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Rudorfer MV, Potter WZ. The Role of Metabolites of Antidepressants in the Treatment of Depression. CNS Drugs. 1997;7(4):273-312doi: 10.2165/00023210-199707040-00003.
Rudorfer, M. V., & Potter, W. Z. (1997). The Role of Metabolites of Antidepressants in the Treatment of Depression. CNS drugs, 7(4), 273-312. https://doi.org/10.2165/00023210-199707040-00003
Rudorfer, M V, and Potter, W Z. "The Role of Metabolites of Antidepressants in the Treatment of Depression." CNS drugs vol. 7,4 (1997): 273-312. doi: https://doi.org/10.2165/00023210-199707040-00003
Rudorfer MV, Potter WZ. The Role of Metabolites of Antidepressants in the Treatment of Depression. CNS Drugs. 1997 Apr;7(4):273-312. doi: 10.2165/00023210-199707040-00003. PMID: 27520753.
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CNS Drugs. 1997 Apr;7(4):273-312. doi: 10.2165/00023210-199707040-00003.

The Role of Metabolites of Antidepressants in the Treatment of Depression.

CNS drugs

M V Rudorfer, W Z Potter

Affiliations

  1. Clinical Treatment Research Branch, Division of Clinical and Treatment Research, National Institute of Mental Health, 5600 Fishers Lane, Room 18-105, Rockville, Maryland, MD 20857, USA.
  2. Section on Clinical Pharmacology, Experimental Therapeutics Branch, National Institute of Mental Health, Bethesda, Maryland, USA.

PMID: 27520753 DOI: 10.2165/00023210-199707040-00003

Abstract

Recognition of the role of active metabolites in mediating therapeutic and/or adverse effects of many antidepressants is an important part of understanding the mechanisms of action of these medications. While virtually all antidepressants except lithium undergo extensive hepatic metabolism, the profile of activity of the resulting breakdown products varies considerably.The metabolites of some antidepressants share the primary biochemical actions of their parent compounds and appear to contribute to the therapeutic efficacy of those medications. Examples of this are the tricyclic antidepressant (TCA) nor-triptyline, the selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitor (SSRI) fluoxetine and the serotonin-noradrenaline (norepinephrine) reuptake inhibitor venlafaxine. Less commonly, the activity of the primary metabolite may differ from that of the parent drug. An example is clomipramine. This drug is a potent serotonin reuptake blocking TCA, but its demethyl-metabolites are noradrenaline reuptake inhibitors. On the other hand, a number of effective anti-depressants, including most of the SSRIs other than fluoxetine, lack active metabolites.On the negative side, antidepressant metabolites may add to the adverse effect burden presented by their drugs of origin. At sufficiently high doses, the amphetamines resulting from the metabolism of some monoamine oxidase inhibitors, e.g. selegiline (deprenyl), may directly produce toxicity from the pharmacodynamic interaction with the parent antidepressant. While hydroxy-nortriptyline produces lesser anticholinergic effects than its parent compound, this metabolite may block the therapeutic action of nortriptyline when present in high concentrations. Excessive plasma concentrations of the major metabolite of amfebutamone (bupropion) have been associated with nonresponse and clinical worsening in some patients.Amfebutamone also illustrates the importance of pharmacokinetic factors in determining the magnitude of the influence of metabolites on antidepressant action. Active metabolites that have long elimination half-lives may predominate over the parent compound in plasma and CSF, exerting considerable clinical impact. With several of the newer drugs, notably amfebutamone, venlafaxine and nefazodone, the presence of active metabolites with half-lives approaching 1 day suggests that once-daily administration may be sufficient.The formation of most antidepressant metabolites is under strong genetic control and the metabolites themselves often exert effects on hepatic enzyme systems. This can lead to the possibility of drug-drug interactions. A key example is norfluoxetine, which is associated with potent inhibition of the cytochrome P450 isozyme 2D6 (and, consequently, reduced metabolism of drugs such as TCAs). This effect lasts for weeks even after fluoxetine discontinuation, due to the fact that norfluoxetine has a half-life of up to 2 weeks.The clearance of most antidepressant metabolites is ultimately dependent on elimination by the kidneys. Therefore, these substances tend to accumulate in states of reduced renal function, including normal aging. The relative increase in TCA hydroxy-metabolite concentrations in the elderly may contribute to the cardiovascular and other toxicities of these antidepressants in this vulnerable patient population.Attention to the existence and implications of active metabolites from the earliest stages of antidepressant drug development may help optimise the benefit: risk ratio of this valuable class of psychotropic medications.

