My son, Toran, killed himself between 4.00 and 4.30pm on 20 March 2008. At 9.30 that
night, I received a phone call from the Crisis Mental Health Team saying Toran was on their
list of people to check in with and asking me how things were with him. I told them he had
hanged himself five hours earlier. After a shocked silence, I was asked if there was anything
they could do for me and my response was “You can stop f***ing killing our kids!”
As I have written before, there was no doubt in my mind from the moment I held my child’s
lifeless body in my arms, that he had died from drug-induced suicide.
My recent blogs have sparked discussion of whether there is sufficient evidence to establish
a causal relationship between SSRIs and suicide or whether the association is a mere
temporal correlation.
This is an important question. While my belief that my son’s suicide was caused by
Fluoxetine is based on my knowledge of him and my observation of the adverse reactions he
exhibited on the drug, I accept fully that this does not constitute an objective and scientific
causality assessment.
For four years I have sought to have such an assessment performed by pharmacovigilance
professionals using the World Health Organisation’s recommended processes. In wanting to
understand what happened to him, it was important to me that my hypothesis about the
cause of Toran’s death could be tested by those whose findings could not be dismissed as
lacking objectivity or scientific rigour or tainted by emotional ties with my son.
A few weeks after Toran died, I was given an adverse reaction reporting form by CCHR NZ.
At that time, I had never heard the term pharmacovigilance, had no knowledge of adverse
reaction reporting and had certainly not had any information about the process, or
encouragement to file a report, from the myriad of government agencies and medical
professionals involved in investigating my son’s death.
In New Zealand, pharmacovigilance is conducted by the Centre for Adverse Reaction
Monitoring (CARM), a unit at Otago University which operates under contract to our
regulator, Medsafe. I completed the form and sent it to CARM, listing the many adverse
reactions Toran had exhibited on the drug – fatigue, anger, aggression, memory loss,
hallucinations, anorexia, akathisia, abnormal dreams, self harm and a range of other
reactions. Despite the fact that in NZ it is required that receipt be acknowledged and
information provided to reporters on the data held by CARM on the drug reported, I
received no response for a year after filing the report.
During that year I learned two important things. One was that CARM do not gather
information to inform their causality assessments. They rely on the data provided by
reporters and merely record ‘unknown’ against factors which are critical to their
assessments but on which data has not been provided. I also learned that the questions ‘did
dechallenge occur’ and ‘did the reaction occur on rechallenge’ (which I had ignored because
I didn’t understand what they meant) were very important questions. They ask whether the
reaction disappeared when the drug was stopped and reappeared when the drug was
restarted. This is a critical factor in assessing causality. A consumer-friendly reporting
questionnaire would explain this term or use language understood by the layperson. The
risk of not doing so is that people like me fail to provide important information because they
do not understand technical terms and causality assessments are flawed.
This knowledge led me to submit a revised adverse reaction report and to understand that if
I wanted a thorough causality assessment, I would need to gather the relevant evidence and
provide it to CARM rather than rely on them to gather the required evidence themselves.
After many follow ups, I finally received acknowledgement of my report and advice from
CARM that in the 20 years since 1989 they had recorded 3 cases of completed suicide where
the victim was taking Fluoxetine at the time of their death. They further advised that none
of these cases could be assessed as being causally associated with the drug given all had
been diagnosed with depression at the time of prescribing.
Three reports since 1989? I didn’t know whether to laugh or cry. As a mother who has lost
her child on these drugs and who runs an organisation to support other families bereaved
by suicide, I get three reports a week! All diagnosed with depression? What about my son
who did not have a diagnosis of any mental disorder following a psychiatric assessment on
the day he was prescribed, 15 days before he died?
The implausibility of this data led me to embark on a study of pharmacovigilance so that I
could understand the processes involved in the conclusions that had been reached. I
learned that the WHO recommends the use of the Naranjo algorithm for determining
whether an adverse drug reaction has occurred or whether the reaction is the result of
other factors. This algorithm poses the following questions
Are there previous conclusive reports on this reaction?
Did the adverse event appear after the suspected drug was administered?
Did the adverse reaction improve when the drug was discontinued or a specific antagonist
was administered?
Did the adverse reaction reappear when the drug was re-administered?
Are there alternative causes (other than the drug) that could solely have caused the
reaction?
Was the drug detected in the blood (or other fluids) in a concentration known to be toxic?
Was the reaction more severe when the dose was increased, or less severe when the dose
was decreased?
Did the patient have a similar reaction to the same or similar drugs in any previous
exposure?
Was the adverse event confirmed by objective evidence?
The answers to these questions result in an assessment of the causal relationship being
certain, probable, possible, unlikely, Conditional/Unclassified, Unassessable/Unclassifiable.
