- Jennifer Middleton, MD, MPH
All antidepressant medications carry a black box warning regarding an increased risk of suicidal behaviors, especially in teens and young adults. That black box warning assigns equal culpability to all antidepressants, but a POEM in the July 1 issue of AFP describes a study that found a higher risk of suicide with mirtazapine and venlafaxine compared with selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs).
The study researchers used a primary care patient database from the United Kingdom and identified patients between the ages of 20-65 with a depression diagnosis. They excluded patients who had other co-morbid psychiatric disease and/or who received a mood stabilizer or antipsychotic medication, ending up with a final cohort of about 240,000 patients. The researchers tracked rates of completed suicides and suicide attempts among these patients and compared these rates among patients taking various antidepressants.
Citalopram was the most commonly prescribed antidepressant, followed by fluoxetine, with venlafaxine and mirtazapine prescriptions in fifth and seventh place, respectively. The adjusted hazard ratios for venlafaxine and mirtazapine for suicidal behavior (successful or not) were 1.70 (1.44 to 2.02) and 1.85 (1.61 to 2.13), respectively, compared with citalopram. All of the SSRIs and TCAs had non-significant hazard ratios compared with citalopram. The highest rates of completed suicide and suicide attempt, regardless of antidepressant, were in the first 28 days of a new prescription and the first 28 days after stopping an antidepressant medication. The researchers did not find a statistically significant difference in suicide risk by age.
It is possible that, in the study cohort, patients taking venlafaxine and mirtazapine had more serious and/or refractory depression compared to patients taking an SSRI or TCA. These patients' physicians may have prescribed venlafaxine or mirtazapine after an SSRI or TCA treatment failure, for example. The researchers attempted to account for patients' depression severity in their analysis, but the documentation of depression severity in the database was inconsistent. They concluded that "the severity of depression is likely to still have a confounding influence on our results." Regardless of the reason, the difference in suicide risk for patients taking venlafaxine or mirtazapine is significant. These medications may still serve a need in certain clinical situations, but they require careful monitoring and should not be first-line medications.
This study compliments the already sizable evidence base regarding SSRIs' efficacy and tolerability; SSRIs remain the first choice for treating most patients with depression. Regardless of antidepressant choice, we need to carefully monitor patients during the first 28 days of any new antidepressant medication as well as during the first 28 days after stopping one. Family Practice Management provides an Immediate Action Protocol for physicians to use once patients screen positive for suicidal thoughts. This protocol provides guidance regarding follow-up questioning and can help physicians determine if a need exists for immediate psychiatric evaluation. Using a protocol like this one can help physicians avoid any language that might, unintentionally, inhibit suicide disclosure by patients. You can read more about depression treatment at the AFP By Topic on Depression and Bipolar Disorder.
Will this POEM change how you prescribe antidepressants and/or monitor patients for suicidal risk?