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Ecchymoses as an adverse effect of fluvoxamine treatment in an adolescent girl
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General Hospital Psychiatry 32 (2010) e9 – e10
Letter to the Editor Ecchymoses as an adverse effect of fluvoxamine treatment in an adolescent girl To the Editor, Reports of bleeding in patients receiving selective serotonin inhibitors (SSRIs) appeared soon after their introduction. Case reports have described adult patients with various bleeding disorders (e.g., ecchymoses, purpura, epistaxis), while observational studies have focused on upper gastrointestinal bleeding, intracranial bleeding and bleeding during surgery [1]. Bleeding complications of fluvoxamine treatment have been described in adults [2,3]. However, reports of bleeding complications of SSRI treatment are not limited to the adult population. Several cases of abnormal bleeding under SSRI treatment have been described in children and adolescents with similar clinical manifestations [4–7]. We report a case of an adolescent girl who manifested ecchymoses during fluvoxamine treatment. This patient started fluvoxamine treatment at the age of 17 years for obsessive-compulsive disorder (OCD) with a total score of 25 on the Children's Yale–Brown Obsessive Compulsive Scale (CYBOCS). The introduction of fluvoxamine was well tolerated and the dosage was gradually increased over 3 months to 300 mg/day. The patient improved over the next 3 months and her OCD had remitted completely (CYBOCS score=0). Nine months after the introduction of fluvoxamine treatment the patient developed spontaneously appearing bruises on her legs and arms. These progressively worsened during the following 2 months reaching to a maximum diameter of 5 cm when she reported them. There was no personal or family history of a bleeding disorder, trauma or self-injurious behavior as reported by family members. She did not take any other medication except fluvoxamine. In the physical examination no abnormality other than ecchymosis was observed. Hepatic function tests, urine analyses, erythrocyte sedimentation rate, hemoglobin level and complete blood count results were all in normal ranges. Bleeding time, prothrombin time, partial prothrombin time, activated partial prothrombin time, international normalized ratio, clotting time and fibrinogen level were also normal. The dosage of fluvoxamine was reduced to 200 mg/day. No new spontaneous ecchymosis occurred and old ones disappeared within 2 weeks. The patient has remained well over the past 3 months. 0163-8343/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
Although abnormal bleeding associated with SSRI treatment is frequently described in the recent literature, its real incidence and its mechanism are still unknown. In this case, the causal relationship between fluvoxamine and bruising may be assumed for several reasons. First, the patient had no personal or family history of hematological abnormalities. Second, the patient did not take any other medication besides fluvoxamine. Third, the time sequences with the onset of ecchymoses during fluvoxamine treatment and of cessation of bruising after fluvoxamine dosage reduction. Fourth, no comorbid mental disorder could be detected to which bruises can be attributed. In the literature, cases of abnormal bleeding in children and adolescents during treatment with sertraline and fluoxetine have been described. To our knowledge, there are no reports in the literature of abnormal bleeding with fluvoxamine treatment in children or adolescents. Our case adds valuable clinical insight to what few case reports have already published regarding bleeding complications of SSRI treatment in children and adolescents. As this case report shows, hemorrhagic complications may occur with a high dose of fluvoxamine and can be successfully managed with dose reduction without the necessity for drug discontinuation. Consistent with previous reports of SSRI-induced bleeding [1,7], we could not find any abnormal standard laboratory results in our case. Platelet aggregation studies detected significant abnormalities in the SSRI patients [1,8], but were not measured in the present case. Given the increase of pediatric SSRI prescriptions, physicians should be attentive to signs of possible rare side-effects of SSRIs. Abnormal bleeding is a rare side-effect of SSRI with unknown longterm consequences that warrant further study. Thorough bleeding histories, education of the patient and careful follow-up remain the major tools for preventing a bleeding diathesis that is caused or aggravated by SSRI medications. Boričević Maršanić Vlatka, M.D. Psychiatric Hospital for Children and Youth 10 000 Zagreb, Croatia E-mail address: [email protected] Aukst-Margetić Branka, M.D., M.Sc. Psychiatric Clinic, University Hospital Center Zagreb 10 000 Zagreb, Croatia E-mail address: [email protected]
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Letter to the Editor / General Hospital Psychiatry 32 (2010) e9–e10
Margetić Branimir, M.D. Neuropsychiatric Hospital Dr. Ivan Barbot Popovača, Croatia E-mail address: [email protected] doi:10.1016/j.genhosppsych.2010.01.005 References [1] Weinrieb RM, Auriacombe M, Lynch KG, Lewis JD. Selective serotonin re-uptake inhibitors and the risk of bleeding. Expert Opin Drug Saf 2005;4:337–44. [2] Leung M, Shore R. Fluvoxamine-associated bleeding. Can J Psychiatry 1996;41(9):604–5.
