Drugs & Aging

, Volume 16, Issue 3, pp 165–177 | Cite as

Differential Pharmacokinetics of Lithium in Elderly Patients

  • Beth A. Sproule
  • Brian G. Hardy
  • Kenneth I. Shulman
Review Article

Abstract

The pharmacotherapeutic use of lithium in the elderly as acute and maintenance therapy in bipolar disorder and augmentation therapy for major depression is well documented. Differences in the response to lithium are explained, in part, by the effect of age-related physiological changes, comorbid conditions, and concurrent medications on the pharmacokinetics of lithium in the elderly. The pharmacokinetic profile of lithium has been studied for many years, primarily in younger adult populations. Lithium pharmacokinetics may be influenced by a number of factors including age. It was first noted several years ago that elderly individuals required lower doses of lithium to achieve serum concentrations similar to those observed in younger adults. This is due to the combination of a reduced volume of distribution and reduced renal clearance. The composition of the human body changes with aging producing an increase in body fat, a decrease in fat-free mass and a decrease in total body water. Lithium clearance decreases as the glomerular filtration rate decreases with increasing age.

The effects of other medical conditions in the elderly on the pharmacokinetics of lithium are less well delineated. Reduced lithium clearance is expected in patients with hypertension, congestive heart failure or renal dysfunction. Larger lithium maintenance doses are required in obese compared with non-obese patients.

The most clinically significant pharmacokinetic drug interactions associated with lithium involve drugs which are commonly used in the elderly. Thiazide diuretics, ACE inhibitors, and nonsteroidal anti-inflammatory drugs can increase serum lithium concentrations.

The tolerability of lithium is lower in the elderly. Neurotoxicity clearly occurs in the elderly at concentrations considered ‘therapeutic’ in general adult populations. There are no placebo-controlled randomised trials of lithium in old age and recommendations for clinical use are based on extrapolations from pharmacokinetic studies, anecdotal reports from mixed age populations and clinical experience in old age psychiatry. Serum concentrations of lithium need to be markedly reduced in the elderly population and particularly so in the very old and frail elderly.

