A large study in Denmark suggests that taking selective serotonin reuptake inhibitor (SSRI) antidepressants alongside cholesterol-lowering statin drugs improved depression more than SSRIs alone. The findings, by Ole Köhler and colleagues were reported in the American Journal of Psychiatry in 2016.
The study included 872,216 people in Denmark’s national health care database who took SSRIs between 1997 and 2012. The most common SSRIs were citalopram, sertraline, and escitalopram. Of these people taking SSRIs, 13.0% also took a statin drug, typically simvastatin. Those patients who were taking both an SSRI and a statin were less likely than those taking an SSRI alone to be hospitalized for any psychiatric problem, or for depression specifically.
Depression is known to be correlated with inflammation throughout the body. Statins reduce this inflammation as well as lowering cholesterol. A 2013 study by Ahmad Ghanizadeh and Arvin Hedayati in the journal Depression and Anxiety showed that the SSRI fluoxetine and the statin lovastatin reduced depression severity compared to fluoxetine alone.
The combination of SSRIs and statins did not seem to reduce deaths or suicidal behavior compared to SSRIs alone. Statins have some side effects, but combining them with antidepressants did not increase the risks associated with their use.
In August 2011, the US Food and Drug Administration issued a warning that doses of the selective serotonin reuptake inhibitor (SSRI) antidepressant citalopram (Celexa) that exceeded 40mg/day could prolong the QT interval, a measure of heart rate used to diagnose abnormal heart rhythms. A study of records from the Veterans Health Administration showed that 35,848 veterans whose dose of citalopram was reduced from an average of 64mg/day to under 40mg/day faced increased deaths, hospitalizations for any cause, and hospitalizations for depression specifically after the reductions.
The FDA warning meant to prevent heart problems had the unintended consequence of increasing hospitalizations and deaths among the veterans affected. These findings by Thomas S. Rector and colleagues were published in the American Journal of Psychiatry in 2016.
Editor’s Note: There are some similarities between this case and findings by researchers Andrew Nierenberg and Andrew Stoll, who noticed that patients taking 40mg/day of fluoxetine (Prozac) had better long-term outcomes than those taking 20mg/day, even though those taking 40mg were more ill and more likely to relapse at the start of the study.
Researchers Ellen Frank and David Kupfer found that 90% of unipolar depressed patients relapsed when their antidepressant doses were halved, even though they had been stable for 5 years before the change.
These and the findings from Rector and colleagues lead this editor to believe that reducing the dosage of effective treatments should not be done without reason—that is, in the absence of side effects, or simply to achieve the minimal effective dose. Dose reductions without cause not only may increase the risk of relapse, but may also put the patient at increased risk of developing tolerance to the medication, for example hastening the onset of ‘Prozac poop-out.’
When long-term maintenance drug therapy is going well, it may be best to be conservative and stay the course. Conversely, in the absence of a good long-term response, be as active and creative as possible to achieve mood stabilization.