Chávez- León E, Ontiveros UMP, Serrano GC

Language: Spanish
References: 116
Page: 307-319
PDF size: 221.12 Kb.

ABSTRACT

Depression is a frequent mental disorder in the general population. Approximately 3.7% of the population will suffer a major depressive episode throughout life. Pharmacological treatment with selective serotonin receptor inhibitors (SSRIs) is useful to treat this condition and other mental disorders. Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine and sertraline, which constitute this group, are characterized by having an easy way of administration and a very extensive security profile.
Objectives: The objectives in this revision were: 1. To establish current indications of selective serotonin receptor inhibitors, using as basis those authorized by the Food and Drug Administration (FDA) of the United States of America. 2. To describe the mechanisms that explain antidepressant action. Initially, the SSRIs inhibit the reuptake of serotonin at the synaptic cleft; later there is a downregulation of the 5HT1A receptors; and finally antidepressants raise the levels of brain derived neurotrophic factor (BDNF). 3. To present its way of administration and dosage. 4. To describe frequent collateral effects and those specifically associated to this group of antidepressants and the recommended treatment.
Results: SSRIs antidepressants are the first choice treatment in depression, in the anxiety disorder, the obsessive-compulsive disorder, the posttraumatic stress disorder, bulimia nervosa and the premenstrual dysphoric disorder. At present, SSRIs displace benzodiacepines in the treatment of generalized anxiety disorder, just as they displaced tricyclic antidepressants in the past. Depressed patients show less activity than normal of the serotonin neurotransmitter (serotonergic hypothesis of depression) and the reuptake blockade at the site of the serotonergic presinaptic receptors 5HT1A, 5HT2C and 5HT3C increases neurotransmission in this system. Desensitization of autoreceptors 5HT1A and the downregulation of the 5HT2 receptors coupled to the G protein, a late effect of the SSRIs, result in the improvement of the depressive symptoms. The mechanism that explains the relatively late antidepressant effect seems to be different to the acute and fast serotonergic effect responsible of improvement in the premenstrual dysphoric disorder. Moreover, these antidepressants, in the same way than mood stabilizers and electroconvulsive therapy, increase serum levels of the brain-derived neuronal growth factor, as well as other neurotrophic factors. Although the SSRIs dosages are variable, it is possible to start antidepressant treatment with therapeutic doses in the majority of cases; at the same time, if necessary, it is possible to augment them gradually up to the largest dose, with a wide security margin. Their most frequent collateral effects occur in the gastrointestinal system, in the sexual response and on bone density. Nevertheless, there are collateral effects specifically related to the use of these antidepressant medications: 1. The serotonergic syndrome, characterized by changes in the mental status, autonomic hyperactivity and neuromuscular anomalies. 2. The syndrome of inappropriate secretion of antidiuretic hormone, which occurs in 25% of the elder depressed patients treated, and which is characterized y a high serum osmolarity, low urinary osmolarity and hyponatremia. Its manifestations are malaise, myalgias, drowsiness and headache, but it may produce also confusion, convulsions and coma. 3. Gastrointestinal bleeding mainly and cutaneous bleeding: Use of SSRIs raises 2 to 4 times the risk of bleeding. When the patient takes aspirin it is raised up to 7 times, and with the concomitant use of anti-inflammatory drugs, by nearly 16 times. Other risk factors are age, the antecedent of bleeding and the potency of SSRIs to inhibit the serotonin reuptake. 4. The discontinuation syndrome, lesser with fluoxetine, and greater with paroxetine and sertraline. It appears by the second day and it lasts two weeks. Its manifestations are nausea, headache, paresthesias, nasal congestion and general malaise. They are due to the decrease in serotonin levels at the synaptic cleft. 6. Effects on the newborn when the SSRIs are used during pregnancy consist in specific congenital malformations. Sertraline has been associated to omphalocele, ventricular septum heart defects and anencephaly. Fluoxetine is associated to craniosynostosis and paroxetine to heart defects, gastroschisis, neural tube defects, omphalocele and anencephaly also. Its use also increases the range of spontaneous abortions up to 1.45 times, premature delivery and low birth weight, problems in the early newborn period (respiratory problems and hypotony), hypoglycemia, cyanosis, restlessness, convulsions and low Apgar. Its use during the third trimester can cause persistent lung hypertension. Although it is a rare condition, it is associated to a mortality range of 10% to 20%. 8) Little is known about the effects caused by the use of SSRIs during breastfeeding. In the case of sertraline and paroxetine, these antidepressant drugs are not detected in the child’s serum; on the other hand, serum levels of citalopram were 1.9 nmol/L, fluoxetine 47 nmol/L, and venlafaxine 91 nmol/L. In the available studies, neither behavioral effects nor effects in the development of the newborn were observed. 9) Suicide risk or suicidality. Although the antidepressant treatment lowers both, ideation and the frequency of suicides in the patients treated, the FDA has established a series of general recommendations for the management of patients who start the treatment with antidepressants. To start with the lowest dose, to make an appointment weekly during six consecutive weeks, to recommend and facilitate contact via telephone, to prohibit the use of alcohol and drugs, to ask on each date about suicidal thoughts or behaviors or about self-mutilation, to document the information in the file and to use supportive psychotherapy or cognitive, behavioral or interpersonal therapies.

