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The Impact of Gender on Antidepressants

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Biological Basis of Sex Differences in Psychopharmacology

Part of the book series: Current Topics in Behavioral Neurosciences ((CTBN,volume 8))

Abstract

There is a large body of literature debating whether and how gender affects the metabolism, side-effect profile, and efficacy of antidepressants. Gender differences in antidepressant pharmacokinetics and efficacy profiles have been attributed to not only anatomic and physiological differences between the sexes, but also behavioral factors, comorbid disorders, and gender-specific conditions, such as pregnancy and menopause. Despite the large body of research on this topic, few definitive conclusions regarding effects of gender on antidepressant treatment exist, and much of this research is incomplete, contradictory, or not fully used to optimize the administration of antidepressants and the response to treatment. This chapter will review the latest research on gender-specific effects of antidepressant treatment, focusing on the overall, gender-related differences in efficacy, metabolism, and side-effect profile of antidepressants, and how these differences can be used to better optimize treatment of depression in a clinical setting.

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References

  • Abe T, Suzuki M, Wada Y, Yamaya Y, Moritsuka T (1985) Clinical and endocrinological features of statistical clusters of women with climacteric symptoms. Tohoku J Exp Med 146:59–68

    PubMed  CAS  Google Scholar 

  • Abernethy DR, Greenblatt DJ, Shader RI (1985) Imipramine and desipramine disposition in the elderly. J Pharmacol Exp Ther 232:183–188

    PubMed  CAS  Google Scholar 

  • Anand A, Charney DS (2000) Norepinephrine dysfunction in depression. J Clin Psychiatry 61(Suppl 10):16–24

    PubMed  CAS  Google Scholar 

  • Andersen SL, Rutstein M, Benzo JM, Hostetter JC, Teicher MH (1997) Sex differences in dopamine receptor overproduction and elimination. Neuroreport 8:1495–1498

    PubMed  CAS  Google Scholar 

  • Angst J, Dobler-Mikola A (1984) Do the diagnostic criteria determine the sex ratio in depression? J Affect Disord 7:189–198

    PubMed  CAS  Google Scholar 

  • Avis NE, Brambilla D, McKinlay SM, Vass K (1994) A longitudinal analysis of the association between menopause and depression. Results from the Massachusetts Women’s Health Study. Ann Epidemiol 4:214–220

    PubMed  CAS  Google Scholar 

  • Baca E, Garcia-Garcia M, Porras-Chavarino A (2004) Gender differences in treatment response to sertraline versus imipramine in patients with nonmelancholic depressive disorders. Prog Neuropsychopharmacol Biol Psychiatry 28:57–65

    PubMed  CAS  Google Scholar 

  • Baron P, Joly E (1988) Sex differences in the expression of depression in adolescents. Sex Roles 18:1–7

    Google Scholar 

  • Bebbington P, Dunn G, Jenkins R, Lewis G, Brugha T, Farrell M, Meltzer H (2003) The influence of age and sex on the prevalence of depressive conditions: report from the National Survey of Psychiatric Morbidity. Int Rev Psychiatry 15:74–83

    PubMed  CAS  Google Scholar 

  • Berlanga C, Flores-Ramos M (2006) Different gender response to serotonergic and noradrenergic antidepressants. A comparative study of the efficacy of citalopram and reboxetine. J Affect Disord 95:119–123

    PubMed  CAS  Google Scholar 

  • Bock KW, Schrenk D, Forster A, Griese EU, Morike K, Brockmeier D, Eichelbaum M (1994) The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine, and paracetamol as probes. Pharmacogenetics 4:209–218

    PubMed  CAS  Google Scholar 

  • Brown AS, Gershon S (1993) Dopamine and depression. J Neural Transm Gen Sect 91:75–109

    PubMed  CAS  Google Scholar 

  • Bruno R, Vivier N, Montay G, Le Liboux A, Powe LK, Delumeau JC, Rhodes GR (1997) Population pharmacokinetics of riluzole in patients with amyotrophic lateral sclerosis. Clin Pharmacol Ther 62:518–526

    PubMed  CAS  Google Scholar 

  • Bryant DN, Sheldahl LC, Marriott LK, Shapiro RA, Dorsa DM (2006) Multiple pathways transmit neuroprotective effects of gonadal steroids. Endocrine 29:199–207

