Fluvoxamine is preferred for management of obsessive compulsive disorder among all SSRIs. SSRIs usually have a safe side effect profile as compared to TCAs. But in recent times alarms have been raised for their association with increased risk of bleeding. Most of the available literature shows their association with gastrointestinal bleeding. But we present a case of recurrent episodes of subconjunctival haemorrhages with fluvoxamine.
Introduction: Fluvoxamine is 2-[[5-methoxy-1-[4-(trifluoromethyl) phenyl] pentylidene] amino] oxyethanamine. It is a newer selective Serotonin Reuptake Inhibitor (SSRI), found to be more effective than other SSRIs in the treatment of OCD. Prior to the introduction of SSRIs in the late 1980s, TCAs were the medication of choice for the treatment of major depressive disorder, panic disorder and other anxiety disorders in spite of their side effect profile. In the initial years of their use SSRIs were considered to have mild side effect profile. But in last few years, there are case reports and uncontrolled studies reporting bleeding events in the form of ecchymoses, purpura, epistaxis, and gastrointestinal bleeding. Similarly we present a case of recurrent episodes of subconjunctival haemorrhages with fluvoxamine.
History: A 36 years old male was diagnosed with OCD and was prescribed fluvoxamine 200mg/day in divided dosages. After an initial improvement, the dose was increased to 300mg after 15 days. The patient improved significantly in four weeks time. The dose was maintained at the same levels. After 8 weeks of starting of fluvoxamine, the patient developed subconjunctival hemmorhage. The patient consulted an ophthalmologist and he was started on topical antibiotics. The haemorrhage subsided within two weeks to appear again within four weeks. The topical antibiotic was started again and haemorrhage subsided. The patient informed the treating team about these subconjunctival bleeds, the patient was interviewed and examined in detail about any other contributing cause for these bleeds. However, there was no history of any bleeding disorder, uncontrolled hypertension, trauma or recent intake of NSAIDs or antiplatelet agents. His blood counts and blood coagulation tests were within normal limits. As fluvoxamine induced bleed was a possibility, the drug was stopped and clomipramine was started. The patient maintained remission on this drug and did not get any further subconjunctival bleeds for next 8 months.
Discussion: Fluvoxamine is commonly used in the treatment of obsessive compulsive disorder because of their efficacy and a favorable safety and tolerability profile. Side effects like sexual dysfunction, nausea, diarrhea, anxiety, insomnia, sedation, nightmares and rare instances of extra pyramidal symptoms are well known. However, episodes of bleeding have also been noticed with SSRIs and it has become a matter of avid research. There have been a few retrospective studies, in recent years, showing higher relative risk in cases as compared to controls.
In the above case, when fluvoxamine was prescribed, recurrent subconjunctival bleeds had occurred, which subsided after stopping the drug. There was neither bleeding nor clotting disorder nor any drug interaction responsible for the causation of subconjunctival hemorrhages. Spontaneous subconjunctival haemorrhages can be considered another differential diagnosis but as the haemorrhages were temporally related to administration of fluvoxamine and did not recur after stopping the drug, fluvoxamine seems to be the likely offending agent.
In literature different mechanisms have been proposed as responsible for SSRI induced haemorrhages. Shen et al., 1999 proposed that SSRIs acting through inhibition of nitric oxide synthase cause disturbances of regulation of platelet aggregation might mediate SSRI-induced bleeding. Hougardy et al., 2008 proposed that SSRIs act on the serotonin transporter located on the platelet cell membranes leading to depletion of serotonin in the platelets which decreases coagulation and may lead to a bleeding tendency in vulnerable individuals. Andersohn et al., 2009 opined that drug- induced immune thrombocytopenia may present another possible mechanism for bleeding in SSRI-treated patients.
The studies and case reports in last few years have shown that the use of SSRIs is associated with increased incidence of episodes of ecchymoses, purpura, epistaxis, and gastrointestinal bleeding and SSRIs may play a causal role in it. The risk decreased to same level as controls in past users of SSRIs indicating that bleeding is likely to be associated with the drug rather than the illness it was prescribed for [Weinrieb et al 2005]. The association also holds when age, gender, and the effects of other drugs such as aspirin and NSAIDs are controlled for.
In the index case, although no other clear cut risk factor could be detected, the temporal relationship between the onset of SSRI therapy and bleeding, more than once, is impressive. Equally impressive is the prompt resolution of the problem with discontinuation of the therapy and hence the association between SSRI therapy and subconjunctival bleed seems to be quite high. The authors however, acknowledge the limitations in establishing the causality. Also, literature mentions hematological side effects with other antidepressants including TCA’s and venlafaxine.
Further studies are needed to investigate whether caution should also be exercised in prescribing SSRIs to those in which other risk factors for bleeding like hypertension are present. Also, as no other clear-cut risk factor could be identified in the index case, the authors wonder whether any genetic predisposition might be present as well, in certain patients. Further studies should seek to inquire this aspect as well.
In view of these findings it is suggested that physicians be cautious in prescribing SSRIs and should seek to find out additional risk factors for bleeding episodes or past history suggestive of the same in patients who are to be prescribed SSRIs, Gastro protection (in the form of proton pump inhibitors or H2 receptor antagonists) is advised, especially when concomitantly using NSAIDS. The effects of SSRIs on bleeding are not predicted by standard blood tests but are revealed by platelet-aggregation tests. As these tests are not likely to be readily available in developing countries, the physicians in these countries should exercise even more caution in finding out other risk factors for GI bleed before prescribing SSRIs.
Key words: Fluvoxamine, Subconjunctival Hemorrhage, NSAID
