Hostname: page-component-cd9895bd7-gvvz8 Total loading time: 0 Render date: 2024-12-23T11:48:14.321Z Has data issue: false hasContentIssue false
  • English
  • Français

Pharmacokinetics and pharmacodinamics of psychotropic drugs: effect of sex

Published online by Cambridge University Press:  04 February 2013

Donatella Marazziti ,
Stefano Baroni ,
Michela Picchetti ,
Armando Piccinni ,
Marina Carlini ,
Elena Vatteroni ,
Valentina Falaschi ,
Amedeo Lombardi  and
Liliana Dell'Osso
Donatella Marazziti*
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
Stefano Baroni
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
Michela Picchetti
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
Armando Piccinni
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
Marina Carlini
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
Elena Vatteroni
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
Valentina Falaschi
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
Amedeo Lombardi
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
Liliana Dell'Osso
Affiliation:
Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Pisa, Italy
*
*Address for correspondence: Donatella Marazziti, MD, Dipartimento di Psichiatria, Neurobiologia, Farmacologia e Biotecnologie, University of Pisa, Via Roma 67, 56100 Pisa, Italy. (Email [email protected])
Get access Rights & Permissions [Opens in a new window]

Abstract

Data on the specific effects of sex on pharmacokinetics, as well as tolerability, safety, and efficacy of psychotropic medications are still meager, mainly because only recently sex-related issues have attracted a certain degree of interest within the pharmacological domain. Therefore, with the present study, we aimed to provide a comprehensive review of the literature on this topic, through careful MEDLINE and PubMed searches of the years 1990–2012.

Generally, data on pharmacokinetics are more consistent and numerous than those on pharmacodynamics. Sex-related differences have been reported for several parameters that influence pharmacokinetics, such as gastric acidity, intestinal motility, body weight and composition, blood volume, liver enzymes (mainly the cytochrome P450), or renal excretion, which may alter plasma drug levels. Sex-related peculiarities may also account for a different sensitivity of men and women to side effects and toxicity of psychotropic drugs. Further, some differences in drug response, mainly to antipsychotics and antidepressants, have been described.

Further studies are, however, necessary to explore more thoroughly the impact of sex on the pharmacokinetics and pharmacodynamics of psychotropic drugs, in order to reach the most appropriate and tailored prescription for each patient.

Keywords

Antipsychoticsbenzodiazepinesgenderpsychotropic drugsSSRIstricyclics
Type
Review Articles
Information
CNS Spectrums , Volume 18 , Issue 3 , June 2013 , pp. 118 - 127
Copyright
Copyright © Cambridge University Press 2013 

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Fankhauser, MP. Psychiatric disorders in women: psychopharmacologic treatments. J Am Pharm Assoc (Wash DC). 1997; 6: 667–678.CrossRefGoogle Scholar
2.Frezza, M, di Padova, C, Pozzato, G, etal. High blood alcohol levels in women: the role of decreased gastric alcohol dehydrogenase activity and first-pass metabolism. N Engl J Med. 1990; 322: 95–99.CrossRefGoogle ScholarPubMed
