eNS Drugs 1 (3): 223-231.

1994
ADVERSE EFFECTS 1172-7047/94/0003-o223/S04.50/0

© Adis International Limited. All rights reserved.

The Fluoxetine and Suicide

Controversy
A Review of the Evidence
David Healy
Academic Sub-Department of Psychological Medicine, North Wales Hospital,
Denbigh, Clwyd, Wales

Contents
Summary ......... . 223
1. A Review of the Evidence. 223
2. Toxicity Indices . . . . . . . 224
3. Catecholamines and Suicide. 225
4. Serotonin and Suicide . . . . . 226
5. Databases versus Case Reports 227
6. A Plausible Mechanism? .... 228
7. Conclusions and Management Recommendations 229

Summary Evidence is emerging that a range of psychotropic drugs may precipitate

akathisia and/or panic reactions in predisposed patients. The use of fluoxetine has
hitherto been the most notable example of this occurrence. These reactions may
foster the genesis of suicidal ideation in a small proportion of patients. At present,
it is not clear what biological mechanism may underlie this finding. The serotonin
(5-hydroxytryptarnine; 5-HT) system may be involved in these reactions.
The best management of such reactions will involve counselling patients be-
forehand about the possibility of these reactions, stopping treatment with the
agents if such a reaction is suspected, or adding an agent with 5-HTIA antagonistic
properties (e.g. propranolol) to the treatment regimen.

In February 1990, a report by Teicher and col- 1. A Review of the Evidence

leagues appeared in the American Journal of Psy-
chiatry claiming that 6 patients who had been tak-
ing the selective serotonin (5-hydroxytryptamine;
5-HT) reuptake inhibitor (SSRI), fluoxetine, had
become intensely suicidal.[1] The present article re-
views this and other evidence in an attempt to answer
the question: can fluoxetine lead to the emergence of
suicidal ideation? In addition, the appropriate man-
agement for such an occurrence is discussed.
The article by Teicher et al.[1] caused consider-
able controversy, probably for 3 reasons.
First, the newer generation of antidepressants,
such as fluoxetine, were specifically designed to be
less toxic in overdose than older agents. Therefore,
they were presumed to be less likely to cause fatal-
ities through suicide. In contrast, the observations
of Teicher and colleagues suggested that these
224
agents somewhat perversely cause suicide fatali-
ties, albeit for a different reason.
Secondly, this report appeared to go against ob-
servations that suggested that antidepressants act-
ing on the noradrenergic system were more liable
to lead to suicide than those acting primarily on the
serotonergic system. Thirdly, the findings con-
tradicted research that points to the existence of a
serotonergic deficit in individuals who commit sui-
cidal acts.
There was immediate criticism of the article by
Teicher et al.[l] The main criticisms are listed in
table I. Subsequently, a meta-analysis of clinical
trials involving 3065 patients[S] and a retrospective
analysis of 1017 patients[6] who had received
fluoxetine was performed. These analyses sug-
gested that fluoxetine was unlikely to lead to the
emergence of suicidal ideation.
Nevertheless, a series of case reports involving
1 to 6 patients have continued to emerge implicat-
ing fluoxetine in the generation of suicidal ide-
ation,l7-I3] In addition to these case reports, a re-
analysis of the data presented by Fava and
Rosenbaum[6] was carried out. This has suggested
that the data can be interpreted such that fluoxetine
does indeed lead to the emergence of suicidal ide-
ation.[I4] The frequency of suicide ideation in pa-
tients receiving fluoxetine was somewhat higher
than that in recipients of tricyclic antidepres-
sants.l I4 ]
2. Toxicity Indices
In the mid 1980s, the use of mianserin was being
questioned because of reports of drug-induced
agranulocytosis. As part of a programme aimed at
'saving' the agent, considerable research was done
on the number of deaths that occurred per million
prescriptions of antidepressants. In the course of
this and other work, the notion of a fatal toxicity
index was developed.lIS-I7]
This index indicated that a number of com-
monly prescribed tricyclic antidepressants, partic-
ularly desipramine, dothiepin and amitriptyline,
were associated with a greater risk of death from
overdose than other antidepressants. Compared
© Adls International limited. All rights reserved.
