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.


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]


Written by: Josephine Neale
Reviewed by: Alex LangfordTracey Roberts
Last updated: Sep 2015
Review due: Sep 2016

Our antipsychotics Blogs

Depot antipsychotics: If you pay me, you can keep injecting me


John Baker looks at the 2-year follow-up results of a cluster RCT on the effectiveness of financial incentives to improve adherence to maintenance treatment with depot antipsychotics.

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The side-effects of antipsychotics: let’s systematically assess, discuss and act! #NPNR2016


A live blog published at the 22nd International Network for Psychiatric Nursing Research conference in Nottingham.

Written by John Baker, Lucy Brazener, Wendy Cross, Vanessa Garrity, Andrew Grundy, Cher Hallett, Ben Hannigan, Elaine Hanzak and Alan Simpson.

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Schizophrenia, antipsychotics and quality of life: measuring the important things


Samei Huda mulls over a recent RCT on the effects of older and newer antipsychotics on quality of life in schizophrenia. The study finds a different result to the 10-year old CUTLASS trial; namely that second generation antipsychotics may be superior to first generation antipsychotics in terms of improving quality of life for people with schizophrenia.

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Adding antidepressants to antipsychotics in schizophrenia: do they work, for what, and are they safe?


Alex Langford explores the emerging findings from a recent meta-analysis looking at the efficacy and safety of antidepressants added to antipsychotics for people with schizophrenia and schizophrenia-like psychosis.

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Evidence-based guidelines for treating bipolar disorder


Joseph Hayes summarises the recent British Association for Psychopharmacology guidelines for the treatment of bipolar disorder, and compares their recommendations with those found in the NICE bipolar disorder guidance from 2014.

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Trends in antipsychotic prescribing in autism


Angela Hassiotis and James Dove summarise a recent meta-analysis of antipsychotic prescribing and use trends in US youth with autism spectrum disorder and/or learning disabilities.

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Antipsychotic overprescribing in people with learning disabilities #UCLJournalClub


Tayla McCloud from the #UCLJournalClub presents the findings of a cohort study showing that antipsychotics are being over-prescribed in people with learning disabilities.

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Cochrane find no evidence for as required PRN medication for mental health inpatients


John Baker summarises an updated Cochrane review on ‘as required’ PRN medication regimens for seriously mentally ill people in hospital, which finds no randomised controlled trials that support this widely used intervention.

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