Cochrane review finds quetiapine is equivalent in efficacy to typical antipsychotics, but possibly causes fewer side effects

Antipsychotic medication is the standard treatment for schizophrenia and psychosis in the UK. Given that psychosis is commonly a chronic condition and therefore that medication used to treat it often needs to be taken for several years, getting the medication “right” is important.

As I mentioned in my first blog post for the Mental Elf, antipsychotic medication can be roughly divided into older ‘typical’ antipsychotics and newer ‘atypical’ antipsychotics. The common perception is that atypical are superior to typical antipsychotics, not least because they are less likely to cause disabling and frightening extra-pyramidal (motor and movement) side effects. However, they are considered more likely to cause metabolic side effects, including weight gain and diabetes.

So, finding the “right” medication is a balancing act: it needs to be effective in reducing symptoms, but it also needs to have a tolerable level of side effects: if your medication makes you feel physically unwell there must seem little incentive to continue taking it, but non-compliance to antipsychotic medication potentially jeopardises your mental health.

It would seem sensible, then for clinicians to have the best possible understanding of what to expect from an antipsychotic in order to help them achieve the elusive balancing act between efficacy and tolerability.

Quetiapine is a widely used atypical antipsychotic – but is it actually any better than the typical antipsychotics (e.g. chlorpromazine and haloperidol)?

Fear not – those lovely Cochrane wizards are back with a review to answer that very question, in the form of Suttajit et al’s (2013) systematic review.

Methods

Suttajit et al’s paper is a systematic review of research comparing oral quetiapine with typical antipsychotics (chlorpromazine, haloperidol and perphenazine). They used electronic searches, reference searching and contact authors of significant papers as well as pharmaceutical companies to identify all relevant randomised trials. As a result, the review comprised 43 randomised controlled trials (RCTs), making a total of 7217 participants.

Once these studies had been identified as appropriate, the data was extracted and analysed in order to assess the following outcome measures:

Finding the “right” medication is a balancing act … to achieve the elusive balance between efficacy and tolerability

Primary outcome: Global state
Secondary outcomes – many and various, including: mental state (positive symptoms; negative symptoms), relapse, leaving the studies early and adverse effects (e.g. cardiac effects, movement disorders, prolactin increase, sedation, weight gain etc.)

Results

The following results were found:

Primary outcome: there was no significant difference in global state between participants taking quetiapine, and participants taking a typical antipsychotic
Mental state outcomes (general, positive and negative symptoms) were equivalent between groups
The percentages of participants leaving the studies early were similar between the quetiapine and typical groups
- However fewer patients taking quetiapine left the studies early due to adverse events.
There were no differences between groups for the following adverse events: suicidality, death, QTc prolongation (cardiac abnormality), low blood pressure, tachycardia, sedation, gyaecomastia, galactorrhoea, menstrual irregularity and white blood cell count
Fewer of the following adverse effects were found in the quetiapine patients: abnormal ECG, extrapyramidal (motor and movement) effects, abnormal prolactin levels and weight gain
There were no significant differences for re-hospitalisation or any of the other secondary outcomes assessed by the review.

Suttajit et al’s Cochrane review appears to find no support for quetiapine being more effective its “first-generation” counterparts

Suttajit et al’s Cochrane review appears to find no support for quetiapine being more effective than its “first-generation” counterparts

Conclusions

When comparing quetiapine with typical antipsychotic medications, Suttajit et al’s Cochrane review appears to find no support for quetiapine being more effective than its older “first-generation” counterparts. Quetiapine performed no better than typical antipsychotics in improving mental state, reducing re-hospitalisation or improving quality of life (amongst other measures).

However, when considering the other important aspect of “getting the medication right” – tolerability – their review found some evidence to suggest that quetiapine may result in fewer occurrences of specific adverse side effects (abnormal ECG, extrapyramidal effects, abnormal prolactin levels and weight gain).

But let’s not get too carried away. The evidence for quetiapine having potentially greater levels of tolerability has been described by Suttajit et al as being of ‘moderate quality’. That is to say:

further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.

Or in other words – the evidence used to provide this conclusion isn’t as compelling as we’d like, over here in the Mental Elf woodland.

In fact, poor quality data is reported as being a significant limiting factor in this review. The authors highlight that:

the evidence is limited due to high attrition rates in almost all studies

and emphasise that outcome reporting in the trials selected for inclusion in the review was ‘insufficient’ and failed to adhere to the CONSORT statement (designed to promote high standards in trial reporting).

So – once again, your ethics committees need you! Suttajit et al ultimately conclude that better reported, medium- and long-term studies into the benefits of quetiapine over typical antipsychotics are required. Ready, steady, get drafting!