새로운 항우울제의 부작용과 약물학적 처치- 드물지 않지만 잘 인지되지 않는 부작용을 중심으로 - = Adverse Effects and Pharmacological Management of Newer Antidepressants - Focusing on Common but Under-Recognized Adverse Effect -

국문 초록 (Abstract)

새로운 항우울제가 개발되어 사용되면서 이 약물들의 다양한 기전과 각 기전에 따른 부작용들이 알려지게 되었고,이에 대한 대처방안도 개발되었다. 본 논문은 널리 사용되고있는 새로운 항우울제 치료 중에 나타날 수 있는 부작용들 중에서 드물지 않지만 잘 인지되지 않는 부작용인 약물유발성수면 운동장애를 중심으로 불면 등의 수면장애, 발한, 떨림,그리고 흔치 않으면서 잘 알려져 있지 않은 출혈 등에 대한원인과 기전 및 발생정도를 알아보고, 또한 이들 부작용에대한 대처방안을 약물학적 치료를 중심으로 알아보았다. 저자는 이 논문을 통하여 정신건강의학과 의사들이 새로운 항우울제를 사용할 때 치료중단의 가장 큰 이유인 부작용을 잘 인지하고 이를 적절히 조절함으로써 환자의 부작용에 따른불편을 감소시키고 새로운 항우울제를 이용한 정신질환의치료성공률을 증가시키는 데 도움을 줄 수 있을 것으로 생각된다.

다국어 초록 (Multilingual Abstract)

Nowadays newer antidepressants are commonly used in clinical practice, since they are as effective as tricyclic antidepressant,but show less adverse effects. However there are many unexpected adverse effects of these drugs. It is one of the most commoncauses of treatment failure. I reviewed these adverse effects and pharmacological management focusing on common butunder-recognized adverse effects of newer antidepressant. I reviewed newer antidepressant-induced sleep related movementdisorder, sweating, tremor, abnormal bleeding. In this paper, newer antidepressants include selective serotonin reuptake inhibitor(fluoxetine, fluvoxamine, citalopram, escitalopram, sertraline, paroxetine), serotonin norepinephrine reuptake inhibitor(venlafaxine, duloxetine), norepinephrine and dopamine reuptake inhibitor (bupropion), noradrenergic and specific serotonergicantidepressant (mirtazapine), and reversible inhibitor of monoamine oxidase A (moclobemide). I suggest that psychiatristsshould know not only well-recognized but also under-recognized common adverse effects and their pharmacological managementof newer antidepressants, so that it will be helpful to treat patients with psychiatric illness using newer antidepressantsand to make better outcome.

참고문헌 (Reference)

1 Handforth A, "Zonisamide for essential tremor: an evaluator-blinded study" 24 : 437-440, 2009

2 Dalton SO, "Use of selective serotonin reuptake inhibitors and risk of upper gastrointestinal tract bleeding: a population-based cohort study" 163 : 59-64, 2003

3 Grimes DA, "Tremor--easily seen but difficult to describe and treat" 30 (30): S59-S63, 2003

4 McCarter SJ, "Treatment outcomes in REM sleep behavior disorder" 14 : 237-242, 2013

5 Anderson IM, "Treatment discontinuation with selective serotonin reuptake inhibitors compared with tricyclic antidepressants: a meta-analysis" 310 : 1433-1438, 1995

6 Carroll JA, "Treating tremor induced by lithium" 38 : 1280-1288, 1987

7 Fox SH, "Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure" 21 : 1578-1594, 2006

8 Lee YM, "Time to discontinuation among the three secondgeneration antidepressants in a naturalistic outpatient setting of depression" 65 : 630-637, 2011

9 Riemann D, "The treatments of chronic insomnia: a review of benzodiazepine receptor agonists and psychological and behavioral therapies" 13 : 205-214, 2009

