Clinical
Corner Ð Anti-Depressants and Suicide
by
Thomas A. M. Kramer, MD ©2004 Medscape
Introduction
Many
people have asked me for advice about how to respond to questions from patients
and the lay public about the recent press, and ultimately US Food and Drug
Administration (FDA) warnings, about suicidality and antidepressants.
A
Matter of Scale
The
first issue that I would suggest addressing is the one of scale. Fluoxetine
(Prozac) became available in 1987, and other selective serotonin reuptake inhibitors
(SSRIs) became available shortly thereafter. In the 17 or so years that we are
talking about here, there have been millions -- if not tens of millions -- of
prescriptions resulting in numerous satisfied patients and practitioners. If
SSRI-associated suicidality truly is a major problem, it is difficult to
understand why it would only be coming to light now. The idea that these
medications might cause some people to commit suicide was discussed in a few
studies in the early 1990s, but these were dismissed as exceptional cases. It
is not at all clear why this is becoming an issue again in 2004.
It
must be emphasized how important the newer generation of antidepressants has
been in improving the lives of many individuals. These medications, despite
their current negative press, have been enormously effective in reducing the
burden of depression. Their side-effect profile is relatively low (although
certainly not zero) and they are considerably safer in overdose than their
predecessors, making them considerably less risky for suicide.
The
Risks
It
is important to directly acknowledge the suicide risk caused by these
medications. It is real and well understood, at least by experienced psycho-pharmacologists.
There are 2 mechanisms that we know about that cause these medications to
potentially precipitate suicidality. One is extremely rare, and the other is
milder but more common. The rare one is the potential for SSRIs to precipitate
an akathisia. This movement disorder, usually associated with antipsychotic medications,
has been reported as a rare side effect of SSRIs. This intense restlessness can
be so dysphoric (anxiety provoking) for patients that they might consider
suicide rather than endure the restlessness. This is something that
practitioners should warn patients about, and look for closely, as it is quite
treatable with adjunctive medication.
The
second mechanism involves the natural history of recovery from depression.
Depression is a disorder with numerous symptoms, and when the disorder is
treated effectively, the symptoms do not resolve all at the same time.
Classically, the physical symptoms of depression (including lack of energy,
difficulty concentrating, and sleeping and eating disturbances) resolve first
and the subjective depressed mood resolves last. As a result, patients who are
being treated for depression can have increased energy and increased
functionality as they recover, while still struggling with subjectively
depressed mood. This increases their suicide risk; they may have lacked the
energy or the ability to attempt suicide prior to starting treatment, but as
they begin to recover they regain ability and motivation before they have a
subjective sense of improvement. As a result, patients are usually at greatest
risk a week to 10 days after starting medication, and by 2-3 weeks later, that
risk is resolved. Experienced clinicians understand this as a function of the
disease, not the specific treatment, and are careful to watch for it and to
instruct family and friends to also be aware of it. The problem may be
exacerbated by the trend of primary care physicians treating depression. They
usually see patients for 10- or 15-minute periods of time and very rarely more
frequently than once a month
Why
Is This an Issue Now?
Why
did this happen? What started this whole process of questioning whether these
drugs are safe, and as such what should be the thresholds for prescribing them?
It appears that this all started in Great Britain, when the UK equivalent of
the FDA began to look at data from clinical trials in children. The concern
that the researchers expressed has been greatly misunderstood. They did not say
that these drugs routinely caused suicide; what they said was that there seemed
to be very little evidence that these drugs were particularly effective in
children. When compared with placebo, the children taking medication did not
seem to be doing all that much better. Thus, there appeared to be little
benefit to the medication, and since there were a few more episodes of suicidal
behavior (there were virtually no completed suicides on these clinical trials),
the risks vs. benefits may not justify prescribing these medications for
children.
There
are a number of reasons why placebo-controlled trials of antidepressants for
children often have trouble separating the responses of the drug group from the
placebo group. Subjects participating in clinical drug trials get a lot of
attention. They come in for frequent visits and talk about depression often.
This talking about depression can get them thinking about depression and can
be, in effect, de facto cognitive therapy. When you consider the fact that
children are considerably more impressionable than adults, it may explain why
medications that are in common clinical use in the treatment of depression in
children may not look so great in a clinical study. If you have concerns about
the efficacy of newer-generation antidepressants in the treatment of depression
in children, talk to child psychiatrists who use them. The enthusiasm for these
medications among the practitioners who pharmacologically treat depression in
children is quite strong. If they didn't work that well, these are the people
who would know.
Public
Opinion
Recently,
the press has been full of heart-wrenching stories of young people who have
been started on antidepressants and shortly thereafter have committed suicide.
No one doubts the veracity of these stories. All of us who are parents can
begin to imagine the horror that the parents of these victims endure. In many
-- if not most -- of these cases, we will probably never fully understand what
happened. Perhaps some of them developed an akathisia, perhaps some of them did
recover somewhat enough so that their negative thinking motivated them to act
on the feeling that life was no longer worth living. What is happening now,
however, is that the sensationalism of these reports is providing the public --
who had previously enthusiastically embraced these medications -- with a very
short memory. If the outcome of this negative press is that it prevents people
from seeking treatment for depression or, more specifically, encourages them to
refuse medication for severe depression, this controversy itself may cause more
suicides than the medications ever did. The risk of suicide goes down most
dramatically when people get treatment and comply with it. It is a
responsibility of all practicing psychopharmacologists
to do whatever they can to reinforce this message. We are the ones with the
experience with these medications. We have seen the successes, and we have seen
the failures. We need to make absolutely clear that the former grossly
outnumber the latter.