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

Experience of psychotropic medication and decision-making

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Jennifer Rose Oulton reviews a qualitative study that explores the experiences of psychotropic medication use and decision-making for adults with learning disabilities and their carers.

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Antipsychotics versus CBT in first episode psychosis: some answers, more questions

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Joe Pierre summarises two recently published and widely reported RCTs, which suggest that antipsychotic medication might not offer an advantage over psychotherapy in broadly-defined first episode psychosis.

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Antipsychotics for schizophrenia: do they provide a longer, healthier life?

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Paul Heron from the Closing the Gap Network writes his debut blog about a 20‐year cohort study of physical morbidity and mortality in relationship to antipsychotic treatment in a huge group of people with schizophrenia in Finland.

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Risperidone and aripiprazole: genotype, metabolism and dosage

CYP2D6 genotyping before starting treatment might be valuable in clinical practice for individualising risperidone and aripiprazole treatment.

Dolly Sud writes her debut elf blog on a recent retrospective analysis, which compares dose changes of risperidone and aripiprazole with patients’ individual genotype.

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Antipsychotics and metabolic function in people with schizophrenia

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Peter Haddad and Sami Ouanes review a network meta-analysis of the impact of antipsychotic drugs on metabolic function in people with schizophrenia.

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The Trial: pharmacotherapy versus psychotherapy for schizophrenia – how do trials compare?

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Keith Laws looks at a systematic review of patient and study characteristics, which asks: are randomised controlled trials on pharmacotherapy and psychotherapy for positive symptoms of schizophrenia comparable?

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Pregnancy and bipolar disorder: international prescribing consensus?

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Dean Connolly looks at an international study which asks: Is there consensus across evidence-based guidelines for the psychotropic drug management of bipolar disorder during the perinatal period?

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Lifestyle training for schizophrenia: STEPWISE fails to make a difference

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Ben Janaway writes his debut elf blog on the STEPWISE RCT which is out today in the British Journal of Psychiatry: Structured lifestyle education for people with schizophrenia, schizoaffective disorder and first-episode psychosis.

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Preventing psychosis: no one intervention is better than the rest

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A group of UCL Mental Health Masters students summarise a recent network meta-analysis that highlights a lack of evidence about specific interventions for preventing psychosis.

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Behavioural and psychological symptoms of dementia: GPs’ perspective on management

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Marie Crabbe presents the findings of a mixed-methods systematic review, which looks at General Practitioners’ knowledge, attitudes and experiences of managing behavioural and psychological symptoms of dementia.

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