10 Wernicke JF, "The side effect profile and safety of fluoxetine" 46 (46): 59-67, 1985

11 Boyer EW, "The serotonin syndrome" 352 : 1112-1120, 2005

12 Lin EH, "The role of the primary care physician in patients’ adherence to antidepressant therapy" 33 : 67-74, 1995

13 Salkeld E, "The risk of postpartum hemorrhage with selective serotonin reuptake inhibitors and other antidepressants" 28 : 230-234, 2008

14 Bengtson H, "The effect of paroxetine on sleepwalking in 8 adults [abstract]" 2 (2): 13-, 1999

15 Yamaguchi T, "The coadministration of paroxetine and low-dose aspirin synergistically enhances gastric ulcerogenic risk in rats" 31 : 1371-1375, 2008

16 Edwards JG, "Systematic review and guide to selection of selective serotonin reuptake inhibitors" 57 : 507-533, 1999

17 Fabre LF, "Sertraline safety and efficacy in major depression: a double-blind fixed-dose comparison with placebo" 38 : 592-602, 1995

18 Carta M, "Serotonin-dopamine interaction in the induction and maintenance of L-DOPA-induced dyskinesias" 172 : 465-478, 2008

19 Andrade C, "Serotonin reuptake inhibitor antidepressants and abnormal bleeding: a review for clinicians and a reconsideration of mechanisms" 71 : 1565-1575, 2010

20 Gerber PE, "Selective serotonin-reuptake inhibitor-induced movement disorders" 32 : 692-698, 1998

21 Serebruany VL, "Selective serotonin reuptake inhibitors and increased bleeding risk: are we missing something?" 119 : 113-116, 2006

22 Ziegelstein RC, "Selective serotonin reuptake inhibitor use by patients with acute coronary syndromes" 120 : 525-530, 2007

23 Kim DH, "Safety of selective serotonin reuptake inhibitor in adults undergoing coronary artery bypass grafting" 103 : 1391-1395, 2009

24 Lane RM, "SSRI-induced extrapyramidal side-effects and akathisia: implications for treatment" 12 : 192-214, 1998

25 Ellison JM, "SSRI-associated nocturnal bruxism in four patients" 54 : 432-434, 1993

26 Pace-Schott EF, "SSRI treatment suppresses dream recall frequency but increases subjective dream intensity in normal subjects" 10 : 129-142, 2001

27 Krejcy K, "Role of nitric oxide in hemostatic system activation in vivo in humans" 15 : 2063-2607, 1995

28 de Abajo FJ, "Risk of upper gastrointestinal tract bleeding associated with selective serotonin reuptake inhibitors and venlafaxine therapy: interaction with nonsteroidal anti-inflammatory drugs and effect of acid-suppressing agents" 65 : 795-803, 2008

29 Natarajan R, "Review of periodic limb movement and restless leg syndrome" 56 : 157-162, 2010

30 Rottach KG, "Restless legs syndrome as side effect of second generation antidepressants" 43 : 70-75, 2008

31 Serebruany VL, "Relationship between release of platelet/endothelial biomarkers and plasma levels of sertraline and N-desmethylsertraline in acute coronary syndrome patients receiving SSRI treatment for depression" 162 : 1165-1170, 2005

32 Paykel ES, "Recognition and management of depression in general practice: consensus statement" 305 : 1198-1202, 1992

33 Vercoulen JH, "Randomised, double-blind, placebo-controlled study of fluoxetine in chronic fatigue syndrome" 347 : 858-861, 1996

34 Trotti LM, "REM sleep behaviour disorder in older individuals: epidemiology, pathophysiology and management" 27 : 457-470, 2010

35 Micheli F, "Quetiapine and essential tremor" 25 : 303-306, 2002

36 Bilici M, "Protective effect of mirtazapine on indomethacin-induced ulcer in rats and its relationship with oxidant and antioxidant parameters" 54 : 1868-1875, 2009

37 Caccia MR, "Propranolol, clonidine, urapidil and trazodone infusion in essential tremor: a double-blind crossover trial" 79 : 379-383, 1989

38 Ohayon MM, "Prevalence of restless legs syndrome and periodic limb movement disorder in the general population" 53 : 547-554, 2002

