586138 research-article2015
APY0010.1177/1039856215586138Australasian PsychiatryKayhan et al.
Australasian
Psychiatry
Case report
Sertraline-induced periorbital purpura: a case report
Australasian Psychiatry 1–3 © The Royal Australian and New Zealand College of Psychiatrists 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1039856215586138 apy.sagepub.com
Fatih Kayhan Department of Psychiatry, Mevlana University Faculty of Medicine, Konya, Turkey Zahide Eris ¸ Eken Department of Dermatology, Istanbul Bilim University, Faculty of Medicine, Istanbul, Turkey Faruk Uguz Department of Psychiatry, Necmettin Erbakan University Faculty of Medicine, Konya, Turkey
Abstract Objective: The incidence of mild to severe levels of spontaneous bleeding due to the usage of selective serotonin reuptake inhibitors (SSRIs) is relatively low. Although the exact mechanism is not known, it is thought that inhibition of the serotonin transporter together with a decrease in platelet serotonin could be responsible for the bleeding. Therefore, the use of SSRIs in conjunction with anti-aggregants may predispose to or exacerbate the risk of bleeding. In this case report, we describe a 44-year-old female patient with a diagnosis of anxiety disorder who spontaneously developed periorbital purpura during treatment with sertraline. Conclusion: Abnormal bleeding after treatment with an SSRI should be kept in mind, and alternative non-SSRI drugs of choice in such cases would be more appropriate. More extensive and comprehensive studies focusing on hemostasis and bleeding disorders are needed for SSRIs such as sertraline. Keywords: bleeding, purpura, sertraline, side effect
S
erotonin generally acts as a vasodilator, becoming a vasoconstrictor when the endothelium is damaged.1 Serotonin is released into the bloodstream at the initiation of platelet aggregation, which activates the cognate 5HT2A receptors on platelet membranes. Although serotonin is a weak activator, it can activate platelets in increasing doses by stimulating adenosine diphosphate (ADP) and thrombin production.2 The use of selective serotonin reuptake inhibitors (SSRIs) causes a decrease in the serotonin levels in platelets by inhibiting serotonin reuptake. In this way it can result in changes in platelet aggregation.3
sertraline can be found in the literature.19–25 Spontaneous ecchymoses were reported associated with fluoxetine, paroxetine and fluvoxamine. Although sertralineinduced hemoptysis, hematuria, menorrhagia and ecchymosis have been reported, there has been no case report about periorbital purpura associated with sertraline. In this case report, the occurrence of periorbital purpura in the early stages of treatment with sertraline is described.
An increased risk of bleeding during the first months of initiating treatment with SSRIs has been reported in many studies.4–7 The presence of a coagulopathy may predispose a patient to bleed when treated with SSRIs.8,9 On the other hand, the usage of SSRIs may be associated with relatively mild bleeding disorders such as spontaneous purpura and epistaxis, and severe bleeding in the gastrointestinal system, genitourinary system, as well as retroperitoneal and intracranial bleeding, which may lead to severe hemorrhage.10–15 The risk of upper gastrointestinal bleeding can be further increased when SSRIs are combined with nonsteroidal anti-inflammatory drugs (NSAIDs),16 antiplatelet agents17 or warfarin.18 Particularly, case reports describing bleeding with use of SSRIs such as fluoxetine, paroxetine, fluvoxamine and
The study subject is a 44-year-old married unemployed female patient. She was admitted to a Psychiatry Outpatient Clinic with complaints boredom, restlessness and anxiety. The complaints had started about 2 months previously and the last 10 days showed an exacerbation in the complaints. The patient had been prescribed various antidepressants such as escitalopram, citalopram, mirtazapine and trazodone in the previous years. She did not describe any adverse effect related to
Case
Corresponding author: Fatih Kayhan, Mevlana University Faculty of Medicine, Aksinne mh. Esmetas¸ sk. No:16, 42040 Meram/Konya, Turkey. Email: [email protected]
1
Australasian Psychiatry
previous antidepressant treatments. She had not used any psychotropic drugs in approximately the 2 years prior to the current complaint. The patient’s family history revealed that her mother had undergone psychotropic treatment for depressive disorder. She did not have any other medical illness or any history of drug use. She had no physical trauma around the periorbital area. A psychiatric interview performed by means of Structured Clinical Interview for Diagnostic (SCID-I) with the patient indicated a diagnosis of anxiety disorder NOS (not otherwise specified) according to the Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Sertraline was started at 50 mg/day. Following a month’s usage of sertraline, the psychiatric complaints were ameliorated; however, the patient then presented with periorbital redness. Periorbital redness was first seen at the second week of treatment and then