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The Central Domains of Personality Pathology in Psychiatric Patients

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Journal of Personality Disorders, 27, 2013, 070
© 2013 The Guilford Press
PERSONALITY DISORDER AND DEPRESSION
NEWTON-HOWES ET AL.

INFLUENCE OF PERSONALITY ON THE

OUTCOME OF TREATMENT IN DEPRESSION:
SYSTEMATIC REVIEW AND META-ANALYSIS
Giles Newton-Howes, MRCPsych, FRANZCP,
Peter Tyrer, MD, FMedSci, Tony Johnson, PhD,
Roger Mulder, PhD, FRANZCP, Simone Kool, MD,
Jack Dekker, PhD, and Robert Schoevers, MD

There continues to be debate about the influence of personality disorder

on the outcome of depressive disorders and is relative interactions with
treatment. To determine whether personality disorder, both generically and
in terms of individual clusters, leads to a worse outcome in patients with
depressive disorders and whether this is influenced by type of treatment, a
systematic electronic search of MEDLINE, CINAHL, and PsycINFO from
1966, 1982, and 1882, respectively, until February 2007 was undertaken.
The keyword terms depression, mental illness, and personality disorder
were used. All references were reviewed and personal correspondence was
undertaken. Only English language papers were considered. Any English
language paper studying a depressed adult population was considered for in-
clusion. Studies needed to clearly define depression and personality disorder
using peer-reviewed instruments or International Classification of Disease/
Diagnostic Statistical Manual criteria. Outcome assessment at greater than 3
weeks was necessary. Final inclusion papers were agreed on by consensus by
at least two reviewers. All data were extracted using predetermined criteria
for depression by at least two reviewers in parallel. Disagreement was settled
by consensus. Complex data extraction was confirmed within the study
group. Data were synthesized using log odds ratios in the Cochrane RevMan
5 program. The finding of comorbid personality disorder and depression
was associated with a more than double the odds of a poor outcome for
depression compared with those with no personality disorder (OR 2.16, CI
1.83–2.56). This effect was not ameliorated by the treatment modality used
for the depressive disorder. This finding led to the conclusion that personal-
ity disorder has a negative impact on the outcome of depression. This finding
is important in considering prognosis in depressive disorders.

This article was accepted under the editorship of Paul S. Links.

From the Department of Psychological Medicine, University of Otago, Wellington, New Zealand (G. N.-
H.); Department of Psychological Medicine, University of Otago, Christchurch, New Zealand, (R. M.);
Department of Psychological Medicine, Imperial College London (G. N.-H., P. T.); Arkin Mental Health
Institute, Amsterdam (S. K.; J. D.); Free University Amsterdam (J. D.); MRC Biostatistics Unit, Univer-
sity of Cambridge Institute of Public Health, Cambridge, and MRC Clinical Trials Unit, London (T. J.);
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen,
The Netherlands (R. S.).
Address correspondence: to Giles Newton-Howes, Department of Psychological Medicine, School of
Medicine and Health Sciences, University of Otago, Wellington, PO Box 7343, Wellington South, New
Zealand; E-mail: giles.newton-howes@otago.ac.nz

1
2 NEWTON-HOWES ET AL.

There has been a long-standing debate within psychiatry about the diag-
nostic position of personality disorders and their influence on the course of
mental state disorders. This is particularly true of the influence of personality
status on depression with the literature stretching back more than 60 years
(Hobson, 1953). As it is becoming increasingly clear that depression can be
both an acute and a chronic disorder (Eaton et al., 2008), understanding
the factors that are linked to a poorer prognosis is becoming increasingly
important.
The impact of personality has been studied with some commentators
challenging the “received wisdom” of poorer outcome in depression with
comorbid personality disorder. In an important narrative review, Mulder
(2002) reported no impact on outcome in depression with personality pa-
thology, and this stance has been supported by others in the field using a
variety of methodologies to combine the literature (Kool, et al., 2005). Not
all reviews have come to this conclusion. An inclusive systematic review and
meta-analysis, including papers with cohort, case-control, and randomized
control methodologies, found poorer outcomes for the comorbid group
(Newton-Howes, Johnson, & Tyrer, 2006), supporting an earlier negative
narrative review (Reich, 2003). Such an approach to systematic reviews, in-
cluding all methodologies, has a sound basis (Concato, Shah, & Horwitz,
2000) and increases the number of patients able to be included in any analy-
sis. This question has clinical importance because the implication of poorer
prognosis in the presence of comorbid personality disorder both aids prog-
nostic accuracy and implies that interventions focused on the comorbid per-
sonality disorder as well as depression may be of benefit. There is a growing
body of evidence that a variety of pharmacological (Coccaro & Kavoussi,
1997; Nickel et al., 2006; Nickel et al., 2005; Sheard, Marini, Bridges, &
Wagner, 1976), psychological (Bateman & Fonagy, 2008; Blum et al., 2008;
Giesen-Bloo et al., 2006; Linehan et al., 2006; McMain et al., 2009; Tyrer et
al., 2004), and social interventions (Tyrer & Tyrer, 2008) can improve out-
comes in personality disorder. If in fact personality disorder does not have
any impact in Axis I disorder, then it does not need to be a primary focus of
treatment in depressed patients as is commonly the case within current day-
to-day psychiatric practice (Tyrer et al., 2007). There is, however, evidence
that this is not the case generally (Crawford et al., 2008), and a degree of
personality–mood interaction would be expected.
Despite the numerous clinical papers and recent reviews on this topic,
the best analysis of the current data is unclear. In order to address this issue,
the authors of the most recent reviews came together as the Personality Dis-
order and Depression Outcome Group (PDDOG) to reexamine the data and
to include all recently published studies. The aim of the meta-analysis was to
examine both (1) the outcome of depressive disorders, irrespective of treat-
ment, in research studies in which both personality status and depression
were measured at baseline, and (2) whether different modalities for treat-
ment for depression had their outcomes altered by the presence of comorbid
personality disorder. The goal was to provide clear clinical advice to practic-
ing psychiatrists as to the impact of personality disorder in depression.
PERSONALITY DISORDER AND DEPRESSION 3