39 Arbaizar B, "Postural induced-tremor in psychiatry" 62 : 638-645, 2008

40 Cenci MA, "Post- versus presynaptic plasticity in LDOPA-induced dyskinesia" 99 : 381-392, 2006

41 WHO Mental Health Collaborating Centres, "Pharmacotherapy of depressive disorders. A consensus statement" 17 : 197-198, 1989

42 Schadt CR, "Pharmacological treatment of disabling tremor" 6 : 419-428, 2005

43 Linazasoro G, "Pharmacological treatment of Parkinson’s disease: life beyond dopamine D2/D3 receptors?" 115 : 431-441, 2008

44 Koller WC, "Pharmacologic treatment of essential tremor" 54 (54): S30-S38, 2000

45 Leeman CP, "Pathophysiology of tricyclic-induced sweating" 51 : 258-259, 1990

46 Guigoni C, "Pathogenesis of levodopa-induced dyskinesia: focus on D1 and D3 dopamine receptors" 11 (11): S25-S29, 2005

47 Gunasekara NS, "Paroxetine. An update of its pharmacology and therapeutic use in depression and a review of its use in other disorders" 55 : 85-120, 1998

48 Finkel MS, "Paroxetine is a novel nitric oxide synthase inhibitor" 32 : 653-658, 1996

49 Samadi P, "Opioids and motor complications in Parkinson’s disease" 27 : 512-517, 2006

50 Haddjeri N, "Noradrenergic modulation of central serotonergic neurotransmission: acute and long-term actions of mirtazapine" 10 (10): 11-17, 1995

51 Quik M, "Nicotine and Parkinson’s disease: implications for therapy" 23 : 1641-1652, 2008

52 Linazasoro G, "New ideas on the origin of L-dopa-induced dyskinesias: age, genes and neural plasticity" 26 : 391-397, 2005

53 Gunal DI, "New alternative agents in essential tremor therapy: double-blind placebo-controlled study of alprazolam and acetazolamide" 21 : 315-317, 2000

54 Lejoyeux M, "Neural symptoms induced by tricyclic antidepressants: phenomenology and pathophysiology" 85 : 249-256, 1992

55 Leo RJ, "Movement disorders associated with the serotonin selective reuptake inhibitors" 57 : 449-454, 1996

56 Smith WT, "Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder" 26 : 191-196, 1990

57 Uccellini D, "Mirtazapine in the treatment of essential tremor: an open-label, observer-blind study" 2 : 95-100, 2006

58 Pahwa R, "Mirtazapine in essential tremor: a doubleblind, placebo-controlled pilot study" 18 : 584-587, 2003

59 Loke YK, "Meta-analysis: gastrointestinal bleeding due to interaction between selective serotonin uptake inhibitors and non-steroidal anti-inflammatory drugs" 27 : 31-40, 2008

60 Butt MM, "Managing antidepressant-induced sweating" 50 : 146-147, 1989

61 Dunn RL, "Longitudinal patterns of antidepressant prescribing in primary care in the UK: comparison with treatment guidelines" 13 : 136-143, 1999

62 Brotchie JM, "Levodopa-induced dyskinesia in Parkinson’s disease" 112 : 359-391, 2005

63 Biary N, "Kinetic predominant essential tremor: successful treatment with clonazepam" 37 : 471-474, 1987

64 Guigoni C, "Involvement of sensorimotor, limbic, and associative basal ganglia domains in L-3,4-dihydroxyphenylalanine-induced dyskinesia" 25 : 2102-2107, 2005

65 Arnold RM, "Insomnia: drug therapies #105" 15 : 243-244, 2012

66 Halperin D, "Influence of antidepressants on hemostasis" 9 : 47-59, 2007

67 Zullino DF, "Increased risk of gastrointestinal adverse effects under SSRI/NSAID combination may be due to pharmacokinetic interactions" 59 : 118-119, 2005

68 Schins A, "Increased coronary events in depressed cardiovascular patients: 5-HT2A receptor as missing link?" 65 : 729-737, 2003

69 Schalekamp T, "Increased bleeding risk with concurrent use of selective serotonin reuptake inhibitors and coumarins" 168 : 180-185, 2008