    PubMed  CAS  Google Scholar 

  • Carretti N, Florio P, Bertolin A, Costa CV, Allegri G, Zilli G (2005) Serum fluctuations of total and free tryptophan levels during the menstrual cycle are related to gonadotrophins and reflect brain serotonin utilization. Hum Reprod 20:1548–1553

    PubMed  CAS  Google Scholar 

  • Daly RC, Danaceau MA, Rubinow DR, Schmidt PJ (2003) Concordant restoration of ovarian function and mood in perimenopausal depression. Am J Psychiatry 160:1842–1846

    PubMed  Google Scholar 

  • Davidson J, Pelton S (1986) Forms of atypical depression and their response to antidepressant drugs. Psychiatry Res 17:87–95

    PubMed  CAS  Google Scholar 

  • Dawkins K, Potter WZ (1991) Gender differences in pharmacokinetics and pharmacodynamics of psychotropics: focus on women. Psychopharmacol Bull 27:417–426

    PubMed  CAS  Google Scholar 

  • Delgado PL, Moreno FA (2000) Role of norepinephrine in depression. J Clin Psychiatry 61(Suppl 1):5–12

    PubMed  CAS  Google Scholar 

  • D'Haenen HA, Bossuyt A (1994) Dopamine D2 receptors in depression measured with single photon emission computed tomography. Biol Psychiatry 35:128–132

    PubMed  Google Scholar 

  • Dhir A, Kulkarni SK (2007) Involvement of dopamine (DA)/serotonin (5-HT)/sigma (sigma) receptor modulation in mediating the antidepressant action of ropinirole hydrochloride, a D2/D3 dopamine receptor agonist. Brain Res Bull 74:58–65

    PubMed  CAS  Google Scholar 

  • Dluzen DE, McDermott JL (2008) Sex differences in dopamine- and vesicular monoamine-transporter functions. Ann N Y Acad Sci 1139:140–150

    PubMed  CAS  Google Scholar 

  • Entsuah AR, Huang H, Thase ME (2001) Response and remission rates in different subpopulations with major depressive disorder administered venlafaxine, selective serotonin reuptake inhibitors, or placebo. J Clin Psychiatry 62:869–877

    PubMed  CAS  Google Scholar 

  • Ereshefsky L, Saklad SR, Watanabe MD, Davis CM, Jann MW (1991) Thiothixene pharmacokinetic interactions: a study of hepatic enzyme inducers, clearance inhibitors, and demographic variables. J Clin Psychopharmacol 11:296–301

    PubMed  CAS  Google Scholar 

  • Frackiewicz EJ, Sramek JJ, Cutler NR (2000) Gender differences in depression and antidepressant pharmacokinetics and adverse events. Ann Pharmacother 34:80–88

    PubMed  CAS  Google Scholar 

  • Franconi F, Brunelleschi S, Steardo L, Cuomo V (2007) Gender differences in drug responses. Pharmacol Res 55:81–95

    PubMed  CAS  Google Scholar 

  • Frank E, Carpenter LL, Kupfer DJ (1988) Sex differences in recurrent depression: are there any that are significant? Am J Psychiatry 145:41–45

    PubMed  CAS  Google Scholar 

  • Freeman EW, Sammel MD, Liu L, Gracia CR, Nelson DB, Hollander L (2004) Hormones and menopausal status as predictors of depression in women in transition to menopause. Arch Gen Psychiatry 61:62–70

    PubMed  CAS  Google Scholar 

  • Freeman EW, Sammel MD, Lin H, Nelson DB (2006) Associations of hormones and menopausal status with depressed mood in women with no history of depression. Arch Gen Psychiatry 63:375–382

    PubMed  CAS  Google Scholar 

  • Gex-Fabry M, Balant-Gorgia AE, Balant LP, Garrone G (1990) Clomipramine metabolism. Model-based analysis of variability factors from drug monitoring data. Clin Pharmacokinet 19:241–255

    PubMed  CAS  Google Scholar 

  • Grigoriadis S, Kennedy SH, Bagby RM (2003) A comparison of antidepressant response in younger and older women. J Clin Psychopharmacol 23:405–407

    PubMed  CAS  Google Scholar 

  • Guiard BP, El Mansari M, Blier P (2009) Prospect of a dopamine contribution in the next generation of antidepressant drugs: the triple reuptake inhibitors. Curr Drug Targets 10:1069–1084

