Schizophrenia - drug therapies

This topic follows along nicely from the last one, and again, is relatively straightforward. AO1 is fairly simple here, and AO2 evaluation works with reference to effectiveness (using research evidence) and appropriateness, (using more specific IDA-style evaluative points.) As with all my posts, if I come across any useful new information at any point, I will update this.

Black: AO1 - Description
Blue: AO2 - Evaluation - studies
Red: AO2 - Evaluation - evaluative points

Typical antipsychotics

First developed in the 1950s, this class includes chlorpromazine, haloperidol and fluphenazine. They act as dopamine antagonists, reducing the neurotransmitter levels by blocking D2 receptors in the brain's dopamine pathways. Generally, they are administered either as a course of tablets, or as a "depot injection", a single injection every 2-4 weeks which releases the medication slowly over time. Both classes of antipsychotics work on the dopamine hypothesis - the idea that abnormally high levels of the dopamine neurotransmitter due to oversensitive receptors cause schizophrenia, and, due to this, only really function to treat the positive symptoms such as hallucinations, delusions and thought disturbances.

There are several potentially harmful side effects than can result from the use of typical antipsychotics. Side effects vary between specific chemicals, but are likely to include muscle stiffness, cramp, tremors, and extrapyramidal symptoms (drug-induced movement disorders) such as muscle spasms, rigidity, involuntary muscle movement and restlessness.

Chronic use of atypical antipsychotics carries the risk of causing development of tardive dyskinesia, a serious degenerative disorder characterised by repetitive and involuntary muscle movements such as excessive blinking, grimacing and limb twitches.

Atypical antipsychotics

Atypical antipsychotics such as clozapine, risperidone and olanzapine also act dopamine antagonists, interfering with post-synaptic D2 dopamine receptors to prevent the transmission of dopamine across the synapse. They can also reduce serotonin levels by blocking receptors.

Compared to the most common typical antipsychotics such as haloperidol, they are less likely to cause extrapyramidal motor impairment, as well as the development of the serious motor disorder tardive dyskinesia. 

However, they have been found to carry an increased risk of stroke, blood clots and sudden cardiac arrest. They can also cause agranulocytosis – low white blood cell count, resulting in immune weakness and increased susceptibility to infection.

Compared to many antipsychotics, atypicals carry a very low risk of withdrawal symptoms – possibly on account of the drugs being absorbed into adipose tissue and slowly released. 

Effectiveness of drug therapies

Stargardt et al (2008) - investigated cost effectiveness of typical and atypical antipsychotics by comparing drug costs to rehospitalisation rates after a course of treatment. Studying 321 patients, they found no statistically significant differences in the effectiveness of either class – Atypical antipsychotics were often more useful in the most severe cases, whereas typical antipsychotics were often more useful in less severe cases. Atypical antipsychotics also have a much smaller risk of harmful side effects – but they are also more expensive. They concluded that in terms of efficiency balanced between cost and effectiveness, there is no great difference between either class of antipsychotic.   

Correll + Schenk (2008) – 28000 participants stratified by age across 12 trials, assessing incidence of tardive dyskinesia in patients treated with typical or atypical antipsychotics. Across all the trials, TD risk is 3.9% for atypical, 5.5% for typical, with significant variations in incidence between trials. Four adult trials even suggest that compared to unmedicated schizophrenics, atypical antipsychotics actually reduce the risk of TD development: 13.1% incidence for atypicals, 15.6% for unmedicated, 32.4% for typicals. Overall, results suggest a lower risk of tardive dyskinesia in patients medicated by atypical antipsychotics than those medicated by typical antipsychotics.

Bagnall et al (2003) – Meta-analysis of studies into attrition across 2000 schizophrenic participants for 2 years of antipsychotic medication. A higher attrition rate was assumed to indicate lower satisfaction with the treatment, resulting from more side effects and less effective relief of symptoms. Generally, fewer participants left trials early from atypical drug groups than from typical drug groups, suggesting that patients found atypical antipsychotics more acceptable. Individuals with schizophrenia may have found atypical antipsychotics more acceptable than typical counterparts – even if they are no more effective in the relief of symptoms, they have fewer negative side effects.

Davis (1980) - analysed the results of 29 studies (3519 people), they found that relapse occurred in 55% of the patients whose drugs were replaced by a placebo compared to 19% in those patients who remained on the real drug. Suggests significant effectiveness of the drug – however, challenged by Ross + Read (2004) – 45% of patients given a placebo did not relapse. The effectiveness of drug treatments is challenged as 45% of patients did well on the placebo therapy. However, the fact that 45% of patients did not relapse when antipsychotics were replaced by a placebo challenges the actual effectiveness of drug treatments.

Overall evaluation of drug therapies

Antipsychotic drugs are a relatively cheap, effective treatment, reducing symptoms in the majority (roughly 70%) of patients and allowing them to live comparatively normal lives.

However, like all drug therapies for mental illness, they treat symptoms, not underlying causes. This means that the underlying disorder is not treated – and relapse is likely when the course of drugs is discontinued. This can lead to “revolving door syndrome” – where patients are readmitted and given a new course of antipsychotics very soon after completing a prescribed course of treatment – remaining on a cycle of rehospitalisation and medication for potentially many years.

Antipsychotics are generally better at treating positive symptoms such as hallucinations and delusions rather than negative symptoms such as apathy and alogia, suggesting that factors other than an excess of dopamine may be responsible for negative symptoms.

Ethical issues can result not only from the often severe side-effects, but also from the use of drugs as a “chemical straitjacket.” There are potential ethical concerns with compulsory medication for schizophrenics – forcing patients to take drugs against their will as a form of social control.