References

  1. 1.
    Young RC, Klennan GL. Mania in late-life: focus on age at onset. Am J Psychiatry 1992; 149: 867–76PubMedGoogle Scholar
  2. 2.
    Koenig HG, Blazer DG. Epidemiology of geriatric affective disorders. Clin Geriatr Med 1992; 8(2): 235–51PubMedGoogle Scholar
  3. 3.
    Kramer M, German PS, Anthony JC, et al. Patterns of mental disorders among the elderly residents of eastern Baltimore. J Am Geriatr Soc 1985; 33(4): 236–45PubMedGoogle Scholar
  4. 4.
    Yassa R, Nair V, Natase C, et al. Prevalence of bipolar disorder in a psychogeriatric population. J Affect Disord 1988; 14(3): 197–201PubMedCrossRefGoogle Scholar
  5. 5.
    Post F. Affective disorders in old age. In: Paykel ES, editors. Handbook of affective disorders. New York: Guilford Press, 1982: 393–402Google Scholar
  6. 6.
    Loranger AW, Levine PM. Age at onset of bipolar affective illness. Arch Gen Psychiatry 1978; 35: 1345–8PubMedCrossRefGoogle Scholar
  7. 7.
    Ghadirian AM, Lalinec-Michaud M, Engelsmann F. Early and late onset affective disorders: clinical and family characteristics. Ann RICP 1986; 19: 53–7Google Scholar
  8. 8.
    Summers WK. Mania with onset in the eighth decade: two cases and a review. J Clin Psychiatry 1983; 44: 141–3PubMedGoogle Scholar
  9. 9.
    Snowdon J. A retrospective case-note study of bipolar disorder in old age. Br J Psychiatry 1991; 158: 485–90PubMedCrossRefGoogle Scholar
  10. 10.
    Young RC. Bipolar mood disorders in the elderly. Psychiatr Clin North Am 1997; 2(1): 121–36CrossRefGoogle Scholar
  11. 11.
    Eastham JH, Jeste DV, Young RC. Assessment and treatment of bipolar disorder in the elderly. Drugs Aging 1998; 12(3): 205–24PubMedCrossRefGoogle Scholar
  12. 12.
    McDonald W, Nemeroff CS. The diagnosis and treatment of mania in the elderly. Bull Menninger Clin 1996; 60(2): 174–96PubMedGoogle Scholar
  13. 13.
    Hays JC, Kirshnan KR, George LK, et al. Age of first onset of bipolar disorder: demographic, family history and psychosocial correlates. Depress Anxiety 1998; 7(2): 76–82PubMedCrossRefGoogle Scholar
  14. 14.
    Shulman KI, Tohen M, Satlin A, et al. Mania compared with unipolar depression in old age. Am J Psychiatry 1992; 149(3): 341–5PubMedGoogle Scholar
  15. 15.
    Dhingra U, Rabins P. Mania in the elderly: a 5–7 year follow-up. J Am Geriatr Soc 1991; 39: 581–3PubMedGoogle Scholar
  16. 16.
    Tohen M, Shulman KI, Satlin A. First-episode mania in late life. Am J Psychiatry 1994; 151(1): 130–2PubMedGoogle Scholar
  17. 17.
    O’Connell JR, Mayo JA, Flatow L, et al. Outcome of bipolar disorder on long-term treatment with lithium. Br J Psychiatry 1991; 159: 123–9PubMedCrossRefGoogle Scholar
  18. 18.
    Van de Velde CD. Effectiveness of lithium carbonate in the treatment of manic-depressive illness. Am J Psychiatry 1970; 127: 345–51PubMedGoogle Scholar
  19. 19.
    Weissman MM, Leaf PJ, Tischler GL, et al. Affective disorders in five United States communities. Psychol Med 1988; 18(1): 141–53PubMedCrossRefGoogle Scholar
  20. 20.
    Weissman MM, Bruce ML, Leaf PJ, et al. Affective disorders. In: Robins LN, Reiger DA, editors. Psychiatric disorders in America: the epidemiologic catchment area study. New York: Free Press, 1991:53–83Google Scholar
  21. 21.
    Lebowitz BD, Pearson JL, Schneider LS, et al. Diagnosis and treatment of depression in late life: consensus statement update. JAMA 1997; 278(14): 1186–90PubMedCrossRefGoogle Scholar
  22. 22.
    Blazer DG. Depression in the elderly: myths and misconceptions. Psychiatr Clin North Am 1997; 20(1): 111–8PubMedCrossRefGoogle Scholar
