A Textbook of Clinical Pharmacology and Therapeutics

SCHIZOPHRENIA 111

Figure 19.2 shows a summary of putative pathways for the
development of schizophrenia.

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.
  risperidoneorolanzapine.


• If the patient is very disturbed/aggressive, add
  benzodiazepine, e.g. lorazepam.
  
  
  • 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. chlorpromazineorhaloperidol,
    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.

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 19.3: 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.

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.

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.