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

Low dose Amisulpride for very late onset schizophrenia-like psychosis: the ATLAS study

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Elwira Lubos summarises the recent ATLAS RCT of antipsychotic treatment for very late-onset schizophrenia-like psychosis, which provides evidence for the effectiveness of a very low dose of Amisulpride (100 mg).

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“Where I End And You Begin”: A personal commentary on Russo’s ‘Through the eyes of the observed’ #PsychDrugDebate

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Sarah Carr shares her own experiences of psychiatric medication and provides a critical reading of Jasna Russo’s new #PsychDrugDebate paper: ‘Through the eyes of the observed: re-directing the research on psychiatric drugs’.

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How should we redirect research on psychiatric drugs? #PsychDrugDebate

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Alison Faulkner dissects the new McPin Foundation Talking Point Paper by Jasna Russo entitled: Through the eyes of the observed: re-directing research on psychiatric drugs.

Follow #PsychDrugDebate today on Twitter for further discussion about this vital issue.

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Sexual function matters to people living with serious mental illness

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Rudiger Pittrof and Elana Covshoff from SHRINE (Sexual and Reproductive Health Rights, Inclusion and Empowerment) explore a recent review, which looks at the impact of severe mental disorders and psychotropic medications on sexual health and its implications for clinical management.

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Polypharmacy for major depression: is practice evidence-based?

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Jessica Bone reports on a recent cross-sectional study that looks at the clinical correlates of augmentation/combination treatment strategies in major depressive disorder.

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Understanding the genetics of antipsychotic treatment response

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Marcus Munafo looks at a Chinese genome-wide association study that claims to have identified some of the genes associated with response to antipsychotic treatment.

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Improving outcomes for people with first episode psychosis

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Elwira Lubos summarises a recent review of reviews looking at the evidence for improving outcomes in first-episode psychosis.

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Person-centred care for dementia: impact on quality of life, agitation and antipsychotic use

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Hilary Shepherd reports on a recent paper from the WHELD trial on the impact of person-centred care training and person-centred activities on quality of life, agitation, and antipsychotic use in people with dementia living in nursing homes.

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Antipsychotic effectiveness: the numbers don’t lie, check the scoreboard

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Students and Teachers from the King’s College London PNoMH Distance Learning MSc summarise a major new meta-analysis that brings together the last 60 years of placebo-controlled antipsychotic drug trials in acute schizophrenia.

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Improving health related quality of life for people with dementia in care homes

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Hilary Shepherd writes her debut blog on a new paper from the WHELD cluster RCT, which looks at the impact of antipsychotic review and psychosocial intervention on health-related quality of life in people with dementia living in care homes.

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