WHO-UMC Causality Categories
Causality Term
Certain
Assessment Criteria*
• Event or laboratory test abnormality, with
plausible time relationship to drug intake
• Cannot be explained by disease or other
drugs
• Response to withdrawal plausible
(pharmacologically, pathologically)
• Event definitive pharmacologically or
phenomenologically (i.e. an objective and
specific medical disorder or a recognised
pharmacological phenomenon)
• Rechallenge satisfactory, if necessary
Probable/Likely
• Event or laboratory test abnormality, with
reasonable time relationship to drug intake
• Unlikely to be attributed to disease or
other drugs
• Response to withdrawal clinically
reasonable
• Rechallenge not required
Possible
Event or laboratory test abnormality, with
reasonable time relationship to drug intake
• Could also be explained by disease or other
drugs
• Information on drug withdrawal may be
lacking or unclear
Unlikely

Conditional/
• Event or laboratory test abnormality
Event or laboratory test abnormality,
with a time to drug intake that makes a
relationship improbable (but not
impossible)
• Disease or other drugs provide plausible
explanations
Unclassified
• More data for proper assessment needed,
or
• Additional data under examination
Unassessable/
Unclassifiable
• Report suggesting an adverse reaction
• Cannot be judged because information is
insufficient or contradictory
• Data cannot be supplemented or verified
In Toran’s case, the answers to the Naranjo algorithm questions were that there was a
significant body of evidence linking suicide and SSRI use, the adverse reactions had been
recorded on his medical file as having commenced after the drug was administered, the
reactions disappeared or improved when he discontinued the drug and reappeared when it
was recommenced, no mental disorder or other possible cause of the reactions was present,
the drug was detected in his blood post-mortem, there was a dose-response relationship
with the reactions intensifying when the dose of the drug was increased, the reaction had
been present on previous exposure and the adverse reactions were confirmed by his family,
friends, teachers and mental health professionals.
Three and a half years after his death, CARM advised me that they had reached the
conclusion that Fluoxetine had been assessed as the probable cause of Toran’s somnolence,
anger and aggression and the possible cause of his suicide.
Confused as to what factors determined a different level of causality for the suicide as
opposed to the other adverse reactions, I called the director of CARM, Dr Michael Tatley to
discuss the issue. To my shock, five minutes into the conversation, Dr Tatley said he agreed
with me that the assessment of the drug’s role in Toran’s suicide should be upgraded to
‘probable.’
This means that CARM accept that “The event (Toran’s suicide) cannot be explained by
concurrent disease (or disorder) or any other drug or chemical” and that Fluoxetine is the
most likely cause of his death. Bizarrely CARM claim that no death can be assessed as
‘certain’ because this would require the death to occur on rechallenge and therefore for the
person to die twice.
After nearly four years of being dismissed as a crazy grieving mother who has no basis on
which to base her belief that her child’s death was treatment-induced, I cannot describe the
elation with which I received the updated CARM assessment. I still believe the correct
assessment is that of ‘certain’ and will continue to engage with CARM on this issue. My key
focus however in relation to pharmacovigilance in NZ is the fact that doctors are not
reporting suspected adverse reactions and that consumer reports are not being encouraged
and are being made unnecessarily difficult.
Did any of the six psychiatrists who reviewed my son’s file for inquest file a suspected
adverse reaction report? No. Did the psychiatric nurse who was his mental health key
worker and who testified at his inquest that he suffered adverse reactions file a report? No.
Did his GP? No. The evidence is overwhelming that mental health professionals do not take
adverse reaction reporting seriously.
In response to an Official Information Act request to CARM recently, I was advised that
consumer reports are not being encouraged because CARM do not have the capacity to
process increased numbers of reports. Despite acknowledging that the technical language
on their forms is a barrier to accurate reporting, this has not been changed.
I was provided with the following data on the source of adverse reaction reports for the past
five years.
Year
2006
2007
2008
2009
2010
2011
Reporter
No.
%
No.
%
No.
%
No.
%
No.
%
No.
%
GP
753
26.04
779
27.53
1125
25.88
1233
26.64
860
20.77
991
22.88
Hospital Doctor
416
14.38
405
14.31
443
10.19
483
10.44
529
12.78
513
11.84
Hospital Pharmacist
82
2.84
87
3.07
110
2.53
205
4.43
251
6.06
216
4.99
Community Pharmacist
77
2.66
203
7.17
508
11.69
573
12.38
161
3.89
233
5.38
Nurses
817
28.25
491
17.35
657
15.11
939
20.29
1211
29.25
1338
30.89
Other HCPs
23
0.80
43
1.52
128
2.94
124
2.68
128
3.09
127
2.93
Pharma Company
541
18.71
442
15.62
621
14.29
792
17.11
714
17.25
713
16.46
2
0.07
0
0.00
211
4.85
40
0.86
32
0.77
46
1.06
Public
Other
181
6.26
380
13.43
544
12.51
239
5.16
254
6.14
154
3.56
Total for Year
2892
100.00
2830
100.00
4347
100.00
4628
100.00
4140
100.00
4331
100.00
Fascinating is the leap from zero reports by consumers in 2007 to 211 reports in 2008. The pattern is
evident in the following graph
Number Adverse Reaction Reports Filed by
Public 2006 - 2011
250
200
150
100
50
0
2006
2007
2008
2009
2010
2011
CARM explain the increase as being driven by media attention given to adverse reactions in
respect of a specific drug in 2008. This is a clear signal that raising awareness of adverse
reactions and the process for reporting them is effective in generating consumer reports.
My organisation CASPER has been asked to work with our regulator to promote consumer
reporting, something we are happy to do on the condition government resources CARM to
accommodate increased reporting. Our focus however will be on encouraging families to
report to the adverse reporting system established by Prof David Healy which will be up and
running in the next month and can be found at https://www.rxisk.org/
When Toran was 15 he got his driver’s licence. We discussed the decision he was required to
make at that time about whether he wished to be an organ donor. He said that if he died, he
would want to help save the lives of others.
Sadly, the manner of his death meant he was unable to donate his organs but I believe that
reporting his case and ensuring those charged with pharmacovigilance assess causality
thoroughly is a way in which he can help save other lives. Contributing to improved
pharmacovigilance in New Zealand is a way in which I can honour my son’s life and take
some meaning from his death. At CASPER we are here to support other consumers and
families to do the same and can be contacted for help with reporting at www.casper.org.nz