    PubMed  CAS  Google Scholar 

  • Halbreich U, Lumley LA (1993) The multiple interactional biological processes that might lead to depression and gender differences in its appearance. J Affect Disord 29:159–173

    PubMed  CAS  Google Scholar 

  • Halbreich U, Rojansky N, Palter S, Tworek H, Hissin P, Wang K (1995) Estrogen augments serotonergic activity in postmenopausal women. Biol Psychiatry 37:434–441

    PubMed  CAS  Google Scholar 

  • Hamilton JA, Grant M, Jensvold MF (1996) Sex and treatment of depression: when does it matter? In: Jensvold MF (ed) Psychopharmacology and women: sex, gender, and hormones. American Psychiatric Press, lnc, Washington, DC, pp 241–257

    Google Scholar 

  • Hamner MB, Diamond BI (1996) Plasma dopamine and norepinephrine correlations with psychomotor retardation, anxiety, and depression in non-psychotic depressed patients: a pilot study. Psychiatry Res 64:209–211

    PubMed  CAS  Google Scholar 

  • Hankin BL, Abramson LY (2001) Development of gender differences in depression: an elaborated cognitive vulnerability-transactional stress theory. Psychol Bull 127:773–796

    PubMed  CAS  Google Scholar 

  • Harlow BL, Wise LA, Otto MW, Soares CN, Cohen LS (2003) Depression and its influence on reproductive endocrine and menstrual cycle markers associated with perimenopause: the Harvard Study of Moods and Cycles. Arch Gen Psychiatry 60:29–36

    PubMed  Google Scholar 

  • Haykal RF, Akiskal HS (1999) The long-term outcome of dysthymia in private practice: clinical features, temperament, and the art of management. J Clin Psychiatry 60:508–518

    PubMed  CAS  Google Scholar 

  • Hildebrandt MG, Steyerberg EW, Stage KB, Passchier J, Kragh-Soerensen P (2003) Are gender differences important for the clinical effects of antidepressants? Am J Psychiatry 160:1643–1650

    PubMed  Google Scholar 

  • Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23:477–501

    PubMed  CAS  Google Scholar 

  • Holsboer F, Barden N (1996) Antidepressants and hypothalamic-pituitary-adrenocortical regulation. Endocr Rev 17:187–205

    PubMed  CAS  Google Scholar 

  • Hunt CM, Westerkam WR, Stave GM (1992) Effect of age and gender on the activity of human hepatic CYP3A. Biochem Pharmacol 44:275–283

    PubMed  CAS  Google Scholar 

  • Hutson WR, Roehrkasse RL, Wald A (1989) Influence of gender and menopause on gastric emptying and motility. Gastroenterology 96:11–17

    PubMed  CAS  Google Scholar 

  • Kessler RC (2003) Epidemiology of women and depression. J Affect Disord 74:5–13

    PubMed  Google Scholar 

  • Kessler RC, McGonagle KA, Swartz M, Blazer DG, Nelson CB (1993) Sex and depression in the National Comorbidity Survey. I: Lifetime prevalence, chronicity and recurrence. J Affect Disord 29:85–96

    PubMed  CAS  Google Scholar 

  • Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS (1994) Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51:8–19

    PubMed  CAS  Google Scholar 

  • Khan A, Brodhead AE, Schwartz KA, Kolts RL, Brown WA (2005) Sex differences in antidepressant response in recent antidepressant clinical trials. J Clin Psychopharmacol 25:318–324

    PubMed  Google Scholar 

  • Kim RB, O'Shea D (1995) Interindividual variability of chlorzoxazone 6-hydroxylation in men and women and its relationship to CYP2E1 genetic polymorphisms. Clin Pharmacol Ther 57:645–655

    PubMed  CAS  Google Scholar 

  • Kim RB, Leake BF, Choo EF, Dresser GK, Kubba SV, Schwarz UI, Taylor A, Xie HG, McKinsey J, Zhou S, Lan LB, Schuetz JD, Schuetz EG, Wilkinson GR (2001) Identification of functionally variant MDR1 alleles among European Americans and African Americans. Clin Pharmacol Ther 70:189–199