References

  1. J Am Acad Child Adolesc Psychiatry. 1992 Jan;31(1):34-44 - PubMed
  2. Int J Psychiatry Med. 1991;21(1):47-56 - PubMed
  3. Psychopharmacology (Berl). 1992;106(3):388-90 - PubMed
  4. Clin Pharmacol Ther. 1984 Sep;36(3):343-9 - PubMed
  5. Int J Clin Pharmacol Ther Toxicol. 1985 Apr;23(4):180-5 - PubMed
  6. Psychopharmacology (Berl). 1986;89(3):388-91 - PubMed
  7. Psychopharmacol Bull. 1992;28(1):45-57 - PubMed
  8. Psychiatry Res. 1991 Jan;36(1):1-17 - PubMed
  9. J Clin Psychopharmacol. 1994 Apr;14(2):90-8 - PubMed
  10. Drug Saf. 1994 Jan;10(1):18-46 - PubMed
  11. Psychopharmacol Bull. 1993;29(1):35-44 - PubMed
  12. J Clin Psychopharmacol. 1988 Feb;8(1):48-53 - PubMed
  13. Psychopharmacol Bull. 1992;28(2):163-8 - PubMed
  14. Clin Pharmacol Ther. 1995 Oct;58(4):390-8 - PubMed
  15. Neuropsychopharmacology. 1994 Oct;11(2):133-41 - PubMed
  16. Clin Chim Acta. 1987 Jun 15;165(2-3):177-87 - PubMed
  17. J Toxicol Clin Toxicol. 1991;29(4):479-84 - PubMed
  18. Pharmacol Toxicol. 1991 Jan;68(1):64-7 - PubMed
  19. J Clin Psychiatry. 1995 Jun;56(6):243-5 - PubMed
  20. Clin Pharmacol Ther. 1991 Jan;49(1):18-23 - PubMed
  21. Am J Psychiatry. 1993 May;150(5):837 - PubMed
  22. Biol Psychiatry. 1993 Jan 1;33(1):3-14 - PubMed
  23. Neuropsychopharmacology. 1988 Sep;1(3):213-5 - PubMed
  24. Arch Gen Psychiatry. 1988 Feb;45(2):145-9 - PubMed
  25. Biol Psychiatry. 1979 Aug;14(4):601-13 - PubMed
  26. Neuropsychopharmacology. 1996 Jul;15(1):1-6 - PubMed
  27. Drugs. 1989 Jul;38(1):123-47 - PubMed
  28. J Clin Psychiatry. 1991 Jun;52 Suppl:23-33 - PubMed
  29. J Clin Psychopharmacol. 1996 Aug;16(4):273-85 - PubMed
  30. Br J Psychiatry. 1986 Jun;148:676-9 - PubMed
  31. J Clin Psychopharmacol. 1995 Feb;15(1):41-8 - PubMed
  32. JAMA. 1993 May 26;269(20):2673-5 - PubMed
  33. J Pharmacol Exp Ther. 1984 Jul;230(1):94-102 - PubMed
  34. J Am Acad Child Adolesc Psychiatry. 1993 Jul;32(4):805-13 - PubMed
  35. Pharmacogenetics. 1996 Feb;6(1):1-42 - PubMed
  36. Eur J Clin Pharmacol. 1977 Mar 11;11(3):219-24 - PubMed
  37. J Clin Psychopharmacol. 1995 Dec;15(6):387-98 - PubMed
  38. Biochem Pharmacol. 1980 Aug 1;29(15):2149-50 - PubMed
  39. Clin Pharmacol Ther. 1995 Jun;57(6):670-7 - PubMed
  40. J Clin Pharmacol. 1990 Mar;30(3):272-84 - PubMed
  41. Br J Clin Pharmacol. 1980 May;9(5):521-3 - PubMed
  42. Psychopharmacol Bull. 1991;27(4):521-32 - PubMed
  43. Am J Psychiatry. 1992 Nov;149(11):1592-4 - PubMed
