Antidepressants Prevent Suicide in Patients with Unipolar Depression

January 18, 2012 · Posted in Current Treatments, Potential Treatments 

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.

depressed woman

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

Using a large cohort of patients whose health reports were collected over a period of 37 years, the study examined specific suicidal acts in individual patients and determined whether each patient was being treated with antidepressants at the time of the act. Since patients tended to go on antidepressants at times of more severe depression, the researchers adjusted the analysis to control for clinical differences in depression severity. This analysis (a propensity-based correction) is powerful because it uses each patient as his or her own control.

This study used real-world patients who are more representative of the general population of depressed patients than the highly selective cohort of patients who are enrolled in randomized placebo-controlled clinical trials of antidepressants. In clinical trials, patients tend to be excluded if they have active suicidal ideation, medical comorbidities, or substance abuse problems, complications that are common in the general population of depressed subjects.

DeLeon’s data do not detract from the FDA warning to exert particular care in the first several months after beginning antidepressants, but clarify that in the long term, antidepressants not only do not cause suicidal behavior, but they actually help prevent it.

Together the data from the study of citalopram with lithium above and the study by DeLeon help to clarify the relationship between antidepressants and suicide. Despite the rare occurrence of suicidal ideation at the beginning of antidepressant treatment as warned about by the FDA, antidepressants with or without lithium rapidly improve suicidal ideation in those who were suicidal at baseline, and in the long term, treatment with antidepressants reduces suicidal actions.

We’ll discuss more reasons to consider long-term use of antidepressants in recurrent unipolar depression on Friday.  However, it should be emphasized that the above findings do not apply to bipolar depression where, instead of antidepressants, long-term use of lithium, mood stabilizing anti-convulsants, and atypical antipsychotics is endorsed.

 

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