Healy
Table I. Major criticisms[2.41 01 the data provided by Teicher et al. ll1
concerning Iluoxetine-indu ed suicide ideation
No patients had major depression
Some patients had a diagnosis 01 borderline personality disorder
(a condition associated with prominent suicidal ideation and
impulsive behaviour)
No patients were treated with Iluoxetine alone
No patients were treated with Iluoxetine at currently
recommended dosages
All patients were or had recently been receiving other medications
All patients had a history 01 suicide ideation or attempted suicide
with these 'unsafe' compounds, mianserin was
found to be a relatively safe agent. This was despite
the fact that it induced agranulocytosis with a
marginally higher frequency than other anti-
depressants (a claim that has not been fully sub-
stantiated).
A considerable part of the initial appeal of the
SSRIs lay in their relative safety in overdose.
While there have been insufficient prescriptions as
yet to construct fatal toxicity indices for each of the
SSRIs, these drugs have been specifically designed
to be safe in overdose. As a result, it can be ex-
pected that their toxicity index will be low.l I8 ]
A standing comment in presentations over re-
cent years has been that if the tricyclic antidepres-
sants were to be developed now, they would not be
approved because of their toxicity. This sugges-
tion has led to the proposal that any programme
aimed at suicide reduction should encourage the
replacement of tricyclic antidepressants as first-
line treatments for depression, with SSRIs. How-
ever, some have argued that in practice this would
make very little difference to the rates of suicide in
general practice.l I9 ,20]
It is against this background that the questions
raised by the fluoxetine controversy must be
judged. When considering the issue, a number of
authorities have pointed to the clear benefits
gained from the use of fluoxetine in terms of its
relative safety in overdose and in patients with a
range of other medical conditions, such as cardio-
vascular disease.[2-4] Such safety is clearly desir-
able for most depressed patients. However, this
eNS Drugs 1 (3) 1994
Fluoxetine and Suicide
property is unlikely to carry much legal weight if
some individuals are inevitably led to take their
own or others' lives as a direct consequence of re-
ceiving fluoxetine. The fact that pertussis vaccines
reduce the overall likelihood of brain damage from
the pertussis virus does not prevent legal action in
the event of vaccine-induced brain damage.
Moreover, it has been pointed out in media re-
ports that antidepressants are often developed us-
ing clinical trials conditions that differ substan-
tially from those found in the real world. It can be
argued that the clinical trials performed in the de-
velopment of the early tricyclic antidepressants
(some of which reached the market place without
any clinical trial programme at all) were biased.
This was because they focused heavily on inpatient
samples of severely depressed patients. However,
criteria for entry into current antidepressant trials
specify that patients should not be suicidal, should
not have any co-existing medical conditions,
should not be receiving any other treatment, and
should not have bipolar disorders. Increasingly, the
patients who enter such trials are recruited from
primary care settings and have depressive episodes
of relatively recent onset and relatively mild to
moderate severity.
Improvements have been made in the conduct
of clinical trials, and there is now a broader defini-
tion of drug-induced adverse events. Despite this,
it can be argued that the use of sophisticated post-
marketing surveillance methods is the only accu-
rate way of assessing the possibility of suicidal ide-
ation induced by the newer agents. Available
post-marketing surveillance data from individual
countries do not suggest that any of the SSRIs are
particularly liable to cause aggressive, impulsive
or suicidal actsJ21-23] If it is later established that
they or other antidepressants do cause such effects,
the question would arise as to whether this is a
direct or indirect effect.
Teicher et al.[1] appear to have initially believed
that the effects they described arose in a manner
that was not open to psychosocial intervention but
later have perhaps modified their positionJ24]
© Adis International Limited. All rights reserved.
225
3. Catecholamines and SuiCide
As early as the mid 1960s, it was suggested that
monoamine oxidase inhibitors (MAOIs) might be
more likely than tricyclic antidepressants to lead to
suicide.
It was thought that this might occur via a
MAOI-induced increase in catecholamine [dopa-
mine, noradrenaline (norepinephrine) and adrena-
line (epinephrine)] levels. This effect might in-
crease drive and arousal more rapidly than the
more sedative tricyclic antidepressants. Activating
patients in this way might enable them to act on
their latent suicidal intentions. This idea never re-
ceived any clear empirical support; however, it has
never fully gone awayJ4,25] Indeed, there have
been suggestions that the newly launched revers-
ible monoamine oxidase A-selective agent,
moclobemide, might be particularly likely to in-
duce suicidal ideation and lead to suicide at-
tempts,l26,27]
More specifically in 1988, Damluji and Fergu-
son[28] reported the occurrence of desipramine-in-
duced dysphoria and suicidal ideation in 4 patients.