continued to increase gradually. The patient therefore consulted with the Dermatology Clinic. After a physical examination, the periorbital redness was diagnosed as periorbital purpura. Complete blood count, biochemical parameters, bleeding time, prothrombin time and activated partial thromboplastin time tests were performed. No significant abnormality was found in any of the blood assays. The patient did not use any other medication during this time of treatment. The periorbital purpura was therefore thought to occur as a result of a coagulation disorder caused by sertraline. Treatment with sertraline was stopped and the periorbital purpura was seen to decrease at the 10-day follow up. By the end of the first month, the purpura had completely disappeared without any treatment.
Discussion As far as we know, this study is the first report of the occurrence of periorbital purpura caused by sertraline. Case reports of bleeding associated with the use of SSRIs, although rare, can be found in the literature.19–25 Cooper et al.22 reported the development of spontaneous ecchymosis in the arms and legs of a patient 15 days after the initiation of treatment with paroxetine. In another patient, upon escalation of the dose of fluoxetine, the occurrence of bruises in the inner thigh and the face was reported.26 In yet another case, the occurrence of ecchymosis and menorrhagia following the use of fluoxetine has been reported.27 Ceylan et al.28 reported the occurrence of hemoptysis and macroscopic hematuria within the first week of treatment with sertraline. The occurrence of bruising and menorrhagia in an adolescent girl in the third week of treatment with sertraline has been reported.29 Similar to the case described in this study, in all of these reported cases bleeding was found to be a standard parameter related to the use of SSRIs. Except in the case report by Ceylan et al.,28 where a history of allergy related to other drugs was found, the other cases, like our case, had no comorbid physical illness.
2
The propensity for purpura to occur in the periorbital area may be explained by its more fragile vasculature. The complete mechanism of action of SSRIs that leads to bleeding is currently unknown. Some pharmacological mechanisms have been suggested. The release of serotonin plays a major role in platelet aggregation. Platelets cannot synthesize their own serotonin; rather, they take up serotonin from the plasma by serotonin transporters. Blockade of serotonin transporters by SSRIs may lead to a lower concentration of serotonin in the platelets. This may be the reason for bleeding observed with the use of SSRIs.2,30,31 In an in vitro study, Hallbäck et al.32 reported that sertraline and citalopram decreased platelet adhesion by more than 50%. Corroborating this, an in vitro study by Serebruany et al.33 showed that addition of SSRIs at therapeutic doses resulted in the inhibition of platelet aggregation. The inhibition of the serotonin transporter with the use of SSRIs has been specifically reported to enhance the risk of bleeding.3 Although several case reports have reported the incidence of abnormal bleeding following the usage of SSRIs, none have shown any differences in the measured coagulation parameters.22,26–29 The coagulation tests are generally sensitive; therefore a negative result in these tests may be due to other inherent factors. When considering these factors, a history of coagulation disorders and drug usage should always be assessed before starting SSRI treatment. Abnormal bleeding after treatment with an SSRI should be kept in mind, and alternative non-SSRI drugs of choice in such cases would be more appropriate. More extensive and comprehensive studies focusing on hemostasis and bleeding disorders are needed for SSRIs such as sertraline. Disclosure The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Golino P, Piscione F, Willerson JT, et al. Divergent effects of serotonin on coronaryartery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med 1991; 324: 641–648. 2. Li N, Wallen NH, Ladjevardi M, et al. Effects of serotonin on platelet activation in whole blood. Blood Coagul Fibrinolysis 1997; 8: 517–523. 3. Andrade C, Sandarsh S, Chethan KB, et al. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: A review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry 2010; 71: 1565–1575. 4. Barbui C, Andretta M, De Vitis G, et al. Antidepressant drug prescription and risk of abnormal bleeding: A case-control study. J Clin Psychopharmacol 2009; 29: 33–38. 5. Dalton SO, Sorensen HT and Johansen C. SSRIs and upper gastrointestinal bleeding: What is known and how should it influence prescribing? CNS Drugs 2006; 20: 143–151. 6. Opatrny L, Delaney JA and Suissa S. Gastro-intestinal haemorrhage risks of selective serotonin receptor antagonist therapy: A new look. Br J Clin Pharmacol 2008; 66: 76–81. 7. Targownik LE, Bolton JM, Metge CJ, et al. Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol 2009; 104: 1475–1482. 8. Lake MB, Birmaher B, Wassick S, et al. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol 2000; 10: 35–38.