3.Hamilton, J, Yonkers, K. Sex differences in pharmacokinetics of psychotropic medication, part I: physiological basis for effects. In: Jensvold M, Halbreich U, Hamilton J, eds. Psychopharmacology and Women: Sex, Gender, and Hormones. Washington, DC: American Psychiatric Press; 1996: 11–42.Google Scholar
4.Rao, S, Read, N, Brown, C, etal. Studies on the mechanism of bowel disturbance in ulcerative colitis. Gastroenterology. 1987; 93: 934–940.CrossRefGoogle ScholarPubMed
5.Grossman, M, Kirsner, J, Gillespie, I. Basal and histalog-stimulated gastric secretion in control subjects and in patients with peptic ulcer or gastric cancer. Gastroenterology. 1963; 45: 14–26.CrossRefGoogle ScholarPubMed
6.Pollock, BG. Gender differences in psychotropic drug metabolism. Psychopharmacol Bull. 1997; 33: 235–241.Google ScholarPubMed
7.Nicolas, JM, Espie, P, Molimard, M. Gender and interindividual variability in pharmacokinetics. Drug Metab Rev. 2009; 41(3): 408–421.CrossRefGoogle ScholarPubMed
8.Chen, ML, Lee, SC, Ng, MJ, etal. Pharmacokinetic analysis of bioequivalence trials: implications for sex-related issues in clinical pharmacology and biopharmaceutics. Clin Pharmacol Ther. 2000; 68(5): 510–521.CrossRefGoogle ScholarPubMed
9.Mayersohn, M. Drug disposition. In: Conrad K, Bressler R, eds. Drug Therapy for the Elderly. St. Louis, MO: CV Mosby; 1982: 31–63.Google Scholar
10.Yonkers, KA, Kando, JC, Cole, JO, etal. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry. 1992; 149: 587–595.Google ScholarPubMed
11.Greenblatt, D, Sellers, E, Shader, R. Drug disposition in old age. N Engl J Med. 1982; 306: 1081–1088.Google ScholarPubMed
12.Sweet, R, Pollock, B, Wright, B, etal. Single and multiple dose bupropion pharmacokinetics in elderly patients with depression. J Clin Pharmacol. 1995; 35: 876–884.CrossRefGoogle ScholarPubMed
13.Brown, SL, Salive, ME, Guralnik, JM, etal. Antidepressant use in the elderly: association with demographic characteristics, health-related factors, and health care utilization. J Clin Epidemiol. 1995; 48: 445–453.CrossRefGoogle ScholarPubMed
14.Simoni Wastila, L. Gender and psychotropic drug use. Med Care. 1998; 36: 88–94.CrossRefGoogle ScholarPubMed
15.Gleiter, CH, Gundert-Remy, U. Gender differences in pharmacokinetics. Eur J Drug Metab Pharmacokinet. 1996; 21: 123–128.CrossRefGoogle ScholarPubMed
16.Hashimoto, S, Miwa, M, Akasofu, K, Nishida, E. Changes in 40 serum proteins of post-menopausal women. Maturitas. 1991; 13: 23–33.CrossRefGoogle ScholarPubMed
17.Blain, PG, Mucklow, JC, Rawlins, MD, etal. Determinants of plasma alpha 1-acid glycoprotein (AAG) concentrations in health. Br J Clin Pharmacol. 1985; 20: 500–502.CrossRefGoogle ScholarPubMed
18.Kishino, S, Nomura, A, Itoh, S, etal. Age- and gender-related differences in carbohydrate concentrations of alpha1-acid glycoprotein variants and the effects of glycoforms on their drug-binding capacities. Eur J Clin Pharmacol. 2002; 58: 621–628.CrossRefGoogle ScholarPubMed
19.Tuck, CH, Holleran, S, Berglund, L. Hormonal regulation of lipoprotein(a) levels: effects of estrogen replacement therapy on lipoprotein(a) and acute phase reactant in postmenopausal women. Arterioscler Thromb Vasc Biol. 1997; 17: 1822–1829.CrossRefGoogle Scholar
20.Israili, ZH, Dayton, PG. Human alpha-1-glycoprotein and its interactions with drugs. Drug Metab Rev. 2001; 33: 161–235.CrossRefGoogle ScholarPubMed
21.Preskorn, SH. Clinically relevant pharmacology of selective serotonin reuptake inhibitors: an overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clin Pharmacokinet. 1997; 1: 1–21.CrossRefGoogle Scholar