As desipramine has a preferential effect on cate-
cholamine rather than serotonin reuptake inhibi-
tion, this appeared consistent with the ideas noted
above.
These ideas also found some support from a trial
by Rouillon and colleagues.[29] These investiga-
tors studied the long term outcome of patients
maintained on maprotiline, a catecholamine re-
uptake inhibitor, compared with those on placebo.
They found that maprotiline alleviated symptoms
of depression and reduced the risk of relapse more
effectively than placebo. However, use of the agent
also led to a greater number of individuals attempt-
ing and completing suicide during the follow-up
year.
These data have interfaced with ideas that sero-
tonin is implicated in the control of impulsive
behaviourspO,31] and that SSRIs might be associ-
ated with reduced rates of impulsivity and at-
tempted or completed suicide.[32] It is clear that
SSRIs have effects on appetitive behaviours that
appear loosely linked to an 'impulse system';
eNS Drugs 1 (3) 1994
226
hence the potential usefulness of SSRIs in eating
and sexual disorders)33,34] Unfortunately, the field
of impulse disorders remains unstandardised, and
it is not clear which disorders qualify as impulse
disorders. As a result, it is not known whether
SSRIs have any specific effect on impulsivity.
4. Serotonin and Suicide
In 1973, Van Praag and colleagues[35] claimed
that probenecid reduced cerebrospinal fluid (CSF)
levels of 5-hydroxyindoleacetic acid (5-HIAA),
the metabolite of serotonin, in depressed individu-
als more than it did in nondepressed individuals.
This finding found some support from other inves-
tigators,l36] Asberg and colleagues[37] also re-
ported a reduction of 5-HIAA levels in the CSF of
depressed patients. This latter finding, however,
was not clearcut and was not associated with any
one category of depression. Subsequent investiga-
tion has suggested that reduced CSF 5-HIAA levels
is not a feature of depressive illness.[38-40]
Nevertheless, investigation in this area contin-
ued. In 1981, Traskman, Asberg and colleagues
found that depressed patients as a group do not
display a particular reduction of 5-HIAA levels.
However, they claimed that there was a disorder of
serotonin metabolism in those who are depressed
and suicidaU4I] Subsequently, the same group[42]
reported that the correlation between reduced 5-
HIAA levels and suicidal behaviour was one that
cut across diagnostic categories.
In supporting this claim, the investigators pre-
sented data suggesting that altered 5-HIAA meta-
bolism might predict future suicide attempts. Oth-
ers have pointed to correlations of 5-HIAA levels
with previous suicide attempts or aggressive
acts,l43] Still others have accounted for heteroge-
neity in the data by appealing to distinctions be-
tween intentional and impulsive acts and distinc-
tions between self-injury and suicide proper.[44]
It would appear that initial claims regarding re-
duced 5-HIAA levels in the CSF were readily ac-
cepted by the biological psychiatry community. In
contrast, subsequent failure to replicate the origi-
nal findings have not been. For example, Annitto
© Adls International Limited, All rights reserved,
Healy
and Shopsin[38] reported that the majority of 14
studies of CSF 5-HIAA levels that had been per-
formed by 1979 did not support the conclusion that
depression was associated with reduced 5-HIAA
levels.
This did not prevent investigators at the Na-
tional Institute of Mental Health predicting respon-
siveness to antidepressants based on alterations in
CSF 5-HIAA levels. It was hypothesised that
agents that supposedly increase serotonergic func-
tion, such as SSRIs, should be more effective in
depressed patients with reduced levels of CSF 5-
HIAA. It followed that agents that preferentially
act on catecholamine reuptake might be expected
to be of greater benefit in individuals with reduced
catecholamine metabolism,l45] However, this has
not been found to be the case,l39,40,46,47]
Quite apart from these negative findings, in gen-
eral, studies of 5-HIAA have not been vigorously
controlled methodologically. They have not ade-
quately controlled for the effects of physical activ-
ity[48-50] or alcohol intake, [5 1,52] both of which are
clearly implicated in suicidal or aggressive states.