Kayhan et al. 9. Nelva A, Guy C, Tardy-Poncet B, et al. [Hemorrhagic syndromes related to selective serotonin reuptake inhibitor (SSRI) antidepressants. Seven case reports and review of the literature]. Rev Med Interne 2000; 21: 152–160.
22. Cooper TA, Valcour VG, Gibbons RB, et al. Spontaneous ecchymoses due to paroxetine administration. Am J Med 1998; 104: 197–198.
10. Pai VB and Kelly MW. Bruising associated with the use of fluoxetine. Ann Pharmacother 1996; 30: 786–788.
23. Ottervanger JP, van den Bemt PM, de Koning GH, et al. [Risk of hemorrhage with the use of fluoxetine (Prozac) or fluvoxamine (Fevarin)]. Ned Tijdschr Geneeskd 1993; 137: 259–261.
11. de Abajo FJ, Rodriguez LA and Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: Population based case-control study. BMJ 1999; 319: 1106–1109.
24. Tielens JA. Vitamin C for paroxetine- and fluvoxamine-associated bleeding. Am J Psychiatry 1997; 154: 883–884.
12. O’Malley P. Selective serotonin reuptake inhibitors and abnormal bleeding. Implications for the clinical nurse specialist. Clin Nurse Spec 2004; 18: 65–67. 13. Duijvestijn YC, Kalmeijer MD, Passier AL, et al. Neonatal intraventricular haemorrhage associated with maternal use of paroxetine. Br J Clin Pharmacol 2003; 56: 581–582.
25. Smith M and Robinson D. Sertraline and vaginal bleeding – a possible association. J Am Geriatr Soc 2002; 50: 200–201. 26. Fountoulakis KN, Samolis S, Iacovides A, et al. Ecchymoses as an adverse effect of fluoxetine treatment. Psychiatry Res 2007; 152: 91–92.
14. de Abajo FJ, Jick H, Derby L, et al. Intracranial haemorrhage and use of selective serotonin reuptake inhibitors. Br J Clin Pharmacol 2000; 50: 43–47.
27. Aranth J and Lindberg C. Bleeding, a side effect of fluoxetine. Am J Psychiatry 1992; 149: 412.
15. Bassotti G, Nzepa FS, de Roberto G, et al. Symptomatic reversible duodenal compression due to iatrogenic retroperitoneal hematoma. Dig Liver Dis 2004; 36: 78–81.
28. Ceylan ME and Alpsan-Omay MH. Bleeding induced by SSRIs. Eur Psychiatry 2005; 20: 570–571.
16. Helin-Salmivaara A, Huttunen T, Gronroos JM, et al. Risk of serious upper gastrointestinal events with concurrent use of NSAIDs and SSRIs: A case-control study in the general population. Eur J Clin Pharmacol 2007; 63: 403–408.
