Are there any differences between different serotonin selective reuptake inhibitors (SSRI:s) with r

Fråga: Are there any differences between different serotonin selective reuptake inhibitors (SSRI:s) with regard to the risk of bleeding?

In the Swedish catalogue of approved medical products (FASS) caution is advised when using citalopram in patients with increased risk of bleeding due to blood disorders or medication with acetyl salicylic acid, NSAID:s or anticoagulants. This is not the case for the other registered SSRI:s (fluoxetine, paroxetine, sertraline and fluvoxamine).

Sammanfattning: All SSRI:s are associated with a slightly increased risk of bleeding. No studies were found comparing different SSRI:s in this aspect. From the adverse effect data in Swedis, it is not possible to draw any conclusions regarding possible differences. Since the increased bleeding time and risk of bleeding complications are thought to be a class effect concerning all SSRI:s there is no theoretical reason to expect significant differences between the substances.

In patients treated with warfarin, fluvoxamine and sertraline could inhibit the metabolism of warfarin, thereby increasing its anticoagulant effects. Likewise, citalopram and paroxetine could enhance the warfarin effect through pharmacodynamic interactions.

Svar: There are reports of bleeding complications for all the SSRI:s mentioned above (1-4). The reports include increased bleeding time, hematomas, petechiae, ecchymoses, epistaxis, menorrhagias and gastrointestinal hemorrhage. The mechanism is not clearly understood, but it has been suggested that the effect on hemostasis is a class effect due to decreased serotonin uptake in platelets (2). This would cause a depletion of stored serotonin, thus hampering platelet aggregation. No comparative studies investigating differences in bleeding risk between SSRI:s were found in Medline, Drugline or standard pharmacological literature.

In Swedis (Swedish Drug Information System) all SSRI:s have reports of bleeding complications, where the connection to SSRI medication is deemed possible or probable (5). There are 23 such reports for citalopram, 13 for sertraline, 6 for paroxetine, 5 for fluvoxamine and 5 for fluoxetine. These differences are probably due to different consumption patterns. From the available data, it is not possible to detect any real differences between these substances, with regard to bleeding risk.

In patients treated with warfarin, SSRI:s could enhance the warfarin effect through pharmacokinetic interactions. This has been described for fluvoxamine and sertraline, both inhibiting the metabolism of warfarin (6). Addition of paroxetine or citalopram to warfarin has been shown to increase the INR in some patients, although the mechanism is thought to be a pharmacodynamic rather than a pharmacokinetic interaction (6-7). 1 Information från Läkemedelsverket 1998; 9: 7-10

2 Drugline no 16320 (year 1999)
3 Drugline no 15428 (year 1999)
4 Drugline no 12753 (year 1995)
5 Swedis (The Swedish Drug Information System)
6 Drugline no 13260 (year 1998)

7 Stockley IH. Drug interactions. 5th ed. London: The Pharmaceutical Press; 1999. p. 743