  23. 23.
    Krishnan KRR, Gadde KM. The pathophysiologic basis for late-life depression: imaging studies of the aging brain. Am J Geriatr Psychiatry 1996; 4Suppl. 1: S22–S33Google Scholar
  24. 24.
    Maier W, Lichtermann D, Minges J, et al. Unipolar depression in the aged: determinants of familial aggregation. J Affect Disord 1991; 23(2): 53–61PubMedCrossRefGoogle Scholar
  25. 25.
    Gurland B. The impact of depression on quality of life of the elderly. Clin Geriatr Med 1992; 8(2): 377–86PubMedGoogle Scholar
  26. 26.
    Philibert RA, Richard SL, Lynch CF, et al. The effect of gender and age at onset of depression on mortality. J Clin Psychiatry 1997; 58(8): 355–60PubMedCrossRefGoogle Scholar
  27. 27.
    Mittmann N, Herrmann N, Einarson TR, et al.. The efficacy, safety and tolerability of antidepressants in late life depression: a meta-analysis. J Affect Disord 1997; 46: 191–217PubMedCrossRefGoogle Scholar
  28. 28.
    Frank E, Karp JF, Rush AJ. Efficacy of treatments for major depression. Psychopharmacol Bull 1993; 29: 457–75PubMedGoogle Scholar
  29. 29.
    Austin MPV, Souza FGM, Goodwin GM. Lithium augmentation in antidepressant-resistant patients: a quantitative analysis. Br J Psychiatry 1991; 159: 510–4PubMedCrossRefGoogle Scholar
  30. 30.
    Lieff S, Herrmann N. Combined drug therapy for an elderly depressed patient. Am J Psychiatry 1988; 145: 1034–5PubMedGoogle Scholar
  31. 31.
    Gash AJ, Chhabra S, Eccleston D. Lithium augmentation in a case of renal impairment: risk vs benefit. J Affect Disord 1995; 35: 51–3CrossRefGoogle Scholar
  32. 32.
    Camprubi ME, Puri BK. The treatment of refractory depression using paroxetine with lithium augmentation. Prog Neuro-psychopharmacol Biol Psychiatry 1995; 19: 515–7CrossRefGoogle Scholar
  33. 33.
    Lafferman J, Soloman K, Ruskin P. Lithium augmentation for treatment-resistant depression in the elderly. Geriatr Psychiatry Neurol 1988; 1:49–52CrossRefGoogle Scholar
  34. 34.
    Kushnir SL. Lithium-antidepressant combinations in the treatment of depressed, physically ill geriatric patients. Am J Psychiatry 1986; 143: 378–9PubMedGoogle Scholar
  35. 35.
    van Marwijk HWJ, Bekker FM, Nolen WA, et al. Lithium augmentation in geriatric depression. J Affect Disord 1990; 20: 217–23PubMedCrossRefGoogle Scholar
  36. 36.
    Parker K, Herrmann N, Shulman KI, et al. Risk/benefit analysis of lithium (Li) augmentation of antidepressant therapy in a geriatric psychiatry outpatient clinic [abstract]. Clin Pharmacol Ther 1993; 53(2): 191Google Scholar
  37. 37.
    Jensen HV, Olafsson K, Lykke-Olesen L, et al. Combination nortriptyline and lithium in elderly depressed patients: a double-blind, placebo-controlled study. Lithium 1992; 3: 259–62Google Scholar
  38. 38.
    Zimmer B, Rosen J, Thornston JE, et al. Adjunctive lithium carbonate in nortriptyline-resistant elderly depressed patients. J Clin Psychopharmacol 1991; 11: 254–6PubMedCrossRefGoogle Scholar
  39. 39.
    Flint LAJ, Rifat SL. A prospective study of lithium agumentation in antidepressant-resistant geriatric depression. J Clin Psychopharmacol 1994; 14: 353–6PubMedCrossRefGoogle Scholar
  40. 40.
    Austin LS, Arana GW, Melvin JA. Toxicity resulting from lithium augmentation of antidepressant treatment in elderly patients. J Clin Psychiatry 1990; 51(8): 344–5PubMedGoogle Scholar
  41. 41.
    Amdisen A, Schou M. Biochemistry of depression. Lancet 1967; I: 507CrossRefGoogle Scholar
  42. 42.