29. Vlatka BM, Branka AM and Branimir M. Ecchymoses as an adverse effect of fluvoxamine treatment in an adolescent girl. Gen Hosp Psychiatry 2010; 32: e9–e10.
17. Labos C, Dasgupta K, Nedjar H, et al. Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ 2011; 183: 1835–1843. 18. Schalekamp T, Klungel OH, Souverein PC, et al. Increased bleeding risk with concurrent use of selective serotonin reuptake inhibitors and coumarins. Arch Intern Med 2008; 168: 180–185. 19. Humphries JE, Wheby MS and VandenBerg SR. Fluoxetine and the bleeding time. Arch Pathol Lab Med 1990; 114: 727–728. 20. Evans T, Buys S and Rodgers G. Acquired abnormalities of platelet function. N Engl J Med 1991; 324: 1670–1672. 21. Ottervanger JP, Stricker BH, Huls J, et al. Bleeding attributed to the intake of paroxetine. Am J Psychiatry 1994; 151: 781–782.
30. Skop BP and Brown TM. Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors. Psychosomatics 1996; 37: 12–16. 31. Javors MA, Houston JP, Tekell JL, et al. Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine. Int J Neuropsychopharmacol 2000; 3: 229–235. 32. Hallbäck I, Hagg S, Eriksson AC, et al. In vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation. Pharmacol Rep 2012; 64: 979–983. 33. Serebruany VL, Gurbel PA and O’Connor CM. Platelet inhibition by sertraline and N-desmethylsertraline: A possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. Pharmacol Res 2001; 43: 453–462.
3
APY0010.1177/1039856215586138Australasian PsychiatryKayhan et al.
Australasian
Psychiatry
Case report
Sertraline-induced periorbital purpura: a case report
Australasian Psychiatry 1–3 © The Royal Australian and New Zealand College of Psychiatrists 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/1039856215586138 apy.sagepub.com
Fatih Kayhan Department of Psychiatry, Mevlana University Faculty of Medicine, Konya, Turkey Zahide Eris ¸ Eken Department of Dermatology, Istanbul Bilim University, Faculty of Medicine, Istanbul, Turkey Faruk Uguz Department of Psychiatry, Necmettin Erbakan University Faculty of Medicine, Konya, Turkey
Abstract Objective: The incidence of mild to severe levels of spontaneous bleeding due to the usage of selective serotonin reuptake inhibitors (SSRIs) is relatively low. Although the exact mechanism is not known, it is thought that inhibition of the serotonin transporter together with a decrease in platelet serotonin could be responsible for the bleeding. Therefore, the use of SSRIs in conjunction with anti-aggregants may predispose to or exacerbate the risk of bleeding. In this case report, we describe a 44-year-old female patient with a diagnosis of anxiety disorder who spontaneously developed periorbital purpura during treatment with sertraline. Conclusion: Abnormal bleeding after treatment with an SSRI should be kept in mind, and alternative non-SSRI drugs of choice in such cases would be more appropriate. More extensive and comprehensive studies focusing on hemostasis and bleeding disorders are needed for SSRIs such as sertraline. Keywords: bleeding, purpura, sertraline, side effect
S
erotonin generally acts as a vasodilator, becoming a vasoconstrictor when the endothelium is damaged.1 Serotonin is released into the bloodstream at the initiation of platelet aggregation, which activates the cognate 5HT2A receptors on platelet membranes. Although serotonin is a weak activator, it can activate platelets in increasing doses by stimulating adenosine diphosphate (ADP) and thrombin production.2 The use of selective serotonin reuptake inhibitors (SSRIs) causes a decrease in the serotonin levels in platelets by inhibiting serotonin reuptake. In this way it can result in changes in platelet aggregation.3
sertraline can be found in the literature.19–25 Spontaneous ecchymoses were reported associated with fluoxetine, paroxetine and fluvoxamine. Although sertralineinduced hemoptysis, hematuria, menorrhagia and ecchymosis have been reported, there has been no case report about periorbital purpura associated with sertraline. In this case report, the occurrence of periorbital purpura in the early stages of treatment with sertraline is described.
