Journal of Affective Disorders 198 (2016) 23–31

Contents lists available at ScienceDirect

Journal of Affective Disorders

journal homepage: www.elsevier.com/locate/jad

Review article

Does psychosis increase the risk of suicide in patients with major

depression? A systematic review
Isheeta Zalpuri a, Anthony J. Rothschild b,n
a
Department of Psychiatry, Stanford University School of Medicine, 401 Quarry Road, Palo Alto, CA 94305, United States
b
Center for Psychopharmacologic Research and Treatment, Department of Psychiatry, University of Massachusetts Medical School, 55 Lake Ave North
Worcester, MA 01655, United States

art ic l e i nf o a b s t r a c t

Article history: Objective: Over the years studies have shown conflicting results about the risk of suicide in psychotic
Received 9 May 2015 depression (MD-psych). To understand this association, we undertook a comprehensive review of the
Received in revised form literature to ascertain whether individuals with MD-psych have higher rates of completed suicides,
12 February 2016
suicide attempts or suicidal ideation compared to those with non-psychotic depression (MD-nonpsych).
Accepted 9 March 2016
Methods: We searched Pubmed, PsycINFO and Ovid in English language, from 1946-October 2015. Stu-
Available online 11 March 2016
dies were included if suicidal ideation, attempts or completed suicides were assessed.
Keywords: Results: During the acute episode of depression, patients with MD-psych have higher rates of suicide,
Major depression suicide attempts, and suicidal ideation than patients with MD-nonpsych, especially when the patient is
Psychotic depression
hospitalized on an inpatient psychiatric unit. Studies done after the acute episode has resolved are less
Suicide
likely to show this difference, likely due to patients having received treatment.
Limitations: Diagnostic interviews were not conducted in all studies. Many studies did not report
whether psychotic symptoms in MD-psych patients were mood-congruent or mood-incongruent; hence
it is unclear whether the type of delusion increases suicide risk. Studies did not describe whether MD-
psych patients experienced command hallucinations encouraging them to engage in suicidal behavior.
Only 24 studies met inclusion criteria; several of them had small sample size and a quality score of zero,
hence impacting validity.
Conclusions: This review indicates that the seemingly conflicting data in suicide risk between MD-psych
and MD-nonpsych in previous studies appears to be related to whether one looks at differences during
the acute episode or over the long-term.
& 2016 Elsevier B.V. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
1.1. Aims of the study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.1. Study population and study design . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
2.1.1. Study selection. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3.1. Completed suicide . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
3.1.1. Studies on inpatient psychiatric units. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.1.2. Population-based studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.1.3. Follow-up studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.2. Suicide attempts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.2.1. Studies on inpatient psychiatric units. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
3.2.2. Studies including both inpatient and outpatient referrals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.2.3. Outpatient studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

n
Corresponding author.
E-mail addresses: izalpuri@stanford.edu (I. Zalpuri), anthony.rothschild@umassmemorial.org (A.J. Rothschild).

http://dx.doi.org/10.1016/j.jad.2016.03.035
0165-0327/& 2016 Elsevier B.V. All rights reserved.
24 I. Zalpuri, A.J. Rothschild / Journal of Affective Disorders 198 (2016) 23–31

3.2.4. Population-based studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29

3.2.5. Follow-up studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3. Suicidal ideation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3.1. Studies on inpatient psychiatric units. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3.2. Outpatient studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 29
3.3.3. Studies including both inpatient and outpatient referrals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
3.3.4. Population-based study . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30

1. Introduction 2. Methods

Major depression with psychotic features (MD-psych) is de-
fined as patients meeting criteria for major depression and then
having features of psychosis, either hallucinations or delusions,
commonly manifesting as nihilistic delusions, overly self-critical or
guilty beliefs. It remains a sub-classification of major depression,
although some authors have argued that a separate designation
from major depression is supported by scientific studies (Schatz-
berg and Rothschild, 1992). Patients with MD-psych have higher
scores on the Hamilton Rating Scale for Depression (Glassman and
Roose, 1981, Nelson et al., 1984, Lykouras et al., 1986) higher rates
of mortality from medical causes (Vythilingam et al., 2003) and
more frequent relapses (Lykouras et al., 1986, Robinson and Spiker,
1985, Aronson et al., 1987, Coryell et al., 1996) when compared to
patients with non-psychotic depression (MD-nonpsych), although
not all studies are in agreement (Coryell et al., 1987, Lykouras et al.,
1994). Clinicians frequently miss the diagnosis of MD-psych
(Rothschild et al., 2008), which can lead to sub-optimal treatment,
potentially increasing the risk of suicide. It is well known that
patients with depression have a higher rate of suicide relative to
general population (Hagnell et al., 1981, Henriksson et al., 1993).
However, over the years, studies have shown mixed results about
whether the risk of suicide in patients with MD-psych is different
than patients with MD-nonpsych.
We searched Pubmed, PsycINFO/Ovid in English language only,
from 1946-October 2015, using keywords suicide, major depres-
sion and psychotic depression. All studies were included in this
report if suicide risk (ideation, attempts) or completed suicides
were assessed in subjects with MD-psych. Studies were cross
sectional, cohort, case control, retrospective and randomized
controlled trials.
2.1. Study population and study design
We considered studies where subjects met DSM III, DSM IV or
ICD-8, ICD-9, ICD-10 criteria for MD-psych and MD-nonpsych. All
of these studies had participants of both genders, older than 18
years of age, except Quinlan et al. (1997) where subjects were
adolescents, 12–18 years of age, Suominen et al. (2009) where
individuals were 16 years or older, Park et al. (2014) where pa-
tients were over 7 years old and Kelleher et al. (2014) where
participants were 12–16 years of age. Exclusion criteria included
substance use and patients meeting DSM III, DSM IV or ICD-8, ICD-
9 or ICD-10 criteria for schizophrenia, schizoaffective disorder or
bipolar disorder. Hospital-based, follow up and population-based
studies were included. Hospital-based studies comprised of both
inpatient and outpatient subjects. Case reports, book chapters and
letters to editors were excluded.