  44. Clin Pharmacokinet. 1994 Sep;27(3):175-90 - PubMed
  45. Pharmacopsychiatry. 1991 Mar;24(2):68 - PubMed
  46. Psychopharmacol Bull. 1991;27(4):401-9 - PubMed
  47. JAMA. 1983 Aug 26;250(8):1069-71 - PubMed
  48. Pediatrics. 1993 Nov;92(5):721-2 - PubMed
  49. J Clin Psychiatry. 1991 Jun;52 Suppl:40-7 - PubMed
  50. Eur J Clin Pharmacol. 1986;31(4):449-55 - PubMed
  51. J Clin Psychiatry. 1993 Aug;54 Suppl:3-15; discussion 16-7 - PubMed
  52. J Am Acad Child Adolesc Psychiatry. 1989 May;28(3):373-5 - PubMed
  53. Psychopharmacol Bull. 1991;27(4):493-502 - PubMed
  54. Arch Gen Psychiatry. 1994 Aug;51(8):607-15 - PubMed
  55. J Neural Transm Gen Sect. 1992;88(2):157-60 - PubMed
  56. J Clin Psychopharmacol. 1995 Dec;15(6):409-16 - PubMed
  57. J Clin Psychiatry. 1991 Jun;52(6):250-4 - PubMed
  58. Psychopharmacology (Berl). 1987;92(1):14-24 - PubMed
  59. J Clin Psychopharmacol. 1990 Jun;10(3):176-83 - PubMed
  60. Arch Gen Psychiatry. 1988 Feb;45(2):139-43 - PubMed
  61. Clin Chem. 1995 Jun;41(6 Pt 1):955-6 - PubMed
  62. J Clin Psychopharmacol. 1988 Dec;8(6):402-8 - PubMed
  63. Br J Psychiatry. 1991 Jun;158:856-7 - PubMed
  64. Clin Pharmacol Ther. 1981 Aug;30(2):189-93 - PubMed
  65. Neuropsychopharmacology. 1993 Jun;8(4):337-44 - PubMed
  66. Am J Psychiatry. 1984 Mar;141(3):432-3 - PubMed
  67. J Clin Psychopharmacol. 1990 Oct;10(5):333-7 - PubMed
  68. Biol Psychiatry. 1995 Nov 15;38(10):696-8 - PubMed
  69. Am J Psychiatry. 1991 Sep;148(9):1234-6 - PubMed
  70. Br J Clin Pharmacol. 1985 Jun;19(6):832-5 - PubMed
  71. J Fam Pract. 1995 Sep;41(3):289-91 - PubMed
  72. Psychopharmacol Bull. 1995;31(1):75-81 - PubMed
  73. Arch Gen Psychiatry. 1993 Aug;50(8):624-35 - PubMed
  74. Br J Psychiatry. 1995 Sep;167(3):370-3 - PubMed
  75. Neurology. 1982 May;32(5):503-9 - PubMed
  76. Clin Pharmacol Ther. 1982 Sep;32(3):322-9 - PubMed
  77. J Am Acad Child Adolesc Psychiatry. 1992 Jul;31(4):691-8 - PubMed
  78. Drugs. 1989 May;37(5):713-38 - PubMed
  79. J Clin Pharmacol. 1992 Aug;32(8):716-24 - PubMed
  80. Br J Clin Pharmacol. 1985 Oct;20(4):411-3 - PubMed
  81. J Clin Psychopharmacol. 1989 Feb;9(1):48-51 - PubMed
  82. Psychopharmacology (Berl). 1987;92(2):169-72 - PubMed
  83. Int Clin Psychopharmacol. 1994 Jun;9 Suppl 3:13-9 - PubMed
  84. Drugs. 1989 Feb;37(2):123-40 - PubMed
  85. J Clin Psychopharmacol. 1995 Oct;15(5):327-33 - PubMed
  86. J Clin Psychiatry. 1992 Apr;53(4):127-9 - PubMed
