SCHRES-07610; No of Pages 9

Schizophrenia Research xxx (2017) xxx–xxx

Contents lists available at ScienceDirect

Schizophrenia Research

journal homepage: www.elsevier.com/locate/schres

Clinical characteristics of primary psychotic disorders with concurrent

substance abuse and substance-induced psychotic disorders: A
systematic review
Lorna Wilson a,⁎, Attila Szigeti b, Angela Kearney c, Mary Clarke b
a
Cluain Mhuire Community Mental Health Service, Newtownpark Avenue, Blackrock, Dublin, Ireland
b
DETECT Early Intervention in Psychosis Service, Avila House, Carysfort Avenue, Blackrock Business Park, Dublin, Ireland
c
St John of God Hospital, Stillorgan, Dublin, Ireland

a r t i c l e i n f o a b s t r a c t

Article history: Background: Distinguishing between a primary psychotic disorder with concurrent substance abuse (PPD + SA)
Received 25 April 2017 and a substance-induced psychotic disorder (SIPD) can be diagnostically challenging. We aimed to determine if
Accepted 1 November 2017 these two diagnoses are clinically distinct, particularly in relation to psychopathology. In addition, we aimed to
Available online xxxx examine the specific clinical features of cannabis-induced psychotic disorder (CIPD) as compared to primary psy-
chotic disorder with concurrent cannabis abuse (PPD + CA) and also to SIPD associated with any substance.
Keywords:
Methods: A systematic review of SIPD literature using Preferred Reporting Items for Systematic Reviews and
Substance-induced psychotic disorder
Cannabis
Meta-Analyses (PRISMA) guidelines.
Substance abuse Results: Using strict inclusion criteria, a total of six studies examining SIPD were included in the review (two of
Psychopathology which only considered psychosis induced by cannabis alone). The findings did not reveal many consistent differ-
Schizophrenia ences in psychopathology. However, we did find that that compared to PPD + SA, individuals with SIPD have a
Psychosis weaker family history of psychotic disorder; a greater degree of insight; fewer positive symptoms and fewer neg-
ative symptoms; more depression (only in CIPD) and more anxiety.
Conclusion: There remains a striking paucity of information on the psychopathology, clinical characteristics and
outcome of SIPD. Our review highlights the need for further research in this area.
© 2017 Elsevier B.V. All rights reserved.

1. Introduction Multiple agents have been implicated in the development of sub-

Substance abuse is common among individuals with primary psy-
chotic disorders. Nearly half of those with a history of schizophrenia re-
port a lifetime coexisting substance use disorder (Kavanagh et al., 2004;
Regier et al., 1990). Alcohol and cannabis are the predominant sub-
stances abused by patients with psychotic disorders (Barnett et al.,
2007; Kavanagh et al., 2004; Weaver et al., 2003). More recently, the
use of novel psychoactive substances (NPS) has become more wide-
spread due to their availability on the internet and in so called “head
shops”. Their use appears to be significantly more common in people
with psychiatric illnesses compared to healthy people (Martinotti et
al., 2014). A recent systematic review on the effects of NPS on individ-
uals with severe mental illness suggested that NPS can have a relatively
severe effect on people with psychotic disorders, resulting in an exacer-
bation in symptoms with increased agitation, aggression and violence
(Gray et al., 2016).
⁎ Corresponding author.
E-mail address: lornaswilson@yahoo.co.uk (L. Wilson).
stance-induced psychotic disorder (SIPD) including alcohol, cocaine,
amphetamines and hallucinogens (Engelhard et al., 2015; Harris and
Batki, 2000; Murray et al., 2013; Vardy and Kay, 1983). Much of the re-
search however has focused on cannabis-induced psychotic disorder
(CIPD). The intimate relationship between cannabis use and psychosis
is well recognized (Andreasson et al., 1987; Arseneault et al., 2002;
Fergusson et al., 2005; Fergusson et al., 2003; Henquet et al., 2005a;
Henquet et al., 2005b; Imade and Ebie, 1991; Kristensen and
Cadenhead, 2007; Kuepper et al., 2011; Semple et al., 2005; Solomons
et al., 1990; van Os et al., 2002). Overall, cannabis use appears to confer
a twofold risk of later schizophrenia or schizophreniform disorder
(Arseneault et al., 2004).
There is still debate as to whether SIPD is a separate entity from
schizophrenia and whether the diagnosis is stable over time. Some au-
thors argue that there are no consistent differences in the symptomatol-
ogy of SIPDs and primary psychotic disorders (PPDs) and that there is
little evidence to support the validity of “cannabis psychosis” as a diag-
nostic entity (Boydell et al., 2007; Imade and Ebie, 1991; McGuire et al.,
1994; Thornicroft, 1992). Others maintain that in spite of certain

https://doi.org/10.1016/j.schres.2017.11.001
0920-9964/© 2017 Elsevier B.V. All rights reserved.

