Vol 3 February 2011 Clinical Pharmacist 41

Schizophrenia is a chronic mental health condition characterised by a distortion of perceptions and

CLINICAL FOCUS
thinking. It is thought to be caused by a combination of biological, social and psychological factors

Schizophrenia
clinical features and diagnosis
By Michele Sie, MSc, MRPharmS
SUMMARY

S
chizophrenia is a severe and enduring mental
Schizophrenia is a mental health disorder that is characterised by
health disorder that is often diagnosed in late
distorted perceptions and behaviours. Symptoms of the condition are
adolescence or early adulthood. It can present with
divided into two categories: positive and negative. Positive symptoms
a wide assortment of symptoms that distort the form and
cause an excess of cognitive function and include delusions and
content of thinking and perceptions, which can lead to the hallucinations. Negative symptoms suppress normal function and include
development of strange behaviours.1 Schizophrenia can be apathy and poor social activity.
chronic or relapsing and remitting. Diagnosis of schizophrenia is based on criteria from the International
In the 1890s Kraeplin, a German psychiatrist, used the Classification of Disease version 10 (ICD-10). Patients can also be
term “dementia praecox” (early dementia) to describe a classified into a type of schizophrenia based on the predominant symptoms
cluster of symptoms including psychosis and deterioration at diagnosis. One episode of psychosis is not enough for a diagnosis of
in cognition. The term “schizophrenia” was introduced in schizophrenia, and other medical conditions (eg, hyperthyroidism) or
1911 when Bleuler, a Swiss psychiatrist, used it to describe medicines (eg, levodopa) must be excluded as causes of psychosis.
a syndrome of distorted perceptions and behaviours.
However, it was not until 1959 that the first diagnostic
criteria were proposed.2 Today, schizophrenia is classified suicide than those in the general population.
into several different subtypes based on presenting Approximately 10% commit suicide — the most common
symptoms.3 cause of premature death in this patient group.9
People with schizophrenia have a lower quality of life
than the general population. This may be related to the Psychiatric comorbidity Psychiatric comorbidities are
side effects of medicines, financial difficulties, lack of frequent among patients with schizophrenia. Substance
social support networks and stigma associated with the misuse is also common; conservative estimates suggest at
disorder.4,5 least half of patients are affected. Comorbid depression
occurs in 50% of patients. Anxiety disorders (particularly
Epidemiology panic disorder, post-traumatic stress disorder and
The World Health Organization estimates that
schizophrenia is the 10th most common non-fatal disease
worldwide.6 Although the yearly incidence is low Stewart Charles | Dreamstime.com
(0.015%), due to the chronic nature of the disorder the
lifetime prevalence is around 1%.1,7 Schizophrenia is more
common among men and among immigrants and urban
populations.1 The average age of onset is 18 years for men
and 25 years for women. Women also have an increased
risk of developing schizophrenia in their mid forties.
It has been estimated that in the UK the direct costs of
schizophrenia treatment and care amount to £2bn per
year.8 The condition is also associated with indirect costs
including: loss of productivity of patients and their carers,
criminal justice system costs and benefit payments. People
with a diagnosis of schizophrenia are at a higher risk of