  87. Clin Pharmacol Ther. 1985 Nov;38(5):586-9 - PubMed
  88. Pharmacol Toxicol. 1989 Jul;65(1):37-9 - PubMed
  89. Clin Pharmacol Ther. 1979 Nov;26(5):600-10 - PubMed
  90. Br J Psychiatry Suppl. 1988 Sep;(3):47-50 - PubMed
  91. Am J Psychiatry. 1994 Nov;151(11):1626-30 - PubMed
  92. Am J Psychiatry. 1996 Mar;153(3):311-20 - PubMed
  93. Clin Pharmacol Ther. 1983 Mar;33(3):322-8 - PubMed
  94. Pharmacotherapy. 1994 Mar-Apr;14(2):127-38 - PubMed
  95. Lancet. 1993 Jan 2;341(8836):63 - PubMed
  96. Neuropsychopharmacology. 1995 May;12(3):185-219 - PubMed
  97. J Clin Psychopharmacol. 1988 Dec;8(6):428-33 - PubMed
  98. Am J Psychiatry. 1995 May;152(5):812-3 - PubMed
  99. JAMA. 1979 Oct 26;242(17):1900-1 - PubMed
  100. Am J Psychiatry. 1985 Dec;142(12):1459-62 - PubMed
  101. Clin Pharmacol Ther. 1993 Aug;54(2):219-27 - PubMed
  102. Arch Dis Child. 1979 May;54(5):405 - PubMed
  103. J Clin Psychiatry. 1993 Sep;54 Suppl:14-34; discussion 55-6 - PubMed
  104. Clin Pharmacol Ther. 1988 Sep;44(3):283-8 - PubMed
  105. Life Sci. 1979 Jan 1;24(1):21-8 - PubMed
  106. Life Sci. 1984 Sep 24;35(13):1379-83 - PubMed
  107. Psychopharmacol Bull. 1991;27(4):577-94 - PubMed
  108. Clin Pharmacol Ther. 1982 May;31(5):609-16 - PubMed
  109. J Clin Psychiatry. 1994 Sep;55(9):391-3 - PubMed
  110. Psychopharmacology (Berl). 1993;110(3):302-8 - PubMed
  111. Clin Pharmacol Ther. 1988 Sep;44(3):353-9 - PubMed
  112. Am J Psychiatry. 1985 Jul;142(7):866-8 - PubMed
  113. Harv Rev Psychiatry. 1994 Nov-Dec;2(4):204-13 - PubMed
  114. Am J Psychiatry. 1996 Jan;153(1):83-92 - PubMed
  115. J Clin Psychopharmacol. 1985 Apr;5(2):83-8 - PubMed
  116. Arch Gen Psychiatry. 1985 Dec;42(12):1171-7 - PubMed
  117. Psychopharmacol Bull. 1991;27(4):503-12 - PubMed
  118. Clin Pharmacol Ther. 1986 Jan;39(1):72-81 - PubMed
  119. J Pharmacol Exp Ther. 1978 Jun;205(3):666-74 - PubMed
  120. Biol Psychiatry. 1991 Dec 1;30(11):1139-66 - PubMed
  121. Psychopharmacol Bull. 1991;27(4):533-40 - PubMed
  122. J Clin Psychopharmacol. 1995 Oct;15(5):306-19 - PubMed
  123. BMJ. 1995 Apr 8;310(6984):897-901 - PubMed
  124. Clin Pharmacol Ther. 1984 Apr;35(4):540-4 - PubMed
  125. Clin Pharmacol Ther. 1984 Jul;36(1):138-44 - PubMed
  126. Eur J Clin Pharmacol. 1986;30(4):475-80 - PubMed
  127. Ther Drug Monit. 1985;7(4):478-80 - PubMed
  128. Pharmacol Res. 1992 Dec;26(4):317-29 - PubMed
  129. Drugs. 1991 Feb;41(2):225-53 - PubMed