Please cite this article as: Wilson, L., et al., Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-
induced psychotic disorders:..., Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.001
2 L. Wilson et al. / Schizophrenia Research xxx (2017) xxx–xxx
similarities the possibility of a nosologically distinct diagnosis remains
(Basu et al., 1999).
In relation to the effect of comorbid drug use on specific symp-
tomatology in those with psychotic disorders, varying outcomes
have been reported. The most consistent finding has been that drug
abusing patients with an underlying psychotic illness tend to experi-
ence fewer negative symptoms than non-drug abusing patients
(Baeza et al., 2009; Baldacchino et al., 2009; Bersani et al., 2002;
Buckley et al., 1994; Compton et al., 2004; Dixon et al., 1991;
Dubertret et al., 2006; Swartz et al., 2006). However, several studies
have noted no difference in negative symptomatology (Addington
and Addington, 2007; Barrowclough et al., 2015; Grech et al., 2005;
Kamali et al., 2009; Katz et al., 2010). More positive symptoms of
schizophrenia are generally observed in patients with drug abuse
(Addington and Addington, 2007; Allebeck et al., 1993; Baeza et al.,
2009; Baldacchino et al., 2009; Bersani et al., 2002; Buhler et al.,
2002; Dubertret et al., 2006; Grech et al., 2005; Kamali et al., 2009;
Katz et al., 2010; Swartz et al., 2006). But once again discrepancies
exist, with some studies reporting fewer or no difference in inci-
dence of positive symptoms (Barrowclough et al., 2015; Buckley et
al., 1994; Compton et al., 2004; Dixon et al., 1991).
Aggarwal et al. (2012) determined that the incidence of patients
presenting with SIPD to an Indian Drug De-addiction and Treatment
Centre over a 13-year period was 1.4%. Over an average follow up of
6 months, 20.3% of patients had a change in diagnosis to either schizo-
phrenia or affective psychosis. Arendt et al. (2005) found that of 535 in-
dividuals who were initially treated for CIPD and followed up for at least
three years, 238 (44.5%) later developed a schizophrenia-spectrum dis-
order. According to Chen et al. (2015) who observed 284 Taiwanese pa-
tients with SIPD over a 15 year period, the progression time from
transient to permanent psychotic disorder was 2.2 years with the ma-
jority of transformations occurring in the first year after diagnosis. Pa-
tients who receive an initial diagnosis of PPD in the context of
substance abuse have more diagnostic stability and are more likely
than SIPD patients to retain their diagnosis over time (Singal et al.,
2015).
Given that the diagnosis has significant implications for future
management, it is important to correctly identify SIPD. If psychot-
ic symptoms can be attributed to drug use rather than to a PPD
then antipsychotic treatment can be seen as a short term option
with the main emphasis being placed on substance abuse
treatment.
The fourth edition of the Diagnostic and Statistical manual of
Mental Disorders (DSM-IV) introduced the term SIPD in 1994
(American Psychiatric Association. and American Psychiatric
Association. Task Force on DSM-IV., 1994). It was intended to dis-
tinguish substance-induced psychotic states from primary psy-
chotic disorders. In the DSM-5, the diagnostic criteria for SIPD
essentially remain unchanged (American Psychiatric Association.
and American Psychiatric Association. DSM-5 Task Force., 2013).
They require the presence of hallucinations and /or delusions
that arise during or soon after substance intoxication or with-
drawal, that are judged to be due to the physiological effects of
the substance, and are not better accounted for by a primary psy-
chotic disorder. The symptoms cannot occur exclusively during
the course of a delirium and must cause significant distress or
impairment.
In clinical practice, distinguishing between SIPDs and PPDs with
concurrent substance use remains a diagnostic difficulty (Schanzer
et al., 2006). There has been criticism of the DSM diagnostic criteria
(Mathias et al., 2008; Rounsaville, 2007). A diagnosis of SIPD is
based on the assumption that most of the symptoms are transient
and disappear after sustained abstinence. In practice, individuals
who have an established pattern of abusing substances may not re-
port any sustained drug-free periods. Therefore, psychotic symp-
toms which appear during periods of heavy drug use may indeed
Please cite this article as: Wilson, L., et al., Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-
induced psychotic disorders:..., Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.001
be substance-induced, but they may also be manifestations of an
underlying PPD.
Regardless of the pathophysiology, patients with psychotic ill-
ness who abuse substances are a complex group of individuals
with multiple different needs. Severe mental illness and co-morbid
substance misuse is associated with a range of negative outcomes
including non-adherence, increased relapse and more frequent
hospitalisations (Caspari, 1999; Caton et al., 2000; Zammit et al.,
2008).
To our knowledge no previous systematic reviews have examined
the specific psychopathology of individuals presenting with a DSM diag-
nosis of SIPD. There is a remarkable paucity of research in this area. We
identified only one major systematic review examining the specific psy-
chopathology of “cannabis psychosis” compared to other psychotic dis-
orders (Baldacchino et al., 2012). However, this study used a very broad
definition of “cannabis psychosis” and only included studies conducted
in an inpatient setting.
2. Aims and objectives
2.1. Aim
The aim of this review was to determine if SIPD is distinct from pri-
mary psychotic disorder with concurrent substance abuse (PPD + SA),
in relation to psychopathology. Furthermore we aimed to examine the
specific clinical features of CIPD as compared to primary psychotic dis-
order with concurrent cannabis abuse (PPD + CA) and also to SIPD as-
sociated with any substance.
2.2. Objectives
The objectives of this paper were to review the demographics,
general psychopathology, positive and negative symptoms, in-
sight and premorbid adjustment of individuals with SIPD and
CIPD.
3. Methods
We identified studies examining SIPD associated either with any
substance use or with cannabis alone. The former included studies
that did not differentiate between illicit drugs, instead examining
more than one type of substance within the same study. Studies in-
vestigating SIPD associated with a single substance of abuse other
than cannabis were not included in the review due to the method-
ological difficulties in meaningfully comparing outcomes between
these trials. Therefore two types of studies were considered of
interest:
1. Those examining the psychopathology of SIPD (associated with any
substance) compared to PPD + SA.
2. Those examining the psychopathology of CIPD compared to PPD
+ CA.
3.1. Search strategy
The PRISMA (Preferred Reporting Items for Systematic reviews and
Meta-Analyses) guidelines (Moher et al., 2009) were used as a frame-
work for our review and reporting procedures. The search criteria
were collaboratively established with assistance from a research librar-
ian. We searched the following databases in February 2016: Pubmed,
Psychology and Behavioral Sciences, PsycINFO, Medline and the Cumu-
lative Index to Nursing and Allied Health Literature (CINAHL). The
search strategy used both free-text words and Medical Subject Headings
(MeSH) terms. We conducted eight separate searches using a combina-
tion of the key words “substance-induced psychosis”, “cannabis”, “THC”,
“psychopathology”, “diagnosis”, “clinical features”, “schizophrenia”,
 L. Wilson et al. / Schizophrenia Research xxx (2017) xxx–xxx 3

