Secondary Schizophrenia (45 page)

sample, cannabis use significantly predicted psychotic
symptoms in participants who did not have psychotic
symptoms before they began using cannabis (OR
=

Amphetamines

2.8). A German study
[34]
followed 2,437 young peo-Although brief amphetamine-induced psychosis is
ple aged 14 to 24 for 4 years between 1996 and 1999.

well documented, the extent to which amphetamine
Any cannabis use at baseline was reported to increase
use contributes to schizophrenia is not known. There
the risk of psychotic symptoms at the 4-year followup
is a high rate of mental health problems among regular
in a dose–response fashion, regardless of confounders.

amphetamine users with more than a quarter (26.7%)
The association was much stronger for those who had
of those with such mental health problems diagnosed
been identified as being prone to psychosis at base-with psychosis and the majority of these (71.4%)
line. A New Zealand study
[35]
was a birth cohort
reportedly having received this diagnosis after com-based on 1,037 people born in Dunedin, New Zealand
mencing regular amphetamine use
[39].
However, a
between 1972 and 1973. Cannabis use at ages 15 and 18

study of amphetamine users found that users with psy-increased the risk of presenting with psychotic symp-chosis were younger when amphetamine use was first
toms or schizophreniform disorder at age 26 (OR
=

initiated and used larger amounts of amphetamines
11.4 for those who had used cannabis before the age
than those without psychosis, leading to the conclu-of 15). Like the other cohort studies, this relation-sion that premorbid schizotypal personality predis-ship was independent of the use of other substances.

poses amphetamine users to psychosis
[4].

Significantly, this study also assessed the presence of
psychotic symptoms at age 11 and was therefore able
to demonstrate that the observed association between
Cocaine

cannabis use and increased risk of psychosis was inde-A number of studies
[5,
39]
have reported that cocaine
pendent from pre-existing psychotic symptoms. A
can induce psychotic symptoms in some users but
second New Zealand study
[36]
followed 1,011 indi-comparatively little research has been conducted to
115

viduals taking part in the Christchurch health and
date.

Organic Syndromes of Schizophrenia – Section 3

Opiates

Validity of the construct of

Research into the relationship between opiate use and
substance-induced psychosis

psychosis is limited. Studies have generally shown a
low comorbidity rate between opiate use and psychosis
Although the term “substance-induced psychosis”

[40, 41],
and there is evidence to suggest that heroin
(SIP) is frequently used in common psychiatric par-users may actually be at lower risk of psychosis than
lance, there is surprisingly little agreement on its valid-users of other substances
[42].

ity. Poole and Brabbins
[2]
have even questioned the
existence of such a syndrome and suggested that the
term be discontinued from use.

Nicotine

Robins and Guze
[46]
listed five criteria for estab-Though it enhances extracellular dopamine in the
lishing the validity of psychiatric diagnoses: i) clin-nucleus accumbens, it does not cause psychosis even
ical description (including symptom profiles, demo-in heavy smokers.

graphic characteristics, and typical precipitants), ii)
Preliminary research evidence supports the obser-laboratory studies (including psychological tests, radi-vation of differential psychotogenetic properties of
ology, and postmortem findings), iii) delimitation
substances. In a study on out-of-treatment substance
from other disorders (by means of exclusion criteria),
abusers, 86% percent of persons dependent on any of
iv) followup studies (including evidence of diagnostic
the substances reported lifetime experiences of
stability), and v) family studies.

psychotic symptoms in the context of use of, or
withdrawal from, those specific substances
[43].

Clinical description

Percentages of dependent persons reporting psy-The clinical descriptions of SIP are extensive and con-chotic symptoms in the context of specific substances
sistent, with minor differences across different sub-were 80% for cocaine, 64% for cannabis, 56% for
stances. They generally present with an acute onset of
amphetamines and 53% for opioids. When sub-psychotic episode in the background of heavy use of
jects dependent on more than one substance were
substances. They are characterized by prominent delu-questioned about psychotic experiences with spe-sions and hallucinations of auditory, visual and tac-cific drugs, the association was significantly greater
tile nature and prominent affective symptoms (eupho-for cocaine than with other substances. In terms
ria and fear are common) but disorganization, neg-of relative association with psychotic symptoms,
ative symptoms, and catatonia are rare. There are
cocaine was followed by cannabis and amphetamines.

occasional reports of disorientation and confusion,
Hallucinogens and phencyclidine were used by
especially with acute cannabis and inhalant intoxi-only a small number of subjects and were not
cation (“toxic psychoses”). Cocaine abuse is associ-considered for analysis. It appears that at the depen-ated with prominent paranoia, especially about being
dence level, cocaine has the greatest psychotogenic
caught by law-enforcing agencies. Tactile hallucina-property.

tions of insects crawling under the skin (“cocaine
It is evident from the earlier review that sub-bugs”), although relatively infrequent, are also typ-stance use is associated with a greater risk of psychotic
ical of cocaine-induced psychosis. Alcohol-induced
experience in the nonclinical population. Although
psychosis is characterized by prominent hallucina-this association is stronger for those who are vul-tions (“alcoholic hallucinosis”); delusions generally
nerable to develop psychosis, substances appear to
occur secondarily in response to them. Only PCP-have an independent association with psychotic expe-induced psychosis is characterized by prominent neg-rience. Some other risk factors for the development
ative symptoms and catatonic behaviors. However, in
of psychotic symptoms in the nonclinical populations
contrast to acute schizophrenic episodes, passivity and
are impairments in development, including neuro-thought alienation phenomena are very rare in SIPs.

