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

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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Antidepressants for depression in schizophrenia: when good-enough evidence is good enough

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Carmine Pariante is positive about a recent systematic review and meta-analysis of antidepressants for the treatment of depression in schizophrenia.

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Antipsychotic combinations for schizophrenia: safe and effective?

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Elena Marcus presents the findings of an updated Cochrane review on antipsychotic combinations for schizophrenia.

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#UnderstandingPsychosis?

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Sameer Jauhar and Paul Morrison consider the revised Understanding Psychosis and Schizophrenia report from the British Psychological Society Division of Clinical Psychology, which includes updated sections on definitions, aetiology and treatment.

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Antipsychotics for acute treatment of first episode schizophrenia

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Elwira Lubos writes her debut blog on a recent systematic review with pairwise and network meta-analyses, looking at antipsychotic drugs for the acute treatment of patients with first episode schizophrenia.

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Medication for mental health: Oral health impacts

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This review of the side effects of medications prescribed for the management of mental health highlights their potential impact on oral health. The commonest problems being xerostomia.

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Should people with schizophrenia be offered depot antipsychotics as first line treatment?

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Murtada Alsaif reports on a new nationwide Swedish cohort study that explores the real-world effectiveness of oral and depot antipsychotics for people with schizophrenia.

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Psychotropic medication: finding ways forward for adults with intellectual disabilities #RSMpsychotropics

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Rory Sheehan and Angela Hassiotis discuss how to optimise psychotropic medication for people with intellectual disabilities; the theme of their #RSMpsychotropics conference taking place in London today.

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Antidepressants for bipolar depression: weighing up the benefits and harms

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Murtada Alsaif considers a recent systematic review on the safety and efficacy of adjunctive second-generation antidepressant therapy with a mood stabiliser or an atypical antipsychotic in acute bipolar depression.

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Antipsychotics for delirium in palliative care: new RCT suggests non-drug alternatives are needed

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Samei Huda highlights a recent RCT of antipsychotics (risperidone and haloperidol) versus placebo for symptoms of delirium in palliative care, which suggests we need non-drug alternatives for this group of patients.

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