Antidepressants or Antiaphrodisiacs? 6 Reasons Why So-Called Antidepressants Should Be Relabeled

Should a drug that produces sexual dysfunction for the majority of users and which doubles the risk of a suicide attempt be labeled as an antidepressant? No, argues a recent Scientifica article “Relabeling the Medications We Call Antidepressants.” The article’s authors, David Antonuccio, psychologist at the Department of Psychiatry and Behavioral Sciences, University of Nevada School of Medicine, and David Healy, psychiatrist at the Department of Psychological Medicine, Bangor University in the United Kingdom, point out that “to call these medications antidepressants may make sense from a marketing standpoint but may be misleading from a scientific perspective.” They conclude that “it may make just as much sense to call these medications antiaphrodisiacs as antidepressants because the negative effects on libido and sexual functioning are so common.”

If a greater percentage of antidepressant users suffer from sexual dysfunction than are relieved of depression, in a scientific sense, it is not silly to label the medication in terms of the condition that it affects most. And while Prozac, Paxil, and Zoloft are antidepressants for some people, for other people they are suicidality inducers, agitation enhancers, and mania stimulators.

Antonuccio and Healy offer six reasons why Prozac, Paxil, Zoloft, Celexa, Lexapro and other so-called antidepressants should not be labeled as antidepressants.

1. An Actual Antidepressant Should Not Interfere with Sexual Functioning

Loss of interest in pleasurable activities such as sex is one symptom of depression, and so it is odd that a medication that results in a loss of interest in sex could be labeled as an antidepressant.

Antidepressant manufacturers estimate that 2% to16% of antidepressant users experience sexual dysfunction. However, a 2001 study in the Journal of Clinical Psychiatry examined 610 women and 412 men with previously normal sexual functioning who were being treated with antidepressants, and it found that 59% reported sexual dysfunction, 62% of the men and 57% of the women (women reported more severe symptoms). Dysfunctions included decreased libido and inability to have an orgasm. Comparable rates of sexual dysfunction have been found in a 2010 Psychiatry Investigation study.

In antidepressant trials, 30% to 40% of subjects routinely gain relief from depression, and so the percentage of antidepressant users who suffer from sexual dysfunction is higher than the percentage who gain relief from depression.

2. An Actual Antidepressant Should Not Increase Suicidal Thoughts and Attempts

The Food and Drug Administration (FDA) analysis of antidepressants trials in 4,400 depressed young people found that antidepressants doubled the risk of “suicidality” (suicidal thoughts and suicidal attempts), which occurred in approximately 4% of those taking antidepressants compared with 2% of those taking a placebo. Antonuccio and Healy note that, “While the risk of increased suicidality appears to be relatively low (i.e., two extra suicidal patients for every 100 treated with an antidepressant compared with a placebo) and no patients actually completed suicide in the FDA database of controlled trials, the stakes are clearly high.” The risk is serious enough to warrant FDA “black box warnings” about increased suicidality for patients under the age of 25.

If, for many depression sufferers, one reason to take antidepressants is to prevent suicidal thoughts and attempts, and if antidepressants even slightly increase such suicidality rather than decrease it, does it make sense to label these drugs as antidepressants?

3. An Actual Antidepressant Should Be Clearly Superior to a Placebo

“To be labeled an antidepressant,” argue Antonuccio and Healy, “a medication should be consistently and clearly superior to a sugar pill.” Earlier this year, CBS’s “60 Minutes” reported on what antidepressant researchers have long known about antidepressants: placebos do almost as well as antidepressants, even in drug-company studies that are biased toward antidepressants. “To be clear,” note Antonuccio and Healy note, “it appears that many depressed patients improve on antidepressants, but this is also true of those who take placebos.”

Research psychologist Irving Kirsch used the Freedom of Information Act to study published and nonpublished results involving 6944 patients from the FDA database trials of the six most popular antidepressants (Prozac, Paxil, Zoloft, Effexor, Celexa, and Serzone), and he found that only 43% of the trials favored the antidepressant over placebo. Kirsch concluded that the impact of antidepressants “are relatively small even for severely depressed patients. . . the relationship between initial severity and antidepressant efficacy is attributable to decreased responsiveness to placebo among very severely depressed patients, rather than to increased responsiveness to medication.”