1.1. Aims of the study 2.1.1. Study selection

Identified studies were reviewed for eligibility by both authors.
We performed a comprehensive and critical review of the First screening was performed based on title and abstract and full
English language literature from 1946-October 2015 to determine texts were retrieved for screening. (Please refer to Fig. 1). Each
whether there is a higher rate of completed suicides, suicide at- manuscript was given a quality score based on PRISMA guidelines
tempts or suicidal ideation in patients with MD-psych as com- (Jadad et al., 1996), which are shown in Tables 1, 2 and 3.
pared to MD- nonpsych. We also make recommendations on the
assessment and treatment of those patients who are at higher risk
for suicide. 3. Results

698 articles identiied 598 articles were excluded The search identified 698 articles. Of these 598 were excluded
through database searching based on title and abstract based on title and abstract. 100 articles were assessed for elig-
ibility. Of these, 76 were excluded based on exclusion criteria and
24 articles were included in the review. 22 were hospital based
(inpatient, outpatient and follow ups) and 2 were population
based. We present the results of our review below in the following
100 full-text articles were 76 articles excluded based sections: Completed Suicide, Suicide Attempts, and Suicidal
assessed for eligibility on exclusion criteria Ideation.

3.1. Completed suicide

Most studies did not find any difference in completed suicides

24 articles included in the
between the two groups, however in some studies the psychiatric
literature review
status of victims at the time of suicide was unknown. Table 1
Fig. 1. Selection of articles included in the review. summarizes pertinent studies comparing completed suicides
Table 1
Studies comparing risk of completed suicides in MD-psych and MD-nonpsych groups.

Study Sample Description Study population Findings Risk of completed suicide Score
in psychotic vs. non-psy-
chotic depression

Coryell et al. Inpatient 40 year follow up study using chart reviews to de- 122 patients with MD-psych and 8 suicides in MD-psych group, 8.4%of the de- No difference 0
(1982) scribe short and long term outcomes in patients 103 patients with MD-nonpsych ceased; 7 suicides in MD-nonpsych group, 10% of
hospitalized 5 years prior to ECT availability the deceased no difference between groups in

I. Zalpuri, A.J. Rothschild / Journal of Affective Disorders 198 (2016) 23–31

death by suicide; marital, occupational or re-
sidential status; psychiatric symptoms or final di-
agnosis of bipolar disorder
Roose et al. (1983) Inpatient Retrospective analysis of suicides in New York State Total 39 patients, 14 of 22 with af- Significant association between delusions and Increased, p o0.05 0
Psychiatric Institute over a 25-year period fective disorder had depression: suicide. Delusionally depressed patients were
definitely delusional: 6 5 times more likely to commit suicide
probably delusional: 4
nondelusional: 10
Robinson and Spi- Inpatient 1-year follow up study of patients in both groups, 52 patients with MD-psych; control Patients in MD-psych group had higher rates of No significant difference 0
ker (1985) following discharge from hospital group consisted of 52 patients with major depression or delusions lasting longer than
MD-nonpsych 9 months and of being in a major depressive epi-
sode at the end of the follow up period
Wolfersdorf et al. Inpatient (followed Retrospective study that assessed the significance of 46 patients with MD-psych com- MD-psych patients were less suicidal than MD No difference 0
(1987) for 0–3 years) delusional symptoms for suicidality in MDpsych pared to 46 MD-nonpsych patients non-psych The two groups did not differ in fre-
patients quency of suicide
Black et al. (1988) Inpatient sample Follow up study; patients with major depression or 2054 patients with affective dis- 3.3% suicides in MD-psych and 3.4% suicides in No difference 0
followed for 2–13 bipolar disorder were followed for 0–14 years and order; 183 MD-psych and 824 MD- MD-nonpsych group. Both MD-psych and MD-
years their suicide rates were compared to that of the state nonpsych patients non-psych patients had similar risks for suicide.
population Authors concluded that psychosis per se does not
dispose patients with affective disorders to suicide
Isometsä et al. Population-based Retrospective study; psychological autopsy examin- 24 patients with MD-psych and 46 No major differences were found between the two Higher proportion of vio- 1
(1994) ing victims in both groups with MD-nonpsych groups in socio-demographic features, comorbid- lent methods in psychotic
ity, clinical history or suicidal ideation patients, p ¼0.028
Suominen et al. Follow-up To assess the outcome of patients in both groups, 1820 individuals; 798 with MD- Psychotic symptoms after major depressive epi- 3 fold Increase [Hazard 0
(2009) following a suicide attempt and effect of psychosis psych and 1022 with MD-nonpsych sode increase the risk of suicide after a serious Ratio ¼3.32(CI:1.95–5.67)]
and depression severity on outcomes at a nation- suicide attempt.
wide 8-year cohort. The study also examined the
frequency of antidepressant treatment after the at-
tempt and its effect on mortality
Leadholm (2014) Follow-up This study looked at the risk factors for suicide in 34,671 individuals; 12,101 with MD- Old age, male gender and previous attempts were No significant difference 0
MDpsy and MD non-psy groups to investigate psych and 26,106 with MD- found to be risk factors for future suicide attempts.
whether the presence of psychotic symptoms in nonpsych
major depression is an independent risk factor for
suicide

25
 26
Table 2
Studies comparing risk of suicide attempts in MD-psych and MD-nonpsych.

Study Sample Description Study Population Findings Risk of suicide at- Score
tempts in psychotic
vs. non-psychotic
depression

Frangos Inpatient Retrospective chart review; the two groups were compared 145 with MD-psych and 119 with MD-psych is a severe variant of major depression Higher but not sta- 0
et al. to assess whether MDpsych represents a distinct subtype MD-nonpsych tistically significant
(1983) or a severe variant of major depression (no significant
difference)
Robinson Inpatient 1-year follow up study following discharge from hospital 52 patients met criteria for MD- Patients in MD-psych group had higher rates of major depression No difference 0
and Spi- psych; control group consisted of or delusions lasting longer than 9 months and of being in a major
ker (1985) 52 patients with MD-nonpsych depressive episode at the end of the follow up period
Miller and Inpatient Retrospective analysis of MDpsych patients admitted to 45 consecutive patients with MD- MD-psych patients with delusions of sinfulness, guilt, deserved 1.5 fold higher, not 0
Chabrier Payne Whitney Clinic with medically serious suicide psych discharged from the hospital punishment, or persecution were more likely to make more ser- statistically
(1987) attempts ious suicide attempts than those with delusions of bodily disease, significant

I. Zalpuri, A.J. Rothschild / Journal of Affective Disorders 198 (2016) 23–31

damage, and malfunction
Wolfersdorf Inpatient Retrospective study that assessed the significance of delu- 46 patients with MD-psych com- MD-psych patients were less suicidal than MD-nonpsych. The two Increased in pre- 0
et al. sional symptoms for suicidality in MDpsych patients pared to 46 MD-nonpsych patients groups did not differ in frequency of suicide. vious case histories,
(1987) p¼ 0.07
Johnson Population- Cross-sectional and 1-year prospective data. This study 114 MD-psych and 662 MD-non- Patients with MD-psych had a more SA, more multiple episodes, Increased, p o 0.05 0
et al. Based examined the rates and associated features of MDpsych in psych patients more persistent illness over 1 year, higher comorbidity with OCD,
(1991) a community sample somatization, phobia. Findings support its inclusion in DSM-IV as
a distinct subtype
Lyness et al. Inpatient Retrospective chart review to describe the psychopatho- Total 168 patients, 25 attempted Affective illness, especially late-onset major depression, was the More severe at- 0
(1992) logical characteristics of elderly suicide attempters ad- suicide. Eighty percent of attemp- major association with suicide attempts. More severe SA were tempts in MD-psych,
mitted to an inpatient psychiatric unit ters had major depressive found in the MD-psych group, although the trend was not but not significant
syndrome significant
Hori et al. Inpatient Retrospective chart review to evaluate differences in sev- 38 patients with MD-psych and 55 Higher mean age of onset of illness, lower incidence of psycho- Increased, p o 0.05 0
(1993) eral variables, including suicide between the two groups with MD-nonpsych motor retardation, higher frequency of suicidal ideation and at-
during a 12-year period of retrospective observation tempts and more violent methods were found in MD-psych group
Lykouras Inpatient Elderly patients with MD-psych and MD-nonpsych con- 40 patients with MD-psych and 64 Psychotic symptoms do not increase the risk of suicide attempt in No significant 0
et al. secutively admitted to hospital were compared for ser- with MD-nonpsych; 11 MD-psych elderly depressed patients difference
(2002) iousness of suicidal behavior and 17 MD-nonpsych patients at-
tempted suicide
Lee et al. Inpatient Cross-sectional study that explored the clinical and phe- 48 patients with MD-psych and 108 MD-psych group had higher risk of SA, guilt, greater daily func- Increased, p ¼ 0.001 0
(2013) nomenological aspects of MDpsych and MD non-psych el- with MD-nonpsych tional impairment. They also had higher scored on Hamilton De-
derly Chinese patients pression Rating Scale and lower scores on Mini-Mental State
Examination
Gaudiano Outpatient Study comparing rates and severity of depressive symp- 1112 patients, of which 60 diag- MD-psych group had higher levels of severity of various depres- Increased, p o 0.05 0
et al. toms between the two groups nosed with MD-psych sive symptoms
(2008)
Holma et al. Inpatient Prospective 5-year study to examine differences in in- Total 249 patients 106 suicide attempts; 98 had psychotic features, 8 did not In- No difference 1
(2010) and cidence of suicide attempts in patients with major de- cidence of suicide attempts varies and is highest during major
outpatient pressive episodes depressive episodes
Adeosun Outpatient Comparison of rates and severity of depression amongst 129 patients with MD-psych and Patients with MD-psych had higher rates of suicidal ideation, Increased, p o 0.009 0
and Jeje the two groups 117 MD-nonpsych suicide attempts, psychomotor agitation, insomnia, reduced 0
(2013) appetite Increased, 0
p¼ 0.023
Inpatient Investigation to identify clinical correlates of MD-psych 24 patients with MD- psych and MD-psych patients had higher rates of inpatient hospitaliza- Odds ratio ¼8.89;
and out- and MD-nonpsych in Korean population with Major De- 942 patients with MD-nonpsych tions, global severity, higher scores on several items on brief 95%confidence In-
patient pressive Disorder psychiatric rating scale and were at higher risk for suicide terval (1.59–
Park et al. Outpatient Clinical case-clinical control study of adolescents, to as- 25 patients with MD-psych and MDpsych had higher rates of suicide attempts; frank psychotic 49.83).
(2014) sess the prevalence of frank psychotic experiences and 12 MD-nonpsych experiences are significant but under-recognized marker of risk
Kelleher their relationship with affective, anxiety, behavioral dis- for psychopathology and poor functioning
et al. orders and suicidal behaviors
(2014)
 I. Zalpuri, A.J. Rothschild / Journal of Affective Disorders 198 (2016) 23–31
between MD-psych and MD-nonpsych groups.
3.1.1. Studies on inpatient psychiatric units
One study included a retrospective analysis of all suicides at the
New York State Psychiatric Institute over a twenty-five year period
from 1955 to 1980 (Roose et al., 1983). Patients were diagnosed
retrospectively according to Research Diagnostic Criteria (Spitzer
et al., 1978). 39 patients had committed suicide during the study
period; 22 had affective disorder and 14 of those met criteria for
major depressive disorder. Of those 14, 10 patients had MD-psych.
Patients with unipolar MD-psych were 5 times more likely to
commit suicide than a patient with a MD-nonpsych (relative risk:
5.3, p o0.05). Delusions were the most powerful predictors of
suicide potential in patients with endogenous depression. 5 out of
10 patients with MD-psych committed suicide when they were
believed to be better by family and medical staff. The study raised
an interesting question as to whether the psychotic process
transforms suicidal thoughts in depressed patients to suicidal acts.
In 1987, a retrospective study of inpatients in the depression
ward of Weissenau State Psychiatric Hospital was conducted
(Wolfersdorf et al., 1987). During the period of their study, 6 pa-
tients committed suicide. 4/46 (8.7%) patients with MD-psych
committed suicide compared to 2/46 (4.3%) patients with MD-
nonpsych. The authors reported no statistically significant differ-
ences in suicide rates; however, their sample size was very small.
On calculating odds ratio, they found that the relative risk that
MD-psych patients would die by suicide was 2.1 times greater than
MD-nonpsych patients.
3.1.2. Population-based studies
In 1994, a psychological autopsy was conducted to study dif-
ferences between MD-psych and MD-nonpsych as part of the
National Suicide Prevention Project in Finland (Isometsä et al.,
1994). Authors retrospectively analyzed suicides committed in
Finland between April 1987-March 1988. Information was ob-
tained by interviewing relatives and health care providers of sui-
cide victims and provisional diagnoses were assigned retro-
spectively using DSM-III-R criteria. The sample consisted of 24
MD-psych and 46 MD-nonpsych patients. The authors reported
that the two groups did not differ in previous suicide attempts or
frequency of suicidal ideation or intent. However, they found that
patients with MD-psych were more likely to use violent methods
of suicide (88% vs. 59%, p¼ 0.028) than patients with MD-non-
psych. A higher proportion of MD-psych patients committed sui-
cide during hospital treatment (21% vs. 11%, p¼ NS), but it was not
found to be statistically significant. Only 21% of the MD-psych
sample was inpatient at the time of suicide.
3.1.3. Follow-up studies
In 1988, a follow up study did not find any significant differ-
ences in rates of suicide between MD-psych and MD-nonpsych
patients in a 0–14 year follow up study of patients admitted to
University of Iowa Psychiatric Hospital between January 1970 and
December 1981 (Black et al., 1988). They found that 10.9% of
subjects with MD-psych committed suicide as compared to 11.5%
subjects with MD-psych. In a 1-year follow up study following
discharge from an inpatient unit, a study (Robinson and Spiker,
1985) matched 52 MD-psych to 52 MD-nonpsych patients and
found no significant differences between the two groups. How-
ever, this was not the primary focus of their study, their power was
low and the study period was short. They found 1 suicide in MD-
psych and no suicides in MD-nonpsych group. A 40 year follow up
study (Coryell et al., 1982) using chart reviews was conducted on
inpatients in Iowa, where 10% (7/70) died by suicide in the MD-
psych group compared to 8.4% (8/95) in the MD-nonpsych group,
although again the primary focus of this study was not to assess
27
suicide risk in the two groups. There was no statistically significant
difference between the two groups. Both in this study and the
study by Black et al. (1988), psychiatric status of suicide victims at
the time of suicide was unknown.
A study (Suominen et al., 2009) reported a 4-year follow up in
Finland where the study population comprised of individuals 16
years or older with ICD-10 diagnosis of MD-psych, MD-nonpsych
and other or unspecified (F32.8, F32.9, F33.8, F33.9). They found
that psychotic symptoms increased the risk of completed suicide
following a suicide attempt by 3-fold in individuals with MD-
psych (Hazard Ratio ¼3.32[Confidence Interval:1.95–5.67]). One
limitation of this study was that diagnoses were not made by
standardized diagnostic interview schedules but were made by
physicians who treated these patients on the unit. A registry based
Danish prospective cohort study (Leadholm et al., 2014) was
conducted to determine suicide risk factors in depressed adults
hospitalized at Danish hospitals between 1994 and 2010. This in-
cluded 755 patients who committed suicide during follow up. Of
these 551 (2.1%) had MD-nonpsych and 280 (2.3%) were diagnosed
with MD-psych by ICD-10 criteria. MD-psych was not found to be
an independent risk factor for suicide. All subjects in this study
were severely depressed, whereas previous studies had reported
on a range of depression severity.
3.2. Suicide attempts
The majority of studies, which looked at attempted suicides,
have shown a higher rate of suicide attempts in MD-psych com-
pared to MD-nonpsych. Table 2 summarizes pertinent studies
comparing the two groups.
3.2.1. Studies on inpatient psychiatric units
In one study (Frangos et al., 1983), authors conducted a retro-
spective chart review of a total of 264 patients: 145 MD-psych and
119 MD-nonpsych, discharged from 6 psychiatric inpatient units of
the State Mental Hospital in Athens. They reported that suicide
attempts were more frequent in MD-psych group, 27.6% vs. 22.7%,
but this finding was not statistically significant. Another study
(Wolfersdorf et al., 1987) also reported that more suicide attempts
were seen in previous case histories of MD-psych patients (37%) as
opposed to MD-nonpsych patients (20%, p ¼ 0.07). Over a 12-year
period, researchers conducted a retrospective chart review (Hori
et al., 1993) of hospitalized patients with MD-psych or MD-non-
psych at University of Tsukuba, Japan, using DSM-III criteria, over a
12-year period. Any self-inflicted injury where the subject thought
that there was a risk of dying was considered as a suicide attempt.
18/38 (47%) and 10/55 (18.2%) patients attempted suicide in the
MD-psych and MD-nonpsych group respectively (p o0.05). Pa-
tients with MD-psych were more likely to use more violent
methods of suicide than the MD-nonpsych group such as pene-
trating or cutting deep into their bodies (9.4%), jumping (9.4%) or
self-immolation by fire (6.3%). Hanging was slightly more common
in the MD-nonpsych group (36.8% vs. 31.2% in MD-psych group).
Another study (Lykouras et al., 2002) compared the two groups in
an inpatient study in Greater Athens Area and did not find any
significant difference in the rate of suicide attempts during pre-
vious (27.5% for MD-psych vs. 26.5% for MD-nonpsych) and current
episodes (12.5% for both). Patients and an informant were inter-
viewed on previous suicide attempts. The small number of suicide
attempters in this study (11 in MD-psych and 17 in MD-nonpsych
group) could reduce the power of comparison and makes results
liable to type II error. They found that half of the subjects in each
group used violent methods (stabbing, shooting or hanging
themselves, severing wrists, drowning), which differed from the
findings of Hori et al. (1993) where patients with MD-psych used
more violent methods of suicide than patients with MD-nonpsych.
 28
Table 3
Studies comparing risk of suicidal ideation in MD-psych and MD-nonpsych groups.

