**L4 - Biological Therapies for Schizophrenia Flashcards
what is the most common treatment for SZ?
drugs - specifically antipsychotic drugs, can be taken in the form of tablets, injection or syrup. 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.
what are the TWO TYPES of ANTIPSYCHOTIC DRUGS?
1) typical antipsychotics (first generation)
2) atypical antipsychotics (second generation)
what are typical antipsychotics?
these drugs are DOPAMINE ANTAGONISTS and work by reducing the effects of dopamine and thus reduce the symptoms of SZ. These drugs bind to DOPAMINE RECEPTORS in the SYNAPSES OF THE BRAIN without stimulating them, THUS BLOCKING THEIR ACTION - this in turn reduces the positive symptoms of SZ. Typical antipsychotics have a strong link to the DOPAMINE HYPOTHESIS explanation of SZ whereby this explanation suggests that SZ symptoms are due to high levels of dopamine. These anatagonist drugs would normalise the dopamine production and transmission - this in turn would reduce the POSITIVE SYMPTOMS OF SZ such as hallucinations.
whats an example of a typical antipsychotic drug?
one typical antipsychotic drug is CHLORPROMAZINE, this can be taken as a tablet, syrup or injection. The MAXIMUM DOSAGE for the tablet would be 1000mg, however patients would start from a lower dosage and gradually work up to this maximum. When the patient would first take CHLORPROMAZINE, DOPAMINE LEVELS would build up but then the production of dopamine would reduce.
what are ATYPICAL ANTIPSYCHOTICS?
these drugs are the second generation of antipsychotics and were used to improve upon the effectiveness of typical antipsychotics and also minimise the side effects that were occuring when patients were given typical antipsychotics. These drugs work like typical antipsychotics by blocking DOPAMINE RECEPTORS, however they only TEMPORARILY occupy these receptors an then they RAPIDLY DISSOCIATE to allow normal dopamine transmission - its this rapid dissociation is thought to be responsible for the lower side effects.
what’s an example of an atypical antipsychotic drug? (C)
CLOZAPINE: after some vigorous testing clozapine was brought onto the market and seen as a more effective treatment for SZ than typical antipsychotics. Clozapine was used as an ALTERNATIVE treatment for SZ if the typical antipsychotics didnt work. Even today, its used as an alternative because of the risk of AGRANULOCYTOSIS (a fatal blood condition) that comes with taking this drug. Patients that are given this drug must take regular blood tests to make sure they dont develop this condition.
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 negative symptoms of SZ like depression and anxiety and improve cognitive functioning. It also IMPROVES MOOD so its likely to be given to SUICIDAL PATIENTS (which represents 30-50% of SZ patients)
what is another example of an ATYPICAL ANTIPSYCHOTIC DRUG? (R)
RISPERIDONE is an example of another ATYPICAL ANTIPSYCHOTIC that emerged as an attempt to reduce the serious SIDE EFFECTS OF CLOZAPINE but still be just as effective. RISPERIDONE like CLOZAPINE works by binding do 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 risperidone leads to fewer side effects than most antipsychotics.
+ THORNLEY ET AL
there is research evidence to support the moderate effectiveness of TYPICAL antipsychotic drugs in treating SZ. THORNLEY ET AL compared the use of CHLORPROMAZINE 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 3 trials with a total of 512 pps showed that RELPASE RATE was LOWER when CHLORPROMAZINE WAS TAKEN. This study shows that TYPICAL ANTIPSYCHOTICS were EFFECTIVE at treating SZ when compared to a placebo showing that drug therapy is appropriate in treating SZ.
+ MELTZER
There is also research evidence to support the appropriateness of ATYPICAL ANTIPSYCHOTICS. In a REVIEW by MELTZER, he concluded that CLOZAPINE is MORE EFFECTIVE than typical antipsychotics and other atypical antipsychotics in treating SZ. 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 as MELTZER clearly showed, even when other drugs failed.
+ LEUCHT ET AL
there is also research evidence to support the fact that RELAPSE RATES are MUCH LOWER when patients take antipsychotic drugs (atypical and typical) AS OPPOSED TO PLACEBOS. LEUCHT ET AL carried out a META ANALYSIS of 65 STUDIES, involving nearly 6000 patients. Some patients were taken off their antipsychotics and given placebos instead. Within 12 months, 64% of those patients who had been given the PLACEBO RELAPSED whereas only 27% relapsed when on antipsychotic medication. The results of this study show that antipsychotic medication is both EFFECTIVE AND APPROPRIATE in PREVENTING SZ PATIENTS from RELAPSING.
- SERIOUS SIDE EFFECTS
The biggest weakness of drug therapy in treating SZ is the SERIOUS SIDE EFFECTS ranging from mild ones to the fatal one. Typical antipsychotics can cause dizziness, agitation, sleepiness, stiff jaw, weight gain and even itchy skin. A more profound side effect is 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) which can ead to high temperature, coma and can cause death. Whilst atypical antipsychotics are only used as alternatives to prevent the side effects, we still have to be cautious when prescribing them - especially drugs like CLOZAPINE which can cause ARGANULOCYTOSIS.
- HEALY
HEALY challenged the evidence for the effectiveness antipsychotics, suggesting that some successful drug trials have had their data published on mulitple occasions thus exaggerating the effectiveness. Also because antipsychotics have powerful calming effects, it seems as though the drugs are more successful, however this does not show how much the drugs actually reduce the symptoms of SZ.
Furthermore, most published studies only assess the SHORT TERM BENEFITS of drug therapy rather than the long term benefits, especially for the patients who have stopped taking the drugs.
- ETHICAL ISSUES
there is ethical issues related to using drug therapy for SZ, the biggest issue is consent - due to the fact that SZ is a psychotic disorder,patients may not be in the right frame of mind to give fully informed consent to be given the drugs and because the drugs do have such severe side effects, one would question the extent of the harm (physical and mental) and whether the effects of the drugs were reversible, especially with side effects such as NMS and TARDIVE DYSKINESIA.