The “real-world” outcomes with antidepressants may actually be much worse than those in the placebo-controlled trials. By real-world outcome, Antonuccio and Healy are referring to a $35 million National Institute of Mental Health (NIMH) study, STAR*D, that was designed to assess antidepressant effectiveness in actual clinical practice. In this study, depressed patients who were not helped by their first antidepressant received up to three additional antidepressant treatments (utilizing different antidepressants). In every STAR*D treatment step, remission rates were either equal to or significantly lower than the customary placebo performance in other antidepressant studies (in Step 1, antidepressants had a 37% remission rate, decreasing to a 13% remission rate by Step 4). Worse, less than 3% of the entire group of depressed patients who began the STAR*D study were ascertained as having a sustained remission (i.e., actually participated in the final assessment without relapsing and/or dropping out).

4. An Actual Antidepressant Should Not Increase Anxiety and Agitation

A 2001 study in Clinical Psychiatry found that more than 8% of patients admitted to the Yale psychiatric facility were admitted for antidepressant-induced mania, and as Antonuccio and Healy, note, “Such adverse events can be frightening, costly, and extremely disruptive to a patient’s life.” One reason for increased diagnosis of bipolar disorder is antidepressant-induced mania. If one source of severe depression is people’s despair about being out of control over debilitating emotional states, it is difficult to justify labeling a drug an antidepressant when it causes anxiety and mania for a significant number of people.

5. An Actual Antidepressant Should Offer a Risk/Benefit Balance That Exceeds That of Alternatives

Antonuccio and Healy argue that “for medications to be considered true antidepressants, they should clearly offer benefit that exceeds the risks and side effects . . .[but] many of the “side effects” of these medications have larger effect sizes than the antidepressant effect size.” Physical side effects most often reported by antidepressant users include sexual dysfunction, dry mouth, jitteriness, nausea, headaches, sweating, dizziness, lethargy, and inability to sleep. Even for patients who are assessed to have positively responded to antidepressants, Antonuccio and Healy report that “almost half indicate that they would not take them again due to unwanted psychological side effects such as narrowing of affect, not feeling like oneself, loss of creativity, and an inability to cry.” The risk of adverse effects is far lower in either psychotherapy or many alternative treatments which have equal efficacy compared with antidepressants.

6. An Actual Antidepressant Should Not Increase Depression Chronicity

An NIMH study compared depressed patients who had taken a placebo with depressed patients who had received tricyclic antidepressants. Those in the study who took antidepressants were more likely to seek treatment during the follow-up period, had a higher probability of relapse, and had fewer weeks of minimal or no symptoms.

And there are also relapse/chronicity problems with selective serotonin reuptake inhibitor (SSRI) antidepressants such as Prozac, Paxil, Zoloft, Celexa, and Lexapro. SSRIs act on the serotonin system by interfering with serotonin reuptake (reabsorption) resulting in greater serotonin within a synapse. However, the brain quickly compensates for this increase in serotonin through reducing the number of serotonin receptors. Thus, “drug tolerance” and the need for increasingly higher dosage occurs. Several researchers believe that this reduction in the number of serotonin receptors increases antidepressant users’ vulnerability to depression relapse, especially following drug withdrawal, especially after long-term use.

Antonuccio and Healy’s Conclusions

Antonuccio and Healy conclude that, “On all of the identified dimensions for what a medication should accomplish to be called an antidepressant, current medications we call antidepressants seem to fall short.”

Scientifically, the outcome with the largest effect sizes should be offered as the primary label for a medication. Specifically, if more antidepressant users experience sexual dysfunction than experience relief from depression, antidepressants should be relabeled as antiaphrodisiacs.

Antonuccio and Healy, conclude, “Of course, the drug industry does not have an incentive to change the label. However, we feel patients ought to be informed of these possible alternative labels because they may apply equally well if not better. The main point is that calling these medications antidepressants is a marketing decision that does not appear to be consistent with the scientific data.”