    Carson SW. Lithium. In: Evans WE, Schentag JJ, Jusko WJ, editors. Applied pharmacokinetics: principles of therapeutic drug monitoring. 3rd ed. Vancouver (WA): Applied Therapeutics, Inc., 1992: 34–1–34–26Google Scholar
  43. 43.
    Nielsen-Kudsk F, Amdisen A. Analysis of the pharmacokinetics of lithium in man. Eur J Clin Pharmacol 1979; 16: 271–7CrossRefGoogle Scholar
  44. 44.
    Amdisen A. Serum level monitoring and clinical pharmacokinetics of lithium. Clin Pharmacokinet 1977; 2: 73–92PubMedCrossRefGoogle Scholar
  45. 45.
    Lehmann K, Merten K. Die elimination von lithium in abhangigkeit vom lebensalter bei gesunden und nieren-insuffizienten. Int J Clin Pharmacol 1974; 10(4): 292–8PubMedGoogle Scholar
  46. 46.
    Perry PJ, Dunner FJ, Hahn RL, et al. Lithium kinetics in single daily dosing. Acta Psychiatr Scand 1981; 64: 281–94PubMedCrossRefGoogle Scholar
  47. 47.
    Platman SR, Fieve RR. Biochemical aspects of lithium in affective disorders. Arch Gen Psychiatry 1968; 19: 659–63PubMedCrossRefGoogle Scholar
  48. 48.
    Amdisen A, Gottfries L, Jacobsson L, et al. Grave lithium intoxication with fatal outcome. Acta Psychiatr Scand 1974; Suppl. 255: 25–33Google Scholar
  49. 49.
    Fyro B, Petterson U, Sedvall G. Pharmacokinetics of lithium in manic-depressive patients. Acta Psychiatr Scand 1973; 49: 237–47PubMedCrossRefGoogle Scholar
  50. 50.
    Yukawa E, Nomiyama N, Higuchi S, et al. Lithium population pharmacokinetics from routine clinical data: role of patient characteristics for estimating dosing regimens. Ther Drug Monit 1993; 15: 75–82PubMedCrossRefGoogle Scholar
  51. 51.
    Taright N, Mentre F, Mallet A, et al. Nonparametric estimation of population characteristics of the kinetics of lithium from observational and experimental data: individualization of chronic dosign regimen using a new Bayesian approach. Ther Drug Monit 1994; 16: 258–69PubMedCrossRefGoogle Scholar
  52. 52.
    Jermain DM, Crismon ML, Martin ES. Population pharmacokinetics of lithium. Clin Pharm 1991; 10: 376–81PubMedGoogle Scholar
  53. 53.
    Goodnick PJ, Fieve RR, Meltzer HL, et al. Lithium elimination half-life and duration of therapy. Clin Pharmacol Ther 1981; 29(1): 47–50PubMedCrossRefGoogle Scholar
  54. 54.
    Reiss RA, Haas CE, Karki SD, et al. Lithium pharmackinetics in the obese. Clin Pharmacol Ther 1994; 55: 392–8PubMedCrossRefGoogle Scholar
  55. 55.
    Lauritsen BJ, Mellerup ET, Plenge P, et al. Serum lithium concentrations around the clock with different treatment regimens and the diurnal variation of the renal lithium clearance. Acta Psychiatr Scand 1981; 64: 314–9PubMedCrossRefGoogle Scholar
  56. 56.
    Hewick DS, Newbury P, Hopwood S, et al. Age as a factor affecting lithium therapy. J Clin Pharmacol 1977; 4(2): 201–5Google Scholar
  57. 57.
    Slater V, Milanes F, Talcott V, et al. Influence of age on lithium therapy. South Med J 1984; 77(2): 153–4,158PubMedCrossRefGoogle Scholar
  58. 58.
    Vestergaard P, Schou M. The effect of age on lithium dosage requirements. Pharmacopsychiatry 1984; 17: 199–201PubMedCrossRefGoogle Scholar
  59. 59.
    Greil W, Stoltzenburg MC, Mairhofer ML, et al. Lithium dos-age in the elderly: a study with matched age groups. J Affect Disord 1985; 9: 1–4PubMedCrossRefGoogle Scholar
  60. 60.
    Coppen A, Abou-Saleh MT. Lithium therapy: from clinical trials to practical management. Acta Psychiatr Scand 1988; 78(6): 754–62PubMedCrossRefGoogle Scholar
  61. 61.
    Bender AD. Effect of age on intestinal absorption: implications for drug absorption in the elderly. J Am Geriatr Soc 1968; 16(12): 1331–9PubMedGoogle Scholar
