Secondary Schizophrenia (44 page)

result, rather than cause, of psychosis. It is clear that it
On the afternoon of December 17, 1992, in an unpro-is too na¨ıve to presume causality on the basis of tem-voked act of violence, Christopher Clunis killed young
poral sequence alone.

musician Jonathan Zito on the platform of Finsbury
The term “substance-induced psychosis” presup-Park subway station in London. One of the several errors
poses that the substance use influences the causation of
identified by the inquiry into the case of Christopher
the psychosis – that is, if the person did not use the sub-Clunis was attribution of his psychotic symptoms as sec-stance, then he/she would not develop the psychosis.

112

ondary to drug use
[1].

Although there is little doubt that substance use is
Chapter 8 – Substance-induced psychosis: an overview

associated with a greater risk of developing either
month of substance intoxication or withdrawal. How-short-lasting or chronic psychoses, whether it causes
ever, the psychotic symptoms must be clearly in excess
psychosis is debatable. In this, chapter, we focus on
of those usually associated with the intoxication or
conditions marked by coexistence of substance use
withdrawal syndrome, or the symptoms must be suf-and psychosis, in which substance use has preceded
ficiently severe to warrant independent clinical atten-the onset of psychosis. This is, admittedly, only one
tion. Further, hallucinations for which the person has
facet of the complex phenomenon of comorbid sub-insight are considered to be a part of intoxication
stance abuse and psychotic disorder. A substantial
and are not considered to be psychotic. The rest of
body of literature details the reasons why patients with
the substance-induced conditions (delirium, psychotic
schizophrenia abuse substances more frequently than
mood disorders) are not considered to be SIP, though
the general population, which we do not discuss in this
they may be associated with psychotic symptoms.

chapter.

Diagnosis of primary psychotic disorder is encouraged
when psychotic features last for more than a month
with sustained abstinence. However, it does recog-

Definition

nize that certain agents can cause longer-lasting psy-Lack of clarity as to what constitutes SIP has been a
chotic disorders. ICD-10 criteria are largely similar but
major hurdle for research in this area. To begin with,
require that the onset of psychosis should occur within
there is no universally accepted definition of the term
48 hours of use of the substance and the disorder may
“psychosis” and it is used to mean different things in
last for up to 6 months, beyond which a primary psy-different contexts. About two decades ago, any impair-chosis would be diagnosed.

ment that grossly interfered with day-to-day func-Both DSM-IV and ICD-10 offer useful criteria
tioning would be called a “psychotic” feature. Cur-to diagnose SIPs, which can be operationalized for
rently, the Diagnostic and Statistical Manual of Men-research purposes. However, most reports of SIP in
tal Disorders-IV (DSM-IV) definition of “psychosis”

existing scientific literature have used inconsistent def-requires the presence of “delusions, prominent hallu-initions or even failed to mention the definition used.

cinations, disorganized speech, disorganized or cata-For instance, reports on amphetamine-induced psy-tonic behavior” and the International Classification of
chosis
[3, 4]
have generally used DSM-III-R or DSM-Disorders-10 (ICD-10) defines it as comprised of “hal-IV diagnoses but those on cocaine-induced psychosis
lucinations, delusions, or a limited number of severe
[5, 6]
have used questionnaires specifically prepared
abnormalities of behavior, such as gross excitement
for cocaine-related disorders, making comparisons
and over-activity, marked psychomotor retardation,
across studies difficult.

and catatonic behavior.” In the context of substance
use, DSM-IV restricts the definition to the presence
Research directions

of delusions or only those hallucinations for which the
individual lacks insight.No such distinction is made in
The question of the relationship between substances
ICD-10.

and psychosis has been approached using different
Persons using psychoactive substances experi-but complementary lines of research. The basic ques-ence psychotic symptoms in various contexts of sub-tions they have tried to answer are i) whether expo-stance use: intoxication, withdrawal, delirium (related
sure to drugs of abuse can cause psychotic symptoms
to intoxication or withdrawal), substance-induced
and, if so, do different drugs differ in their psychoto-mood disorder (with psychotic symptoms), or SIP.

genic properties? ii) Whether substance users are at
Substance-induced psychoses are best conceptualized
an increased risk of developing acute or chronic psy-as those conditions where delusions and prominent
choses? and iii) What is the construct validity of SIP?

hallucinations begin in the context of substance use
but persist for a few days to a few weeks in the absence
Do drugs cause psychoses? If so, which
of continued use of the substance; relapse of psychotic
symptoms upon re-exposure to the substance further
drugs?

supports the diagnosis
[2].

Many studies have administered controlled doses of
DSM-IV defines SIP as those conditions in which
substances of abuse in laboratory settings to assess the
113

delusions and prominent hallucinations occur within a
psychotogenic properties of these drugs.

Organic Syndromes of Schizophrenia – Section 3

Amphetamine-type stimulants worsen psychotic
It is therefore evident that although different sub-symptoms in patients with schizophrenia, particularly
stances consistently produce or exacerbate psychotic
in persons with active symptoms rather than per-symptoms in patients with primary diagnoses of psy-sons with psychosis in remission
[7].
However, healthy
chosis, they differ in their psychotogenic properties in
volunteers rarely experience psychotic symptoms at
“healthy” individuals. It is interesting to speculate on
doses sufficient to cause or exacerbate psychotic symp-the reasons that may underlie this phenomenon. First,
toms in schizophrenia patients (0.25–0.3 mg/kg dex-the reason for the differential effects of substances
amphetamine or 0.5 mg/kg methylphenidate). Given
in producing psychotic symptoms may lie in the dif-in sufficiently high doses, amphetamines can pro-ferential susceptibility of the “healthy” subjects. Sec-duce psychotic symptoms even in healthy individuals
ond, although all substances with reinforcing property
[8].
Similarly,
3,4-meth
ylenedioxymethamphetamine
enhance dopamine transmission, they differ widely
(MDMA) does not provoke psychotic symptoms in
in their ability to directly or indirectly affect other
healthy adults at doses used by recreational users
neurotransmitter systems. Different neurotransmitters
[9, 10, 11].
Sherer (1988)
[12]
found a positive
interact in a complex way to cause psychosis and differ-correlation between cumulative dose of intravenous
ent substances seem to facilitate this interaction vari-

cocaine and degree of paranoia in otherwise healthy
ably in healthy persons.