22.Palmer, K, Benfield, P. Fluvoxamine: an overview of its pharmacological properties and review of its therapeutic potential in nondepressive disorders. CNS Drugs. 1994; 1: 57–87.CrossRefGoogle Scholar
23.Yonkers, K, Hamilton, J. Sex differences in pharmacokinetics of psychotropic medication, part II: effects on selected psychotropics. In: Jensvold M, Halbreich U, Hamilton J, eds. Psychopharmacology and Women: Sex, Gender, and Hormones. Washington, DC: American Psychiatric Press; 1996: 43–72.Google Scholar
24.Fredericson, O. Preliminary studies of the kinetics of citalopram in man. Eur J Clin Pharmacol. 1978; 14: 69–73.Google Scholar
25.Kristensen, C. Imipramine serum protein binding in healthy subjects. Clin Pharmacol Ther. 1983; 34: 689–694.CrossRefGoogle ScholarPubMed
26.Wilson, K. Sex-related differences in drug disposition in man. Clin Pharmacokinet. 1984; 9: 189–202.CrossRefGoogle ScholarPubMed
27.Preskorn, S. Clinical Pharmacology of Selective Serotonin Reuptake Inhibitors. Professional Communications, Inc., Caddo; 1996.Google Scholar
28.Kalra, B. Cytochrome P450 enzyme isoforms and their therapeutic implications: an update. Indian J Med Sci. 2007; 61(2): 102–116.CrossRefGoogle ScholarPubMed
29.Zhou, S, Chan, SY, Goh, BC, etal. Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin Pharmacokinet. 2005; 44(3): 279–304.CrossRefGoogle ScholarPubMed
30.Pollock, B, Altieri, L, Kirshner, M, etal. Debrisoquine hydroxylation phenotyping in geriatric psychopharmacology. Psychopharmacol Bull. 1992; 28: 257–263.Google ScholarPubMed
31.Wadelius, M, Darj, E, Frenne, G, Rane, A. Induction of CYP2D6 in pregnancy. Clin Pharmacol Ther. 1997; 62: 400–407.CrossRefGoogle ScholarPubMed
32.Kashuba, AD, Nafziger, AN, Kearns, GL, etal. Quantification of intraindividual variability and the influence of menstrual cycle phase on CYP2D6 activity as measured by dextromethorphan phenotyping. Pharmacogenetics. 1998; 8: 403–410.CrossRefGoogle ScholarPubMed
33.Labbe, L, Sirois, C, Pilote, S, etal. Effects of gender, sex hormones, time variables and physiological urinary pH on apparent CYP2D6 activity as assessed by metabolic ratios of marker substrates. Pharmacogenetics. 2000; 10: 425–438.CrossRefGoogle ScholarPubMed
34.McCune, JS, Lindley, C, Decker, JL, etal. Lack of gender differences and large intrasubject variability in cytochrome P450 activity measured by phenotyping with dextromethorphan. J Clin Pharmacol. 2001; 41: 723–731.CrossRefGoogle ScholarPubMed
35.Brosen, K. Isoenzyme specific drug oxidation: genetic polymorphism and drug-drug interactions. Nord J Psychiatry. 1993; 47(30): 21–26.CrossRefGoogle Scholar
36.Ketter, T, Flockhart, D, Post, R, etal. The emerging role of cytochrome P4503A in psychopharmacology. J Clin Psychopharmacol. 1995; 15: 387–395.CrossRefGoogle Scholar
37.Edeki, T, Goldstein, JA, de Morais, SMF, etal. Genetic polymorphism of S-mephenytoin 4′-hydroxylation in African-Americans. Pharmacogenetics. 1996; 6: 357–363.CrossRefGoogle Scholar
38.Sviri, S, Shpizen, S, Leitersdorf, E, Levy, M, Caraco, Y. Phenotypic-genotypic analysis of CYP2C19 in the Jewish Israeli population. Clin Pharmacol Ther. 1999; 65: 275–281.CrossRefGoogle ScholarPubMed
39.Price Evans, DA, Krahn, P, Narayanan, N. The mephenytoin (cytochrome P450 2C 19) and dextromethorphan (cytochrome P450 2D6) polymorphisms in Saudi Arabians and Filipinos. Pharmacogenetics. 1995; 5: 64–72.CrossRefGoogle Scholar
