Correspondence
necessary. The authors state that the
symptomatic differences between
unipolar and bipolar depression were
rst described in the 1950s by German
psychiatrist Karl Leonhard and later
validated in the 1960s by Jules Angst,
Carlo Perris, and George Winokur. This
statement is not correct. Leonhard2
distinguished between the broad
syndromes of bipolar disorder and
unipolar depression, mainly on the
grounds of distinct family genetics
an important milestone to separate
these two conditions, which had both
previously been incorporated within
Kraepelins broad diagnostic grouping
of manic-depressive insanity. 3
Indeed, this crucial distinction was
then validated by Angst, Perris, and
Winokur.4 However, none of these
researchers distinguished between
the symptoms of the depressive
phases of bipolar disorder (bipolar
depression) and unipolar depression.
In fact, Angst and Perris4 specically
stated in their publications that no
such dierences existed, although in
retrospect it is clear that both sample
size and methodological approaches
were restricted. As Grande and
colleagues1 state, evidence is growing
for symptomatic dierences between
these forms of depression from many
groups, including our own.5
I declare no competing interests.
*Philip B Mitchell
phil.mitchell@unsw.edu.au
School of Psychiatry, University of New South
Wales, Sydney, NSW 2052, Australia
1 Grande I, Berk M, Birmaher B, Vieta E. Bipolar
disorder. Lancet 2016; 387: 156172.
2 Leonhard K. The Classication of Endogenous
Psychoses. Berlin, Germany:
Akademie-Verlag, 1957.
3 Mitchell PB. The History of Bipolar Disorder.
In: Carlos A, Zarate Jr, Manji HK, eds. Bipolar
Depression: Molecular Neurobiology, Clinical
Diagnosis and Pharmacotherapy, 2nd edn.
Cham, Switzerland: Springer International
Publishing, 2016.
4 Perris C. A study of bipolar (manic-depressive)
and unipolar recurrent depressive psychoses.
Acta Psychiatr Scandi 1966;
42 (suppl 194): 1189.
5 Frankland A, Cerrillo E, Hadzi-Pavlovic D, et al.
Comparing the phenomenology of depressive
episodes in bipolar I and II disorder and major
depressive disorder within bipolar disorder
pedigrees. J Clin Psychiatry 2015; 76: 3238.
www.thelancet.com Vol 388 August 27, 2016
In their Seminar, Iria Grande and
colleagues wrote that the prevalence of
psychiatric and medical comorbidities
was high in patients with bipolar
disorder.1 Among Diagnostic and
Statistical Manual of Mental Disorders
axis I diagnoses, bipolar disorder has one
of the highest rates of comorbid sub-
stance use disorders. In the World Mental
Health Survey Initiative,2 61 392 adults
from 11 countries in the Americas,
Europe, and Asia were assessed using
the Composite International Diagnostic
Interviewa fully structured psychiatric
diagnostic interview. 523% of patients
with bipolar I disorder (odds ratio 84,
95% CI 65108) and 365% of patients
with bipolar II disorder (42, 3256) had
a lifetime diagnosis of substance use
disorder.2 Estimates of the prevalence
of current smoking among individuals
with bipolar I disorder range from 30%
to 70%.
Patients with bipolar disorder and
comorbid substance use disorders
have a more severe course of bipolar
disorder than their counterparts
without substance use disorders, in
particular with more frequent suicide
attempts, depressive episodes,
rapid cycling and mixed mood
episodes, medical comorbidities,
poor treatment compliance, and
more hospital admissions.3 Most of
the excess violent crime reported in a
longitudinal study of 3743 individuals
with bipolar disorder was associated
with substance abuse comorbidity.4
Circulatory disorders, mainly linked
with smoking, are the main cause of
death along with suicide in patients
with bipolar disorder. Thus, dual
diagnosis of substance use disorders
and bipolar disorder should be treated
together with intensive intervention
and follow-up, ideally through
integrated care.5
AD has received honoraria for lectures from
AstraZeneca, Lunbeck, Lilly, and Otsuka. XL declares
no competing interests.
*Alain Dervaux, Xavier Laqueille
a.dervaux@ch-sainte-anne.fr
Service daddictologie, Centre Hospitalier Sainte-
Anne, 1 Rue Cabanis, 75014, Paris, France (AD, XL)
1 Grande I, Berk M, Birmaher B, Vieta E. Bipolar
disorder. Lancet 2016; 387: 156172.
2 Merikangas KR, Jin R, He JP, et al.
Prevalence and correlates of bipolar spectrum
Chris Gallagher/Science Photo Library
disorder in the World Mental Health Survey
Initiative. Arch Gen Psychiatry 2011, 68: 24151.
3 Carr G, Bartoli F, Crocamo C, Brady KT, Clerici M.
Attempted suicide in people with co-occurring
bipolar and substance use disorders: Systematic
review and meta-analysis. J Aect Disord 2014;
167: 12535.
4 Fazel S, Lichtenstein P, Grann M, Goodwin GM,
Lngstrm N. Bipolar disorder and violent
crime: new evidence from population-based
longitudinal studies and systematic review.
Arch Gen Psychiatry 2010; 67: 93138.
5 Farren CK, Hill KP, Weiss RD. Bipolar disorder
and alcohol use disorder: a review.
Curr Psychiatry Rep 2012; 14: 65966.
Authors reply
We appreciate the interest from
Alain Dervaux and Xavier Laqueille,
and Philip Mitchell in our Seminar
on bipolar disorder.1 Substance use
disorders are indeed very common in
patients with bipolar disorder. Tentative
reasons for such frequent comorbidity
include a shared genetic diathesis,
common neurobiological pathways
(ie, dopamine, glutamate), diagnostic
overlap, trauma, self-medication
(ie, use of psychotropics to improve
symptoms or side-effects of drugs),
social diathesis (social environment),
and substance-induced episodes. Some
mediators include impulsivity, sensation
seeking, anxiety, and attention-
decit hyperactivity disorder.2 Of note,
patients who develop bipolar disorder
in the context of substance use can
have a better prognosis than those
who have bipolar disorder first and
substance use later,3 suggesting that
some forms of the condition might be
substance induced or perhaps triggered
by psychotropics, and less impairing
than other phenotypes if substance
use is discontinued. Clearly, as Dervaux
and Laqueille point out, an integrative,
intensive treatment approach is
necessary in patients with bipolar
disorder and substance abuse.
The question raised by Mitchell of who
was the rst to distinguish between the
symptoms of the depressive phases of
bipolar disorder (bipolar depression)
and unipolar depression is tricky. The
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