Lesson 4 Biological Therapies For SZ Flashcards
Most common treatment for SZ
The most common treatment for SZ is drugs – specifically antipsychotic drugs. These drugs can be taken in the form of tablets or syrup or even injections. Injections tend to be given to those patients who are at risk of not taking their medication or don’t take it properly. Injections would be given every 2 – 4 weeks.
To control the symptoms of SZ, nearly all patients are first given antipsychotic drugs either for a short or long period depending on the control of their symptoms. Some patients may have the drugs for a short period and be completely cured whereas
others may need to take these drugs for a long period or even forever. Sometimes, once the patient is stable, they may be given psychological therapies as well such as family therapy or CBT.
Two main types of Antipsychotic drugs
- typical (traditional or first generation) antipsychotics
- atypical (second generation) antipsychotics
Typical Antipsychotics
Typical antipsychotics have a strong link to the dopamine hypothesis explanation of SZ whereby this hypothesis suggests that schizophrenic symptoms are due to high levels of dopamine.
These drugs are dopamine antagonists and work by reducing the effects of dopamine and thus reduce the symptoms of SZ. These drugs therefore bind to but do not stimulate dopamine receptors (particularly the D2 receptors in the mesolimbic dopamine pathway), thus blocking their action. In other words they block the dopamine receptors
in the synapses in the brain reducing the actions of dopamine. This in turn will reduce the positive symptoms of SZ.
Example of a typical antipsychotic
Chlorpromazine
Chlorpromazine
Interestingly, chlorpromazine is also an effective sedative and was actually used to calm patients not only with SZ but also other conditions. Also when schizophrenic patients are first admitted to hospital, they are given chlorpromazine to calm their nerves.
Another interesting point about this drug is that it is faster absorbed in syrup form rather than tablet – hence it being an effective sedative.
The maximum dosage for the tablet would be 1000mg. Of course, when given first, the dosage would be much smaller but gradually increased from about 400mg to 800mg.
When the patient would first take Chlorpromazine, dopamine levels would build up but then the production of dopamine would reduce. This drug would therefore work to normalise the dopamine production and transmission – this in term would then reduce the symptoms of SZ such as hallucinations.
Atypical antipsychotics
These drugs emerged in the 1970s and were used to improve upon the effectiveness of typical antipsychotics and minimize the side effects that were occurring when patients were given typical antipsychotics. They also have a beneficial effect on negative symptoms and cognitive impairment are suitable for treatment-resistant patients
These drugs work like typical antipsychotics by blocking D2 receptors. However, they only temporarily occupy the D2 receptors and then rapidly dissociate to allow normal dopamine transmission – it is this rapid dissociation that is thought to be responsible for the lower levels of side effects.
Examples of atypical antipsychotics
Clozapine and Risperidone
Clozapine
This drug was developed in 1960s but actually trialed in the 1970s. However, due to a number of patients dying from a blood condition called agranulocytosis after taking clozapine, it was withdrawn.
Clozapine then came back in the 1980s as it was seen as a more effective treatment for SZ rather than typical antipsychotics. Clozapine was used as an alternative treatment for SZ if the typical antipsychotic drugs failed to work.
Even today, clozapine is still used as an alternative. However, patients are given regular blood tests to make sure that they don’t have agranulocytosis. Because of its fatal side effects, clozapine is not available as an injection but only in syrup or tablet. The dosage given to patients is between 300 – 450 mg per day – much lower than chlorpromazine.
Clozapine works by binding to dopamine receptors but in addition, acts on serotonin and glutamate receptors. By the drug working on other neurotransmitters, this helps to reduce depression and anxiety and improve cognitive functioning. Because clozapine does improve mood, it is generally given to patients who are at high risk of suicide. This is important as research has shown that between 30-50% of patients with SZ are likely to attempt suicide.
Risperidone
This drug emerged in the 1990s as an attempt to reduce the serious side effects of clozapine but still be as effective as clozapine.
Risperidone can be taken as syrup, tablets or injection. Patients are given a dose of about 4-8mg and up to a maximum of 12mg.
Risperidone like clozapine works by binding to dopamine receptors but works better in binding to dopamine receptors than clozapine leading to less side effects. As a result, much smaller doses are required of risperidone.
Evidence also suggests that this leads to fewer side effects than most other antipsychotics.
Advantages of Drug Therapy
There is research evidence to support the moderate effectiveness of typical antipsychotic drugs in treating SZ. For example: Thornley et al (2003) compared the use of chlorpromazine (typical antipsychotics) with a placebo. Data from 13 trials with a total of 1121 pps showed that chlorpromazine was associated with reduced symptoms and
better overall functioning. Furthermore, data from three trials with a total of 512 pps showed that relapse rate was also lower when chlorpromazine was taken. This study this shows that typical antipsychotics were effective in reducing the symptoms of SZ compared to a placebo showing that drug therapy is appropriate in treating SZ.
There is also research evidence to support the appropriateness of atypical antipsychotics. In a review by Meltzer (2012), he concluded that Clozapine (atypical antipsychotics) is more effective than typical antipsychotics and other atypical
antipsychotics in treating SZ. In fact Clozapine was seen as effective in 30-50% of cases where typical antipsychotics had failed. This study shows that use of clozapine as a treatment for SZ is a very appropriate drug as Meltzer clearly showed especially when other drugs failed!
Interestingly, a number of studies have compared the effectiveness of clozapine and risperidone but results have been inconclusive suggesting that some patients responded better to one drug than the other and also supporting the idea that SZ is a complex psychotic disorder
Disadvantages of Drug Therapy
The biggest weakness of drug therapy in treating SZ is the serious side effects ranging from mild ones to fatal ones. For typical antipsychotics, the side effects include: dizziness, agitation, sleepiness, stiff
jaw, weight gain and itchy skin. A more profound side effect can result in ‘tardive dyskinesia’ which is caused by dopamine supersensitivity and manifests as involuntary facial movements such as grimacing, blinking and lip smacking. The most serious side effect of typical antipsychotics is NMS (neuro malignant syndrome – area of the brain associated with the regulation of a number of body systems) – which could lead to high temperature, delirium and coma and can cause death – this may occur in between 0.1% - 2% of schizophrenics. Whereas atypical antipsychotics were developed to overcome these side effects. However, side effects do exist for atypical antipsychotics such as Clozapine thus
regular blood tests need to be taken of the patients to test for early signs of agranulocytosis (a rare blood condition where the production of white blood cells is prevented – leads to problems with immunity)
There are problems with the evidence for the effectiveness of drugs and this has been challenged by Healy (2012) has suggested that some successful drug trials have had their data published on multiple occasions thus exaggerating the effectiveness. Also
because antipsychotics have powerful calming effects, it seems as though the drugs are successful. However, this does not really show how much the drugs actually reduce the symptoms. Furthermore, most published studies only assess the short-term benefits of drug therapy rather than the long term benefits especially for those patients who have
stopped taking the drugs.
There is of course ethical issues related to using drug therapy for SZ. The most profound ethical issue would be consent – e.g. due to the fact that schizophrenia is a psychotic disorder, patients may not be in the right frame of mind to give fully informed consent in taking the drugs and because the drugs do have such severe side effects, one
would question the extent of the harm (both physical and mental) and whether the effects of the drugs were reversible especially with side effects such as NMS and tardive dyskinesia.