REFERENCES

1. Medina-Mora ME, Borges G, Lara C, Benjet C, Blanco J. Prevalence, service use, and demographic correlates of 12-month DSM- IV psychiatric disorders in Mexico: results from the Mexican National Comorbidity Survey. Psychol Med 2005;35:1773-1783.

2. Chavez-León E. Fármacos antidepresivos. En: Chávez-León E, Del Bosque-Garza J, Ontiveros-Uribe MP (eds). Manual de psicofarmacología. Capítulo 1. México: Asociación Psiquiátrica Mexicana; 2007; 5-9.

3. Soares CN, Joffe H, Viguera AC et al. Paroxetine versus placebo for women in midlife after hormone therapy discontinuation. Am J Med 2008;121(2):159-162.

4. Schatzberg AF, Cole JO, Debattista C. Manual of clinical psychopharmacology. Washington: American Psychiatric Publishing, Inc.; 2007; p. 35-38.

5. Gillman PK. Tricyclic antidepressant pharmacology and therapeutic drug interaction updated. Br J Pharmacol 2007;151:737-748.

6. Krishnan KR. Revisiting monoamine oxidase inhibitors. J Clin Psychiatry 2007;68(supl 8):35-41.

7. Stahl SM. Not so selective serotonin reuptake inhibitors. J Clin Psychiatry 1998;59:343-344.

8. Hansen RA, Gartlehener G, Lohr KN, Gaynes BN, Carey T. Treatment of major depressive disorder. Ann Intern Med 2005;143:415-426.

9. Machado M, Iskedjian M, Ruiz I, Einarson TR. Remission, dropouts, and adverse drug reaction rates in major depressive disorder: A meta- analysis of head-to-head trials. Curr Med Res Opin 2006;22(9):1825-1837.

10. Swenson JR, Doucette S, Fergusson D. Adverse cardiovascular events in antidepressants trials involving high risk patients: A systematic review of randomized trials. Can J Psychiatry 2006;51:923-929.

11. Nemeroff CB, Schatzberg AF. Pharmacological treatments for unipolar depression. En: Nathan PE, Gorman JM (eds). Treatments that work. New York: Oxford University Press; 2007; p. 271-288.

12. Rubino A, Roskell N, Tennis P et al. Risk of suicide during treatment with venlafaxine, citalopram, fluoxetine, and dothiepin: Retrospective cohort study. Br Med J 2007;334(7587):242-247.

13. Fougherty DD, Rauch SL, Jenike MA. Pharmacological treatments for obsessive-compulsive disorder. En: Nathan PE, Gorman JM (eds). Treatments that work. New York: Oxford University Press; 2007; p. 447-474.

14. Golier JA, Legge JA, Yehuda R. Pharmacological treatment of posttraumatic stress disorder. En: Nathan PE, Gorman JM (eds). Treatments that work. New York: Oxford University Press; 2007; p. 475-512.

