Delusional (Paranoid) Disorders:
Etiologic and Taxonomic Considerations.
II. A Possible Relationship Between Delusional
and Affective Disorders*
ALISTAIR MUNRO, M.D.!
Paranoid (delusional) disorders are usually thought to
overlap with schizophrenic disorders, and there may be a
continuum, especially with paranoid schizophrenia.
There is also some recent evidence of an overlap with
affective disorders. This article refers to the author's series
of monodelusional disorders, emphasizing certain mood
concomitants, and discussing the implications ofthese for
delusional disorders in general.
Idelusional
n Part I of this article (I), some emphasis was laid on the
traditional difficulties encountered in diagnosing
disorders. It was suggested that there are at
least two relatively distinct delusional disorders, paranoia
and paraphrenia. Despite their distinctness, it was further
suggested that some form of continuum (the "Paranoid
Spectrum") exists, providing links between paranoia,
paraphrenia, and also paranoid schizophrenia. It is
accepted that this continuum theory is controversial at
present. Lately there have been reports of associations
between delusional and affectivedisorders (seelater). This
topic is discussed and illustrated by reference to the
author's case series of delusional disorder. It should be
noted that these patients conform very closely to the
Kraepelinian (2,3) (and DSM-IIIR) (4) definition of
paranoia/ delusional disorder, that is, of an encapsulated
monodelusional disorder (5). The series does not include a
case of paraphrenia, paranoid schizophrenia or other
delusional disorders, but based on the continuum theory,
it is proposed that findings may apply, at least in part, to
all of the delusional disorders.
Case Material
This consists of 53 individuals diagnosed as suffering
from delusional (paranoid) disorder: 50 with delusional
hypochondriasis, two with erotomania and one with
paranoid jealousy. All have been reported in detail
elsewhere(6-8) and most were treated with pimozide (see
below).
"Manuscript received December 1986; revised April 1987.
'Professor and Head, Dalhousie University, Department of Psychiatry,
Halifax, Nova Scotia
Can. J. Psychiatry Vol. 33, April 1988
175
Eighteen of these patients had had previous psychiatric
treatment, mostly for personality-related or addictive
problems. There did not appear to be a significant family
history of schizophrenia, affective disorder or paranoid
disorder. Although 13 patients admitted to serious
suicidal thoughts as a result of their prolonged and
distressing delusional illness (and 4 had actually made
suicide attempts) there was no convincing previous
history of major affective disorder in any case.
Of the 53 patients, 28 were female and 25 male, and the
average age was 46 years. The mean length of illness was
approximately 5 years, with a range of one month to 20
years.
All patients, except 4 who declined help, were treated
with pimozide. Of the remaining 49, 35 were judged to
have an excellent response (32 hypochondriacal, 2
erotomania, I paranoid jealousy) and 9 a fair response (all
hypochondriacal). The other 5 did not appear to respond.
The study was non-blind and non-comparison, but it
should be noted that previous consensus held that the
monodelusional presentation of paranoia is a virtually
untreatable condition. (Here it is emphasized that the
author is referring specifically to the treatment of
paranoia and not of other delusional disorders).
Of the 49 patients who accepted treatment, 8 (6
hypochondriacal, I erotomania, I paranoid jealousy)
developed depressive symptoms typical of major affective
disorder soon after treatment with pimozide was
commenced. None displayed manic symptoms. Trial-and-
error taught one that withdrawal of the pimozide relieved
the depression but resulted in return of the original
delusion, whereas a tricyclic antidepressant alone did not
relieve the delusion although it might lighten the mood
and reduce the patient's preoccupation somewhat. A
combination of pimozide and antidepressant usually
alleviated both complaints, but in one case a combination
of pimozide and electroconvulsive therapy had to be used.
Interestingly, in all cases the antidepressant could be
withdrawn after a time with no ill effect, but pimozide had
usually to be continued long-term or else the delusions
recurred: this seemed to suggest that the depression was
not a direct effect of the pimozide.
