Summary:

 

http://www.fda.gov/ohrms/dockets/ac/04/transcripts/2004-4065T1.htm

September 13, 2004.

[Testimony from Sara Bostock to the FDA on February 2, 2004 is also included in this article.  It is at the bottom of the page.]

The following slides accompany the presentation of Sept. 2004:  http://ssristories.drugawareness.org/SuicideMechanisms.pdf 

At the February hearing I told the story of my beloved daughter who stabbed herself to death after less than three weeks on Paxil.  Today my focus is on what to include in new warnings. 

            In 1993, over ten years ago, three Harvard doctors published an article in the British journal Drug Safety entitled “Antidepressant Drugs and the Emergence of Suicidal Tendencies”.  This article was brought to my attention a few months after my daughter’s death.  I was stunned when I read it.  In it nine clinically plausible mechanisms are described by which antidepressants can induce or exacerbate suicidal tendencies.  What was described fit closely behavior exhibited by my daughter while she was on antidepressants.  I believe that all of these mechanisms need to be addressed in new warnings.  Many of them relate to acute serotonin dysregulation.

            Here are the nine mechanisms as defined by Drs. Teicher, Glod and Cole.  I will briefly go through each one and describe how it was exhibited in my daughter’s case and read a relevant quote from the article.

            First: the Energizing Role of Antidepressants.  This is the one the medical profession and the media have already latched on to, the only one of the nine mechanisms we ever hear about in the press, the one which states antidepressants may provide the energy to enable depressed patients to act on pre-existing suicidal plans or intentions.  This is the one for which a warning already exists on the label. But, ironically, this is the one mechanism which I believe is most irrelevant for SSRIs.  The doctors themselves affirm its relevance to other classes of antidepressants but state “In no case was there evidence that strong pre-existing self-destructive urges were activated and energized by Prozac. No patient was actively suicidal when Prozac treatment began. These suicidal thoughts were uncharacteristic in that they were more intense, obsessive and violent than anything previously experienced.”  Certainly my daughter had had no history of suicidality.  Furthermore she was not given Paxil for depression but rather for “racing thoughts and anxiety”; her energy did not improve after treatment commenced.

            Second: the Paradoxical Worsening of Depression.  Cecily’s mood did worsen with treatment on Paxil.  She became restless, irritable, unhappy, and had trouble sleeping.  Quote: “A small percentage showed a paradoxical response to antidepressants, with a marked worsening of depression and de novo (new) emergence of suicidal ideation.” 

Third: Akathisia.  In the last days of her life Cecily was jittery, unable to sit still and jumping at the slightest noise.  Quote: “Akathisia produces severe internal distress and has resulted in suicidal states. It is our impression that serious akathetic states seem to occur in patients receiving Prozac or other high potency serotonin uptake inhibitors.”

            Fourth: Panic-Anxiety.  After commencement of treatment Cecily became very fearful upon waking in the morning; I had never seen her this way before.  The last day of her life she came shrieking from her bedroom terrified by the noise of a plane flying overhead, again completely uncharacteristic.  She also demonstrated novel anxiety about news reporting.  Quote: “Prozac can initially exacerbate panic symptoms in some patients. Precipitation of panic attacks may enhance suicidal tendencies in a subset of patients and be a determinant of short term risk.”

            Fifth:  Manic or Mixed Manic and Depressive States.  Although my daughter had no confirmed diagnosis for a mood disorder she was being treated for “manic like symptoms” – racing thoughts, over-analyzing, and being overly sensitive.  She had a history of intermittent sleepless episodes.  She was a talented artist.  I believe Paxil was exactly the wrong medication for her.  Quote: “Great care should be employed in the pharmacological treatment of patients with suspected bipolar illness. They should be closely monitored for the emergence of mixed or manic reactions. The emergence of mania can markedly enhance violent aggressive behavior and a mixed state can seriously augment suicide risk.”

             Sixth:  Insomnia or Disturbances in Sleep Architecture.   My daughter was having trouble sleeping before her treatment commenced, but the first night she took an antidepressant she walked in her sleep.  She had never done this before.  On Paxil she could hardly sleep at all.  And there is evidence she was sleepwalking when she died.  She died in the middle of the night; she did not turn on any lights or make any noise when she stabbed herself twice.   Quote: “Prozac appeared to produce a very dramatic increase in rapid eye movement activity, even during non-REM sleep stages, not observed with any other class of drugs. They reported a significant reduction in delta sleep, causing emergence of day terrors or suicidal ideation, similar to unmedicated patients with a history of suicide attempts.” If people are committing these acts in a state of altered consciousness comparable to dreaming then there may be next to no warning and little means of prevention.   