15. Wilson GT, Fairburn CG. Treatments for eating disorders. En: Nathan PE, Gorman JM (eds). Treatments that work. New York: Oxford University Press; 2007; p. 579-610.

16. Landén M, Nissbrandt H, Allgulander C, Sörvik K, Ysander C et al. Placebo-controlled trial comparing intermittent and continuous paroxetine in premenstrual dysphoric disorder. Neuropsychopharmacol 2007;32:153-161.

17. Chavez-León E, Ng B, Ontiveros-Uribe MP. Tratamiento farmacológico del trastorno límite de personalidad. Salud Mental 2006;29(5):16-24.

18. Davidson JRT: Pharmacotherapy of social anxiety disorder: What does the evidence tell us? J Clin Psychiatry (supl) 2006;67 12:20-26.

19. Hoyer D, Clarke DE, Fozard JR et al. International Union of Pharmacology classification of receptors for 5-hydroxytryptamine (serotonin). Pharmacol Rev 1994;46:157-203.

20. Boyer EW, Shannon M. The serotonin syndrome. N Engl J Med 2005;352:1112-1120.

21. Holmans P, Weissman MM, Zubenko GS et al. Genetics of early-onset major depression (GenRED): final genome scan report. Am J Psychiatry 2007;64:248-258.

22. Kendler KS, Gats M, Gardner CO, Pedersen NL. A Swedish national twin study of lifetime major depression. Am J Psychiatry 2006;163:109-114.

23. Landén M, Thase ME. A model to explain the therapeutic effects of serotonin reuptake inhibitors: the role of 5-HT2 receptors. Psychopharmacol Bull 2006;39(1):147-166.

24. Belmaker RH, Agam G. Mechanisms of disease. Major depressive disorder. N Engl J Med 2008;358(1):55-68.

25. Kerege F, Vaudan G, Schwald M et al. Neurotrophin levels in postmortem brains of suicide victims and the effects of antemortem diagnosis and psychotropic drugs. Brain Res Mol 2005;136:29-37.

26. Monteleone P, Serritella C, Martiadis V, Maj M. Decreased levels of serum brain-derived neurotrophic factor in both depressed and euthymic patients with unipolar depression and in euthymic depressed and euthymic patients with bipolar I and II disorders. Bipolar Disord 2008;10:95-100.

27. Chen B, Dowlatshahi D, Macqueen GM et al. Increased hippocampal BDNF immunoreactivity in subjects treated with antidepressant medication. Biol Psychiatry 2001;50:260-265.

28. Clayton AH, Pradko JF, Croft HA et al. Prevalence of sexual dysfunction among newer antidepressants. J Clin Psychiatry 2002;63:357-366.

29. Williams VSL, Baldwin DS, Hogue SL et al. Estimating the prevalence and impact of antidepressant- induced sexual dysfunction in 2 European countries: a cross sectional patient survey. J Clin Psychiatry 2006;67:204-210.

30. Balon R. Disfunción sexual asociada a los ISRS. Am J Psychiatry (Ed Esp) 2006;9(10):39-64.

31. Diem SJ, Blackwell TL, Stone KL, Yaffe K, Haney EM et al. Use of antidepressants and rates of hip bone loss in older women. Arch Intern Med 2007;167:1240-1245.

32. Richards JB, Papaioannou A, Adachi JD, Joseph L, Whitson HE. For the Canadian Multicenter Osteoporosis Study (CAMOS) Research Group: Effect of selective serotonin reuptake inhibitors on the risk of fracture. Arch Intern Med 2007;167:188-194.

33. Looper KL. Potential medical and surgical complications of serotonergic antidepressant medications. Psychosom 2007;48(1):1-9.

34. Birmes P, Coppin D, Schmitt I et al. Serotonin syndrome: a brief review. Can Med Assoc J 2003;168(11):1439-1442.

35. Ng BKW, Cameron AJD, Liang R, Rahman H Serotonin syndrome following methylene blue infusion during parathyroidectomy: a case report and literature review. Can J Anesthesiol 2008;55:36-41.