40.Tamminga, WJ, Wemer, J, Oosterhuis, B, etal. CYP2D6 and CYP2C19 activity in a large population of Dutch healthy volunteers: indications for oral contraceptive-related gender differences. Eur J Clin Pharmacol. 1999; 55: 177–185.CrossRefGoogle Scholar
41.Hagg, S, Spigset, O, Dahlqvist, R. Influence of gender and oral contraceptives on CYP2D6 and CYP2C19 activity in healthy volunteers. Br J Clin Pharmacol. 2001; 51: 169–177.CrossRefGoogle ScholarPubMed
42.Anderson, GD. Sex differences in drug metabolism: cytochrome P-450 and uridine diphosphate glucuronosyltransferase. J Gend Specif Med. 2002; 5: 25–33.Google ScholarPubMed
43.Scripture, C, Pieper, J. Clinical pharmacokinetics of fluvastatin. Clin Pharmacokinet. 2001; 40: 263–281.CrossRefGoogle ScholarPubMed
44.Ford, J, Truman, C, Wilcock, G, etal. Serum concentrations of tacrine hydrochloride predict its adverse effects in Alzheimer's disease. Clin Pharmacol Ther. 1993; 53: 691–695.CrossRefGoogle ScholarPubMed
45.Hartter, S, Wetzel, H, Hammes, E, etal. Inhibition of antidepressant demethylation and hydroxylation by fluvoxamine in depressed patients. Psychopharmacology. 1993; 110: 302–308.CrossRefGoogle ScholarPubMed
46.Wrighton, SA, Stevens, JC. The human hepatic cytochrome P450 involved in drug metabolism. Crit Rev Toxicol. 1992; 22: 1–12.CrossRefGoogle ScholarPubMed
47.Jennings, TS, Nafziger, AN, Davidson, L, etal. Gender differences in hepatic induction and inhibition of theophylline pharmacokinetics and metabolism. J Lab Clin Med. 1993; 122: 208–217.Google ScholarPubMed
48.Bock, K, Schrenk, D, Forster, A, etal. The influence of environmental and genetic factors on CYP2D6, CYP1A2 and UDP-glucuronosyltransferases in man using sparteine, caffeine and paracetamol as probes. Pharmacogenetics. 1994; 4: 209–219.CrossRefGoogle ScholarPubMed
49.Relling, MV, Lin, JS, Ayers, GD, Evans, WE. Racial and gender differences in N acetyltransferase, xanthine oxidase and CYP1A2 activities. Clin Pharmacol Ther. 1992; 52: 643–653.CrossRefGoogle Scholar
50.Lane, HY, Chang, YC, Chang, WH, etal. Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry. 1999; 60: 36–43.CrossRefGoogle ScholarPubMed
51.Callaghan, JT, Bergstrom, RF, Ptak, LR, Beasley, CM. Olanzapine: pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet. 1999; 37: 177–186.CrossRefGoogle ScholarPubMed
52.Nemeroff, C, De Vane, C, Pollock, B. Newer antidepressants and the cytochrome P450 system. Am J Psychiatry. 1996; 153: 311–320.Google ScholarPubMed
53.Schwartz, JB. The influence of sex on pharmacokinetics. Clin Pharmacokinet. 2003; 42: 107–121.CrossRefGoogle ScholarPubMed
54.Karim, A, Slater, M, Bradford, D, etal. Oral antidiabetic drugs: bioavailability assessment of fixed-dose combination tablets of pioglitazone and metformin. Effect of body weight, gender, and race on systemic exposures of each drug. J Clin Pharmacol. 2007; 47(1): 37–47.CrossRefGoogle ScholarPubMed
55.Lin, Y, Anderson, GD, Kantor, E, Ojemann, LM, Wilensky, AJ. Differences in the urinary excretion of 6-beta-hydroxycortisol/cortisol between Asian and Caucasian women. J Clin Pharmacol. 1999; 39: 578–582.CrossRefGoogle ScholarPubMed
56.Gaudry, SE, Sitar, DS, Smyth, DD, McKenzie, JK, Aoki, FY. Gender and age as factors in the inhibition of renal clearance of amantadine by quinine and quinidine. Clin Pharmacol Ther. 1993; 54(1): 23–27.CrossRefGoogle ScholarPubMed