“psychotic disorders” and “substance abuse”. Only studies published in 3.2. Study selection
English Language were considered for this review. The search was not
limited by publication date or study design. Manual searches were There were three main inclusion criteria for the review:
also conducted using the reference lists from recovered articles. Two in-
vestigators (L.W. and A.S.) read the abstracts and full text of all relevant • Studies comparing SIPD/CIPD to primary psychotic disorders with
studies to assess suitability for inclusion. Where controversy occurred concurrent substance use.
on whether to include or exclude a study, the final decision was made • Studies using ICD-10 or DSM-IV/PRISM criteria for the diagnosis of
by senior author M.C. SIPD/CIPD.

Fig. 1. PRISMA flowchart detailing search strategies and results.

Please cite this article as: Wilson, L., et al., Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-
induced psychotic disorders:..., Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.001
4 L. Wilson et al. / Schizophrenia Research xxx (2017) xxx–xxx
• Studies using validated assessment instruments to measure
psychopathology.
Exclusion criteria included:
• No measure of psychopathology or lack of a validated assessment in-
strument.
• No PPD comparison group or a PPD group which was substance free.
• No validated diagnostic criteria.
• Papers assessing duplicate patient cohorts.
4. Results
4.1. Search results
We considered the abstracts of 671 articles identified through data-
base searching (Fig. 1). Of these, the full text of 133 articles were
reviewed together with 64 articles sourced from hand-searching refer-
ences. In total, 41 studies examining SIPD were identified. Six of these
studies met the full criteria for inclusion and data extraction: four inves-
tigated SIPD associated with any substance, (Caton et al., 2005; Dawe et
al., 2011; Fraser et al., 2012; Weibell et al., 2013) and two examined psy-
chosis induced by cannabis alone (CIPD) (Dragogna et al., 2014; Rubio
et al., 2012).
4.2. Description of studies
Table 1 describes the participants, measures, and methods used by
each of the six identified studies. There were several variations across
the patient cohorts including gender, age and number of participants.
The majority of patients were male with a mean age ranging from
20.6 to 28.4 years. Schizophrenia and psychotic disorder NOS were the
most common diagnoses within the PPD groups.
Most of the studies included in the review examined the demo-
graphic and clinical differences between two groups of patients: those
with a diagnosis of SIPD and those with a diagnosis of PPD + SA. How-
ever, two of the included studies also considered a third patient cohort –
individuals with a diagnosis of PPD who were not abusing substances
(Dragogna et al., 2014; Weibell et al., 2013).
Four of the studies only examined individuals who were psychiatric
inpatients, (Dawe et al., 2011; Dragogna et al., 2014; Fraser et al., 2012;
Rubio et al., 2012) while two studies also included psychotic patients
who were being managed in the community (Caton et al., 2005;
Weibell et al., 2013). There was also some heterogeneity with regard
to onset of psychotic symptoms. While all of the investigators
attempted to only examine individuals in the early stages of their illness,
the definition of this varied between studies. For example, Dragogna et
al. (2014) defined recent onset of illness as a duration of no longer than
five years, while Caton et al. (2005) only included those who had not
been hospitalised or suffered from untreated psychosis in the previous
six months.
Furthermore, there was some inconsistency in participant ethnicity.
Most studies examined populations of European / Caucasian descent
but one study examined a group of patients who were predominantly
black (43.5.%) or of Hispanic origin (42%) (Caton et al., 2005).
4.3. Study findings – sociodemographic data
Of the five studies that compared patient gender, no difference was
found between individuals with SIPD and PPD + SA. However one
study which included a third group of non-substance abusing psychotic
patients found that substance misusers were significantly more likely to
be male (Weibell et al., 2013). This preponderance of males among sub-
stance users was also noted by Dragogna et al. (2014).
There were no consistent findings between groups in relation to dif-
ferences in patient age, onset of drug use, race or level of education.
Please cite this article as: Wilson, L., et al., Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-
induced psychotic disorders:..., Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.001
Fraser et al. (2012) noted that the SIPD group were significantly
more likely to have a forensic history. Similarly, Caton et al. (2005)
