Antipsychotics

antipsychotics

Introduction

Antipsychotics are medications used in the treatment of psychosis. In the past, they have also been known as neuroleptics or major tranquilisers.

However, they can also be used in a number of other conditions, including bipolar affective disorder, depression with psychosis and acutely aggressive/violent behaviour requiring sedation.

Antipsychotics are available in oral form, some in oral quicklet form, which dissolves immediately in the mouth and some in intramuscular form, often referred to as a depot injection.

What we know already

To understand antipsychotics, it is important to understand the key biological theory of what causes psychosis. This theory boils down to an excess of dopamine in the brain, particularly in the mesolimbic pathway, causing psychotic experiences such as delusions and hallucinations. Most antipsychotics (although not all) act by blocking dopamine receptors in order to dampen down the activation of the excess dopamine.

Antipsychotics can be classified in several ways, but the most commonly used method is to divide them into first- or second-generation antipsychotics. This description is partly due to the timing of the development of the drugs, but the main difference between the groups is their side effect profile. First generation antipsychotics are known to cause extra-pyramidal side effects such as parkinsonism, akathisia, dystonia and tardive dyskinesia, whereas second generation drugs are less likely to cause this.

First-generation antipsychotics (or typical antipsychotics) include Chlorpromazine, Haloperidol, Flupentixol and Zuclopenthixol.

Second-generation antipsychotics (or atypical antipsychotics) include Amisulpride, Clozapine, Olanzapine, Paliperidone, Quetiapine and Aripiprazole.

Key side effects that may be seen with antipsychotic use:

Extra-pyramidal side effects (as above, mostly seen with first-generation antipsychotics)
Most antipsychotics have a propensity to induce weight gain and hyperglycaemia
Many antipsychotics can prolong the QT interval on ECG so cardiac side effects are seen
Sexual dysfunction

NICE guidelines suggest the choice of antipsychotic medication should be made by the service user and healthcare professional together, taking into account the views of the carer if the service user agrees.

Areas of uncertainty

The exact mechanisms of action of some antipsychotics.
Which antipsychotics should be used in which order. Generally speaking, clinicians opt for the antipsychotic that suits their patient, usually starting with a second-generation antipsychotic. With the exception of Clozapine (reserved for treatment-resistant schizophrenia), there are no strict guidelines on which antipsychotics to use in which order as part of a treatment ladder.
Using antipsychotics above the BNF upper limits this is often done in clinical practice but higher doses are unlicensed and therefore not as much information is known about the effect of doing this.
Some antipsychotics have been used to treat behavioural and psychological symptoms of dementia, but it has recently been identified that they are associated with an increased risk of stroke in the elderly, so using antipsychotics in older people requires careful consideration of benefits and risks.
The use of antipsychotics in pregnancy and which are safe to use. There is also limited information on what to use during breastfeeding.

What’s in the pipeline

The classification of antipsychotics is likely to change as we learn more about the drugs. The first/second generation divide is becoming a historical description that is becoming less useful as we discover new drugs with different mechanisms of action.
There is currently a drive to improve the physical health of those individuals taking antipsychotic medication.
Research continues into comparison of antipsychotic medication with psychotherapy interventions, such as CBT for psychosis more information available in the blogs on this topic!
The ongoing OPTiMiSE study (Leucht et al) hopes to provide evidence about the effectiveness of switching antipsychotics, including potential guidance on which drugs to use, and in the event of non-response the optimum length of time to wait before switching.

References

NICE guidelines CG178 (2014) ‘Psychosis and schizophrenia in adults: treatment and management’ [PDF]

Leucht S. et al. (2015) The Optimization of Treatment and Management of Schizophrenia in Europe (OPTiMiSE) Trial: Rationale for its Methodology and a Review of the Effectiveness of Switching Antipsychotics. Schizophr Bull (2015) 41 (3): 549-558 first published online March 18, 2015 doi:10.1093/schbul/sbv019 [Abstract]