METHODS

SELECTION AND STUDY CHARACTERISTICS

We selected all papers that studied the outcome of depression in patients

with a diagnosis of comorbid personality disorder. As the diagnostic criteria
for personality disorder (and depression) have evolved over time, any paper
that clearly diagnosed these conditions over time was eligible for selection.
Inclusion criteria were kept broad in order to maximize included studies.
Only papers written in English were reviewed. The principal exclusion crite-
rion for this review was lack of a categorical diagnosis for either personality
disorder or depression. Many papers comment on personality function us-
ing dimensional criteria. Although there is some evidence that this approach
may reflect the structure of personality more appropriately (Livesley, 2007),
it does not accord with clinical decision making and generally has been cri-
tiqued as having less clinical utility (Rottman, Ahn, Sanislow, & Kim, 2009;
Skodol & Bender, 2009). Because the review aimed to assist psychiatrists
with clinical prognosis, categorical diagnosis was considered essential.

SEARCH STRATEGY

A broad search strategy was employed to ensure maximum coverage of the

literature. Initially a search of the databases MEDLINE (from January 1,
1966), CINAHL (from January 1, 1982) and PsycINFO (from January 1,
1882) was undertaken in April 2002 and repeated in February 2007. The
key words depression, mental illness, and personality disorder were entered
and combined. To supplement the electronic search, the Journal of Affective
Disorders was hand searched by one of the authors (G.N.-H.), the references
of all articles were reviewed, and experts in the field were contacted. The
Quality of Reporting of Meta-Analysis statement (Moher et al., 1999) and
other work (McAuley, Pham, Tugwell, & Moher, 2000) has highlighted the
possibilities of publication bias if unreported studies are not included, and
this was considered by the PDDOG group. The gray literature was, however,
not consulted because it was not considered likely that studies would be
“buried” for commercial gain in this area; no obvious source of gray litera-
ture (such as the FDA) could be identified; and due to the difficult nature of
accurately diagnosing personality disorder, the rigor of peer review was felt
to provide an extra safeguard to ensure like was compared to like.

PRINCIPAL OUTCOME

The principal outcome was the odds of an altered outcome in the treatment
of depression in the presence of a personality disorder. The outcome for
each paper was dichotomized and recovered versus chronic/nonrecovered
outcomes compared between personality disordered and nonpersonality dis-
ordered groups. Recovery was identified by a sustained treatment response
for the duration of the trial. In this way recovery was differentiated from re-
4 NEWTON-HOWES ET AL.

sponse, whereby patients may have initially responded but not sustained that
response to the intervention provided. Authors identified a variety of meth-
ods for defining recovery, although cutoff scores for the standard measures
used to rate depressive symptomatology were common, such as a Hamilton
Depression rating scale score of less than 7.

DATA EXTRACTION

Two-by-two tables were designed to ensure uniformity of the data extracted.

As far as possible, all information extracted was stratified by treatment type
and personality cluster. Numbers were extracted directly from the papers
where possible and derived from summary percentages, or reconstructed
from summary statistics such as chi squares when direct extraction was
not possible. All information extracted from each paper was cross-checked
against the other information provided within each paper (by counts, per-
centages, summaries, or test statistics) to check for and resolve inconsisten-
cies. Where dichotomous outcomes were not reported for depression out-
come, but outcomes were presented as means and standard deviations on a
rating scale, “recovered outcome” was used to derive a dichotomous pairing
using the method of Whitehead, Bailey, and Elbourne (1999). All data were
extracted by at least two of the authors with all disagreements resolved by
consensus within the group.

QUANTITATIVE DATA SYNTHESIS

RevMan is the Cochrane Collaboration’s electronic meta-analysis software

(Higgins & Green, 2009). It allows for combination of data and construction
of forest plots and grouped outcomes. Furthermore, its random effects analy-
sis takes into account the lack of a gold standard baseline that is problem-
atic in studies of personality disorder. All dichotomized data were therefore
entered into RevMan 5 and combined using a random effect meta-analysis.
The standard error was used for purposes of comparison, and total numbers
of patients allowed for the weighting of individual papers.

RESULTS

THE SEARCH

The combined 2002 and 2007 searches revealed in excess of 5,000 potential
papers. This very large number was expected secondary to the wide search
criteria used. Of these papers, the majority were rejected on reviewing the
title and abstract as obviously containing no usable data. The primary rea-
son for rejection of papers was no usable data. For example, some papers re-
ported on basic science, used continuous measures of personality only, were
not outcome studies, or presented no data. The hand search of the Journal
of Affective Disorders revealed no additional papers. This indicated that the
electronic search strategy was sound. As with any review, new papers on the
topic continued to be published; however, no paper after the 2007 search
PERSONALITY DISORDER AND DEPRESSION 5

was eligible for inclusion. Fifty-eight papers were eligible for inclusion in the
review.

CHARACTERISTICS OF THE INCLUDED STUDIES

The characteristics of the included studies are summarized in Table 1. The

studies range in publication date from 1981 to 2006, the cutoff date for in-
clusion being February 2007. Fifty-two percent of the included studies were
from North America, and a further 38% came from Europe and Britain.
Of the remaining five studies, one was based in Japan and the other four in
Australasia. When multiple papers are published by a single study group, the
paper from which the data were extracted is presented in Table 1. When it
was not clear whether papers were from one or multiple sources, the authors
were contacted for clarification.
Of the included studies, the majority (35) were prospective case series
and 17 were randomized controlled trials (RCTs). RCTs did not become
more common over time. Slightly more than half the papers focused on out-
patients. The measurement of recovery varied widely within the included
studies, although the Hamilton Rating Scale for Depression (HAM-D) and
the Montgomery-Åsberg Depression Rating Scale (MADRS) were the most
commonly used tools (in 24 papers).
These characteristics allowed for sensitivity analyses on the primary re-
sult according to study type and depression rating.

ASSESSMENT OF PUBLICATION BIAS

Examination of the funnel plot of the included studies was undertaken to

assess for publication bias (see Figure 1). Funnel plotting was assessed using
a fixed effects model. In the absence of publication bias, data should be sym-
metrical around the pooled odds ratio (OR). This appeared to be the case for
the included studies and did not suggest that unpublished data were skewing
the findings.

ODDS RATIOS FOR THE PRINCIPAL OUTCOME

The overall odds of a poorer outcome in patients with a diagnosis of depres-

sion with a personality disorder were 2.16 (1.83–2.56). This finding was
undertaken using a random effects model, taking into account the variation
in the included data. Sensitivity analysis of the data set was undertaken in
two ways: to examine the effect of using only one type of depression rating
(the HAM-D), and by study design. It was assumed that using a single rat-
ing scale for depression in the analysis would give a lower odds ratio with a
smaller confidence interval in a subgroup of patients’ whose depression was
assessed in a uniform way, removing some of the heterogeneity of the data.
The analysis of the data by study design was expected to show a gradation in
odds ratios: the greatest odds ratio (with widest confidence intervals) for the
least methodologically robust design (case series) to a lower odds ratio with
narrower confidence ratios for RCTs.
 6

TABLE 1. Characteristics of Studies Reporting Association Between Personality Disorder and Outcome in Depression
Criteriaa
First Author (year) Depression PD Responseb Treatmentc Timed (weeks)
Charney (1981) DSM-III DSM-III Good or complete Unclear 12
Tyrer (1983) HAM-D PAS 50+%↓ HAM-D, HAM-A Unclear 4
Pfohl (1984,1987) DSM-III DSM-III 50+%↓ HAM-D Unclear 4 (mean)
Davidson (1985) RDC DSM-III HAM-D (cont) MAOIs 4
Shawcross (1985) ICD PAS Clinical judgment TCA+ 60 (mean)
Sauer (1986) DSM-III DSM-III 50+%↓ HAM-D TCA 3
Black (1988) DSM-III DSM-III Recovered—case notes ECT, TCA, Counseling NK
Goethe (1988) DSM-III DSM-III (?) Clinical judgment Various 20 (mean)
Pilkonis (1988) RDC DSM-III Complex (1) TCA + Dynamic 16+
Thompson (1988) RDC DSM-III No MDD CBT, Dynamic 24
Joffe (1989) DSM-III, RDC DSM-III HAM-D < 5 TCA 5
Keitner (1989) DSM-III DSM-III (?) HAM-D < 7 for 3 mos. Various 26
Kocsis (1989) DSM-III Clinical Complex (2) 6
Reich (1990) RDC PDQ, GAS GAS TCA 26
Shea (1990) RDC DSM-III HAM-D < 7 TCA, CBT, Dynamic, 16
Counseling
Tyrer (1990) DSM-III PAS MADRS < 6 Unclear 10
Ansseau (1991) DSM-III DSM-III HAM-D + dropout SSRI 8
Black (1991) DSM-III DSM-III Recovered—case-note review Unclear 6
Stuart (1992) DSM-III-R DSM-III-R HAM-D < 7 for 4+ wks. CBT 16
Diguer (1993) DSM-III-R, RDC DSM-III-R BDI (cont) Dynamic ~16
Kunik (1993) DSM-III-R DSM-III-R Complex (3) Various 5
Sato (1993) DSM-III-R DSM-III-R Complex (4) Various 17
Fava (1994) DSM-III-R DSM-III-R HAMD (cont) SSRI 8
Peselow (1994) DSM-III DSM-III Complex (5) TCA 5
Sullivan (1994) DSM-III-R DSM-III-R HAM-D < 8 TCA 6
Vine (1994) DSM-III-R DSM-III-R Complex (6) Various 120
Hardy (1995) DSM-III DSM-III-R BDI < 7 (?) CBT, Dynamic NK
Patience (1995) DSM-III PAS HAM-D < 7 CBT, TCA 16
Casey (1996) DSM-III-R PAS Re-admission ECT 52
Alnaes (1997) DSM-III DSM-III Depressive relapse Various 312
Ilardi (1997) DSM-III-R DSM-III-R Depressive relapse Various 26
Ekselius (1998) DSM-III-R SCID Complex (7) SSRI 24
Hirschfeld (1998) DSM-III-R DSM-III-R Complex (8) TCA, SSRI 12
NEWTON-HOWES ET AL.
Klein (1998) DSM-III-R DSM-III-R LIFE – 8 wks. no/minimal symptoms 125
Ezquiaga (1999) DSM-III-R DSM-III-R HAMD < 8 Various 26
Leibbrand (1999) DSM-IV DSM-IV BDI (cont) CBT 10 (mean)
Ball (2000) DSM-III-R DSM-III-R BDI < 10 CBT 5
Brown (2000) DSM-III-R DSM-III-R HAM-D <8 and GAS > 70 32
Bschor (2001) ICD-10 ICD-10 Complex (9) TCA+ 4
Kuyken (2001) DSM-IV DSM-IV BDI (cont) ~12
O’Leary (2001) ICD-10 ICD-10 HAM-D < 8, 2 weeks Unclear 26
Brieger (2002) DSM-IV DSM-IV CDRS (cont) Unclear 9 (mean)
Fava (2002) DSM-III-R SCID-P HAM-D (cont) SSRI 8
Meyers (2002) DSM-IV DSM-IV Complex (10) Various 12
Stek (2002) DSM-III-R DSM-III-R Complex (11) Unclear 365
Viinamäki (2002) DSM-III-R SCID-II-P BDI <10 Various 26
Joyce (2003) DSM-IV DSM-III-R MADRS > 59%↓ TCA + SSRI 6
Kool (2003) DSM-III-R DSM-III-R HAMD < 8 Various 24
Merrill (2003) DSM-III-R DSM-III-R BDI < 14 TCA+ 16 (mid)
Papakostas (2003) DSM-III-R SCID-II HAM-D > 49%↓ Various 6
Casey (2004) ICD-10, DSM-IV PAS BDI < 7 Unclear 12
Ezquiaga (2004) DSM-IV DSM-IV HAM-D < 8 Drugs, PSY 52
Feske (2004) DSM-III-R DSM-III-R HAM-D < 11 ECT 4
Melartin (2004) DSM-IV DSM-III-R Below MDE criteria Unclear 78
Szádóczky (2004) DSM-IV DSM-IV 2 months symptom-free SSRI 108
Morse (2005) HAM-D DSM-III-R HAM-D < 11 for 3 weeks TCA + Dynamic 38
Schiavone (2006) DSM-IV DSM-IV HAM-D (cont) Various 3 (mean)
Van den Hout (2006) Clinical (SCL-90) Clinical < 2 SDs above SCL-90 mean CBT+ 18 (mean)
Notes. a BDI: Beck Depression Inventory; HAM-A: Hamilton Rating Scale for Depression and Anxiety; HAM-D: Hamilton Rating Scale for Depression; GAS: Global Assessment Scale; ICD-10:
International Classification of Diseases, 10th ed.; MADRS: Montgomery-Åsberg Depression Rating Scale; PAS: Personality Assessment Schedule; PDQ: Personality Diagnostic Questionnaire; RDC:
Research Diagnostic Criteria; SCID: Structured Clinical Interview for DSM-IV; SCL-90: Symptom Checklist-90.
b
cont = continuous outcome only reported (no dichotomy); complex (1) = algorithm of Frank et al. (1984); complex (2) = HAM-D < 7, > 9-point improvement on GAS, and absence of sufficient
symptoms to meet DSM-III dysthymic disorder; complex (3) = HAM-D < 10, or relative decrease > 50%; complex (4) = HAM-D-17 < 6, and full recovery of social functioning 16 weeks after
starting treatment, and no sign of recurrence of depression during 4 weeks after first two criteria met; complex (5) = 50% decrease in HAM-D, final CGI (Clinical Global Impression) < 3, and final
HAM-D < 12; complex (6) = does not meet criteria for DSM-III-R depressive disorder, no symptoms for more than 2 weeks during follow-up, no inpatient treatment, and no change in outpatient
treatment; complex (7) = 50+% reduction in MADRS at 24 weeks, CGI severity score 1–3, and CGI improvement rated at least “much improved”; complex (8) = CGI-I 1 or 2, and HAM-D < 7, or
HAM-D 50+% reduction with HAM-D < 15 and CGI severity 3; complex (9) = Bech-Rafaelsen Melancholia Scale decline > 50%, and < 10 within 4 weeks; complex (10) = PSR (Psychiatric Rating
Scale) rating of one, or one or more symptoms of no more than a mild degree (PSR of two) over preceding two weeks; complex (11) = no residual symptoms, no readmissions, depressed < 50% of
time, or relapse with readmission and depressed < 50% of time.
c
1. Physical: ECT = electroconvulsive therapy, 2. Drugs: TCA = tricyclic antidepressants (except clomipramine), SSRI = selective serotonin reuptake inhibitors (including clomipramine), MAOI =
monoamine oxidase inhibitors, 3. Therapy: CBT = cognitive-behavioral therapies, Dynamic = dynamic psychotherapies, Counseling = counseling therapies (all as defined by NICE guidelines for
depression, pp. 134–159), 4. Other unclear = authors do not discuss treatments given, various = multiple treatments are given, comma = either/or treatment, + = both treatments given.
PERSONALITY DISORDER AND DEPRESSION 7

d
Interval from start to outcome evaluation.
8 NEWTON-HOWES ET AL.

Sensitivity analysis when separating the included studies by assessment

type gave an odds ratio of 1.95 (1.55–2.44) in studies that used only the
Hamilton assessment tool, indicating a poorer outcome in patients with
comorbid personality disorder. Separation of the data by study design also
produced the expected result. The pooled case series odds ratio was 2.43
(1.83–3.22), the cohort studies odds ratio was 2.68 (2.08–3.46), and the
pooled RCT odds ratio was 1.52 (1.23–1.87). Although the latter ratio was
significantly lower than for the cohort studies, it was still significant.

ODDS RATIOS FOR OUTCOME BY TREATMENT TYPE

Included papers were also stratified by treatment type in order to assess if a

particular treatment modality produced a favorable outcome in depressed
patients with a personality disorder. These finding are presented in Tables 2
and 3.
This plot shows that, irrespective of treatment modality, patients with a
personality disorder have a poorer outcome in the treatment of their depres-
sion than if no personality disorder is present. Interestingly, this is not the
case only for the placebo group. This greatest divergence between groups
occurred if drug therapy was used, irrespective of augmentation with psy-
chotherapy or not (OR 2.16, CI 1.65–2.83, drugs alone; OR 2.16, CI 1.63–
2.87, drugs and psychotherapy). All measures of outcome are included in
this analysis.

CONCLUSIONS

This is now the largest systematic review of the impact of personality disor-
der on the outcome of depression and demonstrates that personality disorder
has a negative impact on the outcome of depressive episodes. The findings
are consistent with the “received wisdom,” a previous meta-analysis, and
narrative reviews. This finding builds on previous work, and in the spirit
of systematic reviews, this revision is an important component of improv-
ing and updating this topic, one of the seven essential components outlined
by the Cochrane Collaboration. The 5-year time frame between the 2002
search and the 2007 search is at the limit for median survival for a review
without the potential need for revision, making this work timely (Shojania
et al., 2007). The conclusions of the negative effect of personality disorder
in depression are now much stronger because of the larger number of studies
and the collective pooling of information from the Personality Disorder and
Depression Outcome Group. This highlights the importance of assessing for
personality disorder in this group and allows clinicians to be more certain
in their prognosis: Presence of a comorbid personality disorder doubles the
likelihood of nonresponse to treatment for depressive disorders.
The findings with regard to treatment modality are less robust. All types
of treatment show a poorer response in the personality disordered group,
and there is no clear evidence that type of treatment influences this despite
some recent comparative trials showing a worse outcome in those given cog-
PERSONALITY DISORDER AND DEPRESSION 9

FIGURE 1. Funnel Plot of Studies Included in the Meta-analysis.

nitive therapy (Fournier et al., 2008). This data set does not allow us to
make definitive treatment recommendations in order to improve outcome. It
interesting to note, however, that in the studies examined, treatment for the
coexisting personality pathology was not undertaken; rather, depressive dis-
orders were treated. One could therefore speculate that the poorer response
is related to the untreated personality pathology and treatment of it would
not only be sensible but also necessary for recovery.
This meta-analysis, like all approaches, has a number of strengths and
weaknesses that are in many cases opposite sides of the same coin. For ex-
ample, we have taken a very broad view of both personality disorder and
depression—simply requiring that both are adequately referenced by a peer-
reviewed technique, a recommendation made by Mulder (2002). This al-
lows for the data set to be reflective of a “normal” clinical population and
subsequently minimizes the question of generalizability of the results to day-
to-day patients. The same basic assumption does, however, lead to a degree
of heterogeneity in the populations included and as such assumes efficacy of
treatment, as its effectiveness is what is examined. Such methodological as-
sumptions are a direct consequence of the aims of applying the data to the
real-world setting, and generalizability was considered of greater importance
than the heterogeneity problem a priori. Interestingly, this approach (“go
broad”) would also be expected to lead to a statistical narrowing to the
mean, strengthening the differences we have found.
This review has also only included studies that provide a categorical
definition of personality disorder, which potentially limits its power. The no-
sology of personality pathology is currently in flux, and even experts in the
field cannot decide how to best classify patients with disrupted personality
structures, although most agree that the present system is flawed (Bernstein,
Iscan, & Maser, 2007). It is likely, therefore, that personality disorder as it
10 NEWTON-HOWES ET AL.

TABLE 2. Random Effects Meta-analysis, Dividing the Data by Treatment Choice

Odds Ratio IV, Random,
Study or Subgroup log[Odds Ratio] SE PD Total No PD Total Weight 95% CI
1.5.1 Placebo
Kocsis (1989) -0.7732 1.1152 8 15 0.5% 0.46 [0.05, 4.11]
Shea (1990) 0.3825 0.6266 48 14 1.2% 1.47 [0.43, 5.01]
Tyrer (1990) 1.6094 0.8682 11 7 0.7% 5.00 [0.91, 27.41]
Subtotal (95% CI) 67 36 2.4% 1.68 [0.53, 5.32]
Heterogeneity: Tau² = 0.35; Chi² = 2.97, df = 2 (P = 0.23); I² = 33%
Test for overall effect: Z = 0.88 (P = 0.38)
1.5.2 ECT
Black (19t88) 1.0622 0.7247 10 41 1.0% 2.89 [0.70, 11.97]
Casey (1996) 0.1446 0.6427 18 22 1.1% 1.16 [0.33, 4.07]
Feske (2004) 1.0704 0.3929 54 60 2.0% 2.92 [1.35, 6.30]
Pfohl (1984) 0.2007 1.0445 8 14 0.5% 1.22 [0.16, 9.47]
Subtotal (95% CI) 90 137 4.6% 2.25 [1.27, 3.98]
Heterogeneity: Tau² = 0.00; Chi² = 1.97, df = 3 (P = 0.58); I² = 0%
Test for overall effect: Z = 2.77 (P = 0.006)
1.5.3 Drugs
Ansseau (1991) -0.9585 0.7666 22 24 0.9% 0.38 [0.09, 1.72]
Black (1988) 0.7489 0.4 39 83 2.0% 2.11 [0.97, 4.63]
Black (1991) 0.8246 0.2162 100 1210 3.0% 2.28 [1.49, 3.48]
Bschor (2001) 1.0549 0.7389 10 58 0.9% 2.87 [0.67, 12.22]
Davidson (1985) 0.5541 0.7311 15 20 0.9% 1.74 [0.42, 7.29]
Ekselius (1998) 0.252 0.4262 189 119 1.9% 1.29 [0.56, 2.97]
Fava (1994) 0.6429 0.4081 62 21 2.0% 1.90 [0.85, 4.23]
Fava (2002) 0.194 0.1981 243 135 3.1% 1.21 [0.82, 1.79]
Goethe (1988) 0.8199 0.2982 124 77 2.5% 2.27 [1.27, 4.07]
Hirschfeld (1998) 0.1581 0.1605 306 317 3.3% 1.17 [0.86, 1.60]
Ilardi (1997) 3.0155 0.742 22 28 0.9% 20.40 [4.76, 87.34]
Joffe (1989) 1.3134 0.8742 33 9 0.7% 3.72 [0.67, 20.63]
Joyce (2003) -0.0393 0.312 75 91 2.5% 0.96 [0.52, 1.77]
Kocsis (1989) 0.5108 0.8612 9 14 0.7% 1.67 [0.31, 9.01]
Kool (2003) 0.5741 0.6445 36 20 1.1% 1.78 [0.50, 6.28]
Melartin (2004) 0.3001 0.6494 85 113 1.1% 1.35 [0.38, 4.82]
O’Leary (2001) 1.4994 0.8746 29 45 0.7% 4.48 [0.81, 24.87]
Papakostas (2003) 0.6686 0.451 34 58 1.8% 1.95 [0.81, 4.72]
Peselow (1994) 0.401 0.4964 29 39 1.6% 1.49 [0.56, 3.95]
Pfohl (1984) 1.6582 0.7054 25 20 1.0% 5.25 [1.32, 20.92]
Reich (1990) 0.1643 0.7609 25 10 0.9% 1.18 [0.27, 5.24]
Sato (1993) 0.9039 0.4377 52 44 1.8% 2.47 [1.05, 5.82]
Sauer (1986) 1.673 1.3878 13 37 0.3% 5.33 [0.35, 80.89]
Shawcross (1985) 2.5982 0.7205 17 33 1.0% 13.44 [3.27, 55.17]
Shea (1990) 0.7404 0.5253 44 13 1.5% 2.10 [0.75, 5.87]
Stek (2002) 1.8632 0.8035 15 32 0.8% 6.44 [1.33, 31.13]
Sullivan (1994) -0.2003 0.4035 53 46 2.0% 0.82 [0.37, 1.80]
Szadocsky (2004) 2.7444 0.5816 57 60 1.3% 15.56 [4.98, 48.63]
Tyrer (1983) 2.1256 0.7151 32 28 1.0% 8.38 [2.06, 34.03]
Tyrer (1990) 1.204 1.2156 7 14 0.4% 3.33 [0.31, 36.11]
Subtotal (95% CI) 1802 2818 43.6% 2.16 [1.65, 2.83]
Heterogeneity: Tau² = 0.26; Chi² = 71.36, df = 29 (P < 0.0001); I² = 59%
Test for overall effect: Z = 5.60 (P < 0.00001)

is classified today will not identify the same patients in the future. The initial
outline of the working group for DSM-V would support this position. None-
theless, by taking a general approach to personality and allowing the use of
any peer-reviewed instrument, this paper gives a reasonable “snapshot” of
the current clinical understanding of personality pathology in patients with
depression. The broad inclusion criteria of this study minimize the possibil-
ity of bias introduced by using a tool derived by a single center and provides
PERSONALITY DISORDER AND DEPRESSION 11

TABLE 2. (continued)
Odds Ratio IV, Random,
Study or Subgroup log[Odds Ratio] SE PD Total No PD Total Weight 95% CI
1.5.4 Psychotherapy
Ball (2000) 1.6487 0.842 49 7 0.8% 5.20 [1.00, 27.09]
Black (1988) 0.6731 0.5587 27 28 1.4% 1.96 [0.66, 5.86]
Casey (2004) 0.7061 0.3634 54 249 2.2% 2.03 [0.99, 4.13]
Diguer (1993) 1.5489 0.9184 12 13 0.7% 4.71 [0.78, 28.47]
Hardy (1995) 0.5787 0.4455 27 85 1.8% 1.78 [0.74, 4.27]
Kuyken (2001) 0.3674 0.6259 102 7 1.2% 1.44 [0.42, 4.92]
Leibbrand (1999) -0.1815 0.5425 39 18 1.4% 0.83 [0.29, 2.42]
Merrill (2003) 1.3 0.59 27 124 1.3% 3.67 [1.15, 11.66]
Persons (1988) 1.5404 0.5327 36 30 1.5% 4.67 [1.64, 13.26]
Pfohl (1984) 1.7918 1.3944 8 3 0.3% 6.00 [0.39, 92.28]
Shea (1990) 0.2109 0.356 86 34 2.2% 1.23 [0.61, 2.48]
Stuart (1992) 0.3629 0.6259 14 39 1.2% 1.44 [0.42, 4.90]
Thompson (1988) 1.3063 0.5341 25 50 1.4% 3.69 [1.30, 10.52]
Tyrer (1990) -0.0488 1.0374 13 9 0.5% 0.95 [0.12, 7.28]
Subtotal (95% CI) 519 696 17.8% 2.01 [1.50, 2.69]
Heterogeneity: Tau² = 0.01; Chi² = 13.25, df = 13 (P = 0.43); I² = 2%
Test for overall effect: Z = 4.68 (P < 0.00001)
1.5.5 Drugs and Psychotherapy
Alnaes (1997) 0.2485 0.7194 77 11 1.0% 1.28 [0.31, 5.25]
Brieger (2002) 0.4329 0.4271 60 57 1.9% 1.54 [0.67, 3.56]
Brown (2000) 0.8969 0.3295 125 56 2.4% 2.45 [1.29, 4.68]
Charney (1981) 2.3979 0.8034 40 24 0.8% 11.00 [2.28, 53.12]
DeRubeis (2005) -0.0905 0.3009 90 90 2.5% 0.91 [0.51, 1.65]
Ezquiaga (1999) 2.0503 0.6039 25 62 1.2% 7.77 [2.38, 25.38]
Ezquiaga (2004) 0.8109 0.6103 20 30 1.2% 2.25 [0.68, 7.44]
Keitner (1989) 0.6332 0.8526 8 70 0.7% 1.88 [0.35, 10.02]
Klein (1998) 0.9808 0.4581 44 42 1.7% 2.67 [1.09, 6.54]
Kool (2003) -0.506 0.5231 49 23 1.5% 0.60 [0.22, 1.68]
Kunik (1993) 0.4261 0.3802 37 117 2.1% 1.53 [0.73, 3.23]
Meyers (2002) 0.8129 0.3466 101 63 2.3% 2.25 [1.14, 4.45]
Morse (2005) 0.4218 0.3609 55 105 2.2% 1.52 [0.75, 3.09]
Patience (1995) 0.7985 0.4207 38 63 1.9% 2.22 [0.97, 5.07]
Pilkonis (1988) 1.2144 0.4149 49 53 1.9% 3.37 [1.49, 7.60]
Schiavone (2006) 0.587 0.3221 155 92 2.4% 1.80 [0.96, 3.38
Van den Hout (2006) 1.3063 0.7596 25 15 0.9% 3.69 [0.83, 16.36]
Viinamaki (2002) 1.8589 0.4579 52 65 1.7% 6.42 [2.62, 15.74]
Vine (1994) 0.991 0.589 18 38 1.3% 2.69 [0.85, 8.55]
Subtotal (95% CI) 1068 1076 31.6% 2.16 [1.63, 2.87]
Heterogeneity: Tau² = 0.17; Chi² = 33.45, df = 18 (P = 0.01); I² = 46%
Test for overall effect: Z = 5.34 (P < 0.00001)
Total (95% CI) 3546 4763 100.0% 2.11 [1.79, 2.47]
Heterogeneity: Tau² = 0.17; Chi² = 125.49, df = 69 (P < 0.0001); I² = 45%
Test for overall effect: Z = 9.13 (P < 0.00001)