    PubMed  CAS  Google Scholar 

  • Klimek V, Schenck JE, Han H, Stockmeier CA, Ordway GA (2002) Dopaminergic abnormalities in amygdaloid nuclei in major depression: a postmortem study. Biol Psychiatry 52:740–748

    PubMed  CAS  Google Scholar 

  • Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, Gelenberg AJ, Davis SM, Harrison WM, Keller MB (2000a) Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry 157:1445–1452

    PubMed  CAS  Google Scholar 

  • Kornstein SG, Schatzberg AF, Thase ME, Yonkers KA, McCullough JP, Keitner GI, Gelenberg AJ, Ryan CE, Hess AL, Harrison W, Davis SM, Keller MB (2000b) Gender differences in chronic major and double depression. J Affect Disord 60:1–11

    PubMed  CAS  Google Scholar 

  • Kumar AM, Weiss S, Fernandez JB, Cruess D, Eisdorfer C (1998) Peripheral serotonin levels in women: role of aging and ethnicity. Gerontology 44:211–216

    PubMed  CAS  Google Scholar 

  • Laakso A, Vilkman H, Bergman J, Haaparanta M, Solin O, Syvalahti E, Salokangas RK, Hietala J (2002) Sex differences in striatal presynaptic dopamine synthesis capacity in healthy subjects. Biol Psychiatry 52:759–763

    PubMed  CAS  Google Scholar 

  • Labbe L, Sirois C, Pilote S, Arseneault M, Robitaille NM, Turgeon J, Hamelin BA (2000) Effect of gender, sex hormones, time variables and physiological urinary pH on apparent CYP2D6 activity as assessed by metabolic ratios of marker substrates. Pharmacogenetics 10:425–438

    PubMed  CAS  Google Scholar 

  • Lambert G, Johansson M, Agren H, Friberg P (2000) Reduced brain norepinephrine and dopamine release in treatment-refractory depressive illness: evidence in support of the catecholamine hypothesis of mood disorders. Arch Gen Psychiatry 57:787–793

    PubMed  CAS  Google Scholar 

  • Lan LB, Dalton JT, Schuetz EG (2000) Mdr1 limits CYP3A metabolism in vivo. Mol Pharmacol 58:863–869

    PubMed  CAS  Google Scholar 

  • Legato MJ (1997) Gender-specific physiology: how real is it? How important is it? Int J Fertil Womens Med 42:19–29

    PubMed  CAS  Google Scholar 

  • Leibenluft E, Hardin TA, Rosenthal NE (1995) Gender differences in seasonal affective disorder. Depression 3:13–19

    Google Scholar 

  • Lucas D, Menez C, Girre C, Berthou F, Bodenez P, Joannet I, Hispard E, Bardou LG, Menez JF (1995) Cytochrome P450 2E1 genotype and chlorzoxazone metabolism in healthy and alcoholic Caucasian subjects. Pharmacogenetics 5:298–304

    PubMed  CAS  Google Scholar 

  • Lucht M, Schaub RT, Meyer C, Hapke U, Rumpf HJ, Bartels T, von Houwald J, Barnow S, Freyberger HJ, Dilling H, John U (2003) Gender differences in unipolar depression: a general population survey of adults between age 18 to 64 of German nationality. J Affect Disord 77:203–211

    PubMed  CAS  Google Scholar 

  • Martenyi F, Dossenbach M, Mraz K, Metcalfe S (2001) Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile. Eur Neuropsychopharmacol 11:227–232

    PubMed  CAS  Google Scholar 

  • McKinlay JB, McKinlay SM, Brambilla DJ (1987) Health status and utilization behavior associated with menopause. Am J Epidemiol 125:110–121

    PubMed  CAS  Google Scholar 

  • Meibohm B, Beierle I, Derendorf H (2002) How important are gender differences in pharmacokinetics? Clin Pharmacokinet 41:329–342

    PubMed  CAS  Google Scholar 

  • Meltzer CC, Drevets WC, Price JC, Mathis CA, Lopresti B, Greer PJ, Villemagne VL, Holt D, Mason NS, Houck PR, Reynolds CF III, DeKosky ST (2001) Gender-specific aging effects on the serotonin 1A receptor. Brain Res 895:9–17