Indeed, the basic question of whether 5-HIAAlev-
els in CSF taken from lumbar samples reveal any-
thing more than the state of serotonin metabolism
in the lumbar spinal cord[53] has not been settled.
Efforts to approach the problem by looking at
other aspects of serotonin metabolism have not
clarified the situation. Evidence in favour of 5-HT2
receptor and [3H]-imipramine binding site abnor-
malities in post mortem brains of suicide victims
has been cited,l3,44,54] Unfortunately, few if any of
these findings have been replicated. [47] In addition,
just as with work on 5-HIAA, post mortem brain
research is subject to many confounding method-
ological variables. The contaminating influence of
such factors has not been well controlled for.
Despite all these caveats, the idea that there is
an abnormality of serotonin metabolism in suicidal
states has gained hold. Indeed, in recent months
reports of cholesterol-lowering agents possibly
precipitating aggressive or suicidal acts have been
greeted with interest. There have been a number of
proposals linking this effect with an association
eNS Drugs 1 (3) 1994
Fluoxetine and Suicide
between suicide and serotonin deficits, by means
of an effect of lipid lowering on serotonergic me-
tabolism.l 55 -60] As Owens has noted)581 however,
the existence of a biologically plausible explana-
tion for this finding may prevent further indepth
analysis of the situation. In a broadly similar man-
ner, were the existence of an association between
reduced serotonin levels and suicide to be con-
firmed, far from solving the problem, this finding
would risk compromising the analysis of the
fluoxetine and suicide data.
Even if the findings of altered serotonin meta-
bolism in suicidal states were to be replicated, it is
not clear that treatment with SSRIs would produce
or reduce suicidal ideation. Even when depressed
individuals with reduced 5-HIAA levels are se-
lected for treatment with SSRIs, responses to treat-
ment do not appear to be particularly enhanced or
compromised.[39,40,46,47]
5. Databases versus Case Reports
In reply to the case reports of fluoxetine-
induced suicidality, Beasley and colleagues
scrutinised the Eli Lilly database for evidence of
increased suicidality in patients receiving fluox-
etine.l 5] No such evidence has been found. These
data from several thousand patients, and the evi-
dence that fluoxetine reduces suicidal ideation,
must on any scientific scale outweigh the dubious
evidence of a handful of case reports.
There are, however, problems with the use of
such a database. The evidence collected as part of
the clinical trial programme for fluoxetine in the
early 1980s did not specifically focus on the ques-
tion of suicidal ideation. There was no reason to
have such a focus. Accordingly, scales that might
be particularly sensitive to variations in mental
state and associated induction of suicide were not
used. The primary variable used in the database
was ratings on item 3 of the Hamilton Rating Scale
for Depression (HRSD). This is a insensitive item,
particularly when it comes to rating possibly emer-
gent suicidal ideation.
Furthermore, clinical investigators will tend to
mark down any scores on this item in line with a
© Adls International limited. All rights reserved.
227
Table II. Criteria required for a case report of a drug-induced
adverse effect to be considered reliable l61 ]
• There should be a close temporal relationship between
administration of the drug and occurrence of the adverse effect
• The adverse effect should not be a manifestation of the
underlying illness
• The individual should not be taking other medications
• The effect should be clearly documented
• Discontinuation of the drug should lead to cessation of the
adverse effect
• The adverse effect should reemerge on readministration of the
compound
general marking down of HRSD scores as patients
in a trial improve. Even in patients in whom suici-
dal ideation may have emerged or increased, there
may be a simultaneous improvement in other as-
pects of their mental state. This effect would have
masked increased ratings on item 3.
In addition, patients have a natural bias to min-
imise cognitive dissonance and so would be un-
likely to volunteer information regarding emerging
suicidal ideation. This is particularly true if they
were experiencing improvements in other aspects
of their mental state. Unless the investigators were
suspicious of the induction of suicidal ideation, it
is unlikely that they would have picked up such
emerging tendencies.
Case reports are clearly an unreliable form of
information. Several criteria have been proposed
to enhance the validity of conclusions that may be
drawn from such reports (see table II). To these we
might add the criterion that there should be a clin-
ically plausible mechanism that might make sense
of the claim of an adverse effect.
While the initial reports by Teicher et al.[l] of
suicidal ideation after fluoxetine administration
were clearly compromised on many of these cri-
teria, subsequent reports[7-11] have not been.
Across all reports there is a broad correspondence
regarding the time of emergence of suicidal ide-
ation - about 10 to 14 days after initiation of
fluoxetine treatment. It is clear from many reports
that some individuals were prescribed fluoxetine
only and in currently recommended doses. The ef-
eNS Drugs 1 (3) 1994
228
fects have been clearly documented. Although sui-
cidal ideation is a manifestation of depressive ill-
ness, intense suicidal ideation of the form reported
is less commonly encountered. Furthermore, it cer-
tainly would not be expected to emerge frequently
in individuals taking placebo.
With this particular adverse effect, there are
problems with a rechallenge. Few investigators or
patients would be anxious to revisit a compound
that had caused suicidal ideation. Rothschild and
Locke[71, however, did just this in 3 patients. They
found that whilst suicidal ideation cleared on dis-
continuation of fluoxetine, it reemerged with
readministration of the agent. However, readmini-
stration of fluoxetine was not done in a double-
blind manner, and hence these reports are open to
some bias. Creaney et a1.[11] found reemergence of
suicidal ideation in 2 individuals who had experi-
enced these effects after receiving fluoxetine when
they were rechallenged with SSRIs other than
fluoxetine. This suggested that the problem of a
possible induction of suicidal ideation was not spe-
cific to fluoxetine.
6. A Plausible Mechanism?
The induction of suicidal ideation by fluoxetine
seems to be in opposition to prevailing knowledge
of the causes of suicide and mechanism of action
of SSRIs. However, a possible mechanism mediat-
ING such an effect can be postulated.
It has commonly been suggested that individu-
als who experienced fluoxetine-induced suicidal
ideation had developed akathisia.l1. 7,1l,62, 631Inde-
pendent of such reports, there have also been case
reports implicating fluoxetine in the development
of akathisia.l 641 Furthermore, fluoxetine seems to
be associated with a higher incidence of ex-
trapyramidal adverse effects than other antidepres-
sants.l651 It has also been noted that the induction
of akathisia by antipsychotics may lead to a precip-
itation of suicidal attempts.[66,67]
The phenomenon induced by fluoxetine may
not be accurately described as 'akathisia'. Aka-
thisia traditionally refers to a visible restlessness
and pacing. While this can be observed in patients
© Adls International limited. All rights reserved.
Healy
receiving fluoxetine, it is not clear that the aka-
thisia referred to in the above case reports has in-
volved this type of effect. The states being referred
to might also be labelled agitation or dysphoria
rather than akathisia. Unfortunately the phenome-
nology of such drug induced restlessness/dys-
phoria is not well clarified.l68-701.
There are 2 mechanisms, possibly related,
whereby drug-induced 'akathisia' may lead to sui-
cidal ideation. First, it would seem likely that some
depressed individuals might misattribute the de-
velopment of drug-induced dysphoria or agitation
to a worsening of their mental state. Seeing this as
a worsening of their depressive illness despite drug
treatment, they may conclude that their case must
be hopeless.l 341
An alternative mechanism has recently
emerged. In 1989, Weissman and colleagues[711 re-
ported an association between suicidality and
panic disorder. In their analysis of findings derived
from the epidemiologic catchment area study,
panic disorder appeared particularly likely to be
associated with both suicide attempts and com-
pleted suicides. In response to criticism from oth-
ers,£72- 741 these authors have revised their esti-
mates downwards of how likely panic is to lead to
suicide.l751 However, they still argue that the data
point strongly toward an association between panic
and suicide, particularly when the symptoms of
panic occur during an episode of depression.
Indeed, panic may provide a final common
mechanism through which a number of unrelated
states lead to suicidal ideation. For example,
Creaney and colleagues[1l1 reported 1 patient who
became suicidal following a dissociative reaction
to SSRIs. This reaction was characterised by pro-
nounced depersonalisation and derealisation. Such
a mechanism may furthermore underline instances
of paradoxical aggression which have been re-
ported following administration of a variety of an-
tidepressants. [761
Against this background, the notion that the pre-
cipitation of agitation by an antidepressant might
lead to suicidal ideations/suicide attempts seems
less remarkable. In addition, it has recently been
eNS Drugs 1 (3) 1994
Fluoxetine and Suicide
recognised that persons who are anxious are par-
ticularly likely to develop a 'jitteriness' syndrome
when treated with antidepressants.l 77 ]
Power and Cowen[l8] have argued that such ad-
verse effects may be related to a serotonin
behavioural syndrome. This can be blocked by pro-
pranolol, a ~-adrenoceptor blocking agent that also
has 5-HTIA antagonistic properties. As a conse-
quence, propranolol might be particularly effective
at alleviating any restlessness/akathisia caused by
SSRIs. Indeed, Rothschild and Locke[7] reported
that propranolol appeared to relieve the akathi-
sialsuicidal ideation precipitated by re-exposure to
fluoxetine.