for a reasonable group of personality disordered patients to be captured—

another recommendation from Mulder (2002). More broadly, there are em-
pirical questions about the position of personality disorders as diagnostic
entities in the presence of depression. The issue of whether two disorders are
comorbid or consanguineous is a diagnostic challenge in psychiatry, both for
multiple Axis I and Axis I/Axis II “comorbidity” (Tyrer, 1996). Some authors
argue that alternate classifications better typify these presentations (Shedler
& Westen, 2004); however, such debate is beyond the scope of this review,
which captures the current conceptualization of depression and personality
pathology.
12 NEWTON-HOWES ET AL.

TABLE 3. Random Effects Meta-analysis, Dividing the Data by Trial Design

Odds Ratio IV,
Study or Subgroup log[Odds Ratio] SE PD Total No PD Total Weight Random, 95% CI
1.6.1 Randomized clinical trials
Davidson (1985) 0.5541 0.7311 15 20 1.0% 1.74 [0.42, 7.29]
Tyrer (1983) 2.1256 0.7151 32 28 1.0% 8.38 [2.06, 34.03]
Joyce (2003) -0.0393 0.312 75 91 2.6% 0.96 [0.52, 1.77]
Kocsis (1989) -0.0357 0.6405 17 29 1.2% 0.96 [0.27, 3.39]
Papakostas (2003) 0.6686 0.451 34 58 1.9% 1.95 [0.81, 4.72]
Sullivan (1994) -0.2003 0.4035 53 46 2.1% 0.82 [0.37, 1.80]
Fava (1994) 0.6429 0.4081 62 21 2.1% 1.90 [0.85, 4.23]
Fava (2002) 0.194 0.1981 243 135 3.2% 1.21 [0.82, 1.79]
Tyrer (1990) 0.9555 0.6233 31 30 1.3% 2.60 [0.77, 8.82]
Casey (2004) 0.7061 0.3634 54 249 2.3% 2.03 [0.99, 4.13]
Hardy (1995) 0.5787 0.4455 27 85 1.9% 1.78 [0.74, 4.27]
Hirschfeld (1998) 0.1581 0.1605 306 317 3.4% 1.17 [0.86, 1.60]
DeRubeis (2005) -0.0905 0.3009 90 90 2.6% 0.91 [0.51, 1.65]
Patience (1995) 0.7985 0.4207 38 63 2.0% 2.22 [0.97, 5.07]
Shea (1990) 0.7985 0.3036 178 61 2.6% 2.22 [1.23, 4.03]
Ekselius (1998) 0.252 0.4262 189 119 2.0% 1.29 [0.56, 2.97]
Kool (2003) -0.1221 0.3968 85 43 2.1% 0.89 [0.41, 1.93]
Thompson (1988) 1.3063 0.5341 25 50 1.5% 3.69 [1.30, 10.52]
Brown (2000) 0.8969 0.3295 125 56 2.5% 2.45 [1.29, 4.68]
Subtotal (95% CI) 1679 1591 39.2% 1.52 [1.23, 1.87]
Heterogeneity: Tau² = 0.07; Chi² = 28.14, df = 18 (P = 0.06); I² = 36%
Test for overall effect: Z = 3.91 (P < 0.0001)
1.6.2 Cohort studies
Sauer (1986) 1.7509 1.0985 13 37 0.5% 5.76 [0.67, 49.60]
Schiavone (2006) 0.587 0.3221 155 92 2.5% 1.80 [0.96, 3.38]
Pfohl (1984) 1.5144 0.4944 41 37 1.7% 4.55 [1.73, 11.98]
Kunik (1993) 0.4261 0.3802 37 117 2.2% 1.53 [0.73, 3.23]
Peselow (1994) 0.401 0.4964 29 39 1.7% 1.49 [0.56, 3.95]
Ball (2000) 1.6487 0.842 49 7 0.8% 5.20 [1.00, 27.09]
Joffe (1989) 1.3134 0.8742 33 9 0.8% 3.72 [0.67, 20.63]
Ansseau (1991) -0.9585 0.7666 22 24 0.9% 0.38 [0.09, 1.72]
Feske (2004) 1.0704 0.3929 54 60 2.1% 2.92 [1.35, 6.30]
Brieger (2002) 0.4329 0.4271 60 57 2.0% 1.54 [0.67, 3.56]
Leibbrand (1999) -0.1815 0.5425 39 18 1.5% 0.83 [0.29, 2.42]
Meyers (2002) 0.8129 0.3466 101 63 2.4% 2.25 [1.14, 4.45]
Stuart (1992) 0.3629 0.6259 14 39 1.3% 1.44 [0.42, 4.90]
Diguer (1993) 1.5489 0.9184 12 13 0.7% 4.71 [0.78, 28.47]
Kuyken (2001) 0.3674 0.6259 102 7 1.3% 1.44 [0.42, 4.92]
Pilkonis (1988) 1.2144 0.4149 49 53 2.0% 3.37 [1.49, 7.60]
Merrill (2003) 1.3 0.59 27 124 1.4% 3.67 [1.15, 11.66]
Sato (1993) 0.9039 0.4377 52 44 1.9% 2.47 [1.05, 5.82]

