Memo to file / prospective expert witness re: SSRI defense — (Margaret Eve Miyasaki)

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Margaret Eve Miyasaki

Sept 1, 2001


John Doe was incarcerated after being convicted of one count of assault with a firearm for striking his next door neighbor and friend, Jack Smith, in the face with a firearm and shooting him in the abdomen. Mr. Doe was taking prescription Prozac at the time of the incident. He has no prior history for violent conduct.

At trial, his defense attorney did not investigate the potential side effects of prescribed fluoxetine (Prozac ®) on Mr. Doe’s state of mind at the time of the crime, nor did he assert a SSRI syndrome defense at trial.

Mr. Doe is seeking release, a new trial or a reduction in sentence. Even if not sufficient to justify a new trial, newly discovered evidence could be material to any mitigating or aggravating circumstances in regards to re-sentencing proceedings if there is a significant possibility that the outcome of the sentencing could have been different.

Within this letter, the designation “Prozac” is used to refer to the Lilly trade name “Prozac ®” and the generic chemical “fluoxetine”. Relevant excerpts from scientific papers and articles regarding SSRI antidepressants, to which I am referring, are incorporated in the body of this letter. The excerpts’ webpage links are provided; therefore, I have not created a bibliography.


The incident occurred at the residence of Mr. Jack Smith, adjacent to Mr. Doe’s residence. Ms. Jane Roe, their mutual woman friend and nearby neighbor, was drunkenly sexually teasing both men. All three had been socializing, and heavily consuming alcohol, together for several hours and were drunk.

When Ms. Roe passed out from being in an alcohol stupor, Mr. Doe strongly believed that Mr. Smith would rape her since she was lying unconscious in his residence. Mr. Doe and Mr. Smith argued and Mr. Smith forcefully ejected him from his residence. Mr. Doe then asked nearby neighbors to assist him in removing Ms. Roe from Mr. Smith’s residence. The neighbors took Ms. Roe to her residence before anyone could have sex with her. Shortly thereafter, Mr. Doe returned to Mr. Smith’s residence, struck him once in the face with a gun, and fired a single shot into his lower abdomen. Mr. Smith was promptly treated and released from the hospital within a few hours. He has a permanent scar and the bullet remains lodged within his buttock.

Mr. Doe strongly believes that Prozac caused him to inflict harm on Mr. Smith. Trial counsel did not investigate the effects of Prozac in relation to Mr. Doe’s mental state and did not raise the issue at trial. Mr. Doe appealed the conviction and sentence. His appointed appellate attorney filed a no-issue brief and the appeal was summarily dismissed. Mr. Doe did not challenge the appellate court decision.

Mr. Doe had been taking Prozac for about one year. He had been prescribed an increased dose within a month prior to the incident, in which he struck and shot his male companion and friend, Mr. Smith, after their quarrel. This conduct was totally out of character for Mr. Doe. He has no prior criminal record, except for an unrelated, non-violent misdemeanor in 1967.

Mr. Doe had never before conducted himself in such a hostile manner when under the influence of alcohol. Though not a consummate heavy drinker, Mr. Doe is an experienced social drinker, who has been capable of holding his alcohol and knowing his limits. On the day of the incident, he ingested no drugs other than alcohol and his prescribed dose of Prozac. Mr. Smith had ingested alcohol and amphetamines prior to the incident.

Nor had Mr. Doe previously experienced such a heightened sense of dread or urgency, which he experienced just prior to, and leading up to, the incident. He felt he had no other choice than to teach Mr. Smith a lesson for attempting to rape Ms. Roe, and to scare him lest he think of raping her again. He struck Mr. Smith with the gun, but never intended to shoot him. At trial, during cross-examination, Mr. Doe continued to insist that Mr. Smith planned to rape Ms. Roe. However, neither Mr. Smith’s testimony, nor the testimony of others, corroborated Mr. Doe’s allegations.

Mr. Doe was taking his prescribed medication regularly; therefore, the Prozac’s effect on his state of mind, at the time of the incident would be relevant. Prior to being treated for depression by prescribing Prozac, he had no prior psychiatric history.


Prozac is in the class of anti-depressant medications known as selective serotonin re-uptake inhibitors (SSRIs).

“SSRIs are selective serotonin re-uptake inhibitors, which are used to treat clinical depression. At one time it was thought that depression was due to low levels of serotonin in the brain. Today serotonin levels can be measured by 5-HT imaging with Positron emission tomography (PET) imaging [2][3] as well as measuring tryptophan plasma[disambiguation needed] levels. Prozac is a well known SSRI. In the 1970’s Bryan Molloy at Eli Lilly and Company created a phenoxyphenyl-propylamines termed LY-94949 but it could not be easily dissolved so David Wong reformulated it as a chloride salt and it was renamed LY-110140. Then on September 1, 1975 it was first called fluoxetine and then later marketed under the name Prozac. Prozac was launched in the United States and Canada in 1988 and in the United Kingdom in 1989.”


Use of SSRIs can lead to a condition called “serotonin syndrome,” characterized by cognitive behavioral changes, extrapyramidal reactions, and an extremely dangerous condition called “akathisia” that can precipitate suicide or violence, as well as, an increased risk of delusions and hallucinations when used with other substances that increase serotonergic activity in the brain. There is a body of scientific reasoning known as “structural activity relationships”, which explains the underlying biochemistry and pharmacology of serotonin syndrome.