  62. 62.
    Geokas MC, Haverback BJ. The aging gastrointestinal tract. Am J Surgery 1969; 117: 881–92CrossRefGoogle Scholar
  63. 63.
    Greenblatt DJ, Sellers EM, Shader RI. Drug disposition in old age. N Engl J Med 1982; 306(18): 1081–8PubMedCrossRefGoogle Scholar
  64. 64.
    Turner N, Scarpace PJ, Lowenthal DT. Geriatric pharmacology: basic and clinical considerations. Annu Rev Pharmacol Toxicol 1992; 32: 271–302CrossRefGoogle Scholar
  65. 65.
    Novak LP. Aging, total body potassium, fat-free mass, and cell mass in males and females between ages 18 and 85 years. J Gerontology 1972; 27(4): 438–43CrossRefGoogle Scholar
  66. 66.
    Barlett HL, Puhl SM, Hodgson JL, et al. Fat-free mass in relation to stature: ratios of fat-free mass to height in children, adults, and elderly subjects. Am J Clin Nutr 1991; 53: 1112–6PubMedGoogle Scholar
  67. 67.
    Borkan GA, Hults DE, Gerzof SG, et al. Age changes in body composition revealed by computed tomography. J Gerontology 1983; 38(6): 673–7CrossRefGoogle Scholar
  68. 68.
    Stachenfeld NS, DiPietro L, Nadel ER, et al. Mechanism of attentuated thirst in aging: role of central volume receptors. Am J Physiology 1997; 272: R148–R157Google Scholar
  69. 69.
    Phillips PA, Rolls BJ, Ledingham JGG, et al. Reduced thirst after water deprivation in healthy elderly men. N Engl J Med 1984; 311: 753–9PubMedCrossRefGoogle Scholar
  70. 70.
    Lindeman RD, Tobin J, Shock NW. Longitudinal studies on the rate of decline in renal function with age. J Am Geriatr Soc 1985; 33(4): 278–85PubMedGoogle Scholar
  71. 71.
    Rowe JW, Andres R, Tobin JD, et al. The effect of age on creatinine clearance in men: a cross-sectional and longitudinal study. J Gerontology 1976; 31(2): 155–63CrossRefGoogle Scholar
  72. 72.
    Cockcroft D, Gault M. Prediction of creatinine clearance from serum creatinine. Nephron 1976; 16: 31–41PubMedCrossRefGoogle Scholar
  73. 73.
    Chapron DJ, Cameron IR, White LB, et al. Observations on lithium disposition in the elderly. J Am Geriatr Soc 1982; 30(10): 651–5PubMedGoogle Scholar
  74. 74.
    Hardy BG, Shulman KI, MacKenzie SP, et al. Pharmacokinetics of lithium in the elderly. J Clin Psychopharmacol 1987; 7: 153–8PubMedCrossRefGoogle Scholar
  75. 75.
    Turnheim K. Drug dosage in the elderly: is it rational? Drugs Aging 1998; 13(5): 357–79PubMedCrossRefGoogle Scholar
  76. 76.
    Le Couteur DG, McLean AJ. The aging liver: drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet 1998; 34(5): 359–73PubMedCrossRefGoogle Scholar
  77. 77.
    Shephard AMM. Physiological changes with aging: relevance to drug study design. In: Cutler NR, Narang PK, editors. Drug studies in the elderly: methodological concerns. New York: Plenum Medical Book Company, 1986; 49–67CrossRefGoogle Scholar
  78. 78.
    Fliser D, Franek E, Joest M, et al. Renal function in the elderly: impact of hypertension and cardiac function. Kidney Int 1997; 51(4): 1196–204PubMedCrossRefGoogle Scholar
  79. 79.
    Tueth MJ, Murphy TK, Evans DL. Special considerations: use of lithium in children, adolescents, and elderly populations. J Clin Psychiatry 1998; 59Suppl. 6: 66–73PubMedGoogle Scholar
  80. 80.
    Liptzin B. Treatment of mania. In: Salzman C, editor. Clinical geriatric psychopharmacology. 2nd ed. Baltimore (MD): Williams & Wilkins, 1992: 175–88Google Scholar
  81. 81.
    Jenike MA. Geriatric psychiatry and psychopharmacology: a clinical approach. Chicago (IL): Year Book Medical Publishers, 1989Google Scholar
