modifying behaviour: antipsychotic drugs for schizophrenia

Question 1

Development into antipsychotic medication.

Answer 1

• before psychiatrists started using antipsychotic medication (phenothiazines), schizophrenia had been unsuccessfuly ‘treated’ with various regimens. some of these treatments included ‘trepanning, where holes were drilled into the head, to let out ‘evil spirits’; whirling where the patient would be places in a chair and spun around until they lost consciousness.
• in the first half of the 20th century, standard care for schizophrenia was institutional care.
• 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.
• antipsychotic can be split into two categories; conventional and atypical.

Question 2

How do Conventional Antipsychotics work?

general) 1/2

Answer 2

• conventional antipsychotics, such as chlorpromazine, work by affecting neurotransmission, specifically by blocking the action of the neurotransmitter dopamine.
• chlorpromazine acts as an antagonist (a blocking agent) of D2 receptors. it also blocks other dopamine receptor subtypes D1 D3 D4 and D5 receptor sites.

Question 3

How do conventional antipsychotics work?

specific 2/2

Answer 3

• 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 the 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.
• however, over time, the production of dopamine 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.

Question 4

How do atypical antipsychotics work?

Answer 4

• 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.

Question 5

What are the differences between conventional and atypical antipsychotics?

Answer 5

• 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 (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).
• the half life on atypical antipsychotic medication is also thought to be less than conventional antipsychotic medication- with atypical antipsychotics the occupancy of D2 receptor sites falls off within 24 hours, however with conventional antipsychotics the fall-off is longer than 24 hours.