Methods of modyfing behaviour - antipsychotic drugs

• The development of antipsychotic medication was a major influence in the decline of psychiatric institutions.
• Before psychiatrists started using the first antipsychotic medication (phenothiazines) schizophrenia had been unsuccessfully 'treated' with various regimens. 
• Some of these treatments included 'trepanning, where holes were drilled into the heads to release evil spirits; 'whirling, where the patient was placed in a chair and spun until they lost consciousness; or insulin shock therapy, where the individual was put into a coma and then revived quickly. 
• In the first half of the 20th century, standard care for schizophrenia was institutional care, possibly with ECT and/or psychosurgery. All of these methods were barbaric and unsuccessful.
• ANTIPSYCHOTIC MEDICATION

  within a year of Jean Delay and Pierre Deniker publishing a paper extolling the virtues of the drug chlorpromazine in 1952, it was being used extensively to treat numerous psychiatric conditions including schizophrenia.
• CONVENTIONAL ANTIPSYCHOTICS

  
  

  Conventional antipsychotics are also known as 'typical', 'older' or 'first generation' antipsychotics. They were first developed in the 1950s. Conventional antipsychotics, such as chlorpromazine, work by affecting neurotransmission, specifically blocking the action of the neurotransmitter dopamine. 
• Chlorpromazine acts primarily as an antagonist (a blocking agent) of D2 receptors. It also blocks other dopamine receptor subtypes D1, D3, D4 and DS receptor sites.
• How it works The blocking' action works as follows. After the presynaptic neuron releases dopamine into the synapse, the receptor sites on the postsynaptic neuron are blockaded by chlorpromazine, thus reducing activity in the postsynaptic neuron. 
• Initially, this causes the presynaptic neuron to increase its release of dopamine into the synapse, meaning an actual rise in the amount of dopamine being secreted. In due course, however, the production of dopamine drops because it is depleted and the amount of dopamine in the synapse decreases.
• Lower levels of dopamine in the synapse in addition to the enduring blockade offered by chlorpromazine leads to a substantial decrease in neural activity.
• Reduction in dopamine activity in the mesolimbic pathway is thought to be responsible for the decline of positive symptoms such as hallucinations and delusions. Chlorpromazine is also seen to affect the serotonin receptors (5-HT1 and 5HT-2) as well as other receptor sites around the brain, but it is mainly a dopamine antagonist.
• ATYPICAL ANTIPSYCHOTICS

  Atypical antipsychotics, such as clozapine, are also known as 'newer' or 'second generation' antipsychotics. They have been developed since the 1990s. Atypical antipsychotics, like conventional antipsychotics, work by acting as a dopamine antagonist, but the precise mechanism with which atypical antipsychotics work is not yet clear.
• DOSAGE

  Largactil (the trade name for chlorpromazine) can be prescribed as a tablet, oral solution, intramuscular injection or suppository. The British National Formulary (a pharmaceutical reference book) notes 1,000mg (1 gram) as being the highest daily dose, although the maximum dose for a child ranges from 40mg to 75mg depending on age.
• Clozaril, Denzapine and Zaponex (all trade names of clozapine) are usually prescribed in tablet form, with a maximum daily dose of 900mg.
• Patients taking clozapine as well as the prescribing physician and the dispensing pharmacist must all be registered with a specialised monitoring service because the drug carries a 3% risk of causing agranulocytosis (a potentially life-threatening drop in white blood cells). Regular blood checks (weekly and then fortnightly) are necessary to monitor if any blood problems arise.
• DIFFERENCES

  Some report that atypical antipsychotics are different from conventional antipsychotics because they are received at fewer dopamine D2 receptor sites and at more D1 and D4 receptor sites.
• Another difference is that most atypical antipsychotics also antagonise (i.e. they bind to a receptor, blocking its usual function) the serotonin receptor 5-HT2A, to the same degree as they antagonise the dopamine D2 receptor.
• Another possible difference between atypical and conventional antipsychotics is the actual amount of time they occupy the D2 receptor sites. Philip Seeman (2002) reports on the 'fast-off theory; this proposes that atypical antipsychotics bind more loosely to the D2 receptor sites than conventional antipsychotics.
• This means that, although the blockade has a therapeutic effect, it does not last long enough to also produce the side effects seen in conventional antipsychotics (such as tardive dyskinesia, which involves involuntary writhing or tic-like movements of the tongue, mouth, face or whole body).
• The 'half-life' of atypical antipsychotic medication is also thought to be less than conventional antipsychotic medication - with atypical antipsychotics the occupancy of D2 receptors falls off within 24 hours, however with conventional antipsychotics the fall- off is longer than 24 hours.