[3] Ottervanger JP, van den Bemt PM, de Koning GH, Stricker BH. Risk of hemorrhage with the use of fluoxetine (Prozac) or fluvoxamine (Fevarin). Ned Tijdschr Geneeskd 1993;137:259–61. [4] Yaryura-Tobias JA, Kirschen H, Ninan P, Mosberg HJ. Fluoxetine and bleeding in obsessive-compulsive disorder [letter]. Am J Psychiatry 1991;148:949. [5] Calhoun JW, Calhoun DD. Prolonged bleeding time in a patient treated with sertraline. [letter]Am J Psychiatry 1996;153:443. [6] Lake MB, Birmaher B, Wassick S, Mathos K, Yelovich AK. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol 2000;10: 35–8. [7] Holzer L, Halfon O. Sertraline and gastrointestinal bleeding in an adolescent girl. J Child Adolesc Psychopharmacol 2006;16:1–2. [8] McCloskey DJ, Postolache TT, Vittone BJ, et al. Selective serotonin reuptake inhibitors (SSRIs): measurement of effect on platelet function. Transl Res 2008;151:168–72.
General Hospital Psychiatry 32 (2010) e9 – e10
Letter to the Editor Ecchymoses as an adverse effect of fluvoxamine treatment in an adolescent girl To the Editor, Reports of bleeding in patients receiving selective serotonin inhibitors (SSRIs) appeared soon after their introduction. Case reports have described adult patients with various bleeding disorders (e.g., ecchymoses, purpura, epistaxis), while observational studies have focused on upper gastrointestinal bleeding, intracranial bleeding and bleeding during surgery [1]. Bleeding complications of fluvoxamine treatment have been described in adults [2,3]. However, reports of bleeding complications of SSRI treatment are not limited to the adult population. Several cases of abnormal bleeding under SSRI treatment have been described in children and adolescents with similar clinical manifestations [4–7]. We report a case of an adolescent girl who manifested ecchymoses during fluvoxamine treatment. This patient started fluvoxamine treatment at the age of 17 years for obsessive-compulsive disorder (OCD) with a total score of 25 on the Children's Yale–Brown Obsessive Compulsive Scale (CYBOCS). The introduction of fluvoxamine was well tolerated and the dosage was gradually increased over 3 months to 300 mg/day. The patient improved over the next 3 months and her OCD had remitted completely (CYBOCS score=0). Nine months after the introduction of fluvoxamine treatment the patient developed spontaneously appearing bruises on her legs and arms. These progressively worsened during the following 2 months reaching to a maximum diameter of 5 cm when she reported them. There was no personal or family history of a bleeding disorder, trauma or self-injurious behavior as reported by family members. She did not take any other medication except fluvoxamine. In the physical examination no abnormality other than ecchymosis was observed. Hepatic function tests, urine analyses, erythrocyte sedimentation rate, hemoglobin level and complete blood count results were all in normal ranges. Bleeding time, prothrombin time, partial prothrombin time, activated partial prothrombin time, international normalized ratio, clotting time and fibrinogen level were also normal. The dosage of fluvoxamine was reduced to 200 mg/day. No new spontaneous ecchymosis occurred and old ones disappeared within 2 weeks. The patient has remained well over the past 3 months. 0163-8343/$ – see front matter © 2010 Elsevier Inc. All rights reserved.