An increased risk of bleeding during the first months of initiating treatment with SSRIs has been reported in many studies.4–7 The presence of a coagulopathy may predispose a patient to bleed when treated with SSRIs.8,9 On the other hand, the usage of SSRIs may be associated with relatively mild bleeding disorders such as spontaneous purpura and epistaxis, and severe bleeding in the gastrointestinal system, genitourinary system, as well as retroperitoneal and intracranial bleeding, which may lead to severe hemorrhage.10–15 The risk of upper gastrointestinal bleeding can be further increased when SSRIs are combined with nonsteroidal anti-inflammatory drugs (NSAIDs),16 antiplatelet agents17 or warfarin.18 Particularly, case reports describing bleeding with use of SSRIs such as fluoxetine, paroxetine, fluvoxamine and
The study subject is a 44-year-old married unemployed female patient. She was admitted to a Psychiatry Outpatient Clinic with complaints boredom, restlessness and anxiety. The complaints had started about 2 months previously and the last 10 days showed an exacerbation in the complaints. The patient had been prescribed various antidepressants such as escitalopram, citalopram, mirtazapine and trazodone in the previous years. She did not describe any adverse effect related to
Case
Corresponding author: Fatih Kayhan, Mevlana University Faculty of Medicine, Aksinne mh. Esmetas¸ sk. No:16, 42040 Meram/Konya, Turkey. Email: [email protected]
1
Australasian Psychiatry
previous antidepressant treatments. She had not used any psychotropic drugs in approximately the 2 years prior to the current complaint. The patient’s family history revealed that her mother had undergone psychotropic treatment for depressive disorder. She did not have any other medical illness or any history of drug use. She had no physical trauma around the periorbital area. A psychiatric interview performed by means of Structured Clinical Interview for Diagnostic (SCID-I) with the patient indicated a diagnosis of anxiety disorder NOS (not otherwise specified) according to the Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV). Sertraline was started at 50 mg/day. Following a month’s usage of sertraline, the psychiatric complaints were ameliorated; however, the patient then presented with periorbital redness. Periorbital redness was first seen at the second week of treatment and then continued to increase gradually. The patient therefore consulted with the Dermatology Clinic. After a physical examination, the periorbital redness was diagnosed as periorbital purpura. Complete blood count, biochemical parameters, bleeding time, prothrombin time and activated partial thromboplastin time tests were performed. No significant abnormality was found in any of the blood assays. The patient did not use any other medication during this time of treatment. The periorbital purpura was therefore thought to occur as a result of a coagulation disorder caused by sertraline. Treatment with sertraline was stopped and the periorbital purpura was seen to decrease at the 10-day follow up. By the end of the first month, the purpura had completely disappeared without any treatment.
Discussion As far as we know, this study is the first report of the occurrence of periorbital purpura caused by sertraline. Case reports of bleeding associated with the use of SSRIs, although rare, can be found in the literature.19–25 Cooper et al.22 reported the development of spontaneous ecchymosis in the arms and legs of a patient 15 days after the initiation of treatment with paroxetine. In another patient, upon escalation of the dose of fluoxetine, the occurrence of bruises in the inner thigh and the face was reported.26 In yet another case, the occurrence of ecchymosis and menorrhagia following the use of fluoxetine has been reported.27 Ceylan et al.28 reported the occurrence of hemoptysis and macroscopic hematuria within the first week of treatment with sertraline. The occurrence of bruising and menorrhagia in an adolescent girl in the third week of treatment with sertraline has been reported.29 Similar to the case described in this study, in all of these reported cases bleeding was found to be a standard parameter related to the use of SSRIs. Except in the case report by Ceylan et al.,28 where a history of allergy related to other drugs was found, the other cases, like our case, had no comorbid physical illness.