  82. 82.
    Abernethy DR, Greenblatt DJ. Drug dispostion in obese humans: an update. Clin Pharmacokinet 1986; 11: 199–213PubMedCrossRefGoogle Scholar
  83. 83.
    Karki SD, Carson SW, Gagnon A. Evaluation of total body water and disposition of lithium in elderly patients. Lithium 1992; 3: 29–33Google Scholar
  84. 84.
    Clericetti N, Beretta-Piccoli C. Lithium clearance in patients with chronic renal disease. Clin Nephrol 1991; 36(6): 281–9PubMedGoogle Scholar
  85. 85.
    Pandita-Gunawardena R, Donaldson D. Decreasing requirement for lithium carbonate therapy in bipolar affective disorders (hypomanic type) following the onset of chronic renal insufficiency. J R Soc Health 1998; 118(1): 35–9PubMedCrossRefGoogle Scholar
  86. 86.
    Finley PR, Warner MD, Peabody CA. Clinical relevance of drug interactions with lithium. Clin Pharmacokinet 1995; 29(3): 172–91PubMedCrossRefGoogle Scholar
  87. 87.
    Miller F, Menninger J. Lithium-neuroleptic neurotoxicity if dose dependent. J Clin Psychopharmacol 1987; 7: 89–91PubMedGoogle Scholar
  88. 88.
    Miller F, Menninger J, Whitcup SM. Lithium-neuroleptic neurotoxicity in the elderly bipolar patient. J Clin Psychopharmacol 1986; 6(3): 176–8PubMedCrossRefGoogle Scholar
  89. 89.
    Binder EF, Cayabyab L, Ritchie DJ, et al. Diltiazem-induced psychosis and a possible diltiazem-lithium interaction. Arch Intern Med 1991; 151:373–4PubMedCrossRefGoogle Scholar
  90. 90.
    Mekler G, Woggon B. A case of serotonin syndrome caused by venlafaxine and lithium. Pharmacopsychiatry 1997; 30:272–3PubMedCrossRefGoogle Scholar
  91. 91.
    Bauer M, Linden M, Schaaf B, et al. Adverse events and toler-ability of the combination of fluoxetine/lithium compared with fluoxetine. J Clin Psychopharmacol 1996; 16(2): 130–4PubMedCrossRefGoogle Scholar
  92. 92.
    Himmelhoch JM, Poust RI, Mallinger AG, et al. Adjustment of lithium dose during lithium-chlorothiazide therapy. Clin Pharmacol Ther 1977; 22: 225–7PubMedGoogle Scholar
  93. 93.
    Kerry RJ, Ludlow JM, Owen G. Diuretics are dangerous with lithium. BMJ 1980; 281: 371PubMedCrossRefGoogle Scholar
  94. 94.
    Macfie AC. Lithium poisoning precipitated by diuretics [letter]. BMJ 1975; 1:516PubMedCrossRefGoogle Scholar
  95. 95.
    Solomon JG. Lithium toxicity precipitated by a diuretic. Psychosomatics 1980; 21: 425–9PubMedGoogle Scholar
  96. 96.
    Saffer D, Coppen A. Frusemide: a safe diuretic during lithium therapy? J Affect Disord 1983; 5: 289–92PubMedCrossRefGoogle Scholar
  97. 97.
    Jefferson JW, Kalin NH. Serum lithium levels and long-term diuretic use. JAMA 1979; 241: 1134–6PubMedCrossRefGoogle Scholar
  98. 98.
    Crabtree BL, Mack JE, Johnson CD, et al. Comparison of the effects of hydrochlorothiazide and furosemide on lithium disposition. Am J Psychiatry 1991; 148(8): 1060–3PubMedGoogle Scholar
  99. 99.
    Baer L, Platman SR, Kassir S, et al. Mechanisms of renal lithium handling and their relationship to mineralocorticoids: a dissociation between sodium and lithium ions. J Psychiatr Res 1971; 8: 91–105PubMedCrossRefGoogle Scholar
  100. 100.
    Kosten TR, Forrest JN. Treatment of severe lithium-induced polyuria with amiloride. Am J Psychiatry 1986; 143(12): 1563–8PubMedGoogle Scholar
  101. 101.
    Batlle DC, von Riotte AB, Gaviria M, et al. Amelioration of polyuria by amiloride in patients receiving long-term lithium therapy. N Engl J Med 1985; 312: 408–14PubMedCrossRefGoogle Scholar
  102. 102.
