antipsychotics

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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]

Acknowledgement

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

Our antipsychotics Blogs

Predicting treatment-resistant psychosis using routine clinical measures

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Lorna Staines summarises a recent study on predicting treatment-resistant psychosis, which suggests that future risk prediction efforts should seek to consider routinely collected data.

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When we help people with PTSD who are suicidal, do we give them the care they need?

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A group of MSc students at UCL summarise a study exploring the secondary mental health care treatment patients with comorbid PTSD and suicidality receive in London.

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Optimal antipsychotic dosing in first-episode schizophrenia: how much is too little, too much, or just right?

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Joe Pierre reports on the first published study exploring the relationship between antipsychotic dose and risk of relapse in first episode schizophrenia, which suggests that standard antipsychotic dosing is best for relapse prevention.

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Uncertainties about stopping or reducing antipsychotics as shared by families

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Amelia Talbot considers a qualitative study that explores family members’ perspectives on reducing or discontinuing antipsychotic medication.

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Do different groups of people with schizophrenia respond differently to different antipsychotics?

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Murtada Alsaif considers a systematic review and meta-analysis published in the Lancet Psychiatry exploring the response of different subgroups of patients with schizophrenia to different antipsychotic drugs.

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To stay on antipsychotics or not to stay on antipsychotics? A longstanding question with an update

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Joe Pierre considers a recent network meta-analysis on continuing, reducing, switching, or stopping antipsychotics in individuals with schizophrenia-spectrum disorders who are clinically stable.

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Youth mental health interventions: umbrella review presents efficacy and acceptability data

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In his debut blog, Nick Meader tackles a huge umbrella review of youth mental health interventions, which presents the efficacy and acceptability of 72 different approaches to help children and young people.

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Choosing between antipsychotics to reduce the risk of breast cancer in women with schizophrenia

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Peter Knapp and Suzy Ker review a recent study from Finland, which suggests that women with schizophrenia who take prolactin-increasing antipsychotics for at least five years, have an increased risk of developing breast cancer.

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Long-acting injectable antipsychotics: more effective than oral medications at preventing hospitalisation and relapse in schizophrenia according to new review

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Joseph Pierre appraises a recent meta-analysis on long-acting injectable antipsychotics compared to oral antipsychotic medication for the maintenance treatment of schizophrenia.

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Living in anxious times? The rise of anxiety disorders in the UK

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Alice Grishkov and Derek Tracy explore a recent paper, which finds that generalised anxiety disorder is on the rise in the UK, especially in young women.

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