Management of psychosis with Long QT


Use of anti-psychotic medications in Long QT

General information:

Anti-psychotics that prolong QT

                                                               i.      Typical anti-psychotics

1.       Low-potency are associated with higher risk of QT prolongation

a.       Especially at higher doses – e.g. 2 g of Chlorpromazine (a phenothiazine)

2.       High-potency anti-psychotics

a.       Fluphenazine (a phenothiazine)

b.       Pimozide (Dopamine blocker) – decreases BP.

                                                             ii.      Atypical anti-psychotics

1.       Ziprasidone

2.       Haloperidol

3.       Quetiapine

4.       Risperidone

5.       Olanzapine

6.       Thioridazine

7.       Sertindole

8.       Iloperidone

b.       Anti-psychotics that do not prolong QT

1.       Lurasidone (beware, not well tested in female)

2.       Clozapine

3.       Aripiprazole (Abilify)


3 categories:

2)    1. At risk for long QT:

a.       Risk factors:

                                                               i.      Hypokalemia, Hypocalcemia, Hypomagnesemia

                                                             ii.      Renal dysfunction, diabetes, hypothyroidism, malnutrition and obesity – may lead to electrolyte imbalance and therefore, may cause prolongation of QT.

b.       Options for management:

                                                               i.      Check electrolytes and for presence of risk factors

                                                             ii.      Telemetry

                                                           iii.      Baseline EKG for QTc

                                                           iv.      Avoid psychotic polypharmacy

                                                             v.      Avoid combining with other meds that prolong QTc

                                                           vi.      Initial meds

1.       Quetiapine or Olanzapine

2.       Aripiprazole

3.       Risperidone

4.       Haloperiodol – only IM. Low or medium-dose (do not use IV – higher risk of QT prolongation and TdP)

                                                          vii.      Atypical anti-psychotics – watch BP.

                                                        viii.      Discontinue Pimozide if used before.

                                                            ix.      If baseline QTc is normal, the following may be used:

1.       Fluphenazine

2.       Low dose chlorpromazine

3.       Ziprasidone (avoid if there is CVD, prior AMI, CMP, electrolyte abnormality or HT).


3)      2. Long QT < 500 ms:

a.       Aripiprazone

b.       Olanzapine

c.       Risperidone

d.       Quetiapine

                                                               i.      All 4 of the above cause decrease in BP. Therefore, watch BP.

e.       Asenapine

f.        Lorazepam (2 mg) or Alprazolam (Zanax)

g.       Others: Ziprasidone, Valproate (check LFT), trazodone.


4)      3. Long QT > 500 ms:

a.       If QTc > 500 ms during treatment – reconsider that medication

b.       Rule out other risk factors – electrolyