'AERS' = the FDA's "Adverse Event Reporting System" (aka FAERS).

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12-12-19 ... CALL TO ACTION for Lupron Victims - see 'Media page':

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It should be emphasized that "[i]n an article in the Journal of American Medical Association, then FDA Commissioner David A. Kessler revealed that 'only about 1% of serious adverse events are reported to the FDA'." (Moore, Thomas J. Prescription for Disaster: The Hidden Dangers in Your Medicine Cabinet. New York. Simon & Schuster, 1998).

And a 2000 GAO report (page 6) noted that "FDA's [AERS] includes an estimated 1 to 10 percent of adverse reactions ... the adverse events that are reported are unlikely to represent the much larger number of unreported events."

Therefore about 90% to 99% of serious adverse events are NOT reported to the FDA.

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FAERS DATA for all Lupron formulations (as of September 30, 2018):

(Bearing in mind that about 90% to 99% of serious adverse events are NOT reported to the FDA:)

The following adverse event report numbers represent reports for all Lupron formulations - Lupron, Lupron Depot, Lupron Depot-PED, leuprolide, leuprolide acetate, leuprolide acetate/lidocaine hydrochloride, Viadur, Lupaneta Pack, and leuprolide acetate/norethindrone acetate - and represent reports submitted since 1985 through September 30, 2018):

--- Reported number of cases = 38,911

--- Reported number of serious cases (including deaths) = 23,842

--- Reported number of deaths = 5,776

--- Reported number hospitalized =7,203 (including 815 deaths)

--- Reported number disabled = 904 (including 45 deaths)

--- Reported number of life threatening events = 786 (including 137 deaths)

--- Reported number of congenital anomalies = 83 (including 9 deaths)

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For comparison, the following are FAERS data for other GnRHas:

Zoladex, goserelin, goserelin acetate (data from 1990 through September 30, 2018): total cases = 5,607; serious cases (including deaths) = 4,944; deaths = 1,185; life threatening = 288 (including 76 deaths); hospitalized = 1,843 (including 207 deaths); disabled = 436 (including 28 deaths); congenital anomalies = 23 (including 1 death).

Synarel, nafarelin, nafarelin acetate (data from 1982 through September 30, 2018): total cases = 2,105; serious cases (including deaths) = 1,423 (including 9 deaths); deaths = 9; disabled = 31; hospitalized = 186 (including 2 deaths); life threatening = 20 (including 2 deaths); congenital anomalies = 6.

Trelstar, triptorelin, triptorelin pamoate (data from 1999 through September 30, 2018): total cases = 1,196; serious cases = 1,010 (including 83 deaths); deaths = 83; disabled = 73 (including 1 death); hospitalized = 468 (including 25 deaths); life threatening = 54 (including 5 deaths); congenital anomalies = 3 (including 2 deaths).

Buserelin, buserelin acetate (data from 1997 through September 30, 2018): total cases = 78; serious cases = 74 (including 4 deaths); deaths = 4; disabled = 7 (including 2 deaths); hospitalized = 34 (including 4 deaths); life threatening = 7 (including 1 death).

Vantas, supprelin, supprelin LA, histrelin, histrelin acetate (data from 1998 through September 30, 2018): total cases = 742; serious cases = 189 (including 39 deaths); deaths = 39; disabled = 6; hospitalized = 42 (including 3 deaths); life threatening = 4.

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FAERS DATA for Lupron Depot-Ped (as of May 2016)

In the 5 (FIVE) year period May 2011 through May 2016 for:

Lupron Depot-PED (pediatric use only):

--- there were 1,075 individual patient case reports

--- representing 3,005 total adverse events

--- including 39 "total deaths".

There were also 10 "events" listing death. (Per FDA, "Total Deaths" is the number of cases where the stated "outcome" for the patient was death. Typically, death is recorded as an "outcome" and not an "event", unless "death" is the only information that is reported on a case. For this reason, the number "total deaths" is usually greater than the number of coded events of "death".)

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In the 5 (FIVE) year period May 2011 through May 2016 for:

Lupron Depot (3.75 mg, 7.5 mg, 11.25 mg, 15 mg, 30 mg, 45 mg):

--- there were 13,929 individual patient case reports

--- representing 48,144 total adverse events

--- including 962 "total deaths".

There were also 3 "events" listing "sudden death", 3 "events" listing "stillbirth", 1 "event" listing "brain death", and 1 "event" listing "euthenasia". (Per FDA, "Total Deaths" is the number of cases where the stated "outcome" for the patient was death. Typically, death is recorded as an "outcome" and not an "event", unless "death" is the only information that is reported on a case. For this reason, the number "total deaths" is usually greater than the number of coded events of "death".)

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In the 5 (FIVE) year period May 2011 through May 2016 for:

Lupron (daily injection):

--- there were 7,240 individual patient case reports

--- representing 19,605 total adverse events

--- including 151 "total deaths".

There were also 30 "events" listing "death", 5 "events" listing "foetal death", 4 "events" listing "abortion induced", 3 "events" listing "completed suicide", 2 "events" listing "sudden death", and 1 "event" listing "stillbirth". (Per FDA, "Total Deaths" is the number of cases where the stated "outcome" for the patient was death. Typically, death is recorded as an "outcome" and not an "event", unless "death" is the only information that is reported on a case. For this reason, the number "total deaths" is usually greater than the number of coded events of "death".)

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Search AERS database.

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See also FDA Quarterly Reports 2004 - 2012.

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As of February 11, 2009, the total tally of reported adverse events to lupron/leuprolide since November 1, 1997, according to the FDA, is as follows:

22,667 reported adverse events, with 651 reported deaths from lupron/leuprolide, involving 5,069 individual safety reports.

In an online data sample, a graph shows an 'uptick' in numbers of death for the years 2008 - 2010. In 2010, it was reported that the FDA had rec'd more than 1,100 reports of deaths.

FDA AERS, for the period of November 1997 through August 2012 report 1,526 Deaths.

NOTE: NO DATA, including number of deaths, were ever provided for the time period of April 1985 (lupron's initial FDA approval) through October 1997 under the old "AERS" system. Under the newly organized "FAERS" system, data (including deaths) can be found going back to 1985.

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For non-lupron/leuprolide GnRHa adverse event reports, see the following reports from 'EudraVigilance' (the central database of reports of suspected adverse reactions for all medicinal products authorized in the European Economic Area): Triptorelin, Goserelin, Buserelin, Histrelin, Nafarelin, Leuprorelin. ('EudraVigilance' was set up in 2001, and the data provided here is for reports through November 2012). See also searchable databases: OpenVigil, Canada Vigilance Adverse Reaction Online Database and Australia Database of Adverse Event Notifications.

The French blog for "Victims Enantone [Lupron], Decapeptyl", as of January 2008, has listed Swiss adverse events for Enantone 11.25 mg., as well as the adverse events reported for Enantone in France.

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Take NOTE: the FDA has received a MedWatch report for lupron with a reported adverse event of "Homicide". (See 'RxISK.org's FDA AERS database, and search for "homicide" in 'side effects reported' search engine). Scroll to bottom of this page for "Lupron and Homicide' details.

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At LEFT column:

Duplication of FDA AERS data from a very small period of time, and from a decade ago, is provided here in order to give the public examples of the types of reported AERS for Lupron/leuprolide (again, just one small snapshot in time).

The adverse events reported to the FDA and reproduced at left involve the use of lupron/leuprolide in women, men, children, babies, and fetuses for the time period of January 2005 through December 2006 only (23 months worth of AERS data). These AERS reports, at left, obtained under FOIA (Freedom of Information Act), are divided as follows:

(#1) Selective reports (and *not* a comprehensive list) of 'Life-Threatening' and 'Disabling' illnesses, 'Hospitalizations' and 'Other' adverse events for the period of January 2005 through December 2006.

(#2) Most (but not all) reports found for the period of January 2005 through December 2006 related to 'Drug Exposure Before Pregnancy', 'Transplacental Exposure' and 'Congenital Anomalies', including death; (for a listing of fetal deaths for period of 11/97 - 12/04, see bottom of 'Deaths' page,)

(#3) All reports found for the period of January 2005 through December 2006 related to Ovarian Hyperstimulation Syndrome (OHSS).

The AERS FOI Reports reproduced at left contain all information as found in the FDA AERS FOIA Reports. Additional information beyond that listed in the AERS FOIA Reports can be obtained from the FDA by requesting individual ISR# (Individual Safety Numbers) reports found in each AERS report.

It should be noted again that only 1% to 10% of all adverse events are reported to the FDA, therefore 90% to 99% of adverse events remain unreported to the FDA AERS database.

The FDA, in it's AERS FOIA Reports, defines "Preferred Term" as "The reported reaction, in medical terminology [coded by MedDRA], describing the event." "Suspect Drug" is defined as "The drug that the initial reporter deemed most likely to be associated with the reactions." And "Concomitant Drug" is defined as "A list of drugs taken at the same time as the suspect medication, but not suspected of causing the adverse event."

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There is also a non-governmental website that has posted a partial selection of lupron/leuprolide adverse events and deaths online: http://www.patientsville.com/medication/lupron1_side_effects.htm.

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Definitions for medical terms can be found at the following links:

www.medterms.com

http://www.nlm.nih.gov/medlineplus/mplusdictionary.html

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Lupron and Homicide:

I have rec'd a request and authorization from an inmate at the Arizona State Prison, Michele Millikan, to relay her situation and to publicize a copy of her MedWatch form reporting the adverse event of Homicide while on lupron. First, here is a little background information:

At least as early as 1994 the lupron adverse event of "homicidal ideation" was reported to the FDA (by an OB/Gyn who felt the "homicidal ideation" evidenced during the patient's treatment for endometriosis was 'due to lupron / hypoestrogenism'). And it should be noted that a patient was dropped from the 1988 endometriosis lupron clinical trials due to "severe mood, dream-like state".

The FDA has rec'd MedWatch reports of the following adverse events to lupron (list is *not* inclusive): "depersonalization", "hallucinations", "memory loss", "memory disorder", "anxiety", "dream abnormalities", "emotional instability","disturbances in thinking", "thinking abnormally", "mood instability", "mental impairment", "depression", "manic reactions", "psychosis", "delusions", "paranoid reactions", "personality disorder", "suicide attempts", "psychotic depression", "suicide", and "homicidal ideation" (and now "homicide").

*Any* lupron 'drug review website' can be searched to find reports of lupron users feeling "in a brain fog", "not like myself", "angry", "paranoid", "delusional", "belligerant", "aggressive", "crazy", "psychotic", "experiencing memory loss", etc. Other various women's issues websites also contain similar posts: for just one example, search HysterSisters for "homicide and lupron". And elsewhere, On this one page alone, references to altered mental status while on lupron can be found -- see entry 'dated 2-10-12' to read post "'out-of-body' experiences, to the point I didn't know who I was" (17 yo endo patient); see entry 'dated 6-2-12' to read post "Absolutely batshit crazy disposition ... my crazy out of control behavior and moods so bad my boyfriend and I did not survive" (40 yo fibroid patient); see entry 'dated 6-12-12' to read post "EXTREME CRAZYNESS! I literally went crazy. Major anger issues. Wasn't myself at all." (30 yo endo patient); see entry 'dated 7-8-12" for "SEVERE panic" (48 yo endo patient).

In a former FaceBook post, one woman asked "Has anyone else has bouts of I guess I would call it amnesia where you losing [sic] a certain amount of time but then comes back within a few hours? and what did you do for it and did you find someone willing to help? (no one is listening. They told me to go to the ER what a waste went there and they said there was nothing they could do). I couldn't even remember marrying my husband. I remembered him thank God but I couldn't remember us getting married. What's next forgetting who my kids are?"

Michele Millikan's May 28, 2013 report to the FDA of the adverse event of homicide to lupron appears to be the first reported homicide associated with lupron or any other GnRHa. Many other drugs have been associated with "Homicide" - should lupron/leuprolide be on this list? Are there other cases similar to Michele's circumstances that have gone unreported?

Michele is currently serving an 18 year prison sentence for 2nd degree murder of her husband, committed while in a dissociative state (abnormal/altered state of mind) apparently caused/induced by lupron. Since Michele had a history of depression prior to lupron's use, and was depressed on lupron, she should not have been prescribed lupron in the first place and/or lupron should have been discontinued. (According to a 1993 study 'Adverse effects of leuprolide acetate depot treatment' ... : "Two of the most disturbing adverse effects experienced by women receiving Lupron were depression and short-term memory loss. ... Although the mechanism of these symptoms are unclear, GnRH-a treatment should be discontinued if depression or short-term memory loss develops.")

In Michele Millikan's MedWatch form filed with the FDA (and mailed to me, along with other documents), in 'Section 5' of the form ("Describe event/problem"), Michele wrote "See attached page". The following is a copy of that attached page (filed May 28, 2013):

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"MedWatch" 'Attached Page' of Michele Millikan:

Several days after my 6th injection of Lupron Depot, in some kind of an impossible-to-understand and difficult-to-explain 'fugue state', I killed my husband with a gunshot to the head while he was sleeping. I have NO MEMORY of waking up at 4 am in the morning on May 25, 1993 (or of the evening before) and I have NO MEMORY of retrieving the gun - the only memory of this horrific event I have is I do remember holding the gun pointed at him and thinking 'what am I doing?' With no further memory, and without any intent, and as if I had no control over my actions, I apparently did shoot and kill him. In shock afterwards, and, again, in an impossible-to-understand and difficult-to-explain state of mind, I told the police it was an 'accidental gun discharge as my husband was putting the gun away', and his death was ruled "inconclusive" in 1993. It was very hard for me to accept the truth that I had to have killed my husband. The severe guilt and utter confusion of how and why I could have done what I apparently did ate at me until 2001 when, against legal advice, I confessed to the police. I am now serving year 11 of the 18 year prison sentence I received for 2nd degree murder.

Our marriage was not perfect and like many marriages had its problems, but we had plans for the future, and were in the process of trying to conceive; and never once had I ever thought of harming, never mind killing my husband. I grew up in a Christian home, attended a Christian School, my father was the founder of a Biblical Counseling and Training Center, and both my husband and I worked at this Center. I did experience feelings of depression related to my infertility and marital stress, but I had no history of any kind of anger issues or emotional instability, had no prior criminal record - not even a speeding ticket. Committing this homicide was and is incomprehensible to me and to those who know me.

But recently I have learned that Lupron has a known history of causing serious, abnormal psychological symptoms, and I have been made aware that the FDA database contains the following reports: "disturbances in thinking", "memory loss", "thinking abnormally", "emotional instability", "mood instability", "mental impairment", "psychosis", "delusions", "paranoid reactions", "personality disorder", "suicide attempts", "suicide", and "homicidal ideation". And I have been made aware of countless public internet postings of women discussing the effects of Lupron and reporting "homicidal ideation", "extreme craziness", "severe mood swings", "out of body experiences", "wasn't myself at all", "not in control of my emtions", "foggy brain", "I didn't recognize myself in my behaviors", "memory loss", "very forgetful", "I turned into a different person", "doing some strange things I would have never done before", "severe episode of anger outburst; threatened to kill my boyfriend", and thousands more comments like these.

Since 1993 I have been plagued by the incomprehensibleness of my apparent actions - now I feel that finally there is an explanation for what happened to my mind and for what happened to my husband. Because of the extremely atypical and violent nature of my apparent actions, the timing of the Lupron injections with my 'fugue state', my life-long stable mental status, and my warm, even-tempered disposition before and since the event, I now strongly believe that Lupron was the causative factor in this homicide.

I also want to report to the FDA that while taking Lupron I suffered from numerous side effects - severe hot flashes, burning up from the inside out and soaking clothes, joint pain, irregular heart beat, depression, and memory lapses. To this day I continue to experience joint pain, irregular heart beat, and serious memory loss. In addition, I also have chronic headaches, numbness in the face, and shooting pains in my back, brain, eyes and chest."

Michele Millikan

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In light of Michele's discovery of the known lupron adverse mental status effects, and the fact that these serious mitigating effects were not considered in her sentencing, Michele is now attempting to explore a possible reduction or commutation of her remaining sentence (she has served 11 years of her 18 year sentence).

Transcripts of Michele's Grand Jury proceedings state that "With regards to mental capacity, at this point in time, that would not be a probable cause determination. That would have to be a determination by the trial judge. It is something you should not take into consideration in your determinations." (emphasis mine). ... In transcripts of the judge's Sentencing of Michele, he states: "And I considered in mitigation the mental state of Michele Millikan, at the time of the offense. I cannot say that I understand it, but it's clear that although Michele Millikan did understand the nature of right and wrong and that this act was wrong, her mental state was -- if there is such a word -- not norm at the time of the event. For a combination of factors that is described by the psychologist in the report that is written to me. And it is too lengthy to go over in detail at this time. It's the Judgment of this Court that the Defendant should be sentenced to the aggravated term of 18 years in the Department of Corrections because this Court thinks the aggravating factors outweigh the mitigating factors." (emphasis mine) The "too lengthy" psychologist's report, in fact, states "all indicators are that Ms. Millikan was in a dissociative state of mind immediately prior to and during the death of [her husband]. Thus, Ms. Millikan can not be said to have intended to cause the death." Contrary to the judge's assessment that "it's clear [] Michele Millikan did understand the nature of right and wrong and that this act was wrong ...", in fact, the psychologist's report states otherwise.

It is hoped that a second look at Michele's circumstances can take place, this time with a clinically accurate understanding of the mitigating factors created by lupron's adverse psychological effects. Although the psychologist's report noted that in the months before the homicide, Michele was found to have a "clinically significant mood alteration", no mention of or association to lupron was ever made or considered. The introduction of the impact of adverse lupron mental status effects should be given the consideration it deserves.

Michele's family and friends have remained steadfastly by her side, are committed to helping her, and are likewise relieved to have some answers to explain Michele's inexplicable actions ("No one who knows Michele can understand how this could have happened".) They have reached out, asking if anyone who might have had abnormal mental state and/or violent experiences on lupron to contact them, as they are trying to find enough evidence to justify asking for a new trial or pardon. To date, they have heard from a woman in Ohio who is willing to testify on Michele's behalf that while she was on lupron, she experienced inexplicable moods and behaviors resulting in her attacking her husband, hitting him in the head and requiring stitches.

If you, or someone you know, have or has experienced (or is experiencing) any of the above reported adverse psychiatric effects from lupron, or know of any instances of violence or homicide committed by someone on lupron, and would like to help Michele, please contact Michele's friend Erin Moosbrugger at erinmoose@cox.net, or email here.

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