Alternatives to Benperidol: Newer, Safer Treatment Options

Benperidol was one of the first antipsychotics introduced for the treatment of schizophrenia and other psychotic disorders. However, its use today is very limited due to intolerable side effects and safety issues. Fortunately, there are many newer antipsychotic medications now available that offer improved efficacy and tolerability compared to older drugs like benperidol.

Atypical antipsychotics were introduced in the late 1980s and differ from typical antipsychotics like benperidol in that they produce fewer extrapyramidal side effects. This is because they have a lower affinity for dopamine D2 receptors and also interact with serotonin 5-HT2A receptors. Examples of atypical antipsychotics include risperidone, olanzapine, quetiapine, and clozapine.


Clozapine was the first atypical antipsychotic introduced and remains the most effective medication for treatment-resistant schizophrenia. However, it can cause significant sedation, weight gain, and hypotension, so has restrictions around its use. Risperidone and paliperidone have a lower likelihood of these side effects but may still produce movement disorders at higher doses due to moderate D2 antagonism.

Olanzapine and quetiapine

Olanzapine and quetiapine have weaker D2 receptor antagonism but prominent antihistamine effects, resulting in higher risks of weight gain, sedation and diabetes. Lower doses and avoiding use in at-risk patients can help reduce side effects. Quetiapine may have lower propensity for movement disorders and weight gain at standard doses, but also shows slightly lower efficacy in some studies.

Aripiprazole, lurasidone, and brexpiprazole

Newer antipsychotics like aripiprazole, lurasidone, and brexpiprazole are more selective targeting D2 and 5-HT1A receptors. They have more favorable metabolic and motor side effect profiles, but may be less effective for some patients, especially in more severe, treatment-resistant psychosis. Thioridazine and iloperidone also show lower risk of weight gain and sedation, but can still cause extrapyramidal side effects and QT prolongation in some cases.

In summary, there are many potential alternatives to benperidol available today with improved safety and tolerability. However, all antipsychotics have the potential for side effects, so choice of medication should be individualized based on patient characteristics such as symptom severity, medical comorbidities, lifestyle factors, and personal preferences around side effect risk. Close monitoring and management of side effects remain imperative with any antipsychotic to maximize long term treatment and health outcomes. While benperidol was a milestone in psychiatry, newer options offer safer and more effective pharmacotherapy for patients with schizophrenia and other psychoses today.

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: