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Learning Objectives Dual Diagnosis
• To develop understanding of key aspects in the
diagnosis and treatment of patients with dual
diagnosis
• To increase awareness of complications with
pharmacological treatment in patients with dual
diagnosis
• To develop knowledge of risk issues in people
with dual diagnosis
• To understand how local services are
implemented to manage dual diagnosis
Expert Led Session
• ICD 10 concepts of Psychotic disorder/Amnesic
syndrome/Residual and late onset psychotic
disorder (F1x.5, F1x.6, F1x.7)
– Also look at DSM V criteria
• Diagnosis and treatment of people with psychosis
and substance misuse
– Epidemiology
– Biological explanations of substances affecting
psychosis
– Risk / complications of pharmacological treatment
/local service implementation
Dual Diagnosis
• A general term referring to comorbidity or the cooccurrence in the same individual of a psychoactive
substance use disorder and another psychiatric
disorder
• Less commonly, the term refers to the co-occurrence of
two psychiatric disorders not involving psychoactive
substance use or to the co-occurrence of two
diagnosable substance use disorders
• Use of this term carries no implications of the nature of
the association between the two conditions or of any
aetiological relationship between them
WHO
DSM V - Substance / medication induced
psychotic disorder
• Presence of delusions and/or hallucinations
• Evidence from Hx/PE/Laboratory that symptoms
developed soon after substance
intoxication/withdrawal/ exposure to medication
• The disturbance not better explained by a
psychotic disorder that is not substance induced
(ie, an independent psychotic disorder)
• Disturbance does not occur exclusively during a
delirium
• Disturbance causes distress, or impairment in
social occupational functioning
DSM V Independent psychotic disorder
• Evidence of an independent psychotic disorder could include the
following
1. The onset of symptoms preceded the onset of the substance use.
2. The symptoms persist for a substantial period of time (e.g., about a
month) after the cessation of severe intoxication or acute withdrawal.
3. A history of recurrent non-substance-related episodes.
F1x.5 Psychotic disorder*
• Vivid hallucinations, misidentifications,
psychomotor disturbances, abnormal affect
• Sensorium clear, some degree of clouding of
consciousness
• Onset of psychotic symptoms during or within
two weeks of substance use.
• Duration of the disorder not exceeding six
months (typically partially resolves within a
month)
*Within chapter: Mental and behavioural disorders due to
psychoactive substance use
F1x.6 Amnesic syndrome
(1) Memory impairment as shown in the
impairment of recent memory(Learning of new
material) disturbances of time sense (
rearrangement of chronological sequences,
telescoping of repeated events into one)
(2) Absence or defect in immediate recall, of
impairment of consciousness and of generalised
cognitive impairment
(3) History of objective evidence of chronic (and
especially high dose) use of alcohol or drugs
F1x.7 Residual disorders and late-onset
psychotic disorder
• Directly related to alcohol or psychoactive
substance
• Persist beyond any period of time during
which direct effects of the psychoactive
substance might be assumed to be operative
• Need to be distinguished from withdrawal
related conditions
• Onset after two weeks after substance misuse
coded as F1x.75 ( Late-onset)
Epidemiology -Methodological
issues
1
2
3
4
5
Ascertainment and sampling
Sociodemographic characteristics e.g., age,
gender
Assessment of substance misuse
Reliability of interview procedures
Medication side effects/ compliance
Epidemiology prevalence 2007
• in 2007 nearly one person in four (23.0 per cent)
in England had at least one psychiatric disorder
and 7.2 per cent had two or more disorders
• In 2007 5.6 per cent of people aged 16 and over
reported having ever attempted suicide but were
not successful
• The overall prevalence of psychotic disorder in
2007 was 0.4%(0.3%of men, 0.5%of women). In
men and women the highest prevalence was
observed in those aged 35 to 44 years (0.7% and
1.1% respectively).
