Suicidal status during antidepressant
treatment in 789 Sardinian patients with
major affective disorder
Suicide is a major public health challenge. Among
persons with severe mood disorders, risk of
suicide is as much as 20 times greater than in
the general population (1), accounting for approx-
imately 990 000 deaths and nearly 25 million
attempts annually worldwide, at an international
average annual suicide rate (per 100 000) of
approximately 15, rate of attempts of 300–450
and estimated rate of suicidal ideation of about
3000 (2–5). Mortality, disability and morbidity
associated with clinical depression and bipolar
disorders, including high rates of suicides and
attempts, exert major adverse effects on individ-
uals, their families and society (6–8), as well as
costing tens of billions of dollars annually in
individual countries (9–14).
Tondo L, Lepri B, Baldessarini RJ. Suicidal status during antidepressant
treatment in 789 Sardinian patients with major affective disorder.
Objective: Relationships between antidepressant treatment and
suicidality remain uncertain in major depressive disorder (MDD), and
rarely evaluated in bipolar disorder (BPD).
Method: We evaluated changes in suicidality ratings (Hamilton
Depression Rating Scale item-3) at the start and after
3.59 ± 2.57 months of sustained antidepressant treatment in a
systematically assessed clinical sample (n = 789) of 605 patients with
MDD, 103 patients with BPD-II and 81 patients with BPD-I (based on
DSM-IV; 68.1% women; aged 44.3 ± 16.1 years), comparing suicidal
vs. non-suicidal and recovered vs. unrecovered initially suicidal
Results: Suicidal patients (103 ⁄789, 16.5%; BPD ⁄MDD risk: 2.2) were
more depressed and were ill longer. During treatment, 81.5% of
suicidal patients became non-suicidal; 0.46% of 656 initially non-
suicidal patients reported new suicidal thoughts, with no new attempts.
Becoming non-suicidal was associated with greater depression severity
and greater improvement.
Conclusion: Suicidal ideation was prevalent in patients with depressed
major affective disorder, but most of the initially suicidal patients
became non-suicidal with antidepressant treatment, independent of
diagnosis, treatment type or dose.
L. Tondo1,2,3, B. Lepri2,3,
R. J. Baldessarini1
1Department of Psychiatry and Neuroscience Program,
Harvard Medical School and McLean Division of
Massachusetts General Hospital, Boston, MA, USA,
2Department of Psychology, University of Cagliari and
3Lucio Bini Mood Disorders Research Center, Cagliari,
Key words: antidepressants; bipolar disorders;
depression rating scale; major depression; suicidality
Dr Ross J Baldessarini, Mailman Research Center,
McLean Hospital, 115 Mill Street, Elmont,
MA 02478-9106, USA.
Accepted for publication February 18, 2008
• During antidepressant treatment, suicidality ratings as well as other depressive symptoms improved
in adults with bipolar disorder as well as major depressive disorder, independent of treatment type or
• Treatments were clinical, involved multiple modalities and suicidality was based on one item of the
HDRS and may simply co-vary with recovery from acute depression.
Acta Psychiatr Scand 2008: 118: 106–115
All rights reserved
Copyright ? 2008 The Authors
Journal Compilation ? 2008 Blackwell Munksgaard
One would expect clinically effective treatments
for mood disorders to reduce risk of suicide (4, 15).
However, consistent evidence for reductions in
risks of suicide and attempts in persons with major
affective disorders has remained elusive. There is
substantial and consistent evidence associated with
long-term treatment with lithium among patients
diagnosed with bipolar disorder (BPD), a mix of
major affective disorders and possibly major
depressive disorder (MDD), including evidence
from randomized, controlled trials (4, 16–19).
There is also emerging evidence that lithium may
be superior in such effects to some anticonvulsants
proposed as alternative mood stabilizers (4, 19–25).
Surprisingly, however, evidence for a suicide risk-
reducing effect of otherwise clinically effective
remains inconclusive (4, 5, 26–35). There have
even been suggestions that risk of suicidal thinking,
and perhaps suicide attempts, may be somewhat
higher among juvenile and young adult patients
treated with serotonin reuptake inhibitors (SRIs)
or other antidepressants compared with a placebo
in randomized trials (36–41). Such risks are of
particular interest in juvenile depression, in which
the clinical effectiveness of most antidepressants
remains less well established than in adult MDD
(42–44). Furthermore, the value of antidepressants
for the management of long-term risk of depres-
sion in BPD remains less certain than for MDD
Finally, in contrast to the inconclusive evidence
for a sparing effect of antidepressant treatment on
suicides or attempts, there is evidence from ran-
domized, controlled trials that antidepressant
treatment is associated with greater decreases
than with placebo treatment, of ratings of suicidal
ideation in depressed adults, along with improve-
ments of other symptoms of depression (47–52).
However, such reduction in suicidal ideation has
rarely been tested in clinical mood disorder pop-
ulations, and not specifically in patients with BPD,
who may have even greater risk of suicide and
attempts than many patients with MDD (4, 7, 53).
Given ongoing uncertainties about potential
beneficial or harmful effects of antidepressant
treatment on suicidality, including ideation and
suicidal acts among men vs. women of various
ages, with various major affective disorders and
duration and severity of illness, we have under-
taken an analysis of suicidality ratings from a large
sample of systematically evaluated, treated and
followed-up patients at a mood disorder research
center affiliated with the University of Cagliari in
Sardinia. The present report is based on an analysis
of item-3 (suicidal thinking and behavior) of the
Hamilton Depression Rating Scale [HDRS: (54)]
before and after at least 1 month of antidepressant
treatment in 789 patients diagnosed with DSM-IV
major affective disorder.
Aims of the study
We hypothesized that: (i) prevalence of elevated
suicidality ratings (Hamilton Depression Rating
Scale item-3 scores) would be greater in patients
with BPD than in those with MDD, in severely
depressed patients, in women and among the eldest
or youngest patients; (ii) most patients with
initially elevated suicidality ratings would show
major improvement in item-3 scores as overall
improvement would vary little by sex, age, diag-
nosis, duration of illness or type of treatment; and
(iii) newly emerging suicidality during antidepres-
sant treatment would be rare.
Material and methods
We analyzed information arising from systematic
clinical assessments of adult patients with mood
disorder at the Lucio Bini Mood Disorders Center
affiliated with the University of Cagliari in Sardi-
nia. Study subjects were drawn from a larger
sample of 2826 patients diagnosed with DSM-IV
major mood disorders, whose suicidal risks were
reported recently (53). For the present analyses,
consecutive subjects were included who met the
following criteria: (i) diagnosed with a DSM-IV
major affective disorder; (ii) received an antide-
pressant; and (iii) had at least two ratings with the
[HDRS-21 (54)]. These ratings supported compar-
ison of scores at intake and the first follow-up
rating during treatment, 1–12 months later, so as
to evaluate treatment effects. Diagnostic and assess-
ment methods were reported previously (53, 55).
All subjects underwent initial diagnostic assess-
ments by the first author (LT), based on semi-
structured interviews that followed the mood dis-
order components of the RDC and SCID-I, as well
as extensive follow-up clinical assessments and
repeated ratings with standard mood disorder
follow-up. Rating scale assessments were consis-
tently administered by the same investigator (LT),
avoiding inter-rater variance. Subjects initially
met DSM diagnostic criteria for major affective
disorders, and diagnoses were updated to meet
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