57.Berg, UB. Differences in decline in GFR with age between males and females: reference data on clearances of inulin and PAH in potential kidney donors. Nephrol Dial Transplant. 2006; 21(9): 2577–2582.CrossRefGoogle ScholarPubMed
58.Hytten, FE, Chamberlain, G. Clinical Physiology in Obstetrics. Oxford, UK: Blackwell Scientific; 1980.Google Scholar
59.Silvaggio, T, Mattison, DR. Setting occupational health standards: toxicokinetic differences among and between men and women. J Occup Med. 1994; 36(8): 849–854.Google ScholarPubMed
60.Kim, JS, Nafziger, AN. Is it sex or is it gender? Clin Pharmacol Ther. 2000; 68(1): 1–3.CrossRefGoogle ScholarPubMed
61.Fromm, MF. P-glycoprotein: a defense mechanism limiting oral bioavailability and CNS accumulation of drugs. Int J Clin Pharmacol Ther. 2000; 38(2): 69–74.CrossRefGoogle ScholarPubMed
62.Yonkers, KA, Kando, JC, Cole, JO, etal. Gender differences in pharmacokinetics and pharmacodynamics of psychotropic medication. Am J Psychiatry. 1992; 149(5): 587–595.Google ScholarPubMed
63.Jerling, M, Merle, Y, Mentre, F, Mallet, A. Population pharmacokinetics of clozapine evaluated with the nonparametric maximum likelihood method. Br J Clin Pharmacol. 1997; 44: 447–453.CrossRefGoogle ScholarPubMed
64.Lane, HY, Chang, YC, Chang, WH, etal. Effects of gender and age on plasma levels of clozapine and its metabolites: analyzed by critical statistics. J Clin Psychiatry. 1999; 60: 36–40.CrossRefGoogle ScholarPubMed
65.Fabrazzo, M, Esposito, G, Fusco, R, Maj, M. Effect of treatment duration on plasma levels of clozapine and N-desmethylclozapine in men and women. Psychopharmacology. 1996; 124: 197–200.CrossRefGoogle ScholarPubMed
66.Rostami-Hodjegan, A, Amin, AM, Spencer, EP, etal. Influence of dose, cigarette smoking, age, sex, and metabolic activity on plasma clozapine concentrations: a predictive model and nomograms to aid clozapine dose adjustment and to assess compliance in individual patients. J Clin Psychopharmacol. 2004; 24: 70–78.CrossRefGoogle ScholarPubMed
67.Gex-Fabry, M, Balant-Gorgia, AE, Balant, LP. Therapeutic drug monitoring of olanzapine: the combined effect of age, gender, smoking, and comedication. Ther Drug Monit. 2003; 25: 46–53.CrossRefGoogle ScholarPubMed
68.Kelly, DL, Conley, RR, Tamminga, CA. Differential olanzapine plasma concentrations by sex in a fixed-dose study. Schizophr Res. 1999; 40: 101–104.CrossRefGoogle Scholar
69.Seeman, MV. Interaction of sex, age, and neuroleptic dose. Compr Psychiatry. 1983; 24: 125–128.CrossRefGoogle ScholarPubMed
70.Morgenstern, H, Glazer, W. Identifying risk factors for tardive dyskinesia among long-term outpatients maintained with neuroleptic medication. Arch Gen Psychiatry. 1993; 50: 723–733.CrossRefGoogle Scholar
71.Yassa, R, Jeste, D. Gender differences in tardive dyskinesia: a critical review of the literature. Schizophr Bull. 1992; 18: 701–715.CrossRefGoogle ScholarPubMed
72.Browne, S, Roc, M, Lane, A, Gavin, N, Morris, M, Kinsella, A, Larkin, C, O'Calloghan, E. Quality of life in schizophrenia: relationship to sociodemographic factors, symptomology and tardive dyskinesi. Acte Psychiat Scan. 1996; 96: 79–87.Google Scholar
73.Wolbrette, D. Gender differences in the proarrhythmic potential of QT-prolonging drugs. Curr Womens Health Rep. 2002; 2: 105–109.Google ScholarPubMed
74.Hatta, K, Takahashi, T, Nakamura, H, etal. The association between intravenous haloperidol and prolonged QT interval. J Clin Psychopharmacol. 2001; 21: 257–261.CrossRefGoogle ScholarPubMed
