Benperidol vs Clozapine Side Effects

Extrapyramidal side effects

Benperidol

High risk of extrapyramidal side effects due to potent D2 antagonism. Can cause dystonia, akathisia, parkinsonism, and tardive dyskinesia, especially at high doses.

Clozapine

Low risk of extrapyramidal side effects due to weaker D2 antagonism and additional 5-HT2A antagonism. Rarely causes movement disorders even at high doses.

Sedation and drowsiness

Benperidol

Moderate sedation and drowsiness due to antihistamine and anticholinergic effects. Risk is dose-dependent and usually highest at start of treatment or dose increases.

Clozapine

Significant sedation and drowsiness, especially at high doses. Due to strong H1 antihistamine effects. Usually most pronounced during titration period but can persist long-term. Requires slow dose titration.

Orthostatic hypotension

Benperidol

Can cause moderate drop in blood pressure upon standing due to alpha-adrenergic blockade. Usually transient but can lead to dizziness, fainting and falls. Blood pressure monitoring recommended.

Clozapine

High risk of orthostatic hypotension due to potent alpha-adrenergic antagonism. Can cause persistent hypotension throughout treatment. Frequent blood pressure monitoring required, especially during titration. Hospitalization often needed for initial dose titration.

Weight gain

Benperidol

Can cause moderate weight gain, especially long term. Due to effects on serotonin, histamine and dopamine receptors. Weight gain may be dose-dependent.

Clozapine

Significant weight gain occurs in most patients. Due to strong 5-HT2C inverse agonism and H1 antihistamine effects. Weight gain can continue even with long term treatment and stable dosing. Strict diet and exercise often have limited effect. Weight gain contributes to increased morbidity and mortality.

Anticholinergic effects

Benperidol

Anticholinergic side effects such as dry mouth, constipation, blurred vision, and urinary retention. Due to muscarinic M1 antagonism. Higher risk in elderly or at high doses.

Clozapine

Rarely causes significant anticholinergic side effects. Weaker binding to muscarinic receptors compared to benperidol and most other typical antipsychotics. Reduces risk of confusion and cognitive impairment, especially in elderly.

In summary, clozapine has a lower risk of extrapyramidal, anticholinergic and orthostatic side effects compared to benperidol, but causes significant sedation, dizziness and weight gain due to its potent antihistamine effects. The choice of antipsychotic depends on weighing up an individual patient’s risk factors for different side effects and tailoring treatment accordingly. Close monitoring and management of side effects is needed with both agents.


There are various forms of drugs available, such as tablets or liquids, and each may have a separate patient information leaflet (PIL) for different doses. It is important to refer to the PIL for the specific form and dose of the drug that you have been prescribed.

You can search for further information and PILs on websites such as:

  • The British National Formulary (BNF)
  • Electronic medicines compendium (emc)
  • The National Library of Medicine's DailyMed
  • The Food and Drug Administration (FDA) 
  • Different drug forms like tablets or liquids have specific patient information leaflets (PIL) for various doses. Refer to the PIL for your prescribed drug form and dose.

    Search for PILs on websites like:

    France

    • ANSM (Agence nationale de sécurité du médicament et des produits de santé): ansm.sante.fr

    Spain

    • AEMPS (Agencia Española de Medicamentos y Productos Sanitarios): aemps.gob.es

    Germany

    • BfArM (Bundesinstitut für Arzneimittel und Medizinprodukte): bfarm.de

    Italy

    For questions about your medication:

    • Consult your doctor, a healthcare professional, or a pharmacist

    France

    • Contact SOS Médecins: 3624
    • For mental health support, contact SOS Suicide: 01 45 39 40 00

    Belgium (French)

    Switzerland (French)

    • La Main Tendue: 143
    • Website: 143.ch

    Canada (French)

    • Centre de prévention du suicide du Québec: 1 866 APPELLE (1 866 277-3553)
    • Website: cpsquebec.ca

    Spain

    • Contact emergency number: 112
    • For mental health support, contact Teléfono de la Esperanza: 717 003 717

    Germany

    • Contact emergency number: 112
    • For mental health support, contact Telefonseelsorge: 0800 111 0 111 or 0800 111 0 222

    Italy

    • Contact emergency number: 112
    • For mental health support, contact Telefono Amico: 199 284 284

    Netherlands

    • Contact emergency number: 112
    • For mental health support, contact 113 Zelfmoordpreventie: 0800 0113

    Portugal

    • Contact emergency number: 112
    • For mental health support, contact Sos Voz Amiga: 21 354 45 45, 91 280 26 69, or 96 352 46 60

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