2
The propensity for purpura to occur in the periorbital area may be explained by its more fragile vasculature. The complete mechanism of action of SSRIs that leads to bleeding is currently unknown. Some pharmacological mechanisms have been suggested. The release of serotonin plays a major role in platelet aggregation. Platelets cannot synthesize their own serotonin; rather, they take up serotonin from the plasma by serotonin transporters. Blockade of serotonin transporters by SSRIs may lead to a lower concentration of serotonin in the platelets. This may be the reason for bleeding observed with the use of SSRIs.2,30,31 In an in vitro study, Hallbäck et al.32 reported that sertraline and citalopram decreased platelet adhesion by more than 50%. Corroborating this, an in vitro study by Serebruany et al.33 showed that addition of SSRIs at therapeutic doses resulted in the inhibition of platelet aggregation. The inhibition of the serotonin transporter with the use of SSRIs has been specifically reported to enhance the risk of bleeding.3 Although several case reports have reported the incidence of abnormal bleeding following the usage of SSRIs, none have shown any differences in the measured coagulation parameters.22,26–29 The coagulation tests are generally sensitive; therefore a negative result in these tests may be due to other inherent factors. When considering these factors, a history of coagulation disorders and drug usage should always be assessed before starting SSRI treatment. Abnormal bleeding after treatment with an SSRI should be kept in mind, and alternative non-SSRI drugs of choice in such cases would be more appropriate. More extensive and comprehensive studies focusing on hemostasis and bleeding disorders are needed for SSRIs such as sertraline. Disclosure The authors report no conflict of interest. The authors alone are responsible for the content and writing of the paper.
References 1. Golino P, Piscione F, Willerson JT, et al. Divergent effects of serotonin on coronaryartery dimensions and blood flow in patients with coronary atherosclerosis and control patients. N Engl J Med 1991; 324: 641–648. 2. Li N, Wallen NH, Ladjevardi M, et al. Effects of serotonin on platelet activation in whole blood. Blood Coagul Fibrinolysis 1997; 8: 517–523. 3. Andrade C, Sandarsh S, Chethan KB, et al. Serotonin reuptake inhibitor antidepressants and abnormal bleeding: A review for clinicians and a reconsideration of mechanisms. J Clin Psychiatry 2010; 71: 1565–1575. 4. Barbui C, Andretta M, De Vitis G, et al. Antidepressant drug prescription and risk of abnormal bleeding: A case-control study. J Clin Psychopharmacol 2009; 29: 33–38. 5. Dalton SO, Sorensen HT and Johansen C. SSRIs and upper gastrointestinal bleeding: What is known and how should it influence prescribing? CNS Drugs 2006; 20: 143–151. 6. Opatrny L, Delaney JA and Suissa S. Gastro-intestinal haemorrhage risks of selective serotonin receptor antagonist therapy: A new look. Br J Clin Pharmacol 2008; 66: 76–81. 7. Targownik LE, Bolton JM, Metge CJ, et al. Selective serotonin reuptake inhibitors are associated with a modest increase in the risk of upper gastrointestinal bleeding. Am J Gastroenterol 2009; 104: 1475–1482. 8. Lake MB, Birmaher B, Wassick S, et al. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol 2000; 10: 35–38.
Kayhan et al. 9. Nelva A, Guy C, Tardy-Poncet B, et al. [Hemorrhagic syndromes related to selective serotonin reuptake inhibitor (SSRI) antidepressants. Seven case reports and review of the literature]. Rev Med Interne 2000; 21: 152–160.
22. Cooper TA, Valcour VG, Gibbons RB, et al. Spontaneous ecchymoses due to paroxetine administration. Am J Med 1998; 104: 197–198.
10. Pai VB and Kelly MW. Bruising associated with the use of fluoxetine. Ann Pharmacother 1996; 30: 786–788.
23. Ottervanger JP, van den Bemt PM, de Koning GH, et al. [Risk of hemorrhage with the use of fluoxetine (Prozac) or fluvoxamine (Fevarin)]. Ned Tijdschr Geneeskd 1993; 137: 259–261.