This paper reports that patients with personality disorder and depres-
sion do more poorly than their counterparts with depression alone. It em-
phasizes the importance of assessing personality status in depression and
highlights one of the potential reasons for the “treatment resistance” so often
encountered in clinical practice—where personality structure often takes a
back seat to any Axis I disorder. As well as recognizing personality disorder
as an aid in prognosis, this paper highlights the need for ongoing assessment
and research into the management of personality disorders in this patient
group to assess if treatments developed for the management of personality
disorder improve overall outcome in this patient group.
PERSONALITY DISORDER AND DEPRESSION 13

TABLE 3. (continued)
Odds Ratio IV,
Study or Subgroup log[Odds Ratio] SE PD Total No PD Total Weight Random, 95% CI
Van den Hout (2006) 1.3063 0.7596 25 15 1.0% 3.69 [0.83, 16.36]
Ezquiaga (1999) 2.0503 0.6039 25 62 1.3% 7.77 [2.38, 25.38]
Ilardi (1997) 3.0155 0.742 22 28 1.0% 20.40 [4.76, 87.34]
Keitner (1989) 0.6332 0.8526 8 70 0.8% 1.88 [0.35, 10.02]
Reich (1990) 0.1643 0.7609 25 10 1.0% 1.18 [0.27, 5.24]
Viinamaki (2002) 1.8589 0.4579 52 65 1.8% 6.42 [2.62, 15.74]
O’Leary (2001) 1.4994 0.8746 29 45 0.8% 4.48 [0.81, 24.87]
Morse (2005) 0.4218 0.3609 55 105 2.3% 1.52 [0.75, 3.09]
Casey (1996) 0.1446 0.6427 18 22 1.2% 1.16 [0.33, 4.07]
Ezquiaga (2004) 0.8109 0.6103 20 30 1.3% 2.25 [0.68, 7.44]
Shawcross (1985) 2.5982 0.7205 17 33 1.0% 13.44 [3.27, 55.17]
Melartin (2004) 0.3001 0.6494 85 113 1.2% 1.35 [0.38, 4.82]
Szadocsky (2004) 2.7444 0.5816 57 60 1.4% 15.56 [4.98, 48.63]
Klein (1998) 0.9808 0.4581 44 42 1.8% 2.67 [1.09, 6.54]
Vine (1994) 0.991 0.589 18 38 1.4% 2.69 [0.85, 8.55]
Stek (2002) 1.8632 0.8035 15 32 0.9% 6.44 [1.33, 31.13]
Subtotal (95% CI) 1404 1610 47.9% 2.68 [2.08, 3.46]
Heterogeneity: Tau² = 0.24; Chi² = 59.90, df = 33 (P = 0.003); I² = 45%
Test for overall effect: Z = 7.58 (P < 0.00001)
1.6.3 Case series reviews
Black (1991) 0.8246 0.2162 100 1210 3.1% 2.28 [1.49, 3.48]
Bschor (2001) 1.0549 0.7389 10 58 1.0% 2.87 [0.67, 12.22]
Black (1988) 0.7184 0.2852 76 152 2.7% 2.05 [1.17, 3.59]
Charney (1981) 2.3979 0.8034 40 24 0.9% 11.00 [2.28, 53.12]
Goethe (1988) 0.8199 0.2982 124 77 2.6% 2.27 [1.27, 4.07]
Persons (1988) 1.5404 0.5327 36 30 1.6% 4.67 [1.64, 13.26]
Alnaes (1997) 0.2485 0.7194 77 11 1.0% 1.28 [0.31, 5.25]
Subtotal (95% CI) 463 1562 12.9% 2.43 [1.83, 3.22]
Heterogeneity: Tau² = 0.01; Chi² = 6.36, df = 6 (P = 0.38); I² = 6%
Test for overall effect: Z = 6.13 (P < 0.00001)
Total (95% CI) 3546 4763 100.0% 2.16 [1.83, 2.56]
Heterogeneity: Tau² = 0.19; Chi² = 121.24, df = 59 (P < 0.00001); I² = 51%
Test for overall effect: Z = 8.98 (P < 0.00001)

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