    CAS  Google Scholar 

  • Meyer JH, Kruger S, Wilson AA, Christensen BK, Goulding VS, Schaffer A, Minifie C, Houle S, Hussey D, Kennedy SH (2001) Lower dopamine transporter binding potential in striatum during depression. Neuroreport 12:4121–4125

    PubMed  CAS  Google Scholar 

  • Miller A, Fox NA, Cohn JF, Forbes EE, Sherrill JT, Kovacs M (2002) Regional patterns of brain activity in adults with a history of childhood-onset depression: gender differences and clinical variability. Am J Psychiatry 159:934–940

    PubMed  Google Scholar 

  • Moreno FA, McGahuey CA, Freeman MP, Delgado PL (2006) Sex differences in depressive response during monoamine depletions in remitted depressive subjects. J Clin Psychiatry 67:1618–1623

    PubMed  CAS  Google Scholar 

  • Morrison MF, Kallan MJ, Ten Have T, Katz I, Tweedy K, Battistini M (2004) Lack of efficacy of estradiol for depression in postmenopausal women: a randomized, controlled trial. Biol Psychiatry 55:406–412

    PubMed  CAS  Google Scholar 

  • Munro CA, McCaul ME, Wong DF, Oswald LM, Zhou Y, Brasic J, Kuwabara H, Kumar A, Alexander M, Ye W, Wand GS (2006) Sex differences in striatal dopamine release in healthy adults. Biol Psychiatry 59:966–974

    PubMed  CAS  Google Scholar 

  • Nafziger AN, Bertino JS Jr (1989) Sex-related differences in theophylline pharmacokinetics. Eur J Clin Pharmacol 37:97–100

    PubMed  CAS  Google Scholar 

  • Naito S, Sato K, Yoshida K, Higuchi H, Takahashi H, Kamata M, Ito K, Ohkubo T, Shimizu T (2007) Gender differences in the clinical effects of fluvoxamine and milnacipran in Japanese major depressive patients. Psychiatry Clin Neurosci 61:421–427

    PubMed  CAS  Google Scholar 

  • Nathorst-Boos J, von Schoultz B, Carlstrom K (1993) Elective ovarian removal and estrogen replacement therapy–effects on sexual life, psychological well-being and androgen status. J Psychosom Obstet Gynaecol 14:283–293

    PubMed  CAS  Google Scholar 

  • Nishizawa S, Benkelfat C, Young SN, Leyton M, Mzengeza S, de Montigny C, Blier P, Diksic M (1997) Differences between males and females in rates of serotonin synthesis in human brain. Proc Natl Acad Sci U S A 94:5308–5313

    PubMed  CAS  PubMed Central  Google Scholar 

  • Nolen-Hoeksema S (1990) Sex differences in depression. Stanford University Press, Stanford CA

    Google Scholar 

  • Nolen-Hoeksema S, Larson J, Grayson C (1999) Explaining the gender difference in depressive symptoms. J Pers Soc Psychol 77:1061–1072

    PubMed  CAS  Google Scholar 

  • Ou-Yang DS, Huang SL, Wang W, Xie HG, Xu ZH, Shu Y, Zhou HH (2000) Phenotypic polymorphism and gender-related differences of CYP1A2 activity in a Chinese population. Br J Clin Pharmacol 49:145–151

    PubMed  CAS  PubMed Central  Google Scholar 

  • Owens MJ, Nemeroff CB (1994) Role of serotonin in the pathophysiology of depression: focus on the serotonin transporter. Clin Chem 40:288–295

    PubMed  CAS  Google Scholar 

  • Pae CU, Mandelli L, Kim TS, Han C, Masand PS, Marks DM, Patkar AA, Steffens DC, De Ronchi D, Serretti A (2009) Effectiveness of antidepressant treatments in pre-menopausal versus post-menopausal women: a pilot study on differential effects of sex hormones on antidepressant effects. Biomed Pharmacother 63:228–235

    PubMed  CAS  Google Scholar 

  • Pariante CM (2003) Depression, stress and the adrenal axis. J Neuroendocrinol 15:811–812

    PubMed  Google Scholar 

  • Parker G, Parker K, Austin MP, Mitchell P, Brotchie H (2003) Gender differences in response to differing antidepressant drug classes: two negative studies. Psychol Med 33:1473–1477

    PubMed  CAS  Google Scholar 

  • Parry BL (1989) Reproductive factors affecting the course of affective illness in women. Psychiatr Clin North Am 12:207–220