found that those with SIPD were more likely than those with PPD
+ SA to have a diagnosis of antisocial personality disorder (17.2% vs.
8.3%. However, there was no difference in rates of violent behaviour or
prison incarceration in the 6–12 months prior to the study.
According to Fraser et al., 2012, SIPD individuals were 23 times more
likely to have a trauma history than those with PPD + SA and to have
experienced their first traumatic event at a significantly older age. This
conflicted with the findings of Caton et al., 2005 and Weibell et al.,
2013 who did not observe any differences between groups with regard
to incidence of PTSD or significant life events.
Caton et al. (2005) found three significant sociodemographic differ-
ences between individuals with SIPD and those with PPD + SA. Patients
with SIPD were more likely to have been involved in a marital or conju-
gal relationship, have poorer family support and to have been homeless
in the six months before intake. These findings however were not repli-
cated in the other studies.
Two studies observed that individuals with SIPD were significantly
less likely to have a family history of psychosis than those with PPD
+ SA (Dawe et al., 2011; Fraser et al., 2012). It was also noted by
Caton et al. (2005) and Rubio et al. (2012) that SIPD patients were
more likely to have parents with substance misuse issues.
4.4. Study findings – clinical characteristics
Fraser et al. (2012), Dawe et al. (2011) and Rubio et al. (2012) all
found that individuals with SIPD had significantly higher rates of am-
phetamine and/or cannabis use prior to the study. Weibell et al.
(2013) noted greater use of opiates in SIPD patients but no significant
differences in rates of other types of substances. Overall, comorbid
DSM-IV diagnoses of substance dependence and/or abuse also tended
to be greater in the SIPD patients. There was no difference between
groups in relation to age of onset of drug use.
Weibell et al. (2013) found that SIPD patients had a significantly
shorter duration of untreated psychosis (DUP) than PPD + SA patients
(5 vs. 20 weeks). However two of the other studies noted no difference
in DUP between groups (Dawe et al., 2011; Fraser et al., 2012).
No significant differences were found between the SIPD and PPD
+ SA groups in relation to previous contact with the psychiatric ser-
vices, (Dragogna et al., 2014) number of psychotic episodes or length
of hospital admission (Dawe et al., 2011). Based on the findings from
four of the studies, there were also no between group differences in re-
lation to premorbid adjustment or level of functioning (Caton et al.,
2005; Dawe et al., 2011; Fraser et al., 2012; Weibell et al., 2013).
Three of the included studies used the Scale to Assess Unawareness
of Mental Disorders (SUMD) and found that individuals with SIPD had
significantly lower scores on the unawareness sub-scale (Caton et al.,
2005; Fraser et al., 2012; Rubio et al., 2012). Two of these studies also
found that SIPD patients scored significantly lower on the misattribu-
tion of symptoms sub-scale (Caton et al., 2005; Rubio et al., 2012).
This indicates that SIPD patients are more aware than PPD + SA patients
of the existence of psychotic symptoms and have a greater understand-
ing that these symptoms are a manifestation of mental illness.
4.5. Study findings-psychopathology
Two studies found between group differences in relation to positive
symptomatology. SIPD patients had significantly lower scores on the
positive symptoms subscale of the Positive and Negative Syndrome
Scale (PANSS) (Caton et al., 2005), and on the psychotic ideation sub-
scale of the Symptoms Checklist-90-R (SCL-90-R) (Rubio et al., 2012),
compared to patients with PPD + SA. Although Dawe et al. (2011)
found that both groups of patients reported a similar severity of positive
symptoms on admission according to the Brief Psychiatric Rating Scale
induced psychotic disorders:..., Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.001
Please cite this article as: Wilson, L., et al., Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-
Table 1
Details of studies reporting on the psychopathology of SIPD and CIPD.
Study Participant demographics
(male/female, age, ethnicity)
Caton et al., 2005 386 psychotic patients
presenting to an ED in New
York, USA 72% male 17–45
yrs. Mean age 28.4 yrs.
43.5% Black, 42% Hispanic,
14.5% White/other
Dawe et al., 2011 98 inpatients with a
psychotic disorder in
Queensland, Australia
74.5% male Mean age –
27.6 yrs. Australian
non-aboriginal 79%,
Australian aboriginal 6%,
New Zealand 7%, other 8%
Dragogna et al., 16 acutely psychotic
2014 inpatients in Milan, Italy
81% male 18-33 yrs. Mean
age 23.3 yrs.
Fraser et al., 61 inpatients in an Early
2012 Psychosis Prevention and
Intervention Centre