Adult Psychiatric Morbidity in
England - 2007
Epidemiology prevalence 2007
• The prevalence of alcohol dependence was 5.9%
(8.7%of men, 3.3%of women)
– Mild (5.4%) moderate (0.4%) severe (0.1%)
• The prevalence of drug dependence was
3.4%(4.5%of men, 2.3%of women)
• Most dependence was on cannabis only (2.5%),
rather than other drugs (0.9%)
• Symptoms of dependence in ages 16 and 24
(13.3% men, 7.0%of women )
• Low threshold for dependence diagnosis used
Adult Psychiatric Morbidity in
England - 2007
Comorbidity
• Drug dependence was strongly associated
with both the personality disorders Antisocial
Personality disorder (ASPD)(0.81), and
Borderline personality disorder (BPD)(0.60)
• Drug dependence was weakly associated with
a range of other conditions except for two
mixed anxiety and depression (0.14) and
eating disorder (0.25) with which it had little
or no association
Adult psychiatric morbidity in England,
2007Results of a household survey
Alcohol co-morbidity
• Alcohol dependence was strongly associated
with only one other condition: ASPD (0.63).
• Alcohol dependence was also associated with
BPD (0.41) and drug dependence (0.43)
• Alcohol dependence was found to have little
or no association with four conditions: mixed
anxiety and depression (0.18), GAD (0.20),
psychosis (0.25), and eating disorder (0.28).
Adult Psychiatric Morbidity in
England - 2007
Comorbidity psychiatric illness in people with drug
or alcohol problems
Number ( percent)
total = 216 (Drug)
Number ( percent)
total = 62 (alcohol)
Non substance induced psychotic
disorder
17(8)
12(19)
Schizophrenia
6(3)
2(3)
BPAD
1(1)
3(5)
Psychosis NOS
10 (5)
7 (11)
Personality disorder
80(37)
33 (53)
Severe depression
58 (27)
21 (34)
Mild depression
87 (40)
29 (47)
Severe anxiety
41 (19)
20 (32)
None
55 (25)
9 (15)
Psychiatric disorder present
161 (75)
53 (85)
Weaver et al. 2003
Comorbidity alcohol or drug use in Community
mental health team
Illicit non prescribed use in the past
year
Number ( percentage)
Total= 282
Any drug use
87 (31)
Cannabis
71 (25)
Sedative
21 (7.4)
Crack cocaine
16 (5.7)
Heroin
11 (3.9)
MMDA (ecstacy)
11(3.9)
Cocaine
8 (2.8)
Opiate substitute
4 (1.4)
Alcohol harmful use
72 (25.5)
Harmful alcohol or drug use
124 (44)
Weaver et al. 2003
Mechanism of dual diagnosis general
theory
1. Primary substance misuse causing / worsening
secondary psychiatric disorder e.g., substance
induced mental disorder
–
Would avoiding substance misuse prevent mental illness?
2. Primary psychiatric disorder causing / worsening
secondary substance misuse e.g., self medication
hypothesis [schizophrenia and amphetamines]
3. Dual primary diagnosis - substance misuse disorder
and independent psychiatric disorder.
4. Common aetiology e.g.,
PTSD
depression and alcoholism
Biological factors for schizophrenia –
overlap with substance misuse
• Dopamine -Presynaptic dopamine availability
and dopamine release are increased in
schizophrenia
– Amphetamine / cocaine release dopamine
• Glutamate – role suggested from effects of
NMDA receptor antagonists
– Ketamine popular drug of misuse
Biological explanations for
schizophrenia
• Combined models of dopamine and
glutamate
Howes 2015
Biological factors for schizophrenia –
overlap with substance misuse
• Cannabis - THC partial agonist at CB1 receptors
– High density in frontal cortex, basal ganglia, hippocampus,
anterior cingulate cortex
– Modulate neurotransmitter release (presynaptic effect)
– Cannabis could influence risk for schizophrenia via its
neurodevelopmental effects
Tetrahydrocannabinol = THC
Wilkinson 2015
Neurodevelopmental model of
Schizophrenia / substance misuse
Children < 15 with second- hand (e.g
death of parent) trauma doubles their risk
of drug use disorder^
Heritability
drug /alcohol
disorders 0.39
to 0.72*
*COMT gene explored
in relation to addiction
Stilo 2015;
*Ducci 2012
^Giordano 2014
Have dual diagnosis patients
different pathology
• Patients with comorbid schizophrenia and
mixed substance dependence displayed
significant blunting of striatal DA release.
• However, DA release was associated with
acute and transient increases in positive
symptoms.
• One way of exploring effects of drugs on
psychosis is to examine outcome of drug
induced psychosis
Thompson 2013
First-episode drug-induced
psychosis Northumberland
• Data collected on all patients ≥ 16 years
seen by consultant psychiatrists
• Exclusion
– presentation outside of the Trust area with a
first-episode psychosis;
– past history of treated psychosis;
– diagnosis of dementia
Crebbin 2009
First-episode drug-induced
psychosis
• 540 patients in Oct 98 to Oct 2005 w FEP
• 73 patients diagnosed with first episode
schizophrenia (F20–21), 27 current illicit
drug users at the time of presentation.
• 40 were diagnosed with a drug-induced
psychosis(F19.5)
– 5 excluded from analysis leaving 35
Stability of diagnosis drug
induced psychosis group
• 10 out of 35 patients changed to schizophrenialike psychosis(F20–29).
• 7 changed to schizophrenia (F20–21),
• 2 patients developed a diagnosis of
schizoaffective disorder (F25.1)
• 1 patient changed to a diagnosis of delusional
disorder (F22)
• 1 changed to unspecified non-organic psychosis
(F29)
• Shows high rate of change of diagnosis- but
difficult to infer effect of the drug
Those who developed a dx of Sz / Sz-like
psychosis compared to those retained DIP
• No significant differences regarding
physical violence to others.
• Drug-induced psychosis + later developed
a diagnosis of schizophrenia psychosis
– spent more days overall in hospital
– higher number of admissions
– slightly more days between their first contact
and their first admission
Drug use in DIP Group compared to
Sz group who were Drug users
DIP (n= 35)
SZ group (n=27)
Cannabis
29 (83%)
Cannabis+ other 25 (71%)
drug
Amphetamine
20 (57%)
24 (89%)
11 (41%)
Cocaine or
4 (14%)
heroin
Alcohol problem 17 (49%)
or dependence
5 (21%)
9 (33%)
6 (22%)
Shows how patients with Schizophrenia also frequently use cannabis
– could be that schizophrenia predispose to cannabis use
Substance induced psychosis (SIP) conversion
to schizophrenia spectrum d/o F20, F22, F23
• Finnish data registers.
• Data from hospital discharges between 1987
and 2003 and main discharge diagnosis was a
mental disorder
• Sample comprised patients (N = 18,478)
discharged after their first admission with a
diagnosis of SIP
• Patients with present or previous diagnoses of
schizophrenia or bipolar disorder after 1980 not
regarded as SIP
Niemi-Pynttäri
et al 2008
Crude rate of conversion from substance
induced psychosis to schizophrenia
spectrum disorders n= 18 478
Cannabis effect more marked than for other substances
Though low numbers
Crude rate is per 100 person years
Niemi-Pynttäri
et al 2008
Cannabis group
much more marked
than other substances
Niemi-Pynttäri
et al 2008
Types of Relationship between
cannabis and psychosis
1. Acute psychosis associated with
cannabis intoxication
2. Acute psychosis that lasts beyond the
period of acute intoxication
3. Persistent psychosis not time-locked to
exposure.
Wilkinson 2015
Acute psychosis
• Cannabinoids can generate positive
symptoms, negative symptoms, cognitive
deficits related to psychosis.