Study Sample Description Study population Findings Risk of suicidal Score

ideation in psycho-
tic vs. non-psychotic
depression

Nelson et al. Inpatient The study examined clinical variables, family his- 13 patients with MD-psych com- MD-psy group had more family history of depression and less of al- Increased, po 0.05 2
(1984) tory, cortisol secretion and 4-week tricyclic anti- pared to 12 MD-nonpsych patients coholism, poorer response to tricyclics, greater frequency of cortisol
depressant response in both groups hypersecretion
Wolfersdorf Inpatient Retrospective study that assessed the significance of 46 patients with MD-psych com- MDpsych patients were less suicidal than MD non-psy. The two Decreased, p o 0.01 0
et al. delusional symptoms for suicidality in MDpsych pared to 46 MD-nonpsych patients groups did not differ in frequency of suicide.
(1987) patients
Johnson Population- Cross-sectional and 1-year prospective data. This 114 MD-psych and 662 MD-non- Patients with MDpsych had a more SA, more multiple episodes, more No significant 0
et al. Based study examined the rates and associated features of psych patients persistent illness over 1 year, higher comorbidity with OCD, somati- difference
(1991) MDpsych in a community sample zation, phobia. Findings support its inclusion in DSM-IV as a distinct
subtype

I. Zalpuri, A.J. Rothschild / Journal of Affective Disorders 198 (2016) 23–31

Quinlan Inpatient, The study systematically examined demographic Total 150 adolescents, 15 with MD- MDpsych group had more frequent and severe SI. Also it was asso- Increased, po 0.017 0
et al. adolescents and clinical differences between the two groups psych and 135 with MD-nonpsych ciated with more frequent PTSD
(1997)
Hori et al. Inpatient Retrospective chart review to evaluate differences 38 patients with MD-psych and 55 Higher mean age of onset of illness, lower incidence of psychomotor Increased, po 0.05 0
(1993) in several variables, including suicide between the with MD-nonpsych retardation, higher frequency of suicidal ideation and attempts and
two groups during a 12-year period of retrospective more violent methods were found in MDpsych group
observation
Thakur et al. Inpatient Case control study where the two groups were 189 patients with MD-psych and 485 Younger age, psychomotor retardation, guilt, feelings of worthless- Increased, p¼ 0.004 0
(1999) and compared on clinical, demographic and social with MD-nonpsych ness, history of delusions and increased SI and intent were found
Outpatient characteristics more commonly in MDpsych group. MDpsych was also associated
with poor subjective social support and bipolar illness.
Lykouras Inpatient Elderly patients with MD-psych and MD-nonpsych 40 patients with MD-psych and 64 Psychotic symptoms do not increase the risk of suicide attempt in No difference 0
et al. Outpatient consecutively admitted to hospital were compared with MD-nonpsych; 11 MD-psych elderly depressed patients Increased, P o 0.05 0
(2002) for seriousness of suicidal behavior and 17 MD- nonpsych patients at-
Study comparing rates and severity of depressive tempted suicide MD-psych group had higher levels of severity of various depressive
Gaudiano symptoms between the two groups 1112 patients, of which 60 were symptoms
et al. diagnosed with MD-psych
(2008)
Adeosun Outpatient Comparison of rates and severity of depression 129 patients with MD-psych and 117 Patients with MD-psych had higher rates of suicidal ideation, suicide Increased, po 0.005 0
and Jeje amongst the two groups MD-nonpsych attempts, psychomotor agitation, insomnia, reduced appetite
(2013)
 I. Zalpuri, A.J. Rothschild / Journal of Affective Disorders 198 (2016) 23–31
This could be due to the age differences between the two studies,
since Lykouras et al. (2002) had enrolled a geriatric population,
whereas patients in the study conducted by Hori et al. (1993) were
relatively younger.
An inpatient cross-sectional study (Lee et al., 2013) was con-
ducted to compare the suicide attempt rates in the MD-psych and
MD-nonpsych groups. Their sample consisted of patients admitted
to a geriatric psychiatry ward of Veterans General Hospital- Taipei,
Taiwan, aged 65 years or older, who met DSM-IV criteria for major
depressive disorder. In MD-psych patients, 14 out of 34 (41.2%)
patients had current suicide attempts, whereas in 98 MD-non-
psych patients, only 10 (10.2%) had current suicide attempts
(p ¼0.001). The odds ratio for suicide attempts in the MD-psych
group was 4.04 times higher than their MD-nonpsych
counterparts.
3.2.2. Studies including both inpatient and outpatient referrals
Incorporating both inpatients and outpatients as part of NIMH
sponsored multisite Study of the Pharmacotherapy of Psychotic
Depression (STOP-PD) study, researchers (Schaffer et al., 2008)
reported that of the first 183 patients with MD-psych: 59.6% re-
ported suicidal ideation or made a suicide attempt during the
current episode; 20.8% had attempted suicide during the current
episode; and, 35.5% had a made a lifetime suicide attempt. In
2009, authors (Meyers et al., 2009) reported on the full sample of
the 259 subjects from the NIMH STOP-PD study: 18.5% subjects
had attempted suicide during the current episode of psychotic
depression. In 2010, another group of researchers (Holma et al.,
2010) conducted a prospective 5-year study in patients with major
depression. They found no difference in the rate of suicide at-
tempts between MD-psych and MD non-psych groups.
In 2014, Park et al., (2014) investigated a cohort of Korean pa-
tients (n¼ 966) of age over 18 years, with MD-psych and MD-
nonpsych to determine which clinical variables were significantly
different between the two groups. Of 24 MD-psych patients, 41.7%
(N ¼10) attempted suicide, whereas of 942 MD-nonpsych patients,