(Melbourne, Australia) 77%
male 15–24 yrs. Mean age
20.6 yrs.
Rubio et al., 2012 154 psychotic inpatients
admitted to 3 hospitals in
Madrid, Italy 87% male
18–45 yrs. Mean age 25.28
yrs.
Weibell et al., 141 psychotic patients
2013 referred to an Early
Identification and
Treatment of Psychosis
(TIPS II) study (Norway)
60% male 17-53 yrs. Mean
age – 26.5 yrs.
SIPD, substance-induced psychotic disorder; CIPD, cannabis-induced psychotic disorder; PPD, primary psychotic disorder; SA, substance abuse; CA, cannabis abuse; SCZ, schizophrenia; BD, bipolar disorder; MDD, major depressive disorder; FEP, first
episode psychosis; PRISM, Psychiatric Research Interview for Substance and Mental Disorders; SCID, Structured Clinical Interview for DSM-IV Axis I; SCID-II, Structured Clinical interview for DSM-IV Axis II Personality Disorders; MINI, Mini Interna-
tional Neuropsychiatry Interview; CCS, Community Care Schedule; PANSS, Positive and Negative Syndrome Scale; PAS, Premorbid Adjustment Scale; TLFB, Timeline Followback; SUMD, Scale to Assess Unawareness of Mental Disorders; IRAOS, In-
terview for the Retrospective Assessment of the Onset and Course of Schizophrenia and other psychoses; BPRS, Brief Psychiatric Rating Scale; FES, Family Environment Scale; CIDI-TL, Composite International Diagnostic Interview-Trauma List;
GAF, Global Assessment of Functioning Scale; SOFAS, DSM-IV Social and Occupational Functioning Assessment Scale; SCL-90-R, Symptom Checklist-90-R; SCS, Strauss-Carpenter Scale.
Patient cohorts
SIPD = 169 PPD + SA = 217
SCZ 36.9% Psychotic mood
disorder 33.6%Psychotic
disorder NOS 14.7%
Schizophreniform disorder
8.3% Schizoaffective disorder
3.9% Delusional disorder 2.8%
SIPD = 47 PPD + SA = 51
SCZ 20.4% Psychotic mood
disorder 14.3% Schizoaffective
disorder 7.1% Psychotic
disorder NOS 5.1%
Schizophreniform disorder
3.1% Delusional disorder 2.0%
CIPD = 5 SCZ + CA = 6
SCZ-CA = 5
SIPD = 34 PPD + SA = 27
CIPD = 50 PPD + CA = 104
SCZ 53% BD 27% Psychotic
disorder NOS 10% Delusional
disorder 6%
Schizophreniform disorder
4%
SIPD = 30 PPD + SA = 45
Psychotic disorder NOS
46.7% SCZ 26.6%
Schizophreniform disorder
24.2% Delusional disorder
8.6% Schizoaffective disorder
4.4% MDD 4.4% BD 4.4% Brief
psychotic disorder 4.4%
PPD-SA = 66 Psychotic
disorder NOS 19.7% SCZ
19.7% Schizophreniform
disorder 4.5%Delusional
disorder 10.6%
Schizoaffective disorder
12.1% MDD 21.2% BD 6.0%
Brief psychotic disorder 3.0%
Onset of psychotic Diagnosis Validated Definition of substance Assessments Follow-up
symptoms ascertainment assessment tools use
Early phase psychosis PRISM CCS PANSS PAS Use of alcohol and/or Baseline 3 years (study
Participants had no psych SUMD other drugs within the only reports
inpatient history nor past 30 days baseline findings)
untreated psychosis in the
previous 6 months
No N2 previous psychotic SCID IRAOS BPRS FES PAS Substance use in the 30 Admission, days 4/5, 8/9, Until discharge
admissions and within 3 Disturbed behaviour days prior to admission 15/16, 22/23, 29/30, 36/37, from hospital
years of initial diagnosis of a rating scale TLFB 43/44 and 50/51 or until (average of 19.1
psychotic disorder (62% discharge. days)
were 1st admissions, average
no. of psychotic episodes –
1.5)
L. Wilson et al. / Schizophrenia Research xxx (2017) xxx–xxx
Duration of illness not longer SCID PANSS Use of cannabis in the Baseline 6 months (to
than 5 yrs. (SCZ patients) weeks prior to ensure diagnostic
(mean duration of illness – admission stability)
25 months)
FEP 1st episode commenced PRISM Major BPRS CIDI-TL SUMD Substance use ≥ 6 Baseline None
b12 months prior depressive and manic GAF SOFAS PAS occasions in the past 12
episode modules of months, with most
the MINI recent use occurring in
the last 30 days
Most subjects identified PRISM SCID-II SCL-90-R SUMD Use of cannabis within Baseline (days 1–3 of 6 months
during 1st admission previous 30 days admission), before discharge
and at 6 months
FEP Not previously receiving SCID GAF PAS PANSS SCS – Baseline Planned at 1,2 and
adequate treatment for 5 years
psychosis
5
6 L. Wilson et al. / Schizophrenia Research xxx (2017) xxx–xxx
(BPRS), those with SIPD experienced a more rapid abatement of these
symptoms which were significantly less severe by day 50/5.
Conversely, Weibell et al. (2013) reported that individuals with SIPD
had significantly more positive symptoms on the PANSS compared to
both those with PPD + SA and those with PPD without concurrent sub-
stance use. However, this finding was only significant across all three
groups. On directly comparing the SIPD patients to those with SIPD
+ SA, the PANNS scores were not considerably different (18.3 vs. 18.0
respectively).
Five of the six included studies reported on negative symptoms
across the patient groups using the PANSS or BPRS. Three of these stud-