cocaine addicts. However, there was no correlation
between plasma cocaine concentration and paranoia;
indeed, the person having a severe psychotic reaction had relatively low plasma cocaine. This points
Epidemiological studies examining

to a complex interaction between interindividual
psychotic experience among

differences and the dose of cocaine in producing
paranoia.

substance abusers

These experiments suggest that the brains of
Psychoses do not follow an “all-or-none” principle.

schizophrenia patients may be sensitized (see later) to
Strauss
[17]
proposed that psychotic symptoms are
the psychotogenic effects of stimulants in such a way
“points on continua of function” rather than being
that even low doses of these substances cause psychotic
dichotomous entities. In many ways, psychotic symp-exacerbations. Use of much higher doses of substances,
toms in patients with psychosis occur in continuity
probable sensitization due to long duration of use, use
with psychosis-like experiences in the general popu-in combination with other drugs, and the presence
lation
[18, 19].
Psychotic symptoms of varying sever-of individual vulnerability factors may explain psy-ity are reported by a large number of individuals in
choses attributed to stimulants in nonschizophrenic
the community, but only a small proportion qualify
individuals.

for the diagnosis of psychosis of any kind
[20, 21].

In contrast,
δ
-9-tetrahydrocannabinol (
δ
-THC)
Substance abuse increases the risk of experiencing
produces significant psychotic symptoms even in
psychotic symptoms. Several studies have concluded
healthy volunteers. Further, it produces not just pos-that the daily use of cannabis or cocaine, cannabis
itive symptoms but negative and cognitive symptoms
dependence, and alcohol use disorders independently
as well, mimicking typical features of schizophrenia
increase the risk of experiencing psychotic symptoms
in the healthy subjects
[13].
These effects are more
by several folds in adults
[19, 22, 23].
After control-pronounced in clinically stable, medicated schizophre-ling for confounding factors including age, sex, ethnic
nia patients than in the healthy controls
[14],
suggest-group, urban living, IQ, life events, neuroses, and vic-ing that schizophrenia patients are particularly prone
timization experience, the risk is substantially reduced
to react adversely to cannabis, as they do to stimu-but nevertheless remains significantly greater in sub-lants. Glutamate-N-methyl-D-aspartic acid (NMDA)-

stance abusers than nonabusers
[22].
Although 4% of
receptor antagonists like phencyclidine (PCP) have
the general population experiences clinically signifi-been consistently shown to produce psychotic symp-cant delusions and hallucinations, which are not sec-toms in healthy volunteers
[15, 16].
Again, similar
ondary to substance use
[19],
those with substance
to
δ
-THC and in contrast to stimulants, these symp-abuse/dependence are five times more likely to expe-toms include positive, negative, and cognitive symp-rience these symptoms. Substance use thus appears to
114

toms resembling schizophrenia.

be associated with a greater likelihood of experiencing
Chapter 8 – Substance-induced psychosis: an overview

psychotic symptoms and is not necessarily secondary
development study from birth. Assessments were con-to substance use.

ducted annually until age 16 and then again at 18, 21,
The studies that are best positioned to test whether
and 25. Those who were daily users of cannabis had
substance use causes psychosis are prospective cohort
rates of psychotic symptoms that were between 2.3 and
studies (preferably from birth) but few of these exist
3.3 times higher than the rates for those who did not
and those that do have focused exclusively on the link
use cannabis.

between cannabis use and psychosis
[24, 25, 26, 27,

28,
29, 30, 31].
There is now a large body of literature
Do substances differ in their association with

on the relationship between cannabis and psychosis:
more than 180 articles have been indexed on PubMed
psychotic symptoms?

since 2000, with more than 100 of these appearing
Although no systematic study has been conducted
in the last two years. A large number of studies have
comparing the psychotogenic properties of different
reported a significant association between cannabis
substances of abuse, clinical observation suggests that
use and psychosis and there is abundant evidence of
it varies widely.

the link between the two in epidemiological studies
involving the general population.

Alcohol

A study from the Netherlands
[32]
followed 4,045

Studies have shown alcohol dependence, but not alco-people between 1996 and 1999. Cannabis users with no
hol use in itself, to be predictive of psychotic experi-psychotic disorder at baseline were at increased risk of
ences in the general population
[22, 23].
Patients with
clinically significant psychotic symptoms at the end of
psychotic symptoms are more likely to abuse alcohol
followup (OR
=
3.5–3.7). This association was inde-than those without psychotic symptoms; alcohol abuse
pendent of any comorbid nonpsychotic psychiatric
may worsen the symptoms of schizophrenia and psy-disorder or use of other substances at baseline. A sec-chotic symptoms may precipitate relapse (e.g. Olfson
ond Netherlands study
[33]
was a 14-year followup of
et al., 2002
[37])
but it is generally accepted that alco-1,580 young adults in the “Zuid Holland” study. In this
hol use does not actually cause schizophrenia
[38].