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.
Intravenous scopolamine has shown promise as a rapid-acting antidepressant in studies by Carlos Zarate and colleagues at the National Institute of Mental Health (NIMH). Improvement on the drug can occur within 24 hours.
In a 6-week 2012 study, an oral preparation of scopolamine was more effective than placebo as an add-on medication to the selective serotonin reuptake intake (SSRI) antidepressant citalopram. Patients who received scopolamine and citalopram had higher rates of response and remission than those who received placebo and citalopram. The scopolamine group experienced more blurred vision and dizziness, which is to be expected from an anticholinergic drug, a drug that blocks the action of the neurotransmitter acetylcholine in the brain.
Researcher A. Kahn reported at the 51st Annual Meeting of the National Institute of Mental Health’s New Clinical Drug Evaluation Unit (NCDEU) in Boca Raton in 2011 that severely depressed and suicidal patients taking citalopram (Celexa) or a combination of citalopram and low dose lithium experienced improvements in depression and suicidal thoughts. This study was unusual because most clinical trials exclude actively suicidal patients. In the group of subjects receiving citalopram plus lithium (300 mg/day and achieving 0.5 mEq/l or higher), there were several indications of better anti-suicide effects than in those on citalopram alone. The authors concluded that with appropriate doses, antidepressants plus lithium may prospectively reduce suicidal thoughts, and that it is possible to conduct clinical trials in severely depressed and suicidal patients if adequate safety measures are included.
Surprisingly, improvement in suicidal ideation preceded improvement in depressed mood per se.
Editor’s note: The study reported here suggests that in those with high suicidal ideation scores at baseline, antidepressants with or without lithium may quickly bring about anti-suicidal effects on thoughts, desires, and behaviors. Whether these effects occur reliably in studies in other groups of patients and in younger individuals remains to be established.
These data are an interesting contrast to data on antidepressant use in those with low levels of suicidality at baseline. A number of studies have suggested that in children and adolescents who were exposed to an antidepressant, a small percentage experienced increases in suicidal ideation in the first two months of treatment compared to patients taking placebo. This led to a Federal Drug Administration (FDA) warning (directed at all patients taking antidepressants) that increases in suicidal ideation and action may occur upon starting antidepressants.
It is important to note that the warning does not refer to completed suicides; the data set that led to the FDA warning included no completed suicides. More than 70% of those with suicidal ideation do not make an attempt, and the vast majority of attempts do not result in a completed suicide.
Most of the studies that found the slight increase in suicidal ideation in some patients after beginning antidepressant treatment actively excluded acutely suicidal patients. Since the study of citalopram and lithium above used a population of severely depressed and suicidal patients and found that antidepressants improved suicidality, it appears important to consider a patient’s baseline state when considering psychiatric interventions. In another example, there is an interesting difference between the way depressed patients and non-depressed normal volunteers respond to one night’s sleep deprivation: depressed patients often show dramatic improvement, while normal volunteers tend to feel worse.
More Evidence that Antidepressants Prevent Suicide in Unipolar Depression
A new study by DeLeon published in the Journal of Clinical Psychiatry in 2011 found that during periods of life when unipolar patients were taking antidepressants (compared to times when they were not taking them) the patients experienced 20% fewer suicidal acts or completed suicides. Read more