75.Kuruvilla, A, Peedicayil, J, Srikrishna, G, Kuruvilla, K, Kanagasabapathy, AS. A study of serum prolactin levels in schizophrenia: comparison of males and females. Clin Exp Pharmacol Physiol. 1992; 19: 603–606.CrossRefGoogle ScholarPubMed
76.Naidoo, U, Kinon, BJ, Gilmore, JA, Liu, H, Halbreich, UM. Hyperprolactinemia in response to antipsychotic drugs: characterization across comparative clinical trials. Psychoneuroendocrinology. 2003; 28(2): 69–82.Google Scholar
77.Melkersson, K, Hulting, AL, Hall, K. Hormonal evaluation in schizophrenic patients treated with neuroleptics. Neuro Endocrinol Lett. 1999; 20: 199–204.Google ScholarPubMed
78.Allison, DB, Mentore, JL, Heo, M, etal. Antipsychotic-induced weight gain: a comprehensive research synthesis. Am J Psychiatry. 1999; 156: 1686–1696.CrossRefGoogle ScholarPubMed
79.Baptista, T, Kin, NM, Beaulieu, S, De Baptista, EA. Obesity and related metabolic abnormalities during antipsychotic drug administration: mechanisms, management and research perspectives. Pharmacopsychiatry. 2002; 35: 205–219.CrossRefGoogle ScholarPubMed
80.Hedenmalm, K, Hagg, S, Stahl, M, Mortimer, O, Spigset, O. Glucose intolerance with atypical antipsychotics. Drug Saf. 2002; 25: 1107–1116.CrossRefGoogle ScholarPubMed
81.Sernyak, MJ, Leslie, DL, Alarcon, RD, Losonczy, MF, Rosenheck, R. Association of diabetes mellitus with use of atypical neuroleptics in the treatment of schizophrenia. Am J Psychiatry. 2002; 159: 561–566.CrossRefGoogle ScholarPubMed
82.Grossman, ML, Kirsner, JB, Cillespie, LE. Basal and histalog-stimulated gastric secretion in control subjects and in patients with peptic ulcer or gastric cancer. Gastroenterology. 1963; 45: 14–26.CrossRefGoogle ScholarPubMed
83.Hutson, WR, Roehrkasse, RL, Wald, A. Influence of gender and menopause on gastric emptying and motility. Gastroenterology. 1989; 96(1): 11–17.CrossRefGoogle ScholarPubMed
84.Wald, A, Van Thiel, DH, Hoechstetter, L, etal. Gastrointestinal transit: the effect of the menstrual cycle. Gastroenterology. 1981; 80(6): 1497–1500.CrossRefGoogle ScholarPubMed
85.Greenblatt, DJ, Friedman, H, Burstein, ES, etal. Trazodone kinetics: effect of age, gender, and obesity. Clin Pharmacol Ther. 1987; 42(2): 193–200.CrossRefGoogle ScholarPubMed
86.Stewart, JJ, Berkel, HJ, Parish, RC, etal. Single-dose pharmacokinetics of bupropion in adolescents: effects of smoking status and gender. J Clin Pharmacol. 2001; 41(7): 770–778.CrossRefGoogle ScholarPubMed
87.Greenblatt, DJ, Divoll, M, Harmatz, JS, Shader, RI. Oxazepam kinetics: effects of age and sex. J Pharmacol Exp Ther. 1980; 215(1): 86–91.Google ScholarPubMed
88.Greenblatt, DJ, Divoll, M, Abernethy, DR, Shader, RI. Physiologic changes in old age: relation to altered drug disposition. J Am Geriatr Soc. 1982; 30(11): S6–10.CrossRefGoogle ScholarPubMed
89.Findling, RL, Nucci, G, Piergies, AA, etal. Multiple dose pharmacokinetics of paroxetine in children and adolescents with major depressive disorder or obsessive-compulsive disorder. Neuropsychopharmacology. 2006; 31(6): 1274–1285.CrossRefGoogle ScholarPubMed
90.Bies, RR, Bigos, Kl, Pollock, BC. Gender differences in the pharmacokinetics and pharmacodynamics of antidepressants. J Gend Specif Med. 2003; 6: 12–20.Google ScholarPubMed
91.Hildebrandt, MG, Steyerberg, EW, Stage, KB, etal., for the Danish University Antidepressant Group. Are gender differences important for the clinical effects of antidepressants? Am J Psychiatry. 2003; 160: 1643–1650.CrossRefGoogle ScholarPubMed