36. Isbister GK, Bowe SJ, Dawson A, Whyte IM. Relative toxicity of selective serotonin reuptake inhibitors (SSRIs) in overdose. J Toxicol Clin Toxicol 2004;42:277-285.

37. Watson WA, Litovitz TL, Rodgers GC Jr. 2002 annual report of the American Association of Poison Control Centers Toxic Exposure Surveillance System. Am J Emerg Med 2003;21:353-421.

38. Gill M, Lovecchio F, Selden B. Serotonin syndrome in a child after a single dose of fluvoxamina. Ann Emerg Med 1999;33:457-459.

39. Isbister GK, Dawson A, Whyte IM et al. Neonatal paroxetine withdrawal syndrome or actually serotonin syndrome? Arch Dis Child Fetal Neonatal Ed 2001;F147-F148.

40. Laine K, Heikkinen T, Ekblad U, Kero P. Effects of exposure to selective reuptake serotonin inhibitors during pregnancy on serotoninérgico symptoms in newborns and cord blood monoamine and prolactin concentrations. Arch Gen Psychiatry 2003;60:720-726.

41. U.S. Food and Drug Administration. Selective serotonin reuptake inhibitors (SSRIs), selective serotonin- norepinephrin reuptake inhibitors (SNRIs), 5-hydroxytryptamine receptor agonists (triptans). http://www.fda.gov/CDER/DRUG/InfoSheets/HCP/triptansHCP.htm Accesada en enero de 2008.

42. Rosenbaum JF, Fava M, Hoog SL, Ascroft RC, Krebs WB. Selective serotonin reuptake inhibitor discontinuation syndrome: a randomized clinical trial. Biol Psychiatry 1998;44:77-87.

43. Verre M, Bossio A, Mammone M et al. Serotonin syndrome caused by olanzapine and clomipramine. Minerva Anestesiol 2007;73:1-5.

44. Lee A, Woo J, Ito S. Frequency of infant adverse events that are associated with citalopram use during breast- feeding. Am J Obstet Gynecol 2004;190:218-221.

45. Palmer BF, Gates JR, Lader M. Causes and management of hiponatremia. Ann Pharmacother 2003; 37:1694-1702.

46. Bouman WP, Pinner G, Johnson H. Incidence of selective serotonin-reuptake inhibitor (SSRI)- induced hyponatraemia due to the syndrome of inappropriate antidiuretic hormone (SIADH) secretion in the elderly. Int J Geriatr Psychiatry 1998;13:12-15.

47. Fabian TJ, Amico JA, Kroboth PD et al. Paroxetine-induced hyponatremia in older adults: a 12- week prospective study. Arch Intern Med 2004;164:327-332.

48. Kirby D, Ames D. Hyponatraemia and selective serotonin-reuptake inhibitors in elderly patients. Int J Geriatr Psychiatry 2001;16:484-493.

49. Meijer WE, Heerdink ER, Nolen WA et al. Association of risk of abnormal bleeding with degree of serotonin-reuptake inhibition by antidepressants. Arch Intern Med 2004;164:2367-2370.

50. Dalton SO, Johansen C, Mellemkjaer L et al. Use of selective serotonin reuptake- inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study. Arch Intern Med 2003;163:59-64.

51. De Abajo FJ, Rodriguez LA, Montero D. Association between selective serotonin reuptake- inhibitors and upper gastrointestinal bleeding: population-based, case-control study. Br Med J 1999;319(7217):1106-1109.

52. Kurdiak PA, Juurlink DN, Kopp A et al. Antidepressants, warfarin, and the risk of hemorrhage. J Clin Psychopharmacol 2005;25:561-564.

53. Tata LJ, West J, Smith C et al. General population based-study of the impact of tricyclic and selective serotonin reuptake-inhibitor antidepressants on the risk of acute myocardial infarction. Heart 2005;91:465-471.

54. Van Walraven C, Mamdani MM, Wells PS et al. Inhibition of serotonin reuptake by antidepressants and upper gastrointestinal bleeding in elderly patients: retrospective cohort study. Br Med J 2001;323(7314):655-658.