Although abnormal bleeding associated with SSRI treatment is frequently described in the recent literature, its real incidence and its mechanism are still unknown. In this case, the causal relationship between fluvoxamine and bruising may be assumed for several reasons. First, the patient had no personal or family history of hematological abnormalities. Second, the patient did not take any other medication besides fluvoxamine. Third, the time sequences with the onset of ecchymoses during fluvoxamine treatment and of cessation of bruising after fluvoxamine dosage reduction. Fourth, no comorbid mental disorder could be detected to which bruises can be attributed. In the literature, cases of abnormal bleeding in children and adolescents during treatment with sertraline and fluoxetine have been described. To our knowledge, there are no reports in the literature of abnormal bleeding with fluvoxamine treatment in children or adolescents. Our case adds valuable clinical insight to what few case reports have already published regarding bleeding complications of SSRI treatment in children and adolescents. As this case report shows, hemorrhagic complications may occur with a high dose of fluvoxamine and can be successfully managed with dose reduction without the necessity for drug discontinuation. Consistent with previous reports of SSRI-induced bleeding [1,7], we could not find any abnormal standard laboratory results in our case. Platelet aggregation studies detected significant abnormalities in the SSRI patients [1,8], but were not measured in the present case. Given the increase of pediatric SSRI prescriptions, physicians should be attentive to signs of possible rare side-effects of SSRIs. Abnormal bleeding is a rare side-effect of SSRI with unknown longterm consequences that warrant further study. Thorough bleeding histories, education of the patient and careful follow-up remain the major tools for preventing a bleeding diathesis that is caused or aggravated by SSRI medications. Boričević Maršanić Vlatka, M.D. Psychiatric Hospital for Children and Youth 10 000 Zagreb, Croatia E-mail address: [email protected] Aukst-Margetić Branka, M.D., M.Sc. Psychiatric Clinic, University Hospital Center Zagreb 10 000 Zagreb, Croatia E-mail address: [email protected]
e10
Letter to the Editor / General Hospital Psychiatry 32 (2010) e9–e10
Margetić Branimir, M.D. Neuropsychiatric Hospital Dr. Ivan Barbot Popovača, Croatia E-mail address: [email protected] doi:10.1016/j.genhosppsych.2010.01.005 References [1] Weinrieb RM, Auriacombe M, Lynch KG, Lewis JD. Selective serotonin re-uptake inhibitors and the risk of bleeding. Expert Opin Drug Saf 2005;4:337–44. [2] Leung M, Shore R. Fluvoxamine-associated bleeding. Can J Psychiatry 1996;41(9):604–5.
[3] Ottervanger JP, van den Bemt PM, de Koning GH, Stricker BH. Risk of hemorrhage with the use of fluoxetine (Prozac) or fluvoxamine (Fevarin). Ned Tijdschr Geneeskd 1993;137:259–61. [4] Yaryura-Tobias JA, Kirschen H, Ninan P, Mosberg HJ. Fluoxetine and bleeding in obsessive-compulsive disorder [letter]. Am J Psychiatry 1991;148:949. [5] Calhoun JW, Calhoun DD. Prolonged bleeding time in a patient treated with sertraline. [letter]Am J Psychiatry 1996;153:443. [6] Lake MB, Birmaher B, Wassick S, Mathos K, Yelovich AK. Bleeding and selective serotonin reuptake inhibitors in childhood and adolescence. J Child Adolesc Psychopharmacol 2000;10: 35–8. [7] Holzer L, Halfon O. Sertraline and gastrointestinal bleeding in an adolescent girl. J Child Adolesc Psychopharmacol 2006;16:1–2. [8] McCloskey DJ, Postolache TT, Vittone BJ, et al. Selective serotonin reuptake inhibitors (SSRIs): measurement of effect on platelet function. Transl Res 2008;151:168–72.