Atypical Antipsychotics


 

Amisulpride, Aripiprazole, Asenapine, Cariprazine, Lurasidone, Paliperidone, Olanzapine, Quetiapine, Risperidone

[For Clozapine – see separate monograph]

  Issues for Surgery


Risk of withdrawal if omitted (see Further Information).

Risk of relapse of schizophrenia or bipolar disorder if omitted.

Risk of Intraoperative Floppy Iris Syndrome (IFIS) in patients undergoing cataract surgery when paliperidone or risperidone continued (see Further Information).


  Advice in the Perioperative period


Elective and Emergency Surgery 

Continue.

For patients taking olanzapine who may decide to quit smoking during the perioperative period see Further Information.

Patients taking Paliperidone or Risperidone and Undergoing Cataract Surgery 
Ensure the Ophthalmologist / Cataract Surgeon is aware the patient is taking paliperidone or risperidone, which has alpha-adrenoceptor blocker activity1, 2, 3, 4 (see Further Information).

Post-operative Advice 

If a long Nil by Mouth (NBM) period is anticipated, or if there are concerns regarding enteral absorption, advice on alternative preparations / routes should be sought from a Psychiatrist.

Patients taking Lurasidone
If treatment with lurasidone (at doses >111mg) is interrupted for >3 days – consult product literature for advice on restarting5, 6.

Patients receiving depot antipsychotic preparations
If a patient’s usual depot antipsychotic intramuscular injection is due whilst an inpatient ensure correct product is prescribed, it is administered by a healthcare professional who is aware of the correct injection technique (including use of z-track technique) and rotate injection site6.


  Interaction(s) with Common Anaesthetic Agents


Central Nervous System (CNS) Depression (also see under Interaction(s) with other Common Medicines used in the Perioperative Period)

Atypical antipsychotics have CNS depressant effects which may be additive with other medicines that also have CNS depressant effects such as1, 2, 6, 7, 8, 9, 10, 11:-

  • benzodiazepines
  • inhalational anaesthetics and intravenous anaesthetics
  • local anaesthetics
  • opioids

(Consult British National Formulary for available drugs in each class)

Hypotension

With the exception of amisulpride, atypical antipsychotics can increase the risk of hypotension when used concomitantly with inhalational and intravenous anaesthetics6.


  Interaction(s) with other Common Medicines used in the Perioperative Period


CNS Depression (also see under Interaction(s) with Common Anaesthetic Agents for information on opioids)

Atypical antipsychotics have CNS depressant effects which may be additive with antiemetics that also have CNS depressant effects such as cyclizine, droperidol and prochlorperazine, 1, 2, 6, 7, 8, 9, 10, 11.

Hypotension

With the exception of amisulpride, atypical antipsychotics can increase the risk of hypotension when used concomitantly with droperidol and prochlorperazine6.

Hypokalaemia

Dexamethasone and hydrocortisone may cause hypokalaemia (potentially increasing the risk of torsades de pointes) with amisulpride, paliperidone or risperidone – use with caution6, 7, 12. If hypokalaemia occurs, corrective action should be taken and QT-interval monitored.

QT-Interval Prolongation

Co-administration of atypical antipsychotics, particularly amisulpride, paliperidone or risperidone, with medicines known to prolong the QT-interval must be based on a careful assessment of the potential risks and benefits for each patient since the risk of torsade de pointes may increase1, 2, 3, 4, 6, 7, 12.

Medicines that may be used in the perioperative period that are known to prolong the QT-interval include6, 12: -

  • ciprofloxacin*
  • clarithromycin*
  • domperidone - avoid
  • droperidol – avoid for amisulpride and paliperidone, for risperidone*
  • erythromycin – particularly intravenous*
  • granisetron - avoid for amisulpiride and paliperidone if risk factors present, for risperidone*
  • haloperidol - avoid
  • loperamide*
  • ondansetron – avoid for amisulpiride and paliperidone, for risperidone*
  • prochlorperazine*

*monitor ECG with concurrent use if risk factors for QT-interval prolongation also present (increasing age, female sex, cardiac disease, and some metabolic disturbances e.g. hypokalaemia)

Antimicrobials (see also QT-Interval Prolongation above)

Macrolides
Clarithromycin is predicted to increase the exposure to aripiprazole, cariprazine, lurasidone, quetiapine and risperidone through inhibition of CYP3A43, 4, 5, 6, 8, 12, 13, 14.