    Perry PJ, Calloway RA, Cook BL, et al. Theophylline precipitated alterations of lithium clearance. Acta Psychiatr Scand 1984; 69: 528–37PubMedCrossRefGoogle Scholar
  103. 103.
    Mester R, Toren P, Mizrachi I, et al. Caffeine withdrawal increases lithium blood levels. Biol Psychiatry 1995; 37: 348–50PubMedCrossRefGoogle Scholar
  104. 104.
    Finley PR, O’Brien BE, Coleman RW. Lithium and angioten-sin-converting enzyme inhibitors: evaluation of a potential interaction. J Clin Psychopharmacol 1996; 16(1): 68–71PubMedCrossRefGoogle Scholar
  105. 105.
    Blanche P, Raynaud E, Kerob D, et al. Lithium intoxication in an elderly patient after combined treatment with losarten [letter]. Eur J Clin Pharmacol 1997; 52: 501PubMedCrossRefGoogle Scholar
  106. 106.
    Ragheb MA, Powell AL. Failure of sulindac to increase serum lithium levels. J Clin Psychiatry 1986; 47: 33–4PubMedGoogle Scholar
  107. 107.
    Reimann IW, Diener U, Frolich JC. Indomethacin but not aspirin increases plasma lithium ion levels. Arch Gen Psychiatry 1983; 40: 283–6PubMedCrossRefGoogle Scholar
  108. 108.
    Stoudemire A, Hill CD, Lewison BJ, et al. Lithium intolerance in a medical-psychiatric population. Gen Hosp Psychiatry 1998; 20: 85–90PubMedCrossRefGoogle Scholar
  109. 109.
    Hardy BG, Shulman KI, Zucchero C. Gradual discontinuation of lithium augmentation in elderly pateints with unipolar depression. J Clin Psychopharmacol 1997; 17: 22–6PubMedCrossRefGoogle Scholar
  110. 110.
    Head L, Dening T. Lithium in the over-65s: who is taking it and who is monitoring it? Int J Geriatr Psychiatry 1998; 13: 164–71PubMedCrossRefGoogle Scholar
  111. 111.
    Sawin CT, Chopra D, Azizi F, et al. The aging thyroid: increased prevalence of elevated serum thyrotropin levels in the elderly. JAMA 1979; 242(3): 247–50PubMedCrossRefGoogle Scholar
  112. 112.
    Smith RE, Helms PM. Adverse effects of lithium therapy in the acutely ill elderly patient. J Clin Psychiatry 1982; 13: 53–60Google Scholar
  113. 113.
    Holroyd S, Rabins PV. A retrospective chart review of lithium side effects in a geriatric outpatient population. Am J Geriatr Psychiatry 1994; 2: 346–51CrossRefGoogle Scholar
  114. 114.
    Murray N, Hopwood S, Balfour DJK, et al. The influence of age on lithium efficacy and side-effects in outpatients. Psychol Med 1983; 13:53–60PubMedCrossRefGoogle Scholar
  115. 115.
    Himmelhoch JM, Neil JF, May SJ, et al. Age, dementia, dyskinesias, and lithium response. Am J Psychiatry 1980; 137: 941–5PubMedGoogle Scholar
  116. 116.
    Nambudiri DE, Meyers BS, Young RC. Delayed recovery from lithium neurotoxicity. J Geriatr Psychiatry Neurol 1991; 4: 40–3PubMedCrossRefGoogle Scholar
  117. 117.
    Shulman KI, Mackenzie S, Hardy BG. The clinical use of lithium carbonate in old age: a review. Prog Neuropsych Biol Psychiatry 1987; 11: 59–64Google Scholar

Copyright information

© Adis International Limited 2000

Authors and Affiliations

  • Beth A. Sproule
    • 1
    • 4
    • 5
  • Brian G. Hardy
    • 2
    • 4
  • Kenneth I. Shulman
    • 3
    • 5
  1. 1.Psychopharmacology Research Program, Sunnybrook and Women’s College Health Sciences CentreUniversity of TorontoTorontoCanada
  2. 2.Pharmacy Department, Sunnybrook and Women’s College Health Sciences CentreUniversity of TorontoTorontoCanada
  3. 3.Psychiatry Department, Sunnybrook and Women’s College Health Sciences CentreUniversity of TorontoTorontoCanada
  4. 4.Faculty of PharmacyUniversity of TorontoTorontoCanada
  5. 5.Department of PsychiatryUniversity of TorontoTorontoCanada

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