Drug Therapy

• Antipsychotics


  Drugs used to treat reduce positive symptoms in disorders like Sz
• Chlorpromazine


  A typical antipsychotic around since the 1950s and is taken as a tablet, syrup or injection. Orally it is administered daily, starting with a low dose and gradually increasing to a maximum of 400-800mg (1000mg maximum). Typical prescribed doses have declined over the last 50 years.
• Typical Antipsychotics as Dopamine Antagonists


  Typical Antipsychotics like chlorpromazine act as antagonists in the dopamine system, blocking dopamine receptors in the synapses of the brain and reducing the action of dopamine. Initially, levels of dopamine build up but then production is reduced. According to the dopamine hypothesis of Sz, this dopamine-antagonist effect normalizes neurotransmission in key areas of the brain, reducing symptoms like hallucinations.
• Sedation Effect of Typical Antipsychotics


  Chlorpromazine is also an effective sedative. This is believed to be because of its effect on the histamine receptors but it is not fully understood how this leads to sedation. Chlorpromazine is often used to calm individuals not only with Sz but also with other conditions. This has often been done when patients are admitted to hospital and are very anxious. Syrup is absorbed faster than tablets so tends to be given for sedation.
• Atypical Antipsychotics


  Atypical antipsychotics have been around since the 1970s and were created to maintain and improve the effectiveness of the drug. There are a range of atypical antipsychotics and they don't all work the same. They typically target a range of neurotransmitters such as dopamine and serotonin. It is unknown how some of them work.
• Typical Antipsychotics


  The first generation of drugs for Sz and other psychotic conditions. They have been used since the 1950s, work as a dopamine antagonist and include Chlorpromazine.
• Clozapine


  Developed in the 1960s and first trialled in early 1970s. It was withdrawn for a while in the 1970s following the deaths of some patients from a blood condition called agranulocytosis. In the 1980s it was discovered to be more effective than typical antipsychotics and was remarked as a treatment for Sz to be used when other treatments failed in combination with regular blood tests for safety. Because of the potentially fatal side effects, it is not available as an injection. Daily dosage is typically 300-400mg per day.
• How Clozapine works


  Clozapine binds dopamine, serotonin and glutamate receptors. It is believed this improves mood, reduces anxiety and depression, and may improve cognitive functioning. Because of this, it may be prescribed when a patient is at high risk of suicide. This is important as 30 to 50% of people with Sz attempt suicide at some point.
• Risperidone


  Having been used since the 1990s, Risperidone was developed to be as effective as Clozapine but without the side effects. It can be taken in the form of tablets, syrup or an injection that lasts around two weeks. A small dose is initially given and then increased to 4-8 mg and a maximum of 12mg. It is believed to bind to dopamine and serotonin receptors but more strongly than Clozapine, therefore more effective in smaller doses. There is evidence to suggest it has less side effects.
• Evidence for the effect of Antipsychotics

  There is evidence supporting their effectiveness. Thornley et al (2003) reviewed studies comparing the effects of chlorpromazine to control conditions. Data from 13 trials with a total of 1121 participants showed chlorpromazine was associated with better overall functioning and reduced symptom severity compared to placebo. Meltzer et al (2012) concluded clozapine was more effective than typical antipsychotics and other atypical antipsychotics, effective in 30-50% of treatment-resistant cases. This means as far as we can tell, antipsychotics work.
• Flaws with the evidence supporting Antipsychotic effectiveness 


  Healy (2012) suggested evidence is flawed, most studies are only on the short-term effects and some of the successful trials have had their data published multiple times, exaggerating the size of the evidence base for its positive effects. Also, because antipsychotics have powerful calming effects, it is easy to demonstrate they have some positive effects on people experiencing Sz symptoms. This is not the same as saying they reduce the severity of psychosis. This means evidence is less impressive than it first appears.
• Side Effects of Antipsychotics


  One limitation of Antipsychotics is they are associated with a range of side effects, including dizziness, agitation, sleepiness, stiff jaw, weight gain and itchy skin. Long-term use can result in tardive dyskinesia, caused by dopamine supersensitivity and cause involuntary facial movements like grimacing, blinking or lip-smacking. The most serious side effect is neuroleptic malignant syndrome (NMS). This means they may be harmful, so individuals may avoid them (making them ineffective)
• Neuroleptic Malignant Syndrome

  NMS is believed to be caused by dopamine being blocked in the hypothalamus, an area responsible for the regulation of various body systems. NMS results in temperature, delirium and a coma, which can be fatal. Its frequency ranges from 0.1% to just over 2%.
• Limitation of Antipsychotics and understanding


  We don't know why they work. The understanding of how antipsychotics work is strongly tied in with the original dopamine hypothesis- that symptoms of Sz are linked to high levels of dopamine in the subcortex of the brain. However, we now know it is not a complete explanation, in some areas dopamine is too low. If this is true, most antipsychotics shouldn't work. Given the questions about the effectiveness of antipsychotics, this adds to the argument they are ineffective. This means at least some antipsychotics may not be the best treatment.
• Ethics of using antipsychotics as a sedation


  If antipsychotics are being used in hospitals in order to make patients easier to work with for the staff's benefit, rather than for the patient's benefit, the ethics may be questioned.

  However, calming distressed people almost certainly makes them feel better, and allows them to engage with other treatments like CBT and services like social workers.