70 Kronfol Z, "Imipramine-induced tremor: effects of a beta-adrenergic blocking agent" 44 : 225-226, 1983

71 Opatrny L, "Gastro-intestinal haemorrhage risks of selective serotonin receptor antagonist therapy: a new look" 66 : 76-81, 2008

72 Ondo W, "Gabapentin for essential tremor: a multiple-dose, double-blind, placebo-controlled trial" 15 : 678-682, 2000

73 Serrano-Dueñas M, "Fluoxetine-induced tremor: clinical features in 21 patients" 8 : 325-327, 2002

74 Abdel Salam OM, "Fluoxetine and sertraline stimulate gastric acid secretion via a vagal pathway in anaesthetised rats" 50 : 309-316, 2004

75 Markowitz JC, "Fluoxetine and dreaming" 52 : 432-, 1991

76 Jiménez-Jiménez FJ, "Extrapyramidal symptoms associated with selective serotonin reuptake inhibitors: epidemiology, mechanisms and management" 14 : 367-379, 2000

77 Caley CF, "Extrapyramidal reactions and the selective serotoninreuptake inhibitors" 31 : 1481-1489, 1997

78 Musselman DL, "Exaggerated platelet reactivity in major depression" 153 : 1313-1317, 1996

79 Salmi P, "Evidence for functional interactions between 5-HT1A and 5-HT2A receptors in rat thermoregulatory mechanisms" 82 : 122-127, 1998

80 Eaddy M, "Evaluating the economic consequences of early SSRI drop-out in depression" 6 : 186-, 2003

81 Garcia-Borreguero D, "European guidelines on management of restless legs syndrome: report of a joint task force by the European Federation of Neurological Societies, the European Neurological Society and the European Sleep Research Society" 19 : 1385-1396, 2012

82 Ondo WG, "Essential tremor: treatment options" 8 : 256-267, 2006

83 Allard P, "Efficacy and tolerability of venlafaxine in geriatric outpatients with major depression: a double-blind, randomised 6-month comparative trial with citalopram" 19 : 1123-1130, 2004

84 Amrein R, "Efficacy and tolerability of moclobemide in comparison with placebo, tricyclic antidepressants, and selective serotonin reuptake inhibitors in elderly depressed patients: a clinical overview" 42 : 1043-1050, 1997

85 Dietrichson P, "Effects of timolol and atenolol on benign essential tremor: placebo-controlled studies based on quantitative tremor recording" 44 : 677-683, 1981

86 Pizzi C, "Effects of selective serotonin reuptake inhibitor therapy on endothelial function and inflammatory markers in patients with coronary heart disease" 86 : 527-532, 2009

87 Taylor CB, "Effects of antidepressant medication on morbidity and mortality in depressed patients after myocardial infarction" 62 : 792-798, 2005

88 Sanz-Cartagena P, "Effectiveness and safety of levetiracetam in patients with essential tremor: data from an open 11-week follow-up trial" 45 : 134-136, 2007

89 Sauer WH, "Effect of antidepressants and their relative affinity for the serotonin transporter on the risk of myocardial infarction" 108 : 32-36, 2003

90 Morgan JC, "Drug-induced tremors" 4 : 866-876, 2005

91 Cheshire WP, "Drug-induced hyperhidrosis and hypohidrosis: incidence, prevention and management" 31 : 109-126, 2008

92 Rivelli S, "Depression and ischemic heart disease: what have we learned from clinical trials?" 22 : 286-291, 2007

93 Ashton AK, "Cyproheptadine for drug-induced sweating" 159 : 874-875, 2002

94 Lapierre YD, "Control of lithium tremor with propranolol" 114 : 619-624, 1976

95 Olanow CW, "Continuous dopamine-receptor treatment of Parkinson’s disease: scientific rationale and clinical implications" 5 : 677-687, 2006

96 de Jong JC, "Combined use of SSRIs and NSAIDs increases the risk of gastrointestinal adverse effects" 55 : 591-595, 2003