  130. Ther Drug Monit. 1989;11(2):165-70 - PubMed
  131. Br J Pharmacol. 1983 Jan;78(1):97-102 - PubMed
  132. Clin Pharmacol Ther. 1985 Mar;37(3):301-7 - PubMed
  133. Psychopharmacol Bull. 1997;33(1):109-12 - PubMed
  134. J Clin Psychiatry. 1992 Dec;53(12):450-1 - PubMed
  135. Arch Gen Psychiatry. 1977 Feb;34(2):236-9 - PubMed
  136. J Clin Psychopharmacol. 1991 Jun;11(3):224-5 - PubMed
  137. J Clin Psychiatry. 1990 Oct;51(10):426-9 - PubMed
  138. J Clin Psychiatry. 1993 Sep;54 Suppl:50-4; discussion 55-6 - PubMed
  139. Drugs. 1992 Apr;43(4):561-96 - PubMed
  140. J Clin Psychiatry. 1982 Apr;43(4):151-6 - PubMed
  141. Ther Drug Monit. 1988;10(2):164-7 - PubMed
  142. Lancet. 1985 Nov 16;2(8464):1124 - PubMed
  143. Clin Pharmacol Ther. 1989 Jun;45(6):650-6 - PubMed
  144. Am J Psychiatry. 1980 Aug;137(8):984-6 - PubMed
  145. J Am Acad Child Adolesc Psychiatry. 1993 Jul;32(4):798-804 - PubMed
  146. Clin Pharmacol Ther. 1983 Mar;33(3):335-42 - PubMed
  147. Arch Gen Psychiatry. 1985 Apr;42(4):361-4 - PubMed
  148. Semin Liver Dis. 1990 Nov;10 (4):235-50 - PubMed
  149. Int J Psychiatry Med. 1995;25(3):277-90 - PubMed
  150. Psychiatr Clin North Am. 1984 Sep;7(3):519-34 - PubMed
  151. Clin Pharmacol Ther. 1980 Nov;28(5):703-6 - PubMed
  152. Clin Pharmacol Ther. 1992 Oct;52(4):350-8 - PubMed
  153. Clin Pharmacol Ther. 1993 Jan;53(1):89-95 - PubMed
  154. Psychopharmacol Ser. 1989;7:232-6 - PubMed
  155. Acta Psychiatr Scand Suppl. 1995;386:8-13 - PubMed
  156. Drug Intell Clin Pharm. 1981 Apr;15(4):263-6 - PubMed
  157. Clin Pharmacol Ther. 1992 Mar;51(3):239-48 - PubMed
  158. Arch Gen Psychiatry. 1982 Sep;39(9):1055-61 - PubMed
  159. Can J Psychiatry. 1986 Nov;31(8):752-4 - PubMed
  160. Psychiatry Res. 1991 Sep;38(3):227-36 - PubMed
  161. J Clin Psychopharmacol. 1995 Dec;15(6):417-20 - PubMed
  162. Pharmacotherapy. 1981 Nov-Dec;1(3):163-78 - PubMed
  163. Psychopharmacol Bull. 1995;31(2):217-21 - PubMed
  164. Ther Drug Monit. 1995 Jun;17 (3):273-9 - PubMed
  165. Br J Clin Pharmacol. 1992 May;33(5):521-3 - PubMed
  166. Ther Drug Monit. 1993 Jun;15(3):243-6 - PubMed
  167. J Clin Psychiatry. 1992 Feb;53 Suppl:13-20 - PubMed
  168. Clin Pharmacol Ther. 1987 Jul;42(1):10-9 - PubMed
  169. Life Sci. 1993;52(12):1023-9 - PubMed
  170. J Nerv Ment Dis. 1988 Apr;176(4):249-51 - PubMed
  171. Eur J Pharmacol. 1977 Apr 21;42(4):403-10 - PubMed
  172. J Pharm Pharmacol. 1981 Jul;33(7):477-8 - PubMed