motor development, receptive language, intelligence
and emotional development, urban residence, lower
Diagnostic stability, delimitation from other disorders,

level of education, life events, neurosis, victimization,
and family history

and lower quality of life
[20, 23,
44, 45].
These are
A recent methodologically rigorous study of 400 sub-also risk factors for the development of substance-use
jects with recent-onset psychosis in substance-using
116

disorders.

persons presenting to emergency psychiatric services
Chapter 8 – Substance-induced psychosis: an overview

[47, 48]
reported that SIPs are distinguishable from
that lasts longer, is more severe, and is associated with
primary psychoses, have diagnostic stability, and a dis-poorer premorbid and familial risk of schizophrenia –
tinct family history. Forty-four percent of the sam-in this they resemble schizophrenic illness precipitated
ple was reliably diagnosed with SIP (DSM-IV crite-or exacerbated by substance use.

ria). These included patients with psychoses induced
Very little work has been done to delineate spe-by cannabis, cocaine, alcohol, hallucinogens, sedatives,
cific SIPs from schizophrenia except for alcoholic
heroin, and stimulants. They differed from the primary
hallucinosis. There is some evidence that there is a
nonorganic psychosis group (schizophrenia, psychotic
genetic vulnerability to develop alcoholic psychosis
mood disorder, psychotic disorder not otherwise spec-that is transmitted separately from the vulnerability to
ified, schizophreniform disorder, schizoaffective dis-develop schizophrenia
[50].
However, the predictive
order, and delusional disorder) on several counts. They
validity of alcoholic hallucinosis is very poor – only
were older and more likely to be married, homeless,
a small proportion of patients with such a diagnosis
have poorer family support, have greater parental sub-retain the diagnosis
[51].

stance abuse, and lesser parental mental illness. They
SIPs seem to fulfill most of Robins and Guze
[46]

scored significantly less on positive syndrome, neg-criteria. As for the laboratory evidence supporting
ative syndrome, general psychopathology, and total
the diagnostic validity, SIPs and psychiatric disorders
scores of PANSS; and had greater awareness and
due to general medical disorders share the common
lesser misattribution of their symptoms and a more
platform. Laboratory evidence, namely qualitative or
common incidence of visual hallucinations. Expect-quantitative assays of drug metabolites in body fluids,
edly, a greater proportion of patients had substance
can support the association of substance use with
abuse/dependence and antisocial personality disorder.

the psychotic state. Studies elucidating the neurobi-At the end of one year, 75% of patients diagnosed
ological substrates for psychotogenic properties of
as SIP had retained their diagnosis; the rest were classi-substances (see later) support the plausibility of SIP as
fied as primary psychotics
[48].
In addition to the dif-a valid construct.

ferences discussed earlier, the followup SIPs showed
lesser parental mental illness than followup primary
Susceptibility for developing SIP

psychotics. Little can be commented on the general-Not all people who abuse substances develop psy-izability of the results to other settings (e.g. commu-chosis. It would appear from the available evidence
nity/clinics). Comparison was made between SIP and
that both i) substance-related and ii) individual risk
a heterogeneous group of psychotic disorders, with sig-factors modulate the susceptibility for SIP.

nificant histories of substance use. How SIPs would
compare with nonaffective psychotic patients without
substance abuse remains to be studied. Family his-Substance-related factors
tory was not assessed using standardized methods.

These include different indices of cumulative expo-Notwithstanding these caveats, the two reports from
sure to substances, including earlier onset of substance
this group of researchers have contributed to validat-use, heavier use, greater lifetime consumption, more
ing SIPs.

severe dependence, and greater amount of money
An earlier report
[49]
of inpatients with substance
spent on substances
[4, 5, 6,
52, 53].
An interesting
abuse and psychosis compared patients with short-phenomenon associated with SIP is that of sensitiza-and long-lasting psychoses (with a 6-month cutoff
tion. Psychosis develops more rapidly and manifests
duration before admission). Patients with long-lasting
more severely at lower doses than used in the past; this
psychoses had more symptoms of psychosis, poorer
is seen even after several years of abstinence
[5,
54,

premorbid adjustment, longer durations of drug treat-

55].
Interestingly, sensitization occurs only for the psy-ment and hospital stay, and greater number of fam-chotic effects but not the other effects of cocaine
[56].

ily members with schizophrenia. This suggested that
Cocaine abusers who experience sensitization to the
at least two kinds of psychoses exist in the context
psychotogenic property of cocaine paradoxically have
of substance abuse: i) one that is brief-lasting, milder,
less naturally occurring craving and are likely to reduce
with better premorbid functioning and without famil-their cocaine and other substance use
[57].

ial risk of schizophrenia; in this, the role of substance
Sensitization in animals generally occurs after
117

as an etiological agent is more compelling; and ii) one
repeated administration of substances. Once initiated,
Organic Syndromes of Schizophrenia – Section 3

the phenomenon lasts for several years without
ily history of psychosis, poor premorbid adjustment,
requiring repeated use of substances. Animals sensi-and comorbid affective illness are likely to start sub-tized to stimulants show cross-sensitization to other
stance use early, use more heavily, and develop more
substances and stress. There appears to be a genetic
severe dependence
[66].
Gene-environment interac-influence in the vulnerability to sensitization. Sev-tions have been hypothesized to underlie this differen-eral molecular mechanisms underlie the development
tial susceptibility to SIP, with some individuals being
of sensitization, which result in expression of genes
genetically vulnerable to the effects of substances.