Ciprofloxacin
Ciprofloxacin is predicted to increase the exposure to olanzapine6, 10, 11.

Myelosuppression
Concomitant use of atypical antipsychotics with the following can increase the risk of myelosuppression6:-

  • co-trimoxazole
  • linezolid
  • trimethoprim

Whilst single surgical prophylactic doses should not pose a problem, monitor for side effects and consider reducing atypical antipsychotic dose if a prolonged course of clarithromycin or ciprofloxacin is required and monitor full blood count if a prolonged course of myelosuppressive medication is required.


  Further Information


Withdrawal

Abrupt withdrawal of antipsychotics may result in symptoms including sweating, insomnia, tremor, anxiety, nausea and vomiting7, 10.

Smoking Cessation

Tobacco is known to induce CYP1A2 resulting in reduced olanzapine plasma concentrations in smokers; this is thought to have limited clinical consequences6, 10. If a patient taking olanzapine decides to quit smoking during the perioperative period, they should be advised to report any increase in side effects to the prescriber as dosage adjustments may be necessary. Smoking status is not expected to affect the metabolism of the other atypical antipsychotics covered in this monograph1, 2, 3, 4, 5, 7, 8, 9, 13, 14.

Venous Thromboembolism (VTE)

Cases of VTE have been reported with antipsychotic drugs, although a causal relationship has not been established10. Patients with schizophrenia often have acquired risk factors for VTE; identify any risk factors and consider if thromboprophylaxis is indicated post-operatively1, 2, 3, 4, 5, 10, 13, 14.

Intraoperative Floppy Iris Syndrome (IFIS)

IFIS has been observed during cataract surgery in some patients on or previously treated with tamsulosin. Isolated reports have also been received with other alpha-adrenoceptor blockers and the possibility of a class effect cannot be excluded. As IFIS may lead to increased procedural complications during the cataract operation current or past use of medications with alpha-adrenoceptor blocking activity, including paliperidone and risperidone, should be made known to the ophthalmic surgeon in advance of surgery1, 2, 3, 4.

 

  References


  1. Summary of Product Characteristics – Invega® (paliperidone) 3mg prolonged-release tablets. Janssen-Cilag Ltd. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text September 2018]
  2. Summary of Product Characteristics – TREVICTA® (paliperidone palmitate) 175mg prolonged release suspension for injection. Janssen-Cilag Ltd. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text September 2018]
  3. Summary of Product Characteristics – Risperdal® (risperidone) 0.5mg Film-Coated Tablets. Janssen-Cilag Ltd. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text September 2018]
  4. Summary of Product Characteristics – RISPERDAL CONSTA® (risperidone) 25 mg powder and solvent for prolonged-release suspension for injection. Janssen-Cilag Ltd. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text September 2018]
  5. Summary of Product Characteristics – Latuda® (lurasidone) 18.5mg film-coated tablets. Sunovion Pharmaceuticals Europe Ltd. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text December 2018]
  6. Joint Formulary Committee. British National Formulary (online) London: BMJ Group and Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 20th August 2019]
  7. Summary of Product Characteristics – Amisulpride 100mg Tablets. Mylan. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text February 2018]
  8. Summary of Product Characteristics – Abilify® (aripiprazole) 10mg Tablets. Otsuka Pharmaceuticals (UK) Ltd. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text April 2019]
  9. Summary of Product Characteristics – Reagila® (asenapine) 10mg sublingual tablets. Recordati Pharmaceuticals Limited. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text July 2017]
  10. Summary of Product Characteristics – Olanzapine 10mg Film-coated Tablets. Accord Healthcare Limited. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text September 2017]
  11. Summary of Product Characteristics – ZYPADHERA® (olanzapine pamoate monohydrate) 210 mg powder and solvent for prolonged release suspension for injection. Eli Lilly and Company Limited. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text November 2018]
  12. Baxter K, Preston CL (eds), Stockley’s Drug Interactions (online) London: Pharmaceutical Press. http://www.medicinescomplete.com [Accessed on 20th August 2019]
  13. Summary of Product Characteristics – SEROQUEL® (quetiapine) 100 mg film-coated tablets. AstraZeneca UK Limited. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text October 2018]
  14. Summary of Product Characteristics – Sycrest® (cariprazine hydrochloride) 1.5mg hard capsules. Lundbeck Limited. Accessed via www.medicines.org.uk 20/08/2019 [date of revision of the text February 2018]