176 CANADIAN JOURNAL OF PSYCHIATRY
Pimozide
This is a diphenylbutylpiperidine drug, closely related
to haloperidol (9). It is a neuroleptic, reported to give
good results in both acute and chronic schizophrenia: in
the latter its euphoriant and activating effect may be
useful. It has proved useful in Tourette's syndrome (10)
and has been repeatedly reported to be highly effective in
delusional (paranoid) disorder, especially of the
hypochondriacal type (6). It is said to be the most potent
and specific antidopaminergic neuroleptic at present.
Although used in Europe, the United Kingdom and
Canada since the 1970's, it only became available in the
United States in 1985.
Affective Symptoms in Paranoid Disorders
This subject is better documented for schizophrenia
than for paranoid disorders because of the poor
recognition until recently of the latter. Johnson mentions
(11) that the presence of affective symptoms in
schizophrenia has been noted since the time of Kraepelin
and Bleuler. While depression is known to occur
prodromally in some schizophrenics, it has been
recognized more frequently in the recovery phase, and
Mayer-Gross (12) presaged the concept of post-psychotic
depression in a classical article. Depressive symptoms
may also occur within the schizophrenic illness and
suicide is common in schizophrenics, but the difference
between anhedonia and major affective illness has not
been clearly drawn in this context.
Post-psychotic depression has been reported to occur in
up to 50% of recovering schizophrenics, although 25% is a
more usual figure (13). Its etiology is unclear: Hirsch (14)
and others have advocated the concept of "revealed
depression", suggesting that it is an integral part of the
schizophrenic illness, uncovered as the psychosis
improves. Another view is that it is related to the patient's
underlying personality or to external stresses. On
occasion, the concept of schizoaffective disorder as a
separate entity has been raised in this context, but never
convincingly (15). In recent times the argument has been
complicated by the use of neuroleptic drugs and by the
effects they have on the illness and on the patient. For
example, drug-induced akinesis may look like depression
but responds to antiparkinsonian treatment (16). There
has been a tendency to blame the neuroleptics for having a
depressant effect: this may explain some individual cases,
but not the great majority of post-psychotic depressions
(11). The present author's own view is that major affective
disorder is a less disorganized condition than schizophre-
nia: as the latter improves with treatment (or natural
remission) and as mental functions begin to reintegrate,
the patient may then become capable of exhibiting the
somewhat less severe symptoms characteristic of
depressive illness.
In recent years there has been a small but suggestive
number of publications indicating a similar phenomenon
in delusional disorders. Unfortunately, diagnosis of
delusional disorders has frequently been suspect in the
Vol. 33, No.3
past and case series have often been very small, but at the
same time varied in composition. As regards the specific
diagnosis of delusional (paranoid) disorder, the patients
reported in this article probably represent the largest and
most closely defined series to date. Their treatment with
pimozide and the subsequent favourable response are
original observations (17), and there are subsequent
reports of similar good outcome, especially as regards
hypochondriacal delusions (18-20).
So far as can be determined, none of the patients in this
series had a significant previous or family history of major
affective disorder, and none was suffering from a
recognizable affective disorder at the time of first
attendance, though nearly all were severely distressed by
their delusions. Previous psychotropic drug therapy by
other physicians (not including pimozide) had not
precipitated depression, and in every case of post-
psychotic depression, treatment with pimozide appeared
to be the initiating factor. One can only speculate whether
the drug engendered or simply uncovered the depression.
Pimozide is not especially notorious for precipitating
depression in other types of patients and, in fact, is more
likely to be euphoriant in psychotics. However, pimozide
has been noted to bring down the mood level in mania
(21).
Although there had been little benefit from previous
neuroleptic treatment, a few of these patients did report
slight lessening of delusional preoccupation while on a
tricyclic antidepressant alone, prior to the author having
seen and treated them. This experience appears to be
confirmed by Cashman and Pollock (22) who described a
good but partial response in hypochondriacal delusional
(paranoid) disorder with imipramine.
However, Brotman and Jenike (23) report on two
patients with hypochondriacal delusional (paranoid)
disorder who apparently responded fully to tricyclic
antidepressants (doxepin and imipramine respectively)
despite failure to improve with several neuroleptics (not
including pimozide) or, in one case, with tranylcyprom-
ine. Akiskal et al. (24) describe five patients with
apparently full blown paranoid disorder who responded
to antidepressants: four with tricyclics and one with
phenelzine. Sheehy (25) has treated one case of paranoid
disorder successfully with trazodone. Tollefson (26)
reports on one case of delusional hypochondriasis,
probably related to a major depressive illness, which
cleared with amoxapine: this is interesting because of
amoxapine's marked antidopaminergic properties.
Singh and Maguire (27) have described a schizophrenic
patient who repeatedly developed mania-like symptoms
on pipothiazine palmitate. On the other hand, there is a
single case report (28) of a patient with depression and
marital difficulties who appeared to be precipitated into a
mono delusional state by the use of the monoamine
oxidase inhibitor, phenelzine.
It is clear that the relationship between affective and
delusional disorders is a complex one, but there is no
doubt that a relationship exists. This point, and the
April, 1988 DELUSIONAL (PARANOID) DISORDERS
questions it raises, are thoughtfully considered in a recent
article (29).
Affective Disorder with Paranoid Features
The contrary situation to the foregoing may obtain and,
for example Logsdail (30) describes three cases of major
affective disorder which, in later life, developed into
paranoid disorders. Fry (31) has pointed out that episodic
delusional disorder may be related to underlying manic-
depressive illness, and Jorgensen (32) has described a
series of cases in which the differentiation between
affective and paranoid disorder is, at times, impossible.
Conclusion
For many years, delusional disorders have been hiding
under the wing of schizophrenia and we are just learning
how to make a distinction. The classification of delusional
disorders remains controversial: for example, delusional
(paranoid) disorder is now regarded as a separate
diagnosis in DSM-IIIR, as is paraphrenia in ICD 9.
However, paraphrenia, which is a useful category, is not
included in DSM-III or in DSM-IIIR. Paranoid
schizophrenia is increasingly regarded as different from
other schizophrenias (33), but despite its name its relation
to other paranoid disorders is unclear.
Just as we begin to make inroads into these diagnostic
and classificatory difficulties, other problems arise. We
are becoming more aware of cases where affective and
delusional features coexist, individual cases which
graduate from affective to delusional disorder or vice
versa, and some evidence that antidepressant and
antipsychotic treatments can overlap considerably when
we are dealing with delusional disorders.
These diagnostic problems raise many questions. One
of the most important is: do we see, in delusional
disorders, some kind of bridge or halfway house between
affective disorder and schizophrenia?
References
1. Munro A. Delusional and paranoid disorders: etiologic and
taxonomic considerations. Part I. The possible significance
of organic brain factors in the etiology of delusional
disorders. Can J Psychiatry 1988; 33(3): 171-174.
2. Kraepelin E. Manic depressive insanity and paranoia.
Barclay RM, Transl. ed. Robertson GM., ed. Edinburgh:
Livingstone, 1921.
3. Lewis A. Paranoia and paranoid: a historical perspective.
Psychol Med 1970; I: 2-12.
4. American Psychiatric Association. DSM-III-R. Diagnostic
and Statistical Manual, 3rd edition (revised). Washington,
D.C.: American Psychiatric Association, 1987.
5. Munro A. Paranoia revisited. Br J Psychiatry 1982; 141:
344-349.
6. Munro A. Delusional hypochondriasis. Toronto: Clarke
Institute of Psychiatry Monograph Series #5, 1982.
7. Munro A, O'Brien JV, Ross D. Two cases of "pure" or
"primary" erotomania successfully treated with pimozide.
Can J Psychiatry 1985; 30(8): 619-622.
8. Munro A. Excellent response of pathologic jealousy to
pimozide. Can Med Assoc J 1984; 131: 852-853.
177
9. Silverstone T, Cookson J, Ball R, et al. The relationship of
dopamine receptor blockade to clinical response in
schizophrenic patients with pimozide or haloperidol. J
Psychiatr Res 1984; 18: 255-268.
10. Colvin CL, Tankanow RM. Pimozide: use in Tourette's
syndrome. Drug Int Clin Pharm 1985; 19: 421-424.
11. Johnson DA W. Depressive symptoms in schizophrenia:
some observations on the frequency, morbidity and possible
causes. In: Kerr A, Snaith P, eds. Contemporary issues in
schizophrenia. London: Gaskell, 1986: 451-458.