  173. J Pharm Pharmacol. 1976 Nov;28(11):849-50 - PubMed
  174. Clin Pharmacol Ther. 1994 Jul;56(1):14-21 - PubMed
  175. Psychopharmacology (Berl). 1991;103(3):287-90 - PubMed
  176. Arch Gen Psychiatry. 1982 May;39(5):505-10 - PubMed
  177. J Clin Psychiatry. 1994 Dec;55 Suppl:38-45; discussion 46-7 - PubMed
  178. J Neural Transm. 1978;43(3-4):271-7 - PubMed
  179. Psychopharmacol Ser. 1989;7:52-9 - PubMed
  180. Biol Psychiatry. 1984 Apr;19(4):549-56 - PubMed
  181. Psychopharmacol Bull. 1991;27(4):611-7 - PubMed
  182. Clin Pharmacol Ther. 1986 Apr;39(4):369-71 - PubMed
  183. J Clin Psychopharmacol. 1990 Oct;10(5):328-32 - PubMed
  184. Clin Pharmacol Ther. 1992 Mar;51(3):278-87 - PubMed
  185. Clin Pharmacol Ther. 1983 Feb;33(2):183-9 - PubMed
  186. Eur J Clin Pharmacol. 1994;46(1):35-9 - PubMed
  187. Life Sci. 1967 Sep 1;6(17):1895-903 - PubMed
  188. J Clin Psychopharmacol. 1995 Jun;15(3):223-4 - PubMed
  189. Am J Psychiatry. 1991 Sep;148(9):1268-9 - PubMed
  190. Drugs. 1995 Feb;49(2):280-94 - PubMed
  191. Life Sci. 1979 Oct 8;25(15):1285-92 - PubMed
  192. J Clin Psychopharmacol. 1995 Jun;15(3):175-81 - PubMed
  193. Clin Pharmacol Ther. 1982 Aug;32(2):208-11 - PubMed
  194. Prog Neuropsychopharmacol Biol Psychiatry. 1989;13(3-4):395-403 - PubMed
  195. J Clin Psychopharmacol. 1995 Dec;15(6):399-408 - PubMed
  196. Pharmacol Rev. 1991 Dec;43(4):527-52 - PubMed
  197. Psychopharmacol Bull. 1991;27(4):513-9 - PubMed
  198. Psychopharmacol Bull. 1996;32(1):27-32 - PubMed
  199. Br J Clin Pharmacol. 1978 Dec;6(6):542-4 - PubMed
  200. Am J Psychiatry. 1990 Sep;147(9):1203-8 - PubMed
  201. Ther Drug Monit. 1986;8(3):279-84 - PubMed
  202. Br J Clin Pharmacol. 1985 Nov;20(5):497-9 - PubMed
  203. Neuropsychopharmacology. 1995 Jul;12(4):323-33 - PubMed
  204. Psychopharmacology (Berl). 1989;98(2):275-82 - PubMed
  205. Br Med J (Clin Res Ed). 1987 Oct 24;295(6605):1021-4 - PubMed
  206. Drugs. 1991 Mar;41(3):450-77 - PubMed
  207. Biol Psychiatry. 1995 Mar 15;37(6):414-6 - PubMed
  208. J Clin Psychiatry. 1995 Sep;56(9):395-401 - PubMed
  209. J Clin Psychopharmacol. 1996 Aug;16(4):307-14 - PubMed
  210. Clin Pharmacol Ther. 1987 Jan;41(1):97-102 - PubMed
  211. Clin Pharmacokinet. 1993 Mar;24(3):203-20 - PubMed
  212. Psychol Med. 1979 May;9(2):377-82 - PubMed
  213. Br J Clin Pharmacol. 1990 Jan;29(1):27-31 - PubMed
  214. J Clin Psychopharmacol. 1995 Oct;15(5):320-6 - PubMed