ies found that SIPD patients had significantly fewer negative symptoms
compared to PPD + SA patients (Caton et al., 2005; Dawe et al., 2011;
Dragogna et al., 2014), the remaining two found no difference (Fraser
et al., 2012; Weibell et al., 2013).
In relation to overall psychopathology, only Caton et al. (2005)
found any significant differences between groups with SIPD patients
scoring lower on the PANSS general psychopathology subscale.
Caton et al. (2005) also observed that visual hallucinations were
more common in the SIPD group (23.7% vs. 14.7%). None of the
other studies noted any other differences in levels of perceptual
disturbance.
Fraser et al. (2012) found that SIPD patients had significantly higher
levels of anxiety on the BPRS than those with PPD + SA. Similarly, Rubio
et al. (2012) noted that subjects with CIPD had psychopathologic symp-
toms belonging to a “neurotic profile” with significantly higher sores in
the following SCL-90-R subscales: Somatization, obsessive-compulsive,
interpersonal sensitivity, depression, anxiety and phobic anxiety. CIPD
individuals were also significantly more likely to have a comorbid diag-
nosis of social phobia (20.0% vs. 3.8%).
According to Dawe et al. (2011) SIPD patients on initial assessment
experienced significantly more severe symptoms of mania and dis-
turbed behaviour compared to those with PPD + SA. However, these
findings were only significant on admission to hospital and symptoms
abated rapidly. Fraser et al. (2012) did not find any difference in
manic excitement scores between groups on the BPRS.
There were no consistent differences between groups in relation to
suicidality.
4.6. Differences between CIPD versus PPD + CA and SIPD versus PPD + SA
In terms of specific sociodemographic differences between those
with SIPD associated with any substance and those with psychosis in-
duced by cannabis alone (CIPD), the included studies revealed two dif-
ferences. Individuals with SIPD were significantly less likely to have a
family history of psychosis than those with PPD + SA (Dawe et al.,
2011; Fraser et al., 2012). However, this finding was not applicable to
those with CIPD; even though the numbers were very small Rubio et
al. (2012) did not find any significant difference in rates of parental psy-
chotic disorders among those with CIPD and those with a PPD + CA
(fisher test, 0.46). Rubio et al. (2012) also noted that individuals with
CIPD were significantly more likely to be employed. This was not rele-
vant to those with SIPD. Three of the four studies comparing SIPD to
PPD + SA did not find any between group differences in relation to like-
lihood of employment (Caton et al., 2005; Dawe et al., 2011; Fraser et al.,
2012).
With regard to psychopathology, CIPD patients scored significantly
higher on the depression subscale of the SCL-90-R compared to patients
with PPD + CA (Rubio et al., 2012). However, when looking at depres-
sive symptoms in those with SIPD, two studies (Dawe et al., 2011; Fraser
et al., 2012) did not find any between group differences in depression/
anxiety scores on the BPRS. SIPD patients also had significantly higher
levels of hostility on the BPRS compared to those with PPD + SA
(Fraser et al., 2012). There was no difference in hostility scores on the
SCL-90-R between CIPD and PPD + CA (Rubio et al., 2012).
Please cite this article as: Wilson, L., et al., Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-
induced psychotic disorders:..., Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.001
5. Discussion
We completed a comprehensive systematic review of the literature
in an attempt to establish if SIPD is a distinct clinical entity from PPD
+ SA, particularly in relation to psychopathology. We also examined
the specific clinical features of CIPD as compared to PPD + CA and to
SIPD associated with any substance. Using stringent inclusion criteria
we only considered six studies in the systematic review. The findings
did not reveal many consistent differences in psychopathology. Howev-
er, we did find that that compared to PPD + SA, individuals with SIPD
have a weaker family history of psychotic disorder; a greater degree of
insight; fewer positive symptoms and fewer negative symptoms;
more depression (only in CIPD) and more anxiety.
Susceptibility to substance-induced psychosis has been related to a
positive family history of psychotic disorders (Chen et al., 2005;
Tsuang et al., 1982). The results from our review indicate that individ-
uals with SIPD associated with any substance are in fact less likely to
have a family history of psychosis. However, this reduced risk does
not appear to be applicable to those with a psychotic disorder induced
by cannabis alone. There was no difference in rates of parental psychotic