    PubMed  CAS  Google Scholar 

  • Parry BL, Newton RP (2001) Chronobiological basis of female-specific mood disorders. Neuropsychopharmacology 25:S102–S108

    PubMed  CAS  Google Scholar 

  • Pinto-Meza A, Usall J, Serrano-Blanco A, Suarez D, Haro JM (2006) Gender differences in response to antidepressant treatment prescribed in primary care. Does menopause make a difference? J Affect Disord 93:53–60

    PubMed  CAS  Google Scholar 

  • Preskorn SH, Mac DS (1985) Plasma levels of amitriptyline: effect of age and sex. J Clin Psychiatry 46:276–277

    PubMed  CAS  Google Scholar 

  • Quitkin FM, Stewart JW, McGrath PJ (2001) Gender differences in treatment response. Am J Psychiatry 158:1531–1533

    PubMed  CAS  Google Scholar 

  • Quitkin FM, Stewart JW, McGrath PJ, Taylor BP, Tisminetzky MS, Petkova E, Chen Y, Ma G, Klein DF (2002) Are there differences between women's and men's antidepressant responses? Am J Psychiatry 159:1848–1854

    PubMed  Google Scholar 

  • Rakofsky JJ, Holtzheimer PE, Nemeroff CB (2009) Emerging targets for antidepressant therapies. Curr Opin Chem Biol 13:291–302

    PubMed  CAS  Google Scholar 

  • Rapaport MH, Thompson PM, Kelsoe JR Jr, Golshan S, Judd LL, Gillin JC (1995) Gender differences in outpatient research subjects with affective disorders: a comparison of descriptive variables. J Clin Psychiatry 56:67–72

    PubMed  CAS  Google Scholar 

  • Renshaw PF, Parow AM, Hirashima F, Ke Y, Moore CM, Frederick Bde B, Fava M, Hennen J, Cohen BM (2001) Multinuclear magnetic resonance spectroscopy studies of brain purines in major depression. Am J Psychiatry 158:2048–2055

    PubMed  CAS  Google Scholar 

  • Rivest R, Falardeau P, Di Paolo T (1995) Brain dopamine transporter: gender differences and effect of chronic haloperidol. Brain Res 692:269–272

    PubMed  CAS  Google Scholar 

  • Roy A, Pickar D, Linnoila M, Potter WZ (1985) Plasma norepinephrine level in affective disorders. Relationship to melancholia. Arch Gen Psychiatry 42:1181–1185

    PubMed  CAS  Google Scholar 

  • Sagud M, Hotujac L, Mihaljevic-Peles A, Jakovljevic M (2002) Gender differences in depression. Coll Antropol 26:149–157

    PubMed  CAS  Google Scholar 

  • Sakai Y, Nishikawa M, Leyton M, Benkelfat C, Young SN, Diksic M (2006) Cortical trapping of alpha-[(11)C]methyl-l-tryptophan, an index of serotonin synthesis, is lower in females than males. Neuroimage 33:815–824

    PubMed  CAS  Google Scholar 

  • Schmidt R, Baumann F, Hanschmann H, Geissler F, Preiss R (2001) Gender difference in ifosfamide metabolism by human liver microsomes. Eur J Drug Metab Pharmacokinet 26:193–200

    PubMed  CAS  Google Scholar 

  • Schmidt PJ, Haq N, Rubinow DR (2004) A longitudinal evaluation of the relationship between reproductive status and mood in perimenopausal women. Am J Psychiatry 161:2238–2244

    PubMed  Google Scholar 

  • Schneider LS, Small GW, Hamilton SH, Bystritsky A, Nemeroff CB, Meyers BS (1997) Estrogen replacement and response to fluoxetine in a multicenter geriatric depression trial. Fluoxetine Collaborative Study Group. Am J Geriatr Psychiatry 5:97–106

    PubMed  CAS  Google Scholar 

  • Schuetz EG, Furuya KN, Schuetz JD (1995) Interindividual variation in expression of P-glycoprotein in normal human liver and secondary hepatic neoplasms. J Pharmacol Exp Ther 275:1011–1018

    PubMed  CAS  Google Scholar 

  • Seeman MV (1997) Psychopathology in women and men: focus on female hormones. Am J Psychiatry 154:1641–1647