22.1% (N ¼208) attempted suicide (p ¼ 0.023).
3.2.3. Outpatient studies
Several outpatient studies have also reported differences in the
frequency of suicide attempts between MD-psych and MD-non-
psych patients. An outpatient study (Gaudiano et al., 2008) en-
rolled outpatient psychiatric patients in a study at the Rhode Is-
land Hospital Department of Psychiatry and reported a higher
degree of suicide attempts in MD-psych compared to MD-non-
psych patients (p o0.05), although the number of suicide at-
tempters was small: 6/60 (10%) in MD-psych and 21/1052 (2%) in
MD-nonpsych. In a recent study (Adeosun and Jeje, 2013), authors
enrolled 129 MD-psych and 117 MD-nonpsych outpatients over a
four-month period at the largest mental health care facility in
Nigeria. Diagnoses were made using Structured Clinical Interview
for DSM-IV. The rates of suicide attempts were significantly higher
in MD-psych subjects compared to MD-nonpsych patients (17.8 vs.
6.8%, p o0.009). In 2014, Kelleher et al. (2014) conducted a clinical
case-clinical control study in the Republic of Ireland, where par-
ticipants were 108 adolescents, 12–16 years of age, with and
without psychotic experiences. Authors aimed to assess the pre-
valence of attenuated psychotic experiences and their relationship
with affective, anxiety and behavioral disorders, multimorbid
psychopathology as well as with global functioning and suicidal
behavior. 37 (34%) individuals were diagnosed with Major De-
pressive Disorder. They found that of those with psychotic ex-
periences (MD-psych ¼25), 64% attempted suicide, whereas of
those with no psychotic experiences (MD-nonpsych ¼12), 17% at-
tempted suicide [Odds Ratio¼ 8.89; 95%Confidence Interval (1.59–
49.83)].
29
3.2.4. Population-based studies
In 1991, using community samples, Johnson et al. (1991) found
a significant difference in the rate of suicide attempts between
MD-psych and MD-nonpsych. They used the community sample
from the NIMH Epidemiologic Catchment Area study (Johnson
et al., 1991), where two sets of interviews were conducted a year
apart at five sites. Patients met DSM III criteria for major depres-
sion and reported delusions or hallucinations. The risk for suicide
attempts was more than double for MD-psych patients compared
to MD-nonpsych patients (27.2% vs. 12.6%, p o 0.05).
3.2.5. Follow-up studies
One study (Robinson and Spiker, 1985) found no difference
between the two groups; however only 2 suicide attempts in MD-
psych and 1 attempt in MD-nonpsych group were reported. In
another inpatient study (Miller and Chabrier, 1987), authors found
the risk of suicide attempts 1.5 times higher in MD-psych group,
but this was not statistically significant. In 1992, a retrospective
chart review of elderly suicide attempters admitted to an inpatient
unit was conducted (Lyness et al.,1992). In this review, authors
reported that patients who had made more severe attempts were
more likely to be diagnosed as MD-psych, although this trend was
not significant.
3.3. Suicidal ideation
Nearly all hospital based studies examining and comparing
rates of suicidal ideation between MD-psych and MD-nonpsych
have reported a higher degree of suicidal ideation in the MD-psych
group. Table 3 summarizes studies comparing suicidal ideation in
the two groups.
3.3.1. Studies on inpatient psychiatric units
Inpatient studies have found a higher degree of suicidal idea-
tion in patients with MD-psych as compared to their MD-non-
psych counterparts (Nelson et al., 1984, Miller and Chabrier, 1987).
Nelson et al. (1984) studied family history, cortisol secretion,
clinical variables and 4-week tricyclic antidepressant response in
13 MD-psych and 12 MD-nonpsych patients admitted to West
Virginia University Medical Center. They found that the Hamilton
Depression Rating scale item for suicidal ideation was significantly
higher in the MD-psych group than the MD-nonpsych group
(2.871.0 vs. 1.4 71.4, p o0.05). Another study (Wolfersdorf et al.,
1987) found that at the time of admission, half of the MD-psych
patients were suicidal as compared to 76% in the MD-nonpsych
group, p o 0.01. In 1993, one study (Hori et al., 1993) found the rate
of suicidal ideation in MD-psych to be 84.2 vs. 67.3 (p o0.05) in
MD-nonpsych. The only inpatient adolescent study conducted
(Quinlan et al., 1997) studied adolescents 12–18 years of age, who
were admitted to the University Medical Center in Michigan, over
a 2-year period. The Suicidal Ideation Questionnaire-JR was used
to assess presence and severity of suicidal ideation. Patients with
MD-psych had statistically significantly higher scores (48.6 722.7)
compared to the MD-nonpsych group (28.3 7 24.2) p ¼0.017 and
were found to express considerable more frequent and severe
suicidal ideation.
3.3.2. Outpatient studies
Several outpatient studies also found similar results. One study
(Gaudiano et al., 2008) reported increased thoughts of death
(OR¼ 3.7) thoughts of suicide (OR¼ 2.8) suicide plan (OR ¼2.4) and
suicide attempt (OR ¼5.5) in MD-psych patients compared with
MD-nonpsych patients. Of 60 MD-psych patients, 78% (47) had
thoughts of death, 48% (29) had thoughts of suicide and 23% (14)
had a suicide plan compared to MD-nonpsych patients where 49%
(520) had thoughts of death, 25% (265) had thoughts of suicide
30 I. Zalpuri, A.J. Rothschild / Journal of Affective Disorders 198 (2016) 23–31
and 12% (126) had a plan. Another study (Adeosun and Jeje, 2013)
found a higher prevalence of suicidal ideation in MD-psych vs.
MD-nonpsych (58.1% vs. 40.2%, p o 0.005).
3.3.3. Studies including both inpatient and outpatient referrals
In 1999, a large case control study (Thakur et al., 1999) re-
cruiting inpatients as well as outpatients at Duke University
Medical Center was conducted. Based on the Carroll Self Rating