55. Wessinger S, Kaplan M, Choi L et al. Increased use of selective-serotonin reuptake inhibitors in patients admitted with gastrointestinal haemorrhage: a multicentre retrospective analysis. Aliment Pharmacol Ther 2006;23:937-944.

56. Loke YK, Trivedi AN, Singh S. Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs. Aliment Pharmacol Ther 2008;27:31-40.

57. De Abajo FJ, Jick H, Derby L et al. Intracraneal haemorrhage and use of selective serotonin reuptake inhibitors. Br J Clin Pharmacol 2003;50:43-47.

58. Hougardy DM, Egberts TC, Van Der Graaf F et al. Serotonin transporter polymorphism and bleeding time during SSRI therapy. Br J Clin Pharmacol (en prensa) 2008.

59. Bogetto F, Bellino S, Revello RB, Patria L. Discontinuation syndrome in dysthymic patients treated with selective serotonin reuptake inhibitor: a clinical investigation. CNS Drugs 2002;16:273-283.

60. Rothschild AJ, Locke CA. Reexposure to fluoxetine alter serious suicide attempts by three patients: the role of acatisia. J Clin Psychiatry 1991;52:491-493.

61. Lane RM. Withdrawal symptoms after discontinuation of selective serotonin reuptake inhibitors (SSRIs). J Serotonin Res 1996;3(2):75-83.

62. Judge R, Parry MG, Quail D, Jacobson JG. Discontinuation symptoms: comparison of brief interruption in fluoxetine and paroxetine treatment. Int Clin Psychopharmacol 2002;17:217-225.

63. Gavin NI, Gaynes BN, Lohr KN et al. Perinatal depression. Obstet Gynecol 2005;106:1071-1083.

64. Dietz PM, Williams SB, Callaghan WM rt al. Clinically identified maternal depression before, during, and alter pregnancies ending in live births. Am J Psychiatry 2007;164:1515-1520.

65. Cooper WO, Willy ME, Pont SJ et al. Increasing use of antidepressants in pregnancy. Am J Obstet Gynecol 2007;196:544.e1-544.e5.

66. Hendrick V, Stowe ZN, Altshuler LL et al. Placental passage of antidepressant medications. Am J Psychiatry 2003;160:993-996.

67. Alwan S, Reefhuis J, Rasmussen S. Use of selective serotonin-reuptake inhibitors in pregnancy and the risk of birth defects. N Engl J Med 2007;356(26):2684-2692.

68. Louik C, Lin AE, Werler MM et al. First-trimester use of selective serotonin-reuptake inhibitors and the risk of birth defects. N Engl J Med 2007;356(26):2675-2683.

69. Rahimi R, Shekoufen N, Abdollahi M et al. Pregnancy outcomes following exposure to serotonin reuptake inhibitors: a meta-analysis of clinical trials. Reprod Toxicol 2005;22(4):571-575.

70. Kallen B. Neonate characteristics alter maternal use of antidepressants in late pregnancy. Arch Pediatr Adolesc Med 2004;158:312-316.

71. Simon GE, Cunningham ML, Davis RL. Outcomes of prenatal antidepressant exposure. Am J Psychiatry 2002;159:2055-2061.

72. Oberlander TF, Misri S, Fitzgerald CE et al. Pharmacologic factors associated with transient neonatal symptoms following prenatal psychotropic medication exposure. J Clin Psychiatry 2004;65:230-237.

73. Sivojelezova A, Shuhaiber S, Sarkissian L et al. Citalopram use in pregnancy: prospective comparative evaluation of pregnancy and fetal outcome. Am J Obstet Gynecol 2005;193:2004-2009.

74. Bairy KL, Madhyastha S, Ashok KP et al. Developmental and behavioral consequences of prenatal fluoxetine. Pharmacol 2007;79:1-11.

75. Levinson-Castiel R, Merlob P, Linder N et al. Neonatal abstinence syndrome after in- utero exposure to selective serotonin- reuptake inhibitors in term infants. Arch Pediatr Adolesc Med 2006;160:173-176.