• Effects dose-related
• Do not last persist after the period of
intoxication
Wilkinson 2015
Cannabis-induced acute
persistent psychosis
• Based on multiple case-series
• Characterized by hallucinations, paranoia,
delusions, depersonalization, emotional
lability, amnesia, confusion and
disorientation
• Improve quicker than schizophrenic
psychotic episodes
• Generally does not return without re-use
of cannabis
Wilkinson 2015
Cannabis induced persistent
psychosis
• Data has suggested that up to 50% of individuals
initially hospitalized for cannabis-induced psychosis
can get re-diagnosed with a schizophrenia-spectrum
on follow up
• Cannabis induced persistent psychosis may result in
a recurrent psychotic disorder similar to
schizophrenia
• Can cannabinoids “cause” persistent psychosis –
answer still being debated
• Studies generally focus on positive symptom
outcomes –rather than negative symptoms or
cognitive deficits.
Wilkinson 2015
Recent Epidemiological Studies
Author
Form
Sample +
Length FU
OR results
Manrique-Garcia
et al 2012)
Anonymous
survey at time of
conscription
50,087 military
conscripts
38 years
Adjusted OR for the
development of
schizophrenia:
3.7 (95% CI 2.3-5.8) in
subjects who used
cannabis >50 times v. nonusers
Davis et al 2013
Cross sectional
analysis
Face-to-face,
focusing on
DSM-IV
diagnoses
34,653 adults
from general
population
Adjusted OR for psychotic
disorder:
3.69 (95% CI 2.49-5.47) in
subjects with lifetime
cannabis dependence
1,923 (ages 1424 at baseline)
from general
population
10 years
OR for psychotic symptoms
at 8.4y follow up:
1.5 (95% CI 1.1-21)
Kuepper, van Os, Cannabis use
et al 2011
and psychosis
assessed at
baseline, 3.5,
and 8.4 years
using CIDI
Wilkinson 2015
Elements of the links between
persistent psychosis & schizophrenia
• Temporal relationship
– Retrospective studies: cannabis use preceded
development of psychosis by years in FEP
• Biological Gradient
– Heavier cannabis use - higher psychosis risk
• Specificity
– association cannabis and psychosis more
than the associations between cannabis and
other mental illnesses, and the associations
between other substances and psychosis
Wilkinson 2015
Window of Exposure factor for
persistent psychosis & schizophrenia
• Earlier exposure to cannabis is associated with a
higher risk for psychosis outcome and that the
risk declines when exposure is after late
adolescence- idea of critical periods of brain
development
• Consistent lag period 7-8 years between age of
onset of cannabis use and the age of onset of
psychosis support idea of cumulative exposure
to cannabis
• Alternatively, cannabis use a/w earlier age of
onset of psychosis- up to 2.7 years Wilkinson 2015
Psychosis with coexisting substance
misuse NICE 2011 - Treatment
• Review the diagnosis of psychosis and the
coexisting substance misuse
• Review the effectiveness of previous and
current treatments and their acceptability
to the person
• Ensure that evidence-based treatments
are used for both conditions
• Use guidances on Bipolar affective
disorder, schizophrenia, alcohol and
misuse of drugs
Treatment using antipsychotic
agents
• Review by Zhornitsky et al., examined use of
antipsychotic agents in patients with substance misuse
with psychosis (DD) and without psychosis (SUD)
• All patients with psychosis (ie, schizophrenia and schizoaffective and bipolar disorders) with concomitant SUD
considered for inclusion in the DD group of studies.
– Treatment needed to be longer than 4 weeks
– Outcomes measured by craving, alcohol/drug use, and/or
relapse
• Only randomized studies were included in the substance
abusers without psychosis (SD) group.
Zhornitsky 2010
Use of antipsychotic in patients: dual
diagnosis (alcohol +/- drugs + psychosis)
Drug use mainly cannabis along with alcohol
Clozapine seemed to be associated with better outcomes
Zhornitsky 2010
Use of antipsychotic in patients: dual
diagnosis (Drugs + psychosis)
Decrease in craving or no effect
Use of antipsychotics in alcohol
related substance misuse
Results are not clear cut
Use of antipsychotics in stimulant
related substance misuse
Not helpful in stimulant dependence
Risk issues – suicide
During 2003-2013, 13,972 deaths (28% of general
population suicides) were identified as patient suicides
1,270 per year.