Depression scale (Carroll et al.,1981), the MD-psych group
(n ¼189) reported more suicidal ideation as compared to the MD-
nonpsych group (n¼ 485) (57% vs. 42%, p ¼0.004). They did not
specify what percentage of this was suicidal ideation and what
percentage were attempts.
3.3.4. Population-based study
In their community sample, Johnson et al. (1991) found no
difference in suicidal ideation between MD-psych and MD-non-
psych (47.8% in MD-nonpsych vs. 55.8% in MD-psych), although
they had found a higher rate of suicide attempts in the MD-psych
group when compared to the MD-nonpsych group.
4. Conclusions
The purpose of this study was to ascertain, by undertaking a
comprehensive and critical review of the psychiatric literature,
whether patients with MD-psych have a higher rate of completed
suicides, suicide attempts or suicidal ideation than patients with
MD-nonpsych. The answer to this question and an explanation for
the seemingly conflicting data in previous studies appears to be
related to whether one looks at differences during the acute epi-
sode or over the long-term.
Our review indicates that during the acute episode of depres-
sion, particularly when the patient is hospitalized on an inpatient
psychiatric unit, patients with MD-psych have higher rates of
suicide, suicide attempts, and suicidal ideation than patients with
MD-nonpsych. This makes sense because in the acute episode the
patient with psychotic depression has the combination of a se-
verely depressed mood and delusions, which are frequently of a
nihilistic and depressing quality.
Studies done after the acute episode has resolved (e.g. long-
term follow-up studies) are less likely to show a difference be-
tween psychotic and non-psychotic depressed patients on rates of
suicide, suicide attempts, or suicidal ideation. We believe this is
due to the fact that the patients may have received treatment and
the patients with MD-psych are less likely to be suffering from the
combination of depression and nihilistic, negativistic delusions.
The findings from our comprehensive literature review have
practical implications for the clinician treating patients with psy-
chotic depression; specifically, that the risk of suicide remains
increased until the patient has had remission of their depressive
and psychotic symptomatology. The first important step in pre-
venting suicide in patients with MD-psych is recognition of the
illness. Unfortunately, psychotic depression is frequently not re-
cognized (Rothschild et al., 2008) which can lead to an under
appreciation of the risk of suicide. It is likely that the missed di-
agnosis rate observed in this study was a conservative estimate of
the rate in the general clinical population, as patients with co-
morbid conditions such as a history of substance abuse in the past
3 months or unstable medical conditions were excluded. MD-
psych was most commonly misdiagnosed as either major de-
pressive disorder without psychotic features, depression NOS, or
mood disorder NOS. It was quite striking that none of the patients
with missed diagnoses were considered to have a psychotic dis-
order. This finding suggests that the physicians were missing the
psychosis rather than the mood disorder.
A missed diagnosis can lead to less than optimal treatment
being rendered (Andreescu et al., 2007) and thus prolong the pa-
tient's recovery time, which in turn may increase the risk of sui-
cide. In addition, many patients with psychotic depression feel
paranoid and will tend to keep their thoughts to themselves. This
includes suicidal thoughts and ideation making it more difficult for
the clinician to assess the patient's risk for suicide.
A limitation of our review is that some of the studies included
in the review were retrospective analyses and did not use formal
diagnostic interviews to distinguish MD-psych from MD-non-
psych. Hence, it is possible that some of the patients in these
studies did not receive the correct diagnosis. Another limitation is
that most studies did not report whether the psychotic symptoms
in the MD-psych patients were mood-congruent or mood-incon-
gruent. Consequently, we cannot make any conclusions as to
whether the type of delusion increases the risk of suicide. The
papers we reviewed did not describe whether the auditory hal-
lucinations observed in the MD-psych patients were command
hallucinations encouraging the patients to engage in suicidal be-
havior and enhancing their risk of suicide. Ultimately, only 24
studies met the inclusion criteria; several had small sample size
and a quality score of zero, thereby impacting validity.
Studies that reported suicide attempts or completed suicides in
the follow up period did not list the psychiatric status of victims at
the time. Since suicidal behavior in depression or bipolar disorders
is state and severity dependent, it is possible that the attempts or
deaths occurred during major depressive episodes. Suicidal beha-
vior in patients with major mood disorder is extremely rare during
euthymia/remission (Holma et al., 2010). Whereas on the other
hand, studies show that psychotic/nonpsychotic nature of de-
pression is quite consequent across consecutive depressive
episodes.
In conclusion, although studies in the literature appear to be
conflicting, our comprehensive review indicates that patients with
psychotic depression tend to have higher rates of suicide, suicide
attempts, and suicidal ideation when compared to patients with
non-psychotic depression. This appears to be particularly true
during the acute episode of the illness.
Acknowledgments
Supported in part by the Irving S. and Betty Brudnick Endowed Chair of Psy-
chiatry at University of Massachusetts Medical School (Dr. Rothschild).
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