76. Sanz EJ, De las Cuevas C, Kiuru A et al. Selective serotonin-reuptake inhibitors in pregnant women and neonatal withdrawal syndrome: a database analysis. Lancet 2005;365(9458):482-487.

77. Chambers CD, Hernandez Diaz S, Van Marter LJ, Werler MM. Selective serotonin-reuptake inhibitors and risk of persistent pulmonary hypertension of the newborn. N Engl J Med 2006;354(6):579-587.

78. Misri S, Reebye P, Kendrick K et al. Internalizing behaviors in 4-yearold children exposed in-utero to psychotropic medications. Am J Psychiatry 2006;163:1026-1032.

79. Nulman I, Rovet J, Stewart DE et al. Neurodevelopment of children exposed in utero to antidepressant drugs. N Engl J Med 1997;336:258-262.

80. Nulman I, Rovet J, Stewart DE et al. Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study. Am J Psychiatry 2002;159:1889-1895.

81. Casper RC, Fleisher BE, Lee-Ancajas JC et al. Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy. J Pediatr 2003;142:402-408.

82. Cohen LS, Altshuler LL, Harlow Bl et al. Relapse of major depression during pregnancy in women who maintain or discontinue antidepressant treatment. J Am Med Assoc 2006;295:499-507.

83. Andersson L, Sundstrom-Poromaa I, Wulff M et al. Implications of antenatal depression and anxiety for obstetric outcome. Obstet Gynecol 2004;104:467-476.

84. Misri S, Oberlander TF, Fairbrother N et al. Relation between prenatal maternal mood and anxiety and neonatal health. Can J Psychiatry 2004;49:684-689.

85. Murray L. The impact of posnatal depression on infant development. J Child Psicol Psychiatry 1992;33:543-561.

86. Spinelli MG, Endicott J. Controlled clinical trial of interpersonal psychotherapy versus parenting education program for depressed pregnant women. Am J Psychiatry 2003;160:555-562.

87. Eberhard-Gran M, Eskild A, Opjordsmoen S. Use of psychotropic medications in treating mood disorders during lactation. CNS Drugs 2006;20(3):187-198.

88. Van Odijk J, Kull I, Borres M et al. Breast feeding and allergic disease: a multidisciplinary review of the literature (1996- 2001) on the mode of early feeding in infancy and its impact on later atopic manifestations. Allergy 2003;58:833-843.

89. Anderson PO, Pochop SL, Manoguerra AS. Adverse drug reactions in breastfed infants: less than imagined. Clin Pediatr 2003;42:325-340.

90. Rampono J, Proud S, Hackett LP et al. A pilot study of newer antidepressant concentrations in cord and maternal serum and possible effects in the neonate. Int J Neuropsychopharmacol 2004;7:329-334.

91. Weissman AM, Levy BT, Hartz AJ et al. Pooled analysis of antidepressant levels in lactating mothers, breast milk, and nursing infants. Am J Psychiatry 2004;161:1066-1078.

92. Berle JO, Steen VD, Aamo TO et al. Breastfeeding during maternal antidepressant treatment with serotonin reuptake inhibitors: infant exposure, clinical symptoms, and cytochrome P450 genotypes. J Clin Psychiatry 2004;65:1228-1234.

93. Merlob P, Stahl B, Sulkes J. Paroxetine during breast- feeding: infant weight gain and maternal adherence to counsel. Eur J Pediatr 2004;163:135-139.

94. Grunebaum MF, Ellis SP, Shuhua L, Oquendo MA, Mann J. Antidepressants and suicide risk in the United States, 1985-1999. J Clin Psychiatry 2004;65(11):1456-1462.

95. Teicher MH, Glod C, Cole JO. Emergence of intense suicidal preoccupation during fluoxetine treatment. Am J Psychiatry 1990;147:207-210.

96. Beasley CM, Dornseif BE, Bosomworth JC et al. Fluoxetine and suicide: A meta-analysis of controlled trials of treatment for depression. Br Med J 1991;303:685-692.

97. Libby AM, Brent DA, Morrato EH et al. Decline in treatment of pediatric depression after FDA advisory on risk of suicidality with SSRIs. Am J Psychiatry 2007;164:884-891.

98. Gibbons RD, Hendricks Brown C, Hur K et al. Early evidence on the effects of regulators’ suicidality warnings on SSRI prescriptions and suicide in children and adolescents. Am J Psychiatry 2007;164:1356-1363.

99. US Department of Health and Human Services. Centers for Disease Control and Prevention. Fatal Injury Report: Web based injury statistics query and reporting system, www.cdc.gov/NCIPC/wisqars. Accesada en enero de 2008.

100. US Food and Drug Administration: Briefing Document for Psychopharmacologic Drugs Advisory Committee, December 13, 2006, http://www.fda.gov/ohrms/dockets/ac/06/briefing/ 2006-4272b1-01-FDA.pdf. Accesada en enero de 2008.

101. Nemeroff CB, Kalali A, Keller MB et al. Impact of publicity concerning pediatric suicidality data on physician practice patterns in the United States. Arch Gen Psychiatry 2007;64:466-472.

102. The Tads Team: The Treatment for Adolescents with Depression Study (TADS): Long-term effectiveness and safety outcomes. Arch Gen Psychiatry 64(10):1132-1143.

103. Juurlink DN, Mamdani MM, Koop A, Redelmeier DA. The risk of suicide with selective serotonin reuptake inhibitors in the elderly. Am J Psychiatry 2006;163:813-821.

104. Nutt DJ. Death and dependence: current controversies over the selective serotonin reuptake inhibitors. J Psychopharmacol 2003;17:355-364.

105. Baldassano CF, Trumen CJ, Nierenberg A et al. Akathisia: a review and case report following paroxetine treatment. Compr Psychiatry 1996;37:122-124.

106. Lipinski JF Jr, Mallya G, Zimmerman P, Pope HG Jr. Fluoxetine-induced akathisia: clinical and theoretical implications. J Clin Psychiatry 1989;50:339-342.

107. Roy-Byrne P, Cowley DS. Pharmacological treatments for panic disorder, generalized anxiety disorder, specific phobia, and social anxiety. En: Nathan PE, Gorman JM (eds). Treatments that work. New York: Oxford University Press; 2007; p.395-430.

108. Mann JJ, Kapur S. The emergence of suicidal ideation and behavior during antidepressant pharmacotherapy. Arch Gen Psychiatry 1991;48:1027-1033.

109. Charlier C, Broly F, Lhermitte M et al. Polymorphisms in the CYP 2D6 gene: association with plasma concentrations of fluoxetine and paroxetine. Ther Drug Monit 2003;25:738-742.

110. Murphy GM Jr, Kremer C, Rodrigues HE, Schatzberg AF. Pharmacogenetics of antidepressant medication intolerance. Am J Psychiatry 2003;160:1830-1835.

111. Perlis RH, Purcell S, Fava M et al. Association between treatment-emergent suicidal ideation with citalopram and polymorphisms near cyclic adenosine monophosphate response element binding protein in the STAR*D study. Arch Gen Psychiatry 2007;64:689-697.

112. Bridge JA, Iyengar S. Salary CB et al. Clinical response and risk for reported suicidal ideation and suicide attempts in pediatric antidepressant treatment. JAMA 2007;297(15):1683-1696.

113. Gibbons RD, Brown CH, Hur K et al. Relationship between antidepressants and suicide attempts: An analysis of the Veterans Health Administration Data Set. Am J Psychiatry 2007;164:1044-1049.

114. Beasley CM Jr, Ball SG, Nilsson ME et al. Fluoxetine and adult suicidality revisited: An updated meta-analysis using expanded data sources from placebo-controlled trials. J Clin Psychopharmacol 2007;27 (6):682-686.

115. Rosebush PI, Margetts P. Serotonin syndrome as a result of clomipramine monotherapy. J Clin Psychopharmacol 1999;19:285-287.

116. Friedman RA, Leon AC. Expanding the Black Box-Depression, antidepressants, and the risk of suicide. N Engl J Med 2007;356(23):2345-2346.