92.Mundo, E, Pirola, R, Bellodi, L, etal. Are gender differences in antiobsessional response related to different clomipramine metabolism? J Clin PsychopharmacoI. 2002; 22: 341–342.CrossRefGoogle ScholarPubMed
93.Cohen, LC, Biederman, J, Wilens, TE, etal. Desipramine clearance in children and adolescents: absence of effect of development and gender. J Am Acad Child Adolesc Psychiatry. 1999; 38: 79–85.CrossRefGoogle ScholarPubMed
94.Physicians’ Desk Reference. 57th ed. Montvale, NJ: Thomson P D R; 2003.Google Scholar
95.De Mendonca Lima, CA, Baumann, P, Braward-Amey, M, etal. Effect of age and gender on citalopram and desmethylcitalopram steady-state plasma concentrations in adults and elderly depressed patients. Prog Neuropsychopharmacol Biol Psychiatry. 2005; 29: 952–956.CrossRefGoogle ScholarPubMed
96.Reis, M, Chermß, MD, Carlsson, B, Bengtsson, F, for the Task Force for TDM of Escitalopram in Sweden. Therapeutic drug monitoring of escitalopram in an outpatient setting. Ther Drug Monit. 2007; 29: 758–766.CrossRefGoogle Scholar
97.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; 32: 22–30.CrossRefGoogle Scholar
98.Ferguson, JM, Hill, H. Pharmacokinetics of fluoxetine in elderly men and women. Gerontology. 2006; 52: 45–50.CrossRefGoogle ScholarPubMed
99.Gex-Fabry, M, Eap, CB, Oneda, B, etal. CYP2D6 and ABCB1 genetic variability: influence on paroxetine plasma level and therapeutic response. Ther Drug Monit. 2008; 30: 474–482.CrossRefGoogle ScholarPubMed
100.Physicians’ Desk Reference. 63rd ed. Montvale, NJ: Thomson Reuters; 2009.Google Scholar
101.Parker, G, Parker, K, Austin, MP, etal. Gender differences in response to differing antidepressant drug classes: two negative studies. Psychol Med. 2003; 33(8): 1473–1477.CrossRefGoogle ScholarPubMed
102.Kornstein, SG, Schatzberg, AF, Thase, ME, etal. Gender differences in treatment response to sertraline versus imipramine in chronic depression. Am J Psychiatry. 2000; 157(9): 1445–1452.CrossRefGoogle ScholarPubMed
103.Baca, E, Garcia-Garcia, M, Porras-Chavarino, A. Gender differences in treatment response to sertraline versus imipramine in patients with non-melancholic depressive disorders. Prog Neuropsychopharmacol Biol Psychiatry. 2004; 28(1): 57–65.CrossRefGoogle Scholar
104.Joyce, PR, Mulder, RT, Luty, SE, etal. Melancholia: definitions, risk factors, personality, neuroendocrine markers and differential antidepressant response. Aust N Z J Psychiatry. 2002; 36(3): 376–383.CrossRefGoogle ScholarPubMed
105.Young, EA, Kornstein, SG, Marcus, SM, etal. Sex differences in response to citalopram: a STAR*D report. J Psychiatr Res. 2009; 43(5): 503–511.CrossRefGoogle ScholarPubMed
106.Thase, ME, Entsuah, R, Cantillon, M, etal. Relative antidepressant efficacy of venlafaxine and SSRIs: sex-age interactions. J Womens Health (Larchmt). 2005; 14(7): 609–616.CrossRefGoogle ScholarPubMed
107.Bano, S, Akhter, S, Afridi, MI. Gender based response to fluoxetine hydrochloride medication in endogenous depression. J Coll Physicians Surg Pak. 2004; 14(3): 161–165.Google ScholarPubMed
108.Marazziti, D, Baroni, S, Giannaccini, G, etal. Plasma fluvoxamine levels and OCD symptoms/response in adult patients. Hum Psychopharmacol. 2012; 27(4): 397–402.CrossRefGoogle ScholarPubMed
109.Marazziti, D, Baroni, S, Faravelli, L, etal. Plasma clomipramine levels in adult patients with obsessive-compulsive disorder. Int Clin Psychopharmacol. 2012; 27(1): 55–60.CrossRefGoogle ScholarPubMed