    PubMed  CAS  Google Scholar 

  • Shah PJ, Ogilvie AD, Goodwin GM, Ebmeier KP (1997) Clinical and psychometric correlates of dopamine D2 binding in depression. Psychol Med 27:1247–1256

    PubMed  CAS  Google Scholar 

  • Shifren JL, Avis NE (2007) Surgical menopause: effects on psychological well-being and sexuality. Menopause 14:586–591

    PubMed  Google Scholar 

  • Shimizu H, Bray GA (1993) Effects of castration, estrogen replacement and estrus cycle on monoamine metabolism in the nucleus accumbens, measured by microdialysis. Brain Res 621:200–206

    PubMed  CAS  Google Scholar 

  • Soares CN, Almeida OP, Joffe H, Cohen LS (2001) Efficacy of estradiol for the treatment of depressive disorders in perimenopausal women: a double-blind, randomized, placebo-controlled trial. Arch Gen Psychiatry 58:529–534

    PubMed  CAS  Google Scholar 

  • Sofuoglu M, Mitchell E, Kosten TR (2004) Effects of progesterone treatment on cocaine responses in male and female cocaine users. Pharmacol Biochem Behav 78:699–705

    PubMed  CAS  Google Scholar 

  • Staley JK, Krishnan-Sarin S, Zoghbi S, Tamagnan G, Fujita M, Seibyl JP, Maciejewski PK, O'Malley S, Innis RB (2001) Sex differences in [123I]beta-CIT SPECT measures of dopamine and serotonin transporter availability in healthy smokers and nonsmokers. Synapse 41:275–284

    PubMed  CAS  Google Scholar 

  • Stewart DE, Rolfe DE, Robertson E (2004) Depression, estrogen, and the Women's Health Initiative. Psychosomatics 45:445–447

    PubMed  Google Scholar 

  • Succari M, Foglietti MJ, Percheron F (1990) Microheterogeneity of alpha 1-acid glycoprotein: variation during the menstrual cycle in healthy women, and profile in women receiving estrogen-progestogen treatment. Clin Chim Acta 187:235–241

    PubMed  CAS  Google Scholar 

  • Swaab DF, Bao AM, Lucassen PJ (2005) The stress system in the human brain in depression and neurodegeneration. Ageing Res Rev 4:141–194

    PubMed  CAS  Google Scholar 

  • Thase ME, Frank E, Kornstein SG, Yonkers KA (2000) Gender differences in response to treatments of depression. In: Frank E (ed) Gender and its effects on psychopathology. American Psychiatric Press, Washington, pp 103–125

    Google Scholar 

  • Thiels C, Linden M, Grieger F, Leonard J (2005) Gender differences in routine treatment of depressed outpatients with the selective serotonin reuptake inhibitor sertraline. Int Clin Psychopharmacol 20:1–7

    PubMed  Google Scholar 

  • Timmer CJ, Sitsen JM, Delbressine LP (2000) Clinical pharmacokinetics of mirtazapine. Clin Pharmacokinet 38:461–474

    PubMed  CAS  Google Scholar 

  • Vadakkadath Meethal S, Atwood CS (2005) The role of hypothalamic-pituitary-gonadal hormones in the normal structure and functioning of the brain. Cell Mol Life Sci 62:257–270

    PubMed  CAS  Google Scholar 

  • van Amelsvoort TA, Abel KM, Robertson DM, Daly E, Critchley H, Whitehead M, Murphy DG (2001) Prolactin response to d-fenfluramine in postmenopausal women on and off ERT: comparison with young women. Psychoneuroendocrinology 26:493–502

    PubMed  Google Scholar 

  • Vredenburg K, Krames L, Flett GL (1986) Sex differences in the clinical expression of depression. Sex Roles 14:37–49

    Google Scholar 

  • Weissman MM, Klerman GL (1977) Sex differences and the epidemiology of depression. Arch Gen Psychiatry 34:98–111

    PubMed  CAS  Google Scholar 

  • Weissman MM, Bland R, Joyce PR, Newman S, Wells JE, Wittchen HU (1993) Sex differences in rates of depression: cross-national perspectives. J Affect Disord 29:77–84

