Description of the condition
Schizophrenia is one of the severe forms of major mental health disorders. It has a high lifetime prevalence rate (four per 1000 people - Saha 2005) but low incident rate because of the chronic nature of the illness. The median incident rate of schizophrenia is 15.2 per 100,000 people (McGrath 2008).
The illness is classified in categories F20-F29 as ‘schizophrenia, schizotypal and delusional disorder’ in the International Classification of Diseases (ICD-10 1992), particularly ‘schizophrenia’ in F-20. In ICD-10, it is described: "the schizophrenic disorders are characterized in general by fundamental and characteristic distortions of thinking and perception, and affects that are inappropriate or blunted". The Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-IV-TR 2000) has also used the term ‘schizophrenia’ (discussed in Chapter 5).
The prognosis of schizophrenia is quite variable, and in the past psychiatrists were not very optimistic about its treatment (Kraeplin 1919). However, recent studies show that the outcome of schizophrenia treatment is better than was previously thought and use of phenothiazines may have played a part along with other factors such as improving community services (Bland 1978).
Description of the intervention
Psychiatrists have been prescribing typical antipsychotic drugs since the 1950s, when the first antipsychotic medication, chlorpromazine, was synthesized. Chlorpromazine was first used as an antihistaminic agent to treat allergies. Later, surgeons started using it as a pre-surgical medication to sedate people before surgical procedures (Laborit 1951). In 1952, Paul Charpentier, from Laboratories Rhône-Poulenc in France, and Delay and Deniker’s team described the antipsychotic properties of chlorpromazine (Delay 1952). Chlorpromazine is considered as a pivotal discovery in the field of psychosis treatment, with other antipsychotics often measured in 'chlorpromazine equivalents' (Turner 2007; Yorston 2000).
There are now many antipsychotic drugs available. They are broadly divided into two groups ‘typical antipsychotic drugs’ and ‘atypical antipsychotic drugs’. Typical antipsychotic drugs are also known as ‘first generation’, ‘conventional’ or ‘classical’ antipsychotic drugs, e.g. chlorpromazine and haloperidol. Atypical antipsychotic drugs are also known as ‘second generation’ or ‘newer antipsychotic drugs’, e.g. clozapine, risperidone, quetiapine and olanzapine. Typical antipsychotic drugs have a good reputation regarding their efficacy in treating the 'positive' symptoms of schizophrenia (e.g. delusions and hallucinations) (Mathews 2007). They are also well known for their adverse effects such as movement disorders (extra-pyramidal symptoms or extra-pyramidal side effects - EPS or EPSE), sedation, metabolic syndromes; and sometimes potentially fatal conditions such as agranulocytosis and neuroleptic malignant syndrome (Arana 2000). The second generation antipsychotic drugs arrived on the market, with notable differences. They had a reputed low side-effect profile and, according to pharmaceutical companies, higher efficacy (Janssen 1988). However, research funded independently of pharmaceutical companies has suggested that there may be little difference between the older and newer drugs, subsequently fuelling debate as to whether new atypical antipsychotics are more effective than older established first-generation antipsychotics, and whether questioning the efficacy of the two classifications of drugs creates an improper generalisation of antipsychotics that do not form a homogenous class (Leucht 2009). Against this backdrop, chlorpromazine remains a benchmark drug in the treatment of schizophrenia, and although imperfect, it is relatively inexpensive and remains one of the most common drugs used for schizophrenia worldwide (Adams 2005).
How the intervention might work
Chlorpromazine is an aliphatic phenothiazine, which is one of the widely-used typical antipsychotic drugs. Chlorpromazine is reliable for its efficacy and one of the most tested first generation antipsychotic drugs. It has been used as a ‘gold standard’ to compare the efficacy of older and newer antipsychotic drugs. It blocks alpha 1, 5HT2A, D2 and D1 receptors in the brain, and thus it works as an antipsychotic. It also has effect on muscarinic, serotonin & H1 receptors. By blocking D2 receptor it can also cause extrapyramidal side-effects. Other adverse effects include dry mouth, blurred vision, restlessness, sedation, neuroleptic malignant syndrome (DSM-IV 1994) etc. On the other hand, atypical antipsychotic drugs by definition may cause decreased or no extrapyramidal side-effects (Kinon 1996). Different atypical antipsychotic drugs act in different ways; for example, Clozapine blocks D2 & 5HT2 receptors (Meltzer 1989). Both clozapine and quetiapine blocks more 5HT2 receptors than D2 receptors. Olanzapine blocks 5HT2A, 5HT6, D1, D2, D3 and muscarinic receptors (Zhang 1999).
Why it is important to do this review
This is one of a family of related reviews on this important compound.
|Chlorpromazine versus placebo||Adams 2007|
|Chlorpromazine versus haloperidol||Leucht 2008|
|Chlorpromazine doses||Liu 2009|
|Chlorpromazine cessation||Almerie 2007|
|Chlorpromazine for acute aggression||Ahmed 2010|
Chlorpromazine is one of two oral antipsychotic drugs on the World Health Organization's Essential Drug list (WHO 2011). It is globally accessible and has been known for its effectiveness in the treatment of schizophrenia since the 1950s (Adams 2007); it is also the most commonly used and inexpensive treatment for schizophrenia (Odejide 1982). Expensive new generation drugs are heavily marketed worldwide as a better treatment for schizophrenia - this may not be the case and an unnecessary drain on very limited resource (Adams 2006). Also, comparisons with new generation drugs, which are coming off-patent and therefore more accessible, are important to assist informed and independent choice.