disorder according to the one study included our review comparing psy-
chiatric family history in CIPD and PPD + CA (Rubio et al., 2012). The
lack of heritability for psychotic disorders among users and non users
of cannabis has also been reported in previous studies (Andreasson et
al., 1989; Arendt et al., 2008; Boydell et al., 2007). A large Danish
study found that predisposition to both psychiatric disorders in general
and psychotic disorders specifically in first-degree relatives contributes
equally to the risk of developing schizophrenia or CIPD (Arendt et al.,
2008). The findings ague against a distinct psychotic disorder caused
by cannabis given that it is impossible to differentiate between the
two disorders on the basis of hereditary predisposition. The authors
suggest that CIPD could be an early sign of schizophrenia rather than a
distinct clinical entity given that approximately half of the subjects in
the study developed a schizophrenia spectrum disorder within nine
years after treatment.
Based on family history, our results could indicate that individuals
with CIPD are genetically similar to those with schizophrenia spectrum
disorders. However, those with SIPD may be less genetically
predisposed to psychosis and require the direct effects of drugs to devel-
op psychotic symptoms. The most significant predictor of developing
SIPD is poly drug use (Rognli et al., 2015). The effect of drug use appears
to have a cumulative effect when it comes to the age of onset of schizo-
phrenia spectrum disorders. An Australian study recently demonstrated
that for participants with schizophrenia spectrum disorders, cannabis
predominant users had a higher hazard of earlier age at onset than for
non-users (Stefanis et al., 2014). Poly-substance users had an even
higher hazard.
Our review showed no difference in the level of functioning or
premorbid adjustment between those with SIPD and those with PPD
+ SA. Previous studies have found that individuals with schizophrenia
who abuse substances have better premorbid adjustment and psycho-
social functioning than individuals with schizophrenia who do not
abuse substances (Arndt et al., 1992; Buckley et al., 1994; Sevy et al.,
2001). It is thought that those with schizophrenia who are more socially
competent have more ready access and exposure to substances through
their peer contacts. However other authors have noted no significant
differences in functioning between substance abusing and non-sub-
stance abusing individuals with psychotic illness (Cantwell, 2003;
Kamali et al., 2009; Large et al., 2014; Van Mastrigt et al., 2004).
The results from our review suggest that individuals with SIPD have
a greater degree of insight into their mental illness than those with PPD
+ SA, as assessed using the SUMD. Intact insight has previously been re-
ported as a common feature among substance users with psychotic
symptoms (Matsumoto et al., 2002; Thacore and Shukla, 1976). Howev-
er the retained insight seen in SIPD is not reflected in the recently pub-
lished DSM 5. Hallucinations that the individual realises are substance-
 L. Wilson et al. / Schizophrenia Research xxx (2017) xxx–xxx
induced are not included in the diagnostic criteria for SIPD but instead
are considered as “perceptual disturbances” relevant to the diagnosis
of substance intoxication or substance withdrawal (American
Psychiatric Association. and American Psychiatric Association. DSM-5
Task Force., 2013). This has been carried forward from the DSM-IV
and has been criticised by other authors (Mathias et al., 2008). By ex-
cluding hallucinations in patients with insight, the DSM 5 diagnostic
criteria for SIPD may risk underdiagnosing and undertreating patients
with distressing symptoms.
In terms of psychopathology, our review indicates that individuals
with SIPD have both fewer positive and fewer negative symptoms com-
pared to individuals with PPD + SA. In a recent systematic review,
Baldacchino et al. (2012) also found that compared to controls, individ-
uals with “cannabis psychosis” achieved lower scores on some negative
symptom measures including affective flattening and avolition-apathy.
Previous meta-analyses comparing symptomatology of substance
abusing and non-substance abusing individuals with schizophrenia
have reported varying results. Two separate papers published a decade
ago both found an association between fewer negative symptoms and
substance use disorders in schizophrenia (Potvin et al., 2006; Talamo
et al., 2006). They also found either no difference (Potvin et al., 2006),
or a greater incidence (Talamo et al., 2006), of positive symptoms
among the substance users. Large et al. (2014) preformed a more recent
meta-analysis comparing the symptoms and social function of patients
with psychosis and current substance use to those with psychosis and
