29th January 2024

Second-Generation Antipsychotics (SGAs)

Similarly to FGAs, SGAs have their mode of action on D2 receptor antagonists as well as 5-HT2A (Serotonin) receptors. SGAs have a higher affinity for 5-HT2A (Serotonin) receptors than D2 receptors, thereby exhibiting fewer extrapyramidal side effects. However, compared with FGAs, SGAs’ have a higher risk of metabolic side effects leading to metabolic syndrome. This can lead to increased risk of HTN, diabetes and cardiovascular complications.

MRCP Part 1 - Pyramid illustrating factors contributing to Metabolic syndrome

Source: Adapted from: National Health Service. Metabolic syndrome [internet]. 2019 [cited 2022 July 15]. Available from: https://www.nhs.uk/conditions/metabolic-syndrome/


Individual risks of Antipsychotics
First generation antipsychotics	Second generation antipsychotics
Phenothiazine: e.g. chlorpromazine, promazine, trifluoperazine (drowsiness, dry mouth ++) Butyrophenones: e.g. haloperidol (Tardive Dyskinesia +) Thioxanthenes: Flupenthixol, zuclopenthixol, clopenthixol Higher rates of Extrapyramidal side effects	Olanzapine (Weight gain ++) Risperidone (hyperprolactinaemia ++) Paliperidone (hyperprolactinaemia ++) Aripiprazole (low doses can be used to lower prolactin levels) Quetiapine (weight gain ++) Amisulpride (hyperprolactinaemia ++) Clozapine (agranulocytosis ++) High risk of metabolic syndrome

Individual risks of Antipsychotics

First generation antipsychotics

Second generation antipsychotics

Phenothiazine:

e.g. chlorpromazine, promazine, trifluoperazine (drowsiness, dry mouth ++)

Butyrophenones:

e.g. haloperidol (Tardive Dyskinesia +)

Thioxanthenes:

Flupenthixol, zuclopenthixol, clopenthixol

Higher rates of Extrapyramidal side effects

Olanzapine (Weight gain ++)

Risperidone (hyperprolactinaemia ++)

Paliperidone (hyperprolactinaemia ++)

Aripiprazole (low doses can be used to lower prolactin levels)

Quetiapine (weight gain ++)

Amisulpride (hyperprolactinaemia ++)

Clozapine (agranulocytosis ++)

High risk of metabolic syndrome

Source: Adapted from: National Institute for Health and Care Excellence. Psychoses and related disorders [internet]. [cited 2022 July 15]. Available from: https://bnf.nice.org.uk/treatment-summaries/psychoses-and-related-disorders/

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