Michele Sie is a consultant pharmacist for women and

children at West London Mental Health NHS Trust
and the assistant registrar of the College of Mental
Health Pharmacy.
E: michele.sie@wlmht.nhs.uk
42 Clinical Pharmacist February 2011 Vol 3
obsessive-compulsive disorder) can also be present to
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varying degrees.10
Causes
The cause of schizophrenia is uncertain — the so-called
nature-versus-nurture concept is heavily debated. The
most established theory is the “stress-vulnerability” model.
This model proposes that schizophrenia is caused by a
combination of three types of factors, specifically:1,11
● Biological — for example family history (a genetic
cause is suggested, but no single gene has been
found to be responsible and it is more likely that
there are small changes in several genes) or brain
injury (caused by birth trauma or fetal exposure to
infection)
● Social — such as low socioeconomic status, poor
housing, social isolation, loss of cultural identity and
discrimination
● Psychological — including early living environment
and stressful life events
Pathophysiology
In the 1970s the “dopamine hypothesis of schizophrenia”
was first proposed, which suggested that psychotic
symptoms arose from a hyperactivity of dopamine in
certain neural pathways. This hypothesis came from the
observation that all medicines with antipsychotic
properties acted as antagonists at dopamine receptors and
that substances that were dopaminergic induced psychotic
symptoms.
Social isolation might contribute to the development of schizophrenia
There are four neural pathways that are important to
❝
consider in the pathophysiology and treatment of
schizophrenia — the mesolimbic, mesocortical,
IT IS COMMON FOR
PEOPLE WITH
tuberofundibular and nigrostriatal pathways. Overactivity
of dopamine in the mesolimbic pathway is thought to
SCHIZOPHRENIA TO
produce the positive symptoms of schizophrenia (see
LACK INSIGHT TO
below). The mesocortical pathway is believed to be
SUCH AN EXTENT
responsible for the negative symptoms (see below). The
THAT THEY DO NOT causes of these dopamine imbalances are still unclear.
BELIEVE THEY ARE The nigrostriatal pathway controls movement, and
ILL blockade of dopamine receptors in this pathway causes the
extrapyramidal side effects observed with some
❞ antipsychotic medicines. Blockade of dopamine in the
tuberofundibular pathway leads to the adverse effect of
hyperprolactinaemia (for more on the treatment of
schizophrenia see the accompanying article, p47).12
Although the dopamine hypothesis remains the
preferred neurochemical theory explaining schizophrenia,
involvement of other neurochemical pathways has been
proposed, including the serotonergic system and the
glutamatergic system.
Symptoms
Schizophrenia symptoms are classified into two groups:
positive and negative. Positive symptoms are those which
cause an excess or distortion of normal function, including:
● Delusions — delusions can be somatic (involving
false beliefs about physical illnesses), grandiose
(containing beliefs of self-importance and having
special powers or abilities) or paranoid (where there
are beliefs of persecution)
● Hallucinations — hallucinations can be auditory,
tactile, visual, olfactory or gustatory, characterised
Marko Skrbic | Dreamstime.com
by experiences when there are no external stimuli
● Disorganised speech and behaviour
● Thought disorders — thought disorder is
characterised by disorganised speech, which is
believed to be due to abnormal thoughts; thoughts
can be blocked (where little or no thoughts occur),
or can appear to have been inserted into, or
withdrawn from, the mind by others
● Ideas of reference — ideas of reference occur when
a person believes that certain external phenomena
such as TV, radio or newspaper articles are
reporting about them or talking directly to them
(ideas of reference can also be considered delusions
if there are beliefs that external happenings relate
directly to the individual)
Negative symptoms are those that lead to a decrease or
loss of normal function, including lack of emotion, apathy,
poor or non-existent social functioning, lack of motivation,
reduced speech, lack of initiative, slow movements and
poor self-care.
It is common for people with schizophrenia to lack
insight to such an extent that they do not believe they are
ill.1
Diagnosis
Schizophrenia is diagnosed using the International
Classification of Diseases Version 10 (ICD-10) criteria.
 Vol 3 February 2011 Clinical Pharmacist 43

Box 1: Summary of ICD-10 classification of schizophrenia3

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PRESENTATION KEY FEATURES

Paranoid schizophrenia Paranoid delusions, auditory hallucinations and perceptual disturbances

Hebephrenic schizophrenia Prominent affective changes, thought disorder, fleeting and fragmented delusions and
hallucinations, irresponsible and unpredictable behaviour, mannerisms, incoherent speech
and social isolation

Catatonic schizophrenia Fluctuating psychomotor disturbances (including hyperkinesis [overactive restlessness] and
stupor), long periods of posturing (voluntary inappropriate or bizarre postures), vivid scenic
hallucinations may be present

Undifferentiated schizophrenia Used when symptoms are not within the above three categories or when symptoms fall into
more than one of these sub-types

Post-schizophrenic depression A depressive episode following an episode of acute illness. Some positive or negative
symptoms of schizophrenia must still be present but they are no longer dominating the
clinical picture

Residual schizophrenia Long standing negative symptoms

Simple schizophrenia Progressively strange behaviours, poor social functioning, deteriorating daily functioning,
negative symptoms, overt psychotic symptoms are generally not present

Other schizophrenia For example: cenesthopathic schizophrenia (somatic hallucinations causing abnormal bodily
sensations)

Schizophrenia, unspecified Any disorder where symptoms have not been fully assessed and classified as above