“Serotonin Syndrome (hereafter written as SS) is a potentially life-threatening complication of psychopharmacologic drug therapy. The syndrome is produced most often by the concurrent use of two or more drugs that increase brainstem Serotonin activity. It is often unrecognized because of the varied and nonspecific nature of its symptoms.
Serotonin syndrome is characterized by changes in awareness and judgement, behavior, autonomic nervous system function and neuromuscular activity. Patients usually respond to discontinuation of drug therapy and supportive care alone, but they may require treatment with a specific antiserotonergic drug such as cyproheptadine, methysergide and/or propanolol.
Serotonin Syndrome only occurs in the setting of drug therapy. It most commonly occurs when two or more serotonergic drugs are given at the same time, but has also been reported with single drug exposure. Commonly, the earliest symptoms of SS are misinterpreted as a worsening of the patient’s underlying psychiatric condition. This mistake may then lead to either inappropriate continuation of drug therapy or even an increased dosage of the offending medication.
Antidepressants are the most common class of drugs to produce SS. Among the antidepressants, the monoamine oxidase inhibitors (MAOI’s) and selective Serotonin reuptake inhibitors (SSRI’s) are equally likely to contribute to SS.”

SOURCE: Mills, Kirk C M.D., University of Kansas Medical Center, American Family Physician, October 1995, page 1263.

“Serotonin Syndrome manifests as mental status changes, changes in vital signs caused by autonomic instability, muscular rigidity, fever, and ultimately coma and death.” 

SOURCE: Identifying serotonin syndrome in the emergency department.  The American Journal of Emergency Medicine, Volume 23, Issue 3, Pages 406-408 R. Christensen

There is progressively more data available that shows there is increased risk of harm to self and others while on SSRI medication, including Prozac. The potential for violence and suicide, although it may differ somewhat from drug to drug within the class, is still a common risk for drugs, purporting to “selectively” inhibit the reuptake of serotonin by blocking serotonin receptor sites.

“The issue of treatment-related activation has since then been considered primarily in terms of possible increases in the risk of suicide among a subgroup of patients who react adversely to treatment. This possibility has led regulatory authorities to warn doctors about the risk of suicide in the early stages of treatment, at times of changing dosage, and during the withdrawal phase of treatment. Some regulators, such as the Canadian regulators, have also referred to risks of treatment-induced activation leading to both self-harm and harm to others.”

SOURCE: Pfizer-Canada, Stronger warning for SSRIs and other newer antidepressants regarding the potential for behavioural and emotional changes, including risk of self-harm. (May 26, 2004)

On October 15, 2004, shortly before the time of Mr. Doe’s sentencing, the Food and Drug Administration (FDA), finally ordered pharmaceutical companies to add a “black box” warning to SSRI antidepressants, saying the drugs could cause suicidal thoughts and actions in children and teenagers. Suicide and homicide are related. Suicide is violence on the self. Nine months later, the FDA issued another advisory, warning doctors to watch for suicidal behavior in adults taking SSRI antidepressants. Since then, there has been some progress in the criminal courts in recognizing that SSRI side effects can cause psychotic behavior in normal people.


For years, the debate has centered around the question of which was more important, a handful of individual cases, the subgroup of patients who react adversely to treatment, or the vastly larger group of patients who respond successfully during large randomized control trials using SSRI medication. Dr. David Healy, North Wales Department of Psychological Medicine of Cardiff University, has shown that there is a risk of violent behavior with selective serotonin reuptake inhibitors and antidepressants.

“Healy designed an experiment to examine if disinhibition, which Healy believes can lead to suicide, is associated with SSRIs.” “He compared Zoloft (an SSRI) to reboxetine (a non-SSRI anti-depressant) in a group of healthy volunteers.”
“The experiment would test if the marketed “better than well” phenomenon for SSRI was true. At the end of the study two-thirds of the participants rated themselves as “better than well”. However, the volunteers’ quality of life and social functioning decreased on Zoloft but remained the same on reboxetine. Approximately half the group reported emotional blunting on the drugs.”
“At the end of the study two-thirds of the participants rated themselves as “better than well”. However, the volunteers’ quality of life and social functioning decreased on Zoloft but remained the same on reboxetine. Approximately half the group reported emotional blunting on the drugs.”
“Two patients in the study became suicidal which Healy associated with disinhibition caused by Zoloft. One patient highlighted the trend of suicide by hanging which is a trend in SSRI suicides [citation needed]. Healy calculated the probability of two healthy volunteers without mental illness and no current interpersonal legal or financial problems becoming suicidal during a two week period on Zoloft as p = 0.0000005. In other words, the chance that Zoloft was unrelated to the two healthy volunteers’ becoming suicidal during the trial period (that is, the chance that it was coincidental) is only 1 in 2000000.”
Healy concluded that he had “accidentally demonstrated conclusively that the drugs could cause the problem”.


Ann Blake Tracy, the author and executive director of the International Coalition for Drug Awareness, gives us some insight into how numbing or emotional blunting affects the state of mind of some patients using an SSRI antidepressant medication.

“Your conscience may dissolve in a heady mix of serotonin and absolution as you stop worrying
They can improve your mood, may make you feel calmer. Well, not actually calmer but numb, blunted we call it.
If you are on a WorkCover claim, it will not bother you that your colleagues are covering for you.
If, like 20% of healthy volunteers, you feel awful, you have two choices: you can discontinue the drug or the doctor can co-prescribe Valium.
Indeed, drug companies co-prescribed Valium and other psychotropic medications in clinical trials but they did not report that to the public.
We still do not really know if some of these drugs work or if it was the Valium.”

SOURCE: Tracy, Ann Blake PhD, Prozac: Panacea or Poison?