12. Mayer-Gross W. Uber die Stellungsnahme auf abgelauf-
enen akuten Psychose. Zeitschrift fur die Gesamte
Neurologie und Psychiatrie 1920; 60: 160-212.
13. Mandell MR, Severe JB, Schooler NR, et al. Development
and prediction of postpsychotic depression in neuroleptic-
treated schizophrenics. Arch Gen Psychiatry 1982;39: 197-
203.
14. Hirsch SR. Depression 'revealed' in schizophrenia: a
discussion. Br J Psychiatry 1982; 140: 421-423.
15. Brockington IF, Leff JP. Schizoaffective psychosis:
definitions and incidence. Psycho! Med 1979; 9: 91-99.
16. Johnson DA W. Studies of depressive symptoms in
schizophrenia. Br J Psychiatry 1981; 139: 89-101.
17. Riding J, Munro A. Pimozide in the treatment of
monosymptomatic hypochondriacal psychosis. Acta
Psychiatr Scand 1975; 52: 23-30.
18. Lindskov R, Baadsgaard O. Delusions of infestation treated
with pimozide: a follow-up study. Acta Dermatologica
Venereologica (Stockholm) 1985; 65: 267-270.
19. Duke EE. Clinical experience with pimozide: emphasis on
its use in postherpetic neuralgia. J Am Acad Dermatol1983;
8: 845-850.
20. Lyell A. Delusions of parasitosis. Br J Dermatol1983; 108:
485-499.
21. Cookson J, Silverstone T, Wells B. Double-blind
comparative clinical trial of pimozide and chlorpromazine
in mania. Acta Psychiatr Scand 1981; 64: 381-397.
22. Cashman FE, Pollock B. Treatment of monosymptomatic
hypochondriacal psychosis with imipramine. Can J
Psychiatry 1983; 28(1): 85.
23. Brotman AW, Jenike MA. Monosymptomatic hypochon-
driasis treated with tricyclic antidepressants. Am J
Psychiatry 1984; 141: 1608-1609.
24. Akiskal HS, Arana GW, Baldessarini RJ, Barreira PJ. A
clinical report of thymoleptic-responsive atypical paranoid
psychoses. Am J Psychiatry 1983; 140: 1187-1190.
25. Sheehy M. Successful treatment of paranoia with
trazodone. Am J Psychiatry 1983; 140: 945.
26. Tollefson G. Delusional hypochondriasis, depression and
amoxapine. Am J Psychiatry 1985; 141: 1518-1519.
27. Singh AN, Maguire J. Pipothiazine palmitate induced
mania. Br Med J 1984; 289: 734.
28. Liebowitz MR, Nuetzel EEJ, Bowser AE, Klein DF.
Phenelzine and delusions of parasitosis: a case report. Am J
Psychiatry 1978; 135: 1565-1566.
29. Ross CA, Siddiqui AR, Matas M. DSM-III: problems in
diagnosis of paranoia and obsessive-compulsive disorder.
Can J Psychiatry 1987; 32(2): 146-148.
30. Logsdail S. Affective illness changing to paranoid state.
Report on three elderly patients. Br J Psychiatry 1984; 144:
209-210.
31. Fry WF. Paranoid episodes in manic-depressive psychosis.
Am J Psychiatry 1978; 135: 974-976.
178 CANADIAN JOURNAL OF PSYCHIATRY
32. Jorgensen P. Manic-depressive patients with delusions.
Acta Psychiatr Scand 1985; 72: 364-368.
33. Houlihan JP. Heterogeneity among schizophrenic patients:
selective review of recent findings (1970-1975). Schizophr
Bull 1977; 3: 246-258.
Resume
On estime generalement que les troubles paranoiaques
(avec delire) chevauchent les troubles schizophreniques et
Vol. 33, No.3
qu'ils peuvent constituer un phenomene continu, surtout
dans le cas de la schizophrenic paranoide. Certaines
etudes recentes permettent de penser qu'il existe un
chevauchement entre les troubles paranoiaques et les
troubles afJectifs. Dans cet article, l'auteur propose une
serie de troubles avec productions delirantes a theme
unique, et symptomes concomittants sur le plan de
l'humeur. II analyse cette serie dans Ie contexte de
l'ensemble des troubles avec productions delirantes.