FDA Petition to Place Sertraline 25 mg Over the Counter

 Dockets Management Branch

Food and Drug Administration

Department of Health and Human Services, Room 1-23

12420 Parklawn Drive

Rockville, MD 20857

Dear Commissioner:

CITIZEN PETITION

This petition is submitted pursuant to 21 C.F.R. § 10.30. This petition requests that the 

Commissioner of Food and Drugs place sertraline 25 mg over the counter, available without a prescription for the treatment of post traumatic stress disorder (PTSD), an FDA approved indication. 

A. ACTION REQUESTED

For the reasons discussed in Section B, this petition requests the Commissioner to do the following:

1. Place sertraline 25 mg over the counter, for post-traumatic stress disorder, an FDA approved indication. It is approved in patients down to age 6. 

2. Require that makers of it include a consumer package insert written at the 6th grade reading level. It should add that a small fraction of people may get anxious or agitated day 1 or 2. Such agitation may lead to dangerous acts, and that such people should stop taking it. This warning is not in the current package insert, but should be. 

B. STATEMENT OF GROUNDS

1. Motivation for this Petition

Petitioner is a board-certified psychiatrist with patients. Petitioner may legally stand in for his patients’ medical interest in federal court. He intends to seek declaratory relief and to  enjoin the FDA if it fails to put this petition in action. FDA obstructionism kills thousands of Americans a year. 

Petitioner respectfully requests that the Commissioner

1. End the prescription requirement to obtain sertraline 25 mg tablets. 

2. Makers should require that makers of it include a consumer package insert written at the 6th grade reading level. It should add that a small fraction of people may get anxious or agitated day 1 or 2. Such agitation may lead to dangerous acts, and that such people should stop taking it. This warning is not in the current package insert, but should be. 

According to the CDC ( https://www.cdc.gov/nchs/data/databriefs/db478.pdf ), PTSD is prevalent in 6% of the population. That rate makes it one of the most common psychiatric condition. 

According to the National Center for PTSD, about 6% of the general population will experience PTSD at some point in their lives. However, the likelihood of developing PTSD varies widely depending on the specific traumatic event and individual circumstances.

Here are some estimates of PTSD prevalence among trauma victims:

- Sexual assault: 50-90%

- Combat veterans: 11-20%

- Natural disasters: 4-20%

- Car accidents: 2-10%

- Physical or emotional abuse: 20-50%

(See: - Sexual assault survivors: Foa, E. B., & Rothbaum, B. O. (1998). Treatment of posttraumatic stress disorder. Journal of Clinical Psychology, 54(2), 171-182.

- Combat veterans: Kang, H. K., & Hyams, K. C. (2005). Mental health care needs among recent theater veterans. Journal of Psychiatric Research, 39(5), 459-466.

- Natural disaster survivors: Galea, S., Nandi, A., & Vlahov, D. (2005). The epidemiology of posttraumatic stress disorder after disasters. Epidemiologic Reviews, 27, 78-91.

- Car accident survivors: Blanchard, E. B., & Hickling, E. J. (2004). After the crash: Assessment and treatment of motor vehicle accident survivors. American Psychological Association.

- Physical or emotional abuse survivors: Heim, C., & Nemeroff, C. B. (2001). The role of early life experiences in the development of depression. Molecular Psychiatry, 6(1), 14-27. )

There is a racial disparity in the prevalence of PTSD. 

Here are some racial disparities in PTSD rates ¹:

- Blacks: 8.7%

- Hispanics: 7.0%

- Whites: 7.4%

- Asians: 4.0%

(See: https://pubmed.ncbi.nlm.nih.gov/20346193/ )

The likelihood of 12 million people going to their health providers for the treatment of PTSD is not realistic. What is more realistic is the likelihood of self diagnosis using multiple available rating scales ( from:  https://www.ptsd.va.gov/ ). 

1. PTSD Checklist for DSM-5 (PCL-5)

The PCL-5 is a self-report measure that assesses the 20 DSM-5 symptoms of PTSD. It asks you to rate how much you've been bothered by each symptom in the past month on a scale from 0 (not at all) to 4 (extremely).

2. Davidson Trauma Scale (DTS)

The DTS is a 17-item self-rating scale that measures the frequency and severity of PTSD symptoms. You rate each symptom based on how often you experienced it and how severe it was over the past week.

3. PTSD Symptom Scale - Self-Report Version (PSS-SR)

The PSS-SR is another self-report questionnaire that evaluates the presence and severity of PTSD symptoms based on the DSM criteria. It includes questions about re-experiencing, avoidance, and hyperarousal symptoms.

This lack of access is especially troublesome for racial minorities. They face race based traumatic stress and racially motivated less access to healthcare, in additional to all the ordinary traumatic events.

 "Racism and Health" by Minority Health, CDC ( https://nihcm.org/publications/systemic-racism-health-care-covid-treatment )

- "Systemic Racism in Health Care" by theSkimm ( https://www.theskimm.com/wellness/systemic-racism-in-health-care )

- "Systemic Racism and Minority Disparities in Health Care" by The Bridge: Interdisciplinary Perspectives on Legal & Social Policy ( https://www.cdc.gov/minorityhealth/racism-disparities/index.html )

- "Systemic Racism & Health Care, COVID & Treatment" by NIHCM ( https://digitalscholarship.tsu.edu/thebridge/vol6/iss3/1/ )

They could then begin effective, FDA approved  treatment with sertraline 25 mg over the counter. Black patients are more impacted by the systemic racism of access to treatment. Only 19% get any form of treatment at all. The consequences of untreated PTSD include the following:

- Increased symptom severity

- Longer recovery time

- Physical health problems, such as:

- Chronic pain

- Headaches

- Gastrointestinal issues

- Heart disease

- Diabetes

- Autoimmune diseases

- Substance abuse

- Relationship problems

- Work and financial problems

- Depression

- Anxiety

- Suicidal thoughts

- Anger and aggression issues

- Cardiovascular and autoimmune diseases

- Obesity

- Metabolic syndrome

- Cognitive impairment

https://www.sabinorecovery.com/what-happens-if-ptsd-is-left-untreated/ 

https://healthmatch.io/ptsd/what-happens-if-ptsd-is-left-untreated 

Far from reducing interest in the psycho social and effective cognitive behavioral treatment of PTSD, such availability will increase it. Availability may also replace the currently harmful remedies of drinking alcohol, and of smoking marijuana. 

Sertraline is far safer in use and in overdose than any other over the counter drug now available, once patients are warned about the low rate of agitation of 1 in 100. It has very few drug-drug interactions with other prescribed and OTC medications. 

4. Why the Current FDA Regulations Must be Changed

Discrimination in medicine is a medical practice that includes both differential treatment on the basis of a protected class (disparate-treatment discrimination) and treatment on the basis of inadequately justified factors that disadvantages a particular group (disparate-impact discrimination).(National Research Council (2004). Measuring Racial Discrimination. The National Academies Press, Washington, DC. p. 40. Available at http://www.nap.edu/catalog.php?record_id=10887 (last accessed Feb. 20, 

2012))

Disparate treatment involves intentional discrimination and is per se unconstitutional. Statistical disparity is sufficient for a legal showing of discrimination. ( Texas Dept. of Housing and Community Affairs v. Inclusive Communities Project, Inc., 576 US ____ (2015).) In contrast, a determination as to the legality of disparate-impact discrimination depends upon whether the practice is supported by a sufficiently compelling reason and whether alternative processes exist that would not give rise to disparities. Disparate-impact liability mandates the “removal of artificial, arbitrary, and unnecessary barriers . . .” ( Griggs v. Duke Power Co., 401 US 424, 431 (1971)).

Petitioner contends that the current FDA regulations governing the use of sertraline are 

unconstitutional because they discriminate against individuals with mental illness, prohibiting such groups of individuals from obtaining what often is the only effective medication available to treat or control their symptoms.

In terms of disparate impact, the current FDA regulations have the effect of discriminating against  individuals with mental illness and of black patients, by prohibiting them from the use of an effective treatment. There is no compelling reason why such a prohibition should exist, especially given the fact that sertraline is safer than all over the counter medications in use and in overdose. 

Petitioner also contends that the current FDA regulations governing the use of  are 

unconstitutional because they constitute an undue burden by placing a substantial obstacle in the  path of millions patients seeking unavailable treatment for PTSD. In Planned Parenthood of Southeastern Pennsylvania v. Casey, the Supreme Court defined undue burden as an invalid provision of law whose purpose or effect is to place a substantial obstacle in the path of a patient seeking treatment. ( Planned Parenthood of Southeastern Pennsylvania v. Casey, 505 US 833 (1972).) The Supreme Court further refined the definition in Whole Woman’s Health v. Hellerstedt, 136 S. Ct. 2292, 2309 (2016), in which the Court held that it was “wrong to equate the judicial review applicable to the regulation of a constitutionally protected personal liberty with the less strict review applicable [in other contexts.” In other words, the undue burden test is a form of heightened scrutiny that rejects the judicial deference to legislative claims afforded under the rational basis test even if the benefits are minimal or the laws is unnecessary to achieve them. The test articulated in Whole Woman’s Health has three requirements: 

1) the law must actually further a valid state interest; 

2) the benefits of the law must outweigh the burdens imposed by the law; 

and, 

3) there must be an evidence-based inquiry based on reliable methodology. 

