ssris, akathisia, and suicidality joseph glenmullen, md clinical instructor in psychiatry, harvard...
TRANSCRIPT
SSRIs, Akathisia, and Suicidality
Joseph Glenmullen, MD
Clinical Instructor in Psychiatry,
Harvard University
Author of Prozac Backlash
Press Briefing at the February 2, 2004 FDA Meeting on the Concern that SSRI Antidepressants Can Make Children and Adolescents Suicidal
Objective: To relate the data from studies of SSRIs to the realities faced by doctors and patients when SSRIs trigger suicidality
I have witnessed this side effect in patients who I treat with SSRIs
Akathisia and Suicidality—Side Effects of SSRIs
Diagnostic and Statistical Manual (DSM)
“Serotonin-specific reuptake inhibitor [SSRI] antidepressant medications may produce akathisia.”
A class effect of all SSRIs American Psychiatric Association 2000 Edition, p. 801
DSM (Continued)
“Akathisia may be associated with dysphoria [psychological distress], irritability, aggression, or suicide attempts.”
APA Textbook of Psychopharmacology “Akathisia, however, is the most
common neurological symptom caused by SSRIs.” p. 939
Edited by Schatzberg and Nemeroff
Second Edition, 1998, p.939
Based on Numerous Reports
American Journal of Psychiatry New England Journal of Medicine Archives of General Psychiatry Journal of Family Practice Journal of the American Academy
of Child and Adolescent Psychiatry Human Psychopharmacology Journal of Family Practice
The Two Faces of Akathisia
Well-known from antipsychotics, an earlier class of drugs
Outer, objective restlessness Inner, subjective agitation
Outer, Visible Restlessness
Mild: Adjust posture, shift weight, cross and uncross legs
Moderate: Visibly jittery, tap feet, pace
Severe: Ceaseless pacing, cannot sit or lie still
Inner, Subjective Agitation
Abject terror Anxiety Tension Irritability Hostility Paranoia Rage reactions Violence
Suicide Offers a “Welcome Relief” from Akathisia
Vulnerable Time Period
Early weeks or month after Starting the drug Increasing the dose
The Suicidality of Akathisia Is Distinctly Different from the Suicidality of Depression
Preoccupation with escape from the abject terror, anxiety, and irritability of physical and psychological state of akathisia versus preoccupation with the guilt, self-hatred,and hopelessness of depression
Treatment of Akathisia
Decrease dose Stop drug Add propranolol or Valium-type
antianxiety agent Switch to another class of
antidepressant
Brain Chemistry of SSRI Akathisia
The serotonin-dopamine connection
Antidepressants “selective” for serotonin appear to pose a greater risk of akathisia than other antidepressants
Other Side Effects of SSRIs that Increase the Risk of Suicide
Mania Insomnia Anxiety Paranoia Psychotic reactions
Primary Care Doctors Now Write 70% of Prescriptions for Antidepressants and Know Little about this Side Effect
Re-Challenge Studies
“Try the drug a second time” in patients who had the side effect to see if they experience it again
The best way to study and describe what actually happens to patients
Re-Challenge Studies of SSRIs Rothschild (Harvard) Journal of
Clinical Psychiatry,1991 Van Putten (UCLA) Archives of
General Psychiatry, 1992 Hamilton and Opler (Columbia)
Journal of Clinical Psychiatry, 1992
All the patients developed akathisia and suicidality again
Eli Lilly Agreed to Fund a Large Re-Challenge Study
Spring 1991 Reached agreement with the FDA
at the height of the crisis over this side effect in the early 1990s
Lilly developed the protocols for the study
Lilly never did the study
The September 1991 FDA Meeting on this Side Effect Is Widely Reported to Have Unanimously Exonerated SSRIs
But…
The FDA had to waive its own standards for conflicts-of-interest for 5 of the 9 committee members and 4 of the 6 consultants because of their ties to the pharmaceutical industry
On one of the votes taken by the committee, one-third of the committee members voted for a warning
Transcript of the 1991 FDA Meeting on this Side Effect
Dr. Nina Schooler: “We really do need to obtain more data…At one level” the data “is a fairly sorry state” because of its inability to adequately describe what happens to patients. Page 329
“Somehow, for me, the responses to this end up being always with that caveat…” Page 303
Transcript of the 1991 FDA Meeting on this Side Effect
Dr. John Mann: “I want to endorse [i.e. second] the need for better data.”
Page 298
Transcript of the 1991 FDA Meeting on this Side Effect
Dr. Daniel Casey (Chairman): “I know you [committee members]
want the caveat that ‘I don’t feel I have all the data.’”
Page 269 “There will be more research. At
least I certainly hope so.”
Page 297
January 2004 FDA Memorandum for this Meeting
12 years later the data is still: “a distinctly insensitive
approach…to [assessing] suicidality” and describing what actually happens to patients.
Page 7
January 2004 FDA Memorandum for this Meeting
The data is “generally inadequate.”
Page 17
January 2004 FDA Memorandum for this Meeting
“There is one caveat to this effort” because the data is of “unknown sensitivity” and “may have missed certain events” related to suicidality.
Page 15
January 2004 FDA Memorandum for this Meeting
12 years later, the FDA still wants “more adequate assessment for emergent suicidality in future studies.”
Page 17
For How Many Decades Are We Going to Get Together to Lament the Inadequacy of the Pharmaceutical Industry’s Efforts to Clarify this Phenomenon?
The Industry Response
Dismiss serious medical case reports and small-scale studies, which are all solo practitioners can afford to do, as “anecdotes”
The Industry Response
Blame patient’s psychiatric conditions
The Industry Response
Scare the media and other interested parties away from the subject by citing a fear that patients will be frightened away from treatment
Authoritarian Approach
Don’t warn patients, you might frighten them
The most dangerous scenario:
When neither the doctor nor the patient knows about akathisia
What if you were considering an SSRI for your child?
If you would want to be informed about this side effect if you were considering an SSRI for your child, please use your power as journalists to inform the public.