Drug/Biological Treatments for Schizophrenia

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Traditional Neuroleptic Drugs

  • Once Chloropromaxine was put on the market on 1954, a sharp drop was seen in institutionalisation
  • Work by blocking excessive dopamine activity at the synapse
  • The drug takes effcet when around 70% of dopamine D2 receptors have been occupied


  • Neuroleptics are the single most effective treatment for schizophrenia
  • Up to 84% efficacy is reported
  • Take effect almost immediately but produce maximum improvement with the first 6 months
  • When treatment is stopped, relapse occurs
  • 16% are drug resistant--> suggests dopamine isn't the only cause of schizophrenia (e.g. influenza A virus)
  • The success of neuroleptics supports the dopamine hypothesis 

Side effects result in 47% non compliance

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Side Effects of Traditional Neuroleptic Medication

Parkinsonian Symptoms

  • 20-40% of patients experience severe and continuous muscle rigidity
  • Dystonia- muscle contractions that cause uncontrollable movements of the face, neck, tongue and back
  • High degree of restlessness, agitation and discomfort in the limbs
  • Symptoms occur once 70-80% of D2 receptors are occupied, 70% of D2 receptors be occupied for the drug to take effect--> side effects cannot be avoided
  • L-dopa can be given alongside the neuroleptic to try to counter the side effects

Tardive Dyskinesia

  • Chewing motions, lipsmacking, jerky movements of limbs
  • The involuntary writhing or tic like movements of the tongue, mouth or whole body
  • Around 20% of patients will develop tardive dyskinesia if they take neuroleptics for a long period of time
  • Doesn't occur until the drug has been taken for at least one year
  • Known to be due to the effect on D2 receptors in the substantia nigra area of the brain
  • Over 45 year olds become 6 more times vulnerable than younger people
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New Generation (atypical) Neuroleptics

  • Developed in the 1990's and referred to as atypical because thei biological impact is different to that of traditional neuroleptics
  • Block dopamine and serotonin receptors
  • Cause fewer extrapyrimidal side effects because they block fewer D2 receptors in the extrapyrimidal area of the brain
  • Block D2 receptors in the limbic system (emotions) and prefrontal cortex (planning and social judgement) to reduce the symptoms of schizophrenia


  • Weak blockade of D2 receptors (40%)
  • High blockade of 5-HT receptors
  • The blockade of 5-HT receptors is thought to be the reason behind the success of atypical neuroleptics in treating the negative symptoms of schizophrenia
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Effectiveness of Atypical Neuroleptics

  • Significantly more effective in helpting Type 2 schizophrenics--> 85% efficacy reported
  • U.S trials found 30% improvement among 318 severely psychotic, drug resistamt schizophrenics
  • The rate of improvements is believed to approach 66% with longer term therapy (Meltzer 1999)
  • Due to there being fewer extrapyramidal side effects, compliance is beeter than the traditional neuroleptics
  • Essock- found 76% of institutionalised patients discharged on Clozapine were still taking the drug 12 months later
  • The drug can be given as an injection every 2 months, increasing compliance further and preventing relapse
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Side Effects of Atypical Neuroleptics

  • Sedation
  • Hypertension
  • Fever
  • Increased salivation
  • Dizziness
  • Weight Gain
  • 3% risk of life-threatening drop in white blood cells- called neutropenia and if left undetected,sudden death can occur--> frequent blood tests required (reason why traditional neuroleptics are still sometimes needed)
  • Few, if any cases of tardive dyskinesia have been reported, even after prolonged treatment
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