11. de Abajo FJ, Rodriguez LA and Montero D. Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: Population based case-control study. BMJ 1999; 319: 1106–1109.
24. Tielens JA. Vitamin C for paroxetine- and fluvoxamine-associated bleeding. Am J Psychiatry 1997; 154: 883–884.
12. O’Malley P. Selective serotonin reuptake inhibitors and abnormal bleeding. Implications for the clinical nurse specialist. Clin Nurse Spec 2004; 18: 65–67. 13. Duijvestijn YC, Kalmeijer MD, Passier AL, et al. Neonatal intraventricular haemorrhage associated with maternal use of paroxetine. Br J Clin Pharmacol 2003; 56: 581–582.
25. Smith M and Robinson D. Sertraline and vaginal bleeding – a possible association. J Am Geriatr Soc 2002; 50: 200–201. 26. Fountoulakis KN, Samolis S, Iacovides A, et al. Ecchymoses as an adverse effect of fluoxetine treatment. Psychiatry Res 2007; 152: 91–92.
14. de Abajo FJ, Jick H, Derby L, et al. Intracranial haemorrhage and use of selective serotonin reuptake inhibitors. Br J Clin Pharmacol 2000; 50: 43–47.
27. Aranth J and Lindberg C. Bleeding, a side effect of fluoxetine. Am J Psychiatry 1992; 149: 412.
15. Bassotti G, Nzepa FS, de Roberto G, et al. Symptomatic reversible duodenal compression due to iatrogenic retroperitoneal hematoma. Dig Liver Dis 2004; 36: 78–81.
28. Ceylan ME and Alpsan-Omay MH. Bleeding induced by SSRIs. Eur Psychiatry 2005; 20: 570–571.
16. Helin-Salmivaara A, Huttunen T, Gronroos JM, et al. Risk of serious upper gastrointestinal events with concurrent use of NSAIDs and SSRIs: A case-control study in the general population. Eur J Clin Pharmacol 2007; 63: 403–408.
29. Vlatka BM, Branka AM and Branimir M. Ecchymoses as an adverse effect of fluvoxamine treatment in an adolescent girl. Gen Hosp Psychiatry 2010; 32: e9–e10.
17. Labos C, Dasgupta K, Nedjar H, et al. Risk of bleeding associated with combined use of selective serotonin reuptake inhibitors and antiplatelet therapy following acute myocardial infarction. CMAJ 2011; 183: 1835–1843. 18. Schalekamp T, Klungel OH, Souverein PC, et al. Increased bleeding risk with concurrent use of selective serotonin reuptake inhibitors and coumarins. Arch Intern Med 2008; 168: 180–185. 19. Humphries JE, Wheby MS and VandenBerg SR. Fluoxetine and the bleeding time. Arch Pathol Lab Med 1990; 114: 727–728. 20. Evans T, Buys S and Rodgers G. Acquired abnormalities of platelet function. N Engl J Med 1991; 324: 1670–1672. 21. Ottervanger JP, Stricker BH, Huls J, et al. Bleeding attributed to the intake of paroxetine. Am J Psychiatry 1994; 151: 781–782.
30. Skop BP and Brown TM. Potential vascular and bleeding complications of treatment with selective serotonin reuptake inhibitors. Psychosomatics 1996; 37: 12–16. 31. Javors MA, Houston JP, Tekell JL, et al. Reduction of platelet serotonin content in depressed patients treated with either paroxetine or desipramine. Int J Neuropsychopharmacol 2000; 3: 229–235. 32. Hallbäck I, Hagg S, Eriksson AC, et al. In vitro effects of serotonin and noradrenaline reuptake inhibitors on human platelet adhesion and coagulation. Pharmacol Rep 2012; 64: 979–983. 33. Serebruany VL, Gurbel PA and O’Connor CM. Platelet inhibition by sertraline and N-desmethylsertraline: A possible missing link between depression, coronary events, and mortality benefits of selective serotonin reuptake inhibitors. Pharmacol Res 2001; 43: 453–462.
3
