Kaufmann, 2009 Selective Serotonin Reuptake Inhibitor (SSRI) Drugs: More Risks Than Benefits?

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Kauffman, J. M. (2009). American Physicians and Surgeons, 14(1), 7–12.

Selective Serotonin Reuptake Inhibitor (SSRI) Drugs: More. Risks than Benefits?

 

Full text (pdf) at http://www.jpands.org/vol14no1/kauffman.pdf

 

ABSTRACT

 

Anecdotal reports have suggested that selective serotonin reuptake inhibitors (SSRIs) may cause suicidal or violent behavior in some patients. Because of the publicity surrounding certain events, and the numerous lawsuits that have been filed, a review of benefits and risks is needed.

 

At most 30% of patients receive a benefit from SSRIs beyond the large placebo effect in certain mental conditions, especially depression, according to a recent meta-analysis of published trials. An equally recent meta-analysis of all SSRI trials submitted to the FDA showed a small benefit for the severely depressed patients only. Many early unpublished trials did not show any benefit.

 

Adverse effects are common, occurring in up to 75% of subjects. Severe adverse effects may be underreported. Metaanalyses of controlled trials did not include any actual suicides or murders, but only suicidality, some finding, in 1991 and 2007, no evidence even of suicidality. Other meta-analyses using many of the same trials found that suicidality doubled to 1 in 500 on SSRIs compared with placebo or non-SSRI antidepressants, but did not include any actual suicides or murders. The trial designs were devised by SSRI makers to prevent reports of suicides, by eliminating subjects with the slightest trace of suicidal tendencies. Retrospective studies by others showed actual suicides on SSRIs with a relative risk (RR) of 2–3 compared with non-SSRI antidepressants, with an increased incidence of 123/100,000.

 

Lower doses than the smallest available ones were found to maintain benefits in a majority of patients while reducing risks. No causal connection between SSRIs and suicide and/or violence has been proved; neither has it been ruled out. Physicians need to be vigilant, and aware of legal precedents that may subject them to enhanced liability when prescribing these drugs.

 

From the paper:

 

CONCLUSION

Antidepressants are extraordinarily difficult to assess for risks or benefits in trials.

 

At most, 11%–30% of patients with depression or related conditions who take SSRIs actually benefited beyond the placebo effect on normal doses. Of the perceived benefit, 32%–67% can be attributed to the placebo effect.

 

Adverse effects, mostly dose-dependent, will appear in up to 75% of patients on normal doses. Of these, studies suggest that suicidality will be observed in an additional 2%–13% (1 in 50 to 1 in 8 ) of patients on normal doses, beyond what is seen on placebo or many non-SSRI antidepressant drugs. This is sufficiently frequent that a typical prescribing physician should observe examples in routine practice.

 

The actual suicide rate could be about 123/100,000 (1 in 813) higher in patients on SSRIs than in those on tricyclics or placebo. Studies show that many more suicides are on normal doses of SSRIs beyond what is seen on placebo or many non-SSRI antidepressant drugs.

 

Available data suggest that actual murders may be committed at about the rate of 250/100,000 (1 in 400) SSRI-treated patients beyond what is seen on placebo or many non-SSRI antidepressant drugs, and that many more murders will be attempted on normal doses as well. While correlation does not prove causation, and results of court trials are not medical science, the data for suicide are solid, and the association of murder with suicide is very suggestive.

 

Now that there is a stronger Black Box warning, physicians who ignore it may be liable for damages; the warning primarily protects the manufacturers of SSRIs.

 

There is obviously great peril in drawing conclusions about causation from press reports or court decisions. While manufacturers have a vested interest in exonerating their drugs, plaintiffs have an interest in blaming it, and defendants in exonerating themselves. We need careful, independent analysis of existing study data. In addition to randomized controlled trials, evidence from basic science (neuropharmacology) and challenge/dechallenge/rechallenge investigations needs to be sought. Both the public and individual patients are imperiled by an incorrect answer to the pressing questions about these widely prescribed drugs.

 

Future studies may show lower levels of murder and suicide with close supervision, and with better matching of this drug type to patient type.

 

Joel M. Kauffman, Ph.D., is professor of chemistry emeritus at the University of the Sciences, 600 S. 43rd St., Philadelphia, PA 19104-4495, Contact: kauffman@bee.net.

 

Acknowledgements: Frances E. H. Pane edited the manuscript. David Moncrief piqued my interest by providing a review copy of The Cult of Pharmacology: How America Became the World's Most Troubled Drug Culture by Richard DeGrandpre.