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December 2007

Index, Volume 30, 2007

High-Dose Ziprasidone
Patients with treatment-resistant psychosis may benefit from higher-than-recommended doses of ziprasidone (Geodon).

Baby Steps
Our clinical knowledge in psychiatry has increased over the past year, but scientific understanding and intervention technology still leaves much to be desired.

High Doses of Venlafaxine
Higher doses of venlafaxine (Effexor and others) likely increase the chance of antidepressant response, but also increase the risk of side effects.

SSRIs and Bleeding Risk in Patients with Hepatitis C
The risk of selective serotonin reuptake inhibitors causing bleeding in patients with hepatitis C is modest.

Bupropion versus SSRIs for Anxiety in MDD
According to Papakostas and colleagues, bupropion (Wellbutrin and others) appears to work as well as selective serotonin reuptake inhibitors to treat anxiety in patients with major depressive disorder.

Torsades de Pointes with Haloperidol
Intravenous administration of haloperidol (Haldol and others), especially at high doses, can cause QT prolongation and torsades de pointes.

In Brief
Ziprasidone for borderline personality disorder: A negative trial; Adjunctive medications for weight loss in patients with schizophrenia or bipolar disorder

SSRIs and Bleeding Risk in Patients with Hepatitis C

December 2007

Selective serotonin reuptake inhibitors (SSRIs) are thought to initiate treatment of depression by inhibiting serotonin reuptake into neurons. SSRIs similarly block the reuptake of serotonin by platelets, which affects their aggregation and, as we have described in the past, increases the risk of bleeding (BTP 2005;28:9) and spontaneous hemorrhage (BTP 2004;27:1, 2000;23:26).1,2

Hepatitis C virus (HCV) infects an estimated 3.9 million people in America, and given the relative youth of the infected population, the disease burden is expected to increase over the next two decades. Current standard treatment is a combination of interferon (Intron A, Infergen, or Pegasys) and ribavirin (Rebetol and others). Interferon causes depression in 21% to 58% of patients taking it, so SSRIs are frequently prescribed to prevent or treat interferon-associated depression. Both HCV infection and the drugs used to treat it can increase the risk of bleeding, as may SSRIs. In 2003, Weinrieb et al reported that 79% of HCV patients who experienced gastrointestinal bleeding were taking SSRIs.3 This danger with SSRIs is even greater when patients are concomitantly taking aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs).

To further assess this issue, Martin and coworkers conducted a retrospective chart review of 303 HCV-infected patients treated at the Mayo Clinic in Arizona between 2001 and 2005.4 The standard protocol in their program was to start antidepressants 3 to 4 weeks before beginning interferon-ribavirin combination treatment. Most patients took citalopram (Celexa and others) or escitalopram (Lexapro), although clinicians could elect fluoxetine (Prozac and others), paroxetine (Paxil and others), or sertraline (Zoloft and others).

During 4 years of observation, only one episode of bleeding occurred among the 303 patients (0.3%). That patient was a 53-year-old man with hemophilia who developed a hematoma after falling.

Martin et al conclude that the risk of SSRIs causing serious bleeding in an HCV population on antiviral therapy is modest and does not warrant foregoing prophylactic use of SSRIs in these patients. At the same time, they suggest caution in HCV patients with multiple risk factors for bleeding.

1Movig KL, Janssen MW, de Waal Malefijt J, Kabel PJ, Leufkens HG, Egberts AC: Relationship of serotonergic antidepressants and need for blood transfusion in orthopedic surgical patients. Arch Intern Med 2003;163:2354–2358.

2de Abajo FJ, Rodriguez LA, Montero D: Association between selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: Population based case-control study. BMJ 1999;319:1106–1109.

3Weinrieb RM, Auriacombe M, Lynch KG, Chang KM, Lewis JD: A critical review of selective serotonin reuptake inhibitor-associated bleeding: Balancing the risk of treating hepatitis C-infected patients. J Clin Psychiatry 2003;64:1502–1510.

4Martin KA, Krahn LE, Balan V, Rosati MJ: Selective serotonin reuptake inhibitors in the context of hepatitis C infection: Reexamining the risks of bleeding. J Clin Psychiatry 2007;68:1024-1026.