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

Evidence-based guidelines for treating bipolar disorder

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

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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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Psychotropic medication in pregnancy: new evidence may help achieve a safe balance

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Joanne Wallace considers a recent health technology assessment on the risks and benefits of psychotropic medication in pregnancy, which supports previous associations between valproate and adverse child outcomes.

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What do you want from your psychiatric medication?

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John Baker presents a systematic review of preferences for medication-associated outcomes in mental disorders, which concludes that we just don’t know what value mental health service users place on the different outcomes that come from taking psychiatric medication.

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Commonly prescribed psychiatric drugs: do they work?

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John Baker summarises a review of commonly prescribed medication that covers seven psychiatric drugs, including antidepressants, antipsychotics, benzodiazepines, amphetamines, methylphenidate and cholinesterase inhibitors.

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Integrated treatment for first episode psychosis: media hype versus reality

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Alex Langford reflects on the media hype surrounding a new RCT of the NAVIGATE intervention; a comprehensive, multidisciplinary, team-based treatment approach for first episode psychosis.

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Can early improvement be used to predict later response to antipsychotics in schizophrenia?

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Tracey Roberts summarises a recent diagnostic test review, which suggests that early improvement can act as a predictor of later response to antipsychotics in schizophrenia.

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What impact are psychotropic drugs having on our physical health?

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John Baker summarises the findings of a recent review of people with schizophrenia, bipolar disorder and depression. The study looks at the adverse effects on physical health of psychotropic drugs (antipsychotics, antidepressants and mood stabilisers).

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Psychotropic medications: scale and patterns of prescribing to people with learning disabilities

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In this blog, John Northfield considers a study of rates and patterns of prescribing psychotropic medications by GPs to people with learning disabilities and/or autism.

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The antipsychotic drugs don’t work for anorexia nervosa

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Helen Bould appraises a recent meta-analysis of second-generation antipsychotics for anorexia nervosa, which finds that the drugs don’t lead to weight gain or improve eating disorder symptoms. So why are antipsychotics being used in this group of patients?

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