NCI 2015
Risk issues – suicide in patients with
drug and alcohol misuse problems
(NCI 2015)
6,124 patient suicides had hx of alcohol misuse, (45% of total )
- 557 deaths per year
4,345 had hx a history of drug misuse, (32% of total )
- 395 deaths per year
7,381 had hx of either alcohol or drug misuse or both, (54% of total)
- 671 deaths per year.
Drug overdoses
Commonest Drug in fatal overdose by MH patients now opiates
Clinicians … should enquire about patients’ access to these drugs when
assessing suicide risk.
(NCI 2015)
Risk issues – homicide
During 2003-2013, a total of 630 patient homicides identified
An average of 57 homicides per year
NCI 2015
Risk issues – homicide in patients with
drug and alcohol misuse problems
(NCI 2015)
444 (75%) patients had a history of alcohol misuse - 40 per year
469 (78%) patients had a history of drug misuse - 43 per year
536 (89%, excluding unknowns) had a history of
either alcohol or drug misuse or both - 49 per year
Health concerns patients with
dual diagnosis
• Both groups have particular health
concerns
• Substance misuse – alcohol related
illnesses / IV drug use related illnesses
(e.g., hepatitis C)
• Psychosis – factors relating to medication
(e.g., DM)
• Cardiovascular and respiratory illnesses*
in both groups
*Partti 2015
Clients (n=4817 ) aged 11–65 years
who sought treatment for drug use
1600
1400
1200
1000
800
600
400
200
0
Dead (n= 496)
Alive (n= 4321)
Onyeka,2014
Standardised mortality rate
• People with schizophrenia have a median
standardized mortality ratio 2.6 for all-cause
mortality (McGrath, 2008)
• People with opioid dependence in NSW 1985–2006,
SMR was 6.5 (Degenhardt 2013)
• Patients with alcohol dependence discharged from
a general hospital in Korea 1989 to 2006 - SMR
6.7 (Park 2013)
• This shows how both groups have high SMR
thereby likely patients with dual diagnosis at risk
Medication factors
• QTc prolongation effects
– Drugs with known TdP risk* :Chlorpromazine,
Droperidol, Haloperidol,Pimozide, Sulpiride
– Antipsychotic IV use / higher than recommended
doses
– QT longer in drug-free patients with schizophrenia
compared controls+
– Methadone doses greater than 100 mgs
• Over sedation
– Psychotropic medications and illicit benzodiazepine /
alcohol/ opioids
*https://www.crediblemeds.org
+Fujii (2014)
Systems view
Interaction between substance misuse services and
Mental health trusts
1. Integrated –same team for both
2. Parallel systems- working together
3. Sequential one team follows from another
Parallel would seem most practical UK health system
Good working relationships and communications
important
Can be difficult when frequent re-tendering: links can
be broken
Psychosis with coexisting
substance misuse NICE 2011
• Secondary care mental health services
– Do not exclude patients with psychosis and
coexisting substance misuse from mental
healthcare because of their substance
misuse
– Do not exclude patients with psychosis and
coexisting substance misuse from substance
misuse services because of a diagnosis of
psychosis.
Psychosis with coexisting
substance misuse NICE 2011
• For most adults with psychosis and coexisting
substance misuse, treatment for both conditions
should be within secondary care mental health
services such as community-based mental
health teams
• Delivery of care and transfer between services
for adults and young people with psychosis and
coexisting substance misuse should include a
care coordinator and use the Care Programme
Approach
Psychosis with coexisting substance
misuse NICE 2011 Joint working
• Healthcare professionals in substance misuse services
should
– be present at CPA meetings for their patients
• Specialist substance misuse services (SMS) should
provide
– advice, consultation, and training for healthcare
professionals in adult mental health services and
CAMHS
• Specialist SMS should work closely with secondary care
mental health services to develop local protocols
Expert Led Session
• ICD 10 concepts of Psychotic
disorder/Amnesic syndrome/Residual and
late onset psychotic disorder
• Diagnosis and treatment of people with
psychosis and substance misuse
– Epidemiology
– Biological explanations of substances affecting
psychosis
– Risk / complications of pharmacological treatment
/local service implementation