A-Textbook-of-Clinical-Pharmacology-and-Therapeutics-5th-edition

114 SCHIZOPHRENIA AND BEHAVIOURAL EMERGENCIES
that atypical antipsychotics should be considered in newly
diagnosed schizophrenic patients and in those who have
unacceptable effects from, or inadequate response to, conventional
antipsychotic drugs. Risperidone blocks D 2 , D 4 and in
particular 5HT 2 receptors. Careful dose titration reduces the
risk of adverse effects, but extrapyramidal side effects are common
at high doses. It is available as an intramuscular injection
for acute control of agitation and disturbed behaviour. Weight
gain and, more worryingly, an increased incidence of stroke in
elderly patients with dementia have been reported wih both
risperidone and olanzapine. Aripiprazole is a long-acting
atypical antipsychotic which is a partial agonist at D 2 receptors,
as well as blocking 5HT 2 . It is not associated with
extrapyramidal effects, prolactin secretion or weight gain.
Key points
Pharmacological treatment
• Receptor blockade:
– D 2 , D 4 , 5HT 2 .
• Although there may be a rapid behavioural benefit, a
delay (usually of the order of weeks) in reduction of
many symptoms implies secondary effects (e.g. receptor
up/downregulation).
• Conventional antipsychotics (e.g. chlorpromazine,
haloperidol, fluphenazine), act predominantly by D 2
blockade.
• Atypical antipsychotics (e.g. clozapine, risperidone,
olanzapine) are less likely to cause extrapyramidal side
effects.
Key points
Adverse effects of antipsychotic drugs
• Extrapyramidal motor disturbances, related to
dopamine blockade.
• Endocrine distributions (e.g. gynaecomastia), related to
prolactin release secondary to dopamine blockade.
• Autonomic effects, dry mouth, blurred vision,
constipation due to antimuscarinic action and postural
hypotension due to α-blockade.
• Cardiac dysrhythmias, which may be related to
prolonged QT, e.g. sertindole (an atypical antipsychotic),
pimozide.
• Sedation.
• Impaired temperature homeostasis.
• Weight gain.
• Idiosyncratic reactions;
– jaundice (e.g. chlorpromazine);
– leukopenia and agranulocytosis (e.g. clozapine);
– skin reactions;
– neuroleptic malignant syndrome.
BEHAVIOURAL EMERGENCIES
MANIA
Acute attacks are managed with antipsychotics, but lithium
is a common and well-established long-term prophylactic
treatment. The control of hypomanic and manic episodes with
chlorpromazine is often dramatic.
ACUTE PSYCHOTIC EPISODES
Patients with organic disorders may experience fluctuating
confusion, hallucinations and transient paranoid delusions.
Violent incidents sometimes complicate schizophrenic illness.
Case history
A 60-year-old man with schizophrenia who has been
treated for 30 years with chlorpromazine develops involuntary
(choreo-athetoid) movements of the face and tongue.
Question 1
What drug-induced movement disorder has developed
Question 2
Will an anticholinergic drug improve the symptoms
Question 3
Name three other drug-induced movement disorders
associated with antipsychotic drugs.
Answer 1
Tardive dyskinesia.
Answer 2
No. Anticholinergic drugs may unmask or worsen tardive
dyskinesia.
Answer 3
1. Akathisia.
2. Acute dystonias.
3. Chronic dystonias.
4. Pseudo-parkinsonism.
MANAGEMENT
Antipsychotics and benzodiazepines, either separately or
together, are effective in the treatment of patients with violent
and disturbed behaviour. Lorazepam by mouth or parenteral
injection is most frequently used to treat severely disturbed
behaviour as an in-patient.
Haloperidol can rapidly terminate violent and psychotic
behaviour, but hypotension, although uncommon, can be
severe, particularly in patients who are already critically ill.
Doses should be reduced in the elderly.
Intramuscular olanzapine or liquid risperidone are gradually
supplanting more conventional antipsychotics in the
acute management of psychosis.
When treating violent patients, large doses of antipsychotics
may be sometimes needed. Consequently, extrapyramidal
toxicity, in particular acute dystonias, develops in up to
one-third of patients. Prophylactic anti-parkinsonian drugs,
such as procyclidine, may be given, especially in patients who
are particularly prone to movement disorders.
The combination of lorazepam and haloperidol has
been successful in treating otherwise resistant delirious
behaviour.