Drug/Biological Treatments for Schizophrenia

• 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

Effectiveness

• 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

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

• 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

Clozapine

• 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

• 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

• 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