no substance use. Substance abusers were found to have more positive
symptoms, but there were no between group differences in terms of
negative symptoms. Interestingly, older studies reported a stronger as-
sociation between current substance use and positive symptoms than
more recently published studies. This could possibly reflect changes in
the types and patterns of substance use over time.
Our findings in relation to SIPD patients experiencing fewer positive
and fewer negative symptoms appear to persist over time. Morales-
Munoz et al. (2014) preformed a follow up study on the Rubio et al.
(2012) patient cohort included in our review. After nine months of ab-
stinence from cannabis, 54 individuals with a history of schizophrenia
and cannabis abuse were compared to 48 symptom-free CIPD individ-
uals. In keeping with the findings at initial assessment the CIPD patients
achieved significantly lower scores on the PANSS for positive symptoms
and negative symptoms. Similarly, a two year follow up study of the
Caton et al. (2005) cohort found that patients with SIPD had consistent-
ly lower rates of positive and negative symptoms of psychosis compared
to PPD + SA patients (Drake et al., 2011).
Several studies report no difference in rates of depression between
psychotic individuals who abuse substances and those who do not
(Large et al., 2014; Lejoyeux et al., 2014; Sevy et al., 2001). However,
the bulk of the literature supports the notion that substance abusing in-
dividuals with schizophrenia spectrum disorders experience more de-
pression and anxiety (Chakraborty et al., 2014; Kerfoot et al., 2011;
Krausz et al., 1996; Moller and Linaker, 2004; Seddon et al., 2016;
Wobrock et al., 2009). It would seem that these symptoms are even
more prevalent in SIPD. In our review, patients with SIPD were generally
found to have higher levels of anxiety compared to those with PPD
+ SA. Individuals with psychosis induced by cannabis alone (but not
in association with any substance) were also found to suffer from
more depressive symptoms.
In terms of other affective symptoms, an association between canna-
bis use and symptoms of mania has been reported (Baldacchino et al.,
2012; Gibbs et al., 2015; Rottanburg et al., 1982; Seddon et al., 2016;
Stone et al., 2014). However, we did not find any conclusive between
group differences in relation to manic symptoms.
The results of this review should be considered within the follow-
ing limitations. Given the strict inclusion criteria used for this sys-
tematic review a very small number of papers were included for
analysis. Therefore the results should be interpreted with caution
and not generalised. Well-defined psychopathology for SIPD has
Please cite this article as: Wilson, L., et al., Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-
induced psychotic disorders:..., Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.001
7
not been consistently demonstrated. However, possible factors spe-
cific to SIPD which indicate that it might be diagnostically distinct
from PPD + SA include: a weaker family history of psychotic disor-
der; a greater degree of insight; fewer positive symptoms and
fewer negative symptoms; more depression (only in CIPD) and
more anxiety. Conversely, features which suggest that SIPD and
PPD + SA are not clinically distinct include lack of consistent differ-
ences in: family history of psychotic disorder (CIPD only), social
characteristics, premorbid adjustment, perceptual disturbances,
suicidality and manic symptoms.
The growing number of substances available poses a significant chal-
lenge in clinical practice. Our review shows that despite this increase
there remains a striking paucity of information on the psychopathology,
clinical characteristics and outcome of SIPD.
Role of funding source
No funding source.
Contributors
Lorna Wilson and Angela Kearney designed the search criteria and undertook the lit-
erature searches under the supervision of Mary Clarke. Lorna Wilson and Attila Szigeti
reviewed articles for inclusion in the systematic review. The first draft of the manuscript
was written by Lorna Wilson and Mary Clarke. All authors contributed to and have ap-
proved the final manuscript.
Conflict of interest
The authors report no conflict of interest.
Acknowledgement
We would like to acknowledge Carla Senf and Daria Brennan, from the St John of God
Hospital Library Service, for their assistance in sourcing articles included in this review.
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Please cite this article as: Wilson, L., et al., Clinical characteristics of primary psychotic disorders with concurrent substance abuse and substance-
induced psychotic disorders:..., Schizophr. Res. (2017), https://doi.org/10.1016/j.schres.2017.11.001