronal actions of dehydroepiandrosterone: possible roles in brain development, aging, memory, and affect.  Ann N Y Acad Sci 1995;774111- 120PubMedGoogle ScholarCrossref
Abadie  JMWright  BCorrea  GBrowne  ESPorter  JRSvec  F Effect of dehydroepiandrosterone on neurotransmitter levels and appetite regulation of the obese Zucker rat: the Obesity Research Program.  Diabetes 1993;42662- 669PubMedGoogle ScholarCrossref
Debonnel  GBergeron  Rde Montigny  C Potentiation by dehydroepiandrosterone of the neuronal response to N-methyl-D-aspartate in the CA3 region of the rat dorsal hippocampus: an effect mediated via sigma receptors.  J Endocrinol 1996;150 ((suppl)) S33- S42PubMedGoogle ScholarCrossref
Monnet  FPMahé  VRobel  PBaulieu  EE Neurosteroids, via σ receptors, modulate the [3H]norepinephrine release evoked by N-methyl-D-aspartate in the rat hippocampus.  Proc Natl Acad Sci U S A 1995;923774- 3778PubMedGoogle ScholarCrossref
Kalimi  MShafagoj  YLoria  RPadgett  DRegelson  W Anti-glucocorticoid effects of dehydroepiandrosterone (DHEA).  Mol Cell Biochem 1994;13199- 104PubMedGoogle ScholarCrossref
Karishma  KKHerbert  J Dehydroepiandrosterone (DHEA) stimulates neurogenesis in the hippocampus of the rat, promotes survival of newly formed neurons and prevents corticosterone-induced suppression.  Eur J Neurosci 2002;16445- 453PubMedGoogle ScholarCrossref
Hajszan  TMacLusky  NJLeranth  C Dehydroepiandrosterone increases hippocampal spine synapse density in ovariectomized female rats.  Endocrinology 2004;1451042- 1045PubMedGoogle ScholarCrossref
Zhang  LLi  BMa  WBarker  JLChang  YHZhao  WRubinow  DR Dehydroepiandrosterone (DHEA) and its sulfated derivative (DHEAS) regulate apoptosis during neurogenesis by triggering the Akt signaling pathway in opposing ways.  Brain Res Mol Brain Res 2002;9858- 66PubMedGoogle ScholarCrossref
Wolkowitz  OMReus  VI Dehydroepiandrosterone in psychoneuroendocrinology. Wolkowitz  OMRothschild  AJeds. Psychoneuroendocrinology The Scientific Basis of Clinical Practice Washington, DC American Psychiatric Publishing Inc2003;205- 242Google Scholar
Buvat  J Androgen therapy with dehydroepiandrosterone.  World J Urol 2003;21346- 355PubMedGoogle ScholarCrossref
Original Article
February 2005

Dehydroepiandrosterone Monotherapy in Midlife-Onset Major and Minor Depression

Author Affiliations

Author Affiliations: Behavioral Endocrinology Branch, National Institute of Mental Health, Rockville, Md (Drs Schmidt, Daly, Bloch, Smith, and Rubinow, and Mss Simpson St Clair, Murphy, and Haq); and Clinical Center Nursing Department, National Institutes of Health, Department of Health and Human Services, Bethesda, Md (Ms Danaceau).

Arch Gen Psychiatry. 2005;62(2):154-162. doi:10.1001/archpsyc.62.2.154

Context  Alternative and over-the-counter medicines have become increasingly popular choices for many patients who prefer not to take traditional antidepressants. The adrenal androgen and neurosteroid dehydroepiandrosterone (DHEA) is available as over-the-counter hormonal therapy and previously has been reported to have antidepressant-like effects.

Objective  To evaluate the efficacy of DHEA as a monotherapy treatment for midlife-onset depression.

Design  A double-blind, randomized, placebo-controlled, crossover treatment study was performed from January 4, 1996, through August 31, 2002.

Settings  The National Institute of Mental Health Midlife Outpatient Clinic in the National Institutes of Health Clinical Center, Bethesda, Md.

Patients  Men (n = 23) and women (n = 23) aged 45 to 65 years with midlife-onset major or minor depression participated in this study. None of the subjects received concurrent antidepressant medications.

Intervention  Six weeks of DHEA therapy, 90 mg/d for 3 weeks and 450 mg/d for 3 weeks, and 6 weeks of placebo.

Main Outcome Measures  The 17-Item Hamilton Depression Rating Scale and Center for Epidemiologic Studies Depression Scale. Additional measures included the Derogatis Interview for Sexual Functioning. Results were analyzed by means of repeated-measures analysis of variance and post hoc Bonferroni t tests.

Results  Six weeks of DHEA administration was associated with a significant improvement in the 17-Item Hamilton Depression Rating Scale and the Center for Epidemiologic Studies Depression Scale ratings compared with both baseline (P<.01) and 6 weeks of placebo treatment (P<.01). A 50% or greater reduction in baseline Hamilton Depression Rating Scale scores was observed in 23 subjects after DHEA and in 13 subjects after placebo treatments. Six weeks of DHEA treatment also was associated with significant improvements in Derogatis Interview for Sexual Functioning scores relative to baseline and placebo conditions.

Conclusion  We find DHEA to be an effective treatment for midlife-onset major and minor depression.