Whole Woman’s Health v. Hellerstedt, 136 S. Ct. 2292, 2309 (2016) issued in the context of a woman’s right to seek an abortion, they are broadly applicable to cases in which laws limit individual rights when their constitutionality depends on whether the law is actually advancing valid interests in a way that justifies the harm placed on the individual. Here,  it may be argued that the regulations at issue further a valid state interest in that they seek to minimize the risk of sertraline. 

With respect to the third requirement, the Court held that “The statement [] that legislatures, and not courts, must resolve questions of medical uncertainty is also inconsistent with this Court’s case law.” Thus, Petitioner believes the prescription requirement for sertraline 25 mg constitutes an undue burden and consequently an unconstitutional regulation. Petitioner is confident that should the FDA refuse to place sertraline 25 mg over the counter, the current regulations would not withstand a disparate-impact discrimination challenge brought by Petitioner on behalf of his patients under Title II of the Americans with Disabilities Act Amendments Act of 2008. Should Petitioner’s petition be denied, Petitioner also intends to pursue an undue burden challenge, which, given recent jurisprudence, Petitioner believes the will not survive. Petitioner prays that wisdom will prevail, making initiation of such a challenge unnecessary.

5. Public Benefit of Action

The actions in this petition have great public benefit. Petitioner finds it difficult to put into words how significant the increase in quality of life for those patients will be. The savings in terms of societal and social costs are difficult to quantify but would be significant. In addition, adopting these requests will decrease the disparity that currently exists with respect to the use of second-generation antipsychotics in the treatment of schizophrenia, which, as noted above, is an acute problem in the United States; as the Department of Health and Human Services noted, “‘the combined costs of health inequalities and premature death in the United States were $1.24 trillion’ between 2003 and 2006.”26 Finally, the requests herein are fully aligned with the HHS’s goals 

7. Request for Action as Direct Final Rule

FDA regulations at 21 C.F.R. § 10.40(e)(1) provide that “[t]he requirements of notice and public procedure . . . do not apply . . . [w]hen the Commissioner determines for good cause that they are . . . unnecessary . . .”28 This FDA exemption mirrors a similar exemption in the Administrative Procedure Act (“APA”).29 When enacting the APA exemption, Congress stated that the “lack of public interest in rule-making warrants an agency to dispense with public procedure.”30 Here, as there appears to be no question of law or fact in dispute, the Commissioner may dispense with advance notice and opportunity for comment. Therefore, Petitioner requests that the FDA effect creation of a national registry for clozapine patients having benign ethnic neutropenia and the proposed changes to package inserts and regulations by direct final rule.

C. ENVIRONMENTAL IMPACT

FDA regulations at 21 C.F.R. § 10.30 require Petitioner to prepare an environmental assessment under 21 C.F.R. § 25.40. However, an environmental assessment is not necessary here. 21 C.F.R. § 25.40 defines environmental assessment as “a concise public document that serves to provide sufficient evidence and analysis for an agency to determine whether to prepare an [environmental impact statement] or a [finding of no significant impact].” (21 C.F.R. § 25.40; see also 40 C.F.R. § 1508.9.)  The environmental assessment fulfills the FDA’s obligations under the National Environmental Policy Act of 1969 (“NEPA”).32 NEPA requires all federal agencies to assess the environmental impact of their actions “significantly affecting the quality of the human environment.” ( 42 U.S.C.A. § 4332.) The requests embodied in the instant petition have no environmental implications. Consequently, no environmental assessment is warranted. 

D. ECONOMIC IMPACT

Pursuant to 21 C.F.R. § 10.30, information under this section is to be submitted only when 

requested by the Commissioner following review of the petition.

(Id. at p. 8.; 28 21 C.F.R. § 10.40(e)(1); Administrative Procedure Act, 5 U.S.C.A. § 553(b)(B). S. Doc. No. 248, 79th Cong., 2d Sess. at 200 (1946); SW Environmental Impact Statements, 38 Fed. Reg. 7001 (Mar. 15, 1973), amended by 42 Fed. Reg. 19986 (Apr. 15, 1977) and 50 Fed. Reg. 16636 (Apr. 26, 1985).)

E. CERTIFICATION

The undersigned certifies that, to the best knowledge and belief of the undersigned, this petition includes all information and views on which the petition relies, and that it includes representative data and information known to Petitioner that are unfavorable to the petition.

F. CONCLUSION

For the foregoing reasons, Petitioner requests that this petition be granted and that the 

Commissioner contemporaneously require modifications to package inserts and FDA guidance and regulations to place sertraline 25 mg over the counter.

Respectfully submitted,

David Behar, M.D.