    PubMed  CAS  Google Scholar 

  • Weissman MM, Bland RC, Canino GJ, Faravelli C, Greenwald S, Hwu HG, Joyce PR, Karam EG, Lee CK, Lellouch J, Lepine JP, Newman SC, Rubio-Stipec M, Wells JE, Wickramaratne PJ, Wittchen H, Yeh EK (1996) Cross-national epidemiology of major depression and bipolar disorder. JAMA 276:293–299

    PubMed  CAS  Google Scholar 

  • White TL, Justice AJ, de Wit H (2002) Differential subjective effects of D-amphetamine by gender, hormone levels and menstrual cycle phase. Pharmacol Biochem Behav 73:729–741

    PubMed  CAS  Google Scholar 

  • Wilhelm K, Roy K, Mitchell P, Brownhill S, Parker G (2002) Gender differences in depression risk and coping factors in a clinical sample. Acta Psychiatr Scand 106:45–53

    PubMed  CAS  Google Scholar 

  • Williams JB, Spitzer RL, Linzer M, Kroenke K, Hahn SR, deGruy FV, Lazev A (1995) Gender differences in depression in primary care. Am J Obstet Gynecol 173:654–659

    PubMed  CAS  Google Scholar 

  • Winokur G (1973) Depression in the menopause. Am J Psychiatry 130:92–93

    PubMed  CAS  Google Scholar 

  • Wohlfarth T, Storosum JG, Elferink AJ, van Zwieten BJ, Fouwels A, van den Brink W (2004) Response to tricyclic antidepressants: independent of gender? Am J Psychiatry 161:370–372

    PubMed  Google Scholar 

  • Xiao L, Becker JB (1994) Quantitative microdialysis determination of extracellular striatal dopamine concentration in male and female rats: effects of estrous cycle and gonadectomy. Neurosci Lett 180:155–158

    PubMed  CAS  Google Scholar 

  • Yonkers KA, Brawman-Mintzer O (2002) The pharmacologic treatment of depression: is gender a critical factor? J Clin Psychiatry 63:610–615

    PubMed  Google Scholar 

  • Yonkers KA, Kando JC, Cole JO, Blumenthal S (1992) Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry 149:587–595

    PubMed  CAS  Google Scholar 

  • Young EA (1995) The role of gonadal steroids in hypothalamic-pituitary-adrenal axis regulation. Crit Rev Neurobiol 9:371–381

    PubMed  CAS  Google Scholar 

  • Young SN, Gauthier S, Anderson GM, Purdy WC (1980) Tryptophan, 5-hydroxyindoleacetic acid and indoleacetic acid in human cerebrospinal fluid: interrelationships and the influence of age, sex, epilepsy and anticonvulsant drugs. J Neurol Neurosurg Psychiatry 43:438–445

    PubMed  CAS  PubMed Central  Google Scholar 

  • Young MA, Scheftner WA, Fawcett J, Klerman GL (1990) Gender differences in the clinical features of unipolar major depressive disorder. J Nerv Ment Dis 178:200–203

    PubMed  CAS  Google Scholar 

  • Young EA, Midgley AR, Carlson NE, Brown MB (2000) Alteration in the hypothalamic-pituitary-ovarian axis in depressed women. Arch Gen Psychiatry 57:1157–1162

    PubMed  CAS  Google Scholar 

  • Young EA, Kornstein SG, Marcus SM, Harvey AT, Warden D, Wisniewski SR, Balasubramani GK, Fava M, Trivedi MH, John Rush A (2009) Sex differences in response to citalopram: a STAR*D report. J Psychiatr Res 43:503–511

    PubMed  PubMed Central  Google Scholar 

  • Zanardi R, Rossini D, Magri L, Malaguti A, Colombo C, Smeraldi E (2007) Response to SSRIs and role of the hormonal therapy in post-menopausal depression. Eur Neuropsychopharmacol 17:400–405

    PubMed  CAS  Google Scholar 

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Acknowledgment

The authors acknowledge Andrew Kuhlman for his assistance in compiling, writing, and editing this chapter.

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Sramek, J.J., Cutler, N.R. (2011). The Impact of Gender on Antidepressants. In: Neill, J., Kulkarni, J. (eds) Biological Basis of Sex Differences in Psychopharmacology. Current Topics in Behavioral Neurosciences, vol 8. Springer, Berlin, Heidelberg. https://doi.org/10.1007/7854_2010_118

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