If suicidal or homicidal ideation develops in pa-
tients taking SSRIs or antipsychotics as a conse-
quence of the development of akathisia or panic
and aggravated by a process of misattribution or
other cognitive process, such states would not be
directly drug-induced. Whether or not such states
occur is still a matter that needs to be determined
conclusively. Nevertheless, there appears to an in-
creasing consensus that these states arise via some
secondary indirect process rather than directly. As
such, it is likely that the burden of responsibility
for drug-induced injury, should any cases be con-
tested, is likely to shift from the makers of SSRIs
to the prescribers and to issues of clinical practice.
The induction of significant akathisia or panic
during antidepressant treatment is infrequent and
unpredictable. Furthermore, there is a range of
variables that might confound the interpretation of
causation. Therefore, large scale clinical trials are
unlikely to settle the question of whether and how
often such reactions occur. A more promising line
of investigation might be to investigate genetic fac-
tors influencing pharmacokinetic and behavioural
responses to psychotropic drugs.
Brunner and colleagues[78] have recently iden-
tified a point mutation in a structural gene for
monoamine oxidase A. This mutation is associated
with an increased incidence of impulsive aggres-
sion, arson, attempted rape and exhibitionism.
Thus, it might be possible to investigate those in-
dividuals who have significantly unusual re-
© Adis International Limited. All rights reserved.
229
sponses to psychotropic agents for a range of mu-
tant genes. If the genes were found to be abnormal,
family members could be invited to undergo a dou-
ble-blind challenge with the psychotropic drug of
particular concern in their relative. Such a method
might lead to conclusive findings relatively rap-
idly, and might in due course lead to the estab-
lishment of diagnostic tests to determine whether
there are particular psychotropic drugs that certain
individuals should avoid.
7. Conclusions and Management
Recommendations
In the opinion of this author, the volume of case
reports and other studies is sufficient to demonstr-
ate that antidepressants and antipsychotics may in-
duce suicidal ideation in certain individuals under
certain conditions. These reports must be set
against a general recognition that the peak time for
suicide attempts is shortly after individuals start
treatment with a new antidepressant or antipsy-
chotic. Therefore, it seems a reasonable proposi-
tion that, in some patients, taking a new psy-
chotropic agent may lead to the emergence of
suicidal ideation.
The fluoxetine controversy, for a number of rea-
sons, has served to highlight this issue. Some of the
case reports regarding fluoxetine-induced suicidal
ideation do appear sufficiently well documented
and detailed to sustain an argument that fluoxetine
may lead to the emergence of suicidal ideation.
However, this effect is uncommon.
Suicidal ideation associated with fluoxetine is
probably not a direct effect of fluoxetine, but is
mediated through the induction of akathisialagita-
tion/panic. This may occur through changes in 5-
HTIA or 5-HT2 receptors. The effects may be suc-
cessfully blocked by propranolol.
Inappropriate reactions to akathisia, agitation or
panic may also playa significant part in any sub-
jective distress that emerges. Any deleterious ef-
fects of such reactions will be prevented by a clear
awareness on the part of the therapist and patient
that such reactions may develop. Patients should
be instructed to report any such effects promptly,
eNS Drugs 1 (3) 1994
230
so that potential misattributions by the patient may
be dealt with.
Such reactions to fluoxetine are rare, and undue
concern over them may lead to more suicides by
virtue of patients giving up treatment. It is this au-
thor's opinion that acknowledging that such reac-
tions may occur with all psychotropic drugs, and
developing management guidelines for such reac-
tions, is essential for all parties involved in the
therapy.
Acknowledgement
Dr Healey acts as a consultant for Eli Lilly.
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Correspondence and reprints: Dr David Healy, Academic
Sub-Department of Psychological Medicine, North Wales
Hospital, Denbigh, Clwyd LL16 5SS, Wales.
eNS Drugs 1 (3) 1994