For a diagnosis to be made there must be clear evidence of

either:
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Generally, a diagnosis of schizophrenia will not be robust supply chain across the portfolio.
made based on a single episode of psychosis. This is Atropine 1% 10ml Eye Drops are available from
because psychosis can occur as part of a number of January 4th 2011.
different mental health conditions or be due to another
cause (see below).1
Atropine sulphate is an antimuscarinic agent used as a
cycloplegic and mydriatic. The eye drops are used in
The onset of the first episode of psychosis of
the treatment of iritis and uveitis, and in the
schizophrenia is usually preceded by a prodromal phase.
determination of refraction in children below six years
This phase includes symptoms that can cause a
and children with convergent strabismus.
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The ICD-10 criteria are also used to classify a patient
with schizophrenia based on his or her prominent
symptoms at presentation (see Box 1).3 For example,
paranoid schizophrenia has prominent symptoms of
paranoid delusions accompanied by auditory
001u1b
hallucinations.3
44 Clinical Pharmacist February 2011 Vol 3
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The use of certain prescription medicines and illicit drugs can induce psychosis
Differential diagnoses
Some medical conditions can present as psychosis.
Thought disorder, delusions, visual and auditory
hallucinations and paranoia have been documented with
long-standing untreated hypothyroidism and
hyperthyroidism. Olfactory hallucinations are commonly
experienced in temporal lobe epilepsy. Systemic lupus
erythematosus, central nervous system tumours,
migraines, diabetes, human immunodeficiency virus, head
injury and delirium have also all been associated with
psychotic symptoms.15
There are a number of medicines that can induce
psychosis. Levodopa (the amino-acid precursor of
dopamine) and dopamine agonists such as bromocriptine
and pergolide can all cause psychotic symptoms.
Furthermore, psychotic symptoms can be caused or
worsened by some medicines, including antimuscarinics,
some anti-infectives (eg, isoniazid), beta-blockers,
corticosteroids and amphetamines.16 Psychoactive
substances (such as alcohol, hallucinogens, opioids and
cannabis) have also been associated with psychotic
symptoms.16
Cannabis One of the pharmacological effects of cannabis
is to increase dopamine release in the brain. As already
discussed, an overactivity of dopamine is considered to be
the neurochemical basis for schizophrenia. Drug-induced
psychosis is a commonly observed syndrome and there are
concerns about the long-term effects of cannabis use on
the risk of developing schizophrenia. Recent research has
indicated that heavy cannabis users have a sixfold
increased risk of developing schizophrenia compared with
non-users.17
Baseline tests A range of baseline tests should be
carried out for those with a suspected diagnosis of
schizophrenia to exclude any physical conditions that
could account for the psychotic symptoms. These should
include:
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● Thyroid function tests to assess for hyper- or
hypothyroidism
● Liver function tests to assess alcohol use
● Blood sugar level to assess for diabetes
● Urine drug screening to rule out (or identify)
substance misuse
References
1 Gelfer M, Harrison P, Cowen P. Shorter Oxford Textbook of Psychiatry 5th
edition. Oxford: Oxford University Press. 2006.
2 Adityanjee M, Yekeen A, Aderibigbe M, et al. Dementia praecox to
schizophrenia: The first 100 years. Psychiatry and Clinical Neurosciences
1999;53:437–48.
3 World Health Organization. International Classification of Diseases (10th
edition). Geneva: World Health Organisation; 2007.
4 Kovess-Masféty V, Xavier M, Kustner B, et al. Schizophrenia and quality
of life: a one-year follow-up in four EU countries. BMC Psychiatry
2006;6:39–49.
5 Thornicroft G, Brohan E, Rose D, et al. Global pattern of experienced and
anticipated discrimination against people with schizophrenia: a cross-
sectional survey. The Lancet 2009;373:408–15.
6 World Health Organization. Mental Health. Global burden of
schizophrenia in the year 2000. www.who.int/healthinfo/statistics/
bod_schizophrenia.pdf (accessed 20 December 2010).
7 McGrath J. Variations in the incidence of schizophrenia: data versus
dogma. Schizophrenia Bulletin 2006;32:195–7.
8 National Institute for Health and Clinical Excellence. Core interventions in
the treatment and management of schizophrenia in primary and secondary
care (update). www.nice.org.uk/cg82 (accessed 20 December 2010).
9 Hawton K, Sutton L, Haw C, et al. Schizophrenia and suicide: systematic
review of risk factors. British Journal of Psychiatry 2005;187:9–20.
10 Buckley P, Miller B, Lehrer D, et al. Psychiatric comorbidities and
schizophrenia. Schizophrenia Bulletin 2009;35:383–402.
11 Nuechterlein K, Dawson M, Ventura J, et al. The vulnerability/stress
model of schizophrenic relapse: a longitudinal study. Acta Psychiatrica
Scandinavica 1994;89(s382):58–64.
12 Carlsson A. The neurochemical circuitry of schizophrenia.
Pharmacopsychiatry 2006;39:10–4.
13 Gourzis P, Katrivanou A, Beratis S. Symptomatology of the initial prodromal
phase in schizophrenia. Schizophrenia Bulletin 2002;28:415–29.
14 Haas G, Garratt L, Sweeney J. Delay to first antipsychotic medication in
schizophrenia: impact on symptomatology and clinical course of illness.
Journal of Psychiatric Research 1998;32:151–9.
15 Isenberg K, Garcia K. Syndromes of brain dysfunction presenting with
cognitive impairment or behavioural disturbance: delirium, dementia and
mental disorders due to a general medical condition. In: Fatemi SH,
Clayton PJ (Eds). The medical basis of psychiatry. New Jersey: Humana
Press; 2008.
16 Bazire S. Psychotropic Drug Directory. Aberdeen: HealthComm UK
Limited; 2007.
17 Grotenhermen F, Russo EB (Eds). Cannabis and cannabinoids: pharmacology,
toxicology, and therapeutic potential. New York: Haworth Press; 2002.