            Seventh: Obsessive Suicidal Preoccupation.  On the last few days of her life, Cecily had a look of abject terror on her face.  The last afternoon she confessed to me a strange and uncharacteristic preoccupation with the literal meaning of her name which is “nearly blind.”  The last evening she had a strange expression on her face as she gazed at a Cuisinart blade and our kitchen knives during dinner clean-up.  This frightened me but I never dreamed she was contemplating self-harm; she had never done anything before.  Quote: “Strong obsessive suicidal thoughts emerged after Prozac treatment. Patients tried to conceal their suicidal impulses.  It was remarkable how violent they were. The serotonin system enables us to dismiss normally fleeting and transient suicidal thoughts and prevents us from acting on aggressive impulses.  Excessive augmentation may render patients unable to dismiss these thoughts, leading to uncharacteristic obsessions.”

             Eighth:  Borderline States or Hostiity.  Symptoms of borderline personality disorder are suggestive of a state of serotonin dysregulation.  My daughter’s autopsy revealed an extremely high blood level of Paxil that must have led to an acute state of serotonin dysregulation.  Quote: “Patients who do not suffer from borderline disorder may have drug-induced borderline reactions that include emergence of uncharacteristic aggression, self-mutilation and suicide.  Depending on the basal state of serotonin release, Prozac may augment serotonin neurotransmission in some and diminish it in others. Furthermore these effects may change over time and may vary with dose.”             Ninth:  Alterations in EEG Activity.  Cecily said a few things to me about her antidepressant treatment.  She said when she took a pill she felt like it was “frying her brain”; she said she felt like her brain was “on fire.” Quote: “One pioneering study on physiological determinants of suicide reported a strong positive association between EEG disturbances and suicidal ideation and assaultive-destructive behavior.  EEG disturbance led to enhanced vulnerability to impairments in impulse control and ability to reject suicidal thoughts.  Antidepressants can induce EEG disturbances and precipitate seizures and may enhance suicidal tendencies.”             Needless to say, if I had read this article while my daughter was still alive, I believe things would have transpired very differently.  I never dreamed that someone who had never been suicidal could become so by taking a pill.  And this is the clincher.  “Suicidal ideation rapidly disappeared within a week of discontinuation of Prozac.”  Please make these warnings as strong as they need to be to save the subgroup of patients who are seriously at risk of dying. 

http://www.fda.gov/ohrms/dockets/AC/04/transcripts/4006T1. doc

[February 2, 2004:  FDA Advisory Committee Meeting]
The following slides accompany the Feb. 2004 presentation.:  http://ssristories.drugawareness.org/PowerToHarmSlides.pdf

DR. RUDORFER:  Thank you.
 
 24             We are up to Number 13.
 
 25                           Sara Bostock
 
                                                               101
 
  1             MS. BOSTOCK:  I have slides, so please
 
  2   look at the screen.
 
  3             My daughter Cecily had only been taking
 
  4   Paxil for two weeks before she died, during which
 
  5   time her condition greatly worsened.
 
  6             By the day of her death, was pale, unable
 
  7   to sleep, almost unable to converse, and in a
 
  8   frightened, agitated state, jumping at the
 
  9   slightest noise.  That night she got up and without
 
 10   turning on any lights, went into our kitchen only
 
 11   40 feet from where I was half asleep.  She stabbed
 
 12   herself twice in the chest with a large chef's
 
 13   knife.  The only noise was a slight yelp and a
 
 14   thump when she fell on the floor.
 
 15             This was a young woman who had everything
 
 16   to live for.  She had just completed applications
 
 17   to grad school and received a large pay increase
 
 18   the month before.
 
 19             She had a boyfriend who loved her and
 
 20   scores of wonderful friends.  She had never been
 
 21   suicidal.  To die in this violent, unusual fashion
 
 22   without making a sound after  the marked worsening
 
 23   of her condition led me to believe that Paxil must
 
 24   have put her over the edge.
 
 25             Her autopsy revealed she had a very high
 
                                                               102
 
  1   blood level of Paxil, which reflects poor
 
  2   metabolization and is a feature common to many of
 
  3   these suicides.  I believe this induced an
 
  4   intensely dissociative state, perhaps even
 
  5   sleepwalking.  SSRIs suppress rapid eye movement
 
  6   and block the muscle paralysis which occurs in this
 
  7   stage of sleep.
 
  8             The whole regulation of waking, sleeping,
 
  9   dreaming occurs in the brain stem where the
 
 10   serotonin neurons are clustered and where SSRIs are
 
 11   having their impact.  Patients taking SSRIs had
 
 12   rapid eye movement during non-REM sleep and while
 
 13   awake when they were not paralyzed.  This atypical
 
 14   REM is often associated with strange behaviors
 
 15   including hallucinations.
 
 16             The effects of SSRIs on sleeping, waking,
 
 17   unconsciousness itself are ill understood.  From
 
 18   accounts of people under the influence of these
 
 19   drugs, I believe SSRIs can alter consciousness in
 
 20   some mysterious and frightening way that is not
 
 21   normally seen even in mental illness.  I am certain
 
 22   this is what happened to my daughter.
 
 23             Untold thousands have died because of the
 
 24   drug companies and the FDA's failure to heed the
 
 25   evidence over the past 17 years.
 
                                                               103
 
  1             DR. RUDORFER:  Thank you.
 
  2             Again, I apologize for the short time.
 
  3             Number 14, please.