  215. Arch Gen Psychiatry. 1988 Feb;45(2):167-72 - PubMed
  216. Clin Pharmacol Ther. 1991 Jan;49(1):32-8 - PubMed
  217. Clin Pharmacokinet. 1991 Jun;20(6):447-62 - PubMed
  218. Int J Clin Pharmacol Res. 1993;13(3):167-71 - PubMed
  219. J Chromatogr. 1991 Sep 18;570(1):129-38 - PubMed
  220. Neuropsychopharmacology. 1992 Jan;6(1):1-10 - PubMed
  221. J Psychiatr Res. 1989;23(1):73-9 - PubMed
  222. Br J Clin Pharmacol. 1984 Apr;17 (4):433-40 - PubMed
  223. Psychopharmacol Bull. 1991;27(4):541-50 - PubMed
  224. N Engl J Med. 1991 Aug 29;325(9):633-42 - PubMed
  225. J Chromatogr. 1992 Aug 7;579(1):99-106 - PubMed
  226. J Clin Psychopharmacol. 1995 Apr;15(2):125-31 - PubMed
  227. Clin Pharmacokinet. 1995 Jan;28(1):26-40 - PubMed
  228. J Clin Psychopharmacol. 1996 Aug;16(4):286-93 - PubMed
  229. Psychopharmacology (Berl). 1993;113(2):222-4 - PubMed
  230. Arch Gen Psychiatry. 1988 Feb;45(2):150-4 - PubMed
  231. Clin Pharmacol Ther. 1982 Jan;31(1):51-5 - PubMed
  232. J Clin Psychiatry. 1995 Jan;56(1):17-20 - PubMed
  233. Clin Pharmacol Ther. 1987 Oct;42(4):395-404 - PubMed
  234. Clin Pharmacol Ther. 1994 Dec;56(6 Pt 2):742-9 - PubMed
  235. Eur J Clin Pharmacol. 1986;30(1):43-9 - PubMed
  236. Clin Pharmacokinet. 1990 Sep;19(3):241-55 - PubMed
  237. Eur J Clin Pharmacol. 1992;43(4):405-11 - PubMed
  238. Drug Metab Dispos. 1994 Mar-Apr;22(2):304-11 - PubMed
  239. Br J Psychiatry. 1995 Sep;167(3):412-3 - PubMed
  240. Br Med J. 1971 Aug 7;3(5770):331-4 - PubMed
  241. Clin Neuropharmacol. 1990;13 Suppl 1:S45-53 - PubMed
  242. Clin Pharmacol Ther. 1992 Mar;51(3):288-95 - PubMed
  243. Biol Psychiatry. 1987 Oct;22(10):1283-7 - PubMed
  244. Psychopharmacol Bull. 1991;27(4):417-26 - PubMed
  245. Clin Pharmacol Ther. 1982 Nov;32(5):664-7 - PubMed
  246. Clin Pharmacol Ther. 1986 Oct;40(4):444-50 - PubMed
  247. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11825-9 - PubMed
  248. Clin Pharmacol Ther. 1995 Oct;58(4):399-403 - PubMed
  249. J Pharmacol Exp Ther. 1993 Aug;266(2):964-71 - PubMed
  250. Clin Pharmacol Ther. 1982 Mar;31(3):393-401 - PubMed
  251. Am J Psychiatry. 1986 Aug;143(8):1069-70 - PubMed
  252. Clin Pharmacol Ther. 1986 Sep;40(3):261-7 - PubMed
  253. Xenobiotica. 1993 Apr;23(4):349-59 - PubMed
  254. Psychopharmacology (Berl). 1982;76(1):94-5 - PubMed
  255. Arch Gen Psychiatry. 1986 Jan;43(1):86-90 - PubMed

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