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

SCHIZOPHRENIA 111
Box 19.1: Dopamine theory of schizophrenia
• There is excess dopamine activity in the mesolimbic
system in schizophrenia.
• Antipsychotic potency is often proportional to
D 2 -blocking potency.
• Amphetamine (which increases dopamine release) can
produce acute psychosis that is indistinguishable from
acute schizophrenia (positive symptoms).
• D 2 agonists (bromocriptine and apomorphine)
aggravate schizophrenia in schizophrenic patients.
• There is an increase in D 2 and D 4 receptors on PET in
schizophrenic patients.
• L-Dopa can cause hallucinations and acute psychotic
reactions and paranoia, but does not cause all the
features of these conditions.
• There is no definite increase in brain dopamine in vivo
and post mortem.
• Dopamine receptor blockade does not fully alleviate
symptoms.
Box 19.2: 5-Hydroxytryptamine and schizophrenia
• LSD acts on 5HT receptors, causing hallucinations and
dramatic psychological effects which may mimic some
features of schizophrenia.
• 5HT has a modulatory effect on dopamine pathways.
• Many effective antipsychotic drugs have dopamine and
5HT 2 receptor-blocking properties.
• 5HT 2 receptor blockade is not essential for drug efficacy.
Figure 19.2 shows a summary of putative pathways for the
development of schizophrenia.
• Chlorpromazine may be preferred if sedation is
advantageous, e.g. in very agitated patients.
• Antimuscarinic drugs, e.g. procyclidine, should be used if
acute dystonia or Parkinsonian symptoms develop.
• Psychosocial support/treatment should be offered.
• Behaviour usually improves quickly, but hallucinations,
delusions and affective disturbance may take weeks or
months to improve.
• Once first-rank symptoms have been relieved, the patient
can usually return home and resume work on low-dose
antipsychotic treatment.
• Conventional drugs, e.g. chlorpromazine or haloperidol,
are as effective in treatment of acute positive symptoms as
atypical antipsychotic drugs and are less expensive, but
adverse effects may be troublesome.
MAINTENANCE TREATMENT
• Only 10–15% of patients remain in permanent remission
after stopping drug therapy following a first
schizophrenic episode.
• The decision to attempt drug withdrawal should be taken
with regard to the individual patient, their views, adverse
drug effects, social support, relatives and carers.
• Cognitive behavioural therapy is a treatment option.
• Most patients require lifelong drug therapy, so the correct
diagnosis is essential (e.g. beware drug-induced psychosis,
as amphetamines in particular can produce acute
schizophreniform states). All antipsychotic drugs have
adverse effects. Continuing psychosocial support is critical.
• Oral or intramuscular depot therapy (Box 19.3), e.g.
olanzapine (oral) or flupentixol (i.m.) should be
considered. The latter ensures compliance.
GENERAL PRINCIPLES OF MANAGEMENT
ACUTE TREATMENT
The main principles are:
• Prompt drug treatment should be instigated, usually as an
in-patient.
• Oral ‘atypical antipsychotics’ should be administered, e.g.
risperidone or olanzapine.
• If the patient is very disturbed/aggressive, add
benzodiazepine, e.g. lorazepam.
Box 19.3: Intramuscular depot treatment
• Esters of the active drug are formulated in oil.
• There is slow absorption into the systemic circulation.
• It takes several months to reach steady state.
• After an acute episode, reduce the oral dose gradually
and overlap with depot treatment.
• Give a test dose in case the patient is allergic to the oil
vehicle or very sensitive to extrapyramidal effects.
• Rotate the injection site, e.g. flupentixol is given once
every two to four weeks (ester of active drug
formulated in an oil) or risperidone once every two
weeks.
Genetic predisposition
Obstetric complications
and other early insults
affecting CNS
Neurodevelopmental
abnormalities
Neurocognitive
impairment
Social anxiety
Isolation
Odd ideas
Frank
psychosis
Abuse of dopaminergic drugs
Social stress/isolation
Figure 19.2: Pathways for development of
schizophrenia.