97 Muñoz A, "Combined 5-HT1A and 5-HT1B receptor agonists for the treatment of L-DOPA-induced dyskinesia" 131 (131): 3380-3394, 2008

98 Serrano-Dueñas M, "Clonidine versus propranolol in the treatment of essential tremor. A double-blind trial with a one-year follow-up" 18 : 248-254, 2003

99 Feder R, "Clonidine treatment of excessive sweating" 56 : 35-, 1995

100 Milne RJ, "Citalopram. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in depressive illness" 41 : 450-477, 1991

101 Wise M, "Citalopram-induced bruxism" 178 : 182-, 2001

102 Koponen H, "Citalopram in the treatment of obsessive-compulsive disorder: an open pilot study" 96 : 343-346, 1997

103 Zaninelli R, "Changes in quantitatively assessed tremor during treatment of major depression with lithium augmented by paroxetine or amitriptyline" 21 : 190-198, 2001

104 Kirschner N, "Changes in dream content after drug treatment" 9 : 195-200, 1999

105 Dhillon S, "Bupropion: a review of its use in the management of major depressive disorder" 68 : 653-689, 2008

106 Garber A, "Benztropine in the treatment of venlafaxineinduced sweating" 58 : 176-177, 1997

107 Pierre JM, "Benztropine for venlafaxine-induced night sweats" 20 : 269-, 2000

108 de Abajo FJ, "Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: population based case-control study" 319 : 1106-1109, 1999

109 Rosholm JU, "Are there differences in the use of selective serotonin reuptake inhibitors and tricyclic antidepressants? A prescription database study" 56 : 923-929, 2001

110 Kockler DR, "Antidepressants as a treatment for hot flashes in women" 61 : 287-292, 2004

111 Mayers AG, "Antidepressants and their effect on sleep" 20 : 533-559, 2005

112 Wilson S, "Antidepressants and sleep: a qualitative review of the literature" 65 : 927-947, 2005

113 Yang C, "Antidepressants and periodic leg movements of sleep" 58 : 510-514, 2005

114 Dilsaver SC, "Antidepressant withdrawal phenomena" 19 : 237-256, 1984

115 Thase ME, "Antidepressant treatment of the depressed patient with insomnia" 60 (60): 28-31, 1999

116 Lejoyeux M, "Antidepressant discontinuation: a review of the literature" 58 (58): 11-15, 1997

117 Mago R, "Antiadrenergic treatment of antidepressant-induced excessive sweating in 3 patients" 68 : 639-640, 2007

118 Dall M, "An association between selective serotonin reuptake inhibitor use and serious upper gastrointestinal bleeding" 7 : 1314-1321, 2009

119 Fruensgaard K, "Amoxapine versus amitriptyline in endogenous depression. A doubleblind study" 59 : 502-508, 1979

120 Raethjen J, "Amitriptyline enhances the central component of physiological tremor" 70 : 78-82, 2001

121 Wilson SJ, "Adult night terrors and paroxetine" 350 : 185-, 1997

122 Diaz-Martinez A, "A randomized, open-label comparison of venlafaxine and fluoxetine in depressed outpatients" 20 : 467-476, 1998

123 Goldenberg D, "A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia" 39 : 1852-1859, 1996

124 Gironell A, "A randomized placebo-controlled comparative trial of gabapentin and propranolol in essential tremor" 56 : 475-480, 1999

125 Lee KS, "A multicenter randomized crossover multiple-dose comparison study of arotinolol and propranolol in essential tremor" 9 : 341-347, 2003

126 Connor GS, "A double-blind placebo-controlled trial of topiramate treatment for essential tremor" 59 : 132-134, 2002

127 Chouinard G, "A double-blind controlled clinical trial of fluoxetine and amitriptyline in the treatment of outpatients with major depressive disorder" 46 (46): 32-37, 1985

128 Ramage AG, "5-hydroxytryptamine and cardiovascular regulation" 29 : 472-481, 2008

129 Kornischka J, "40 years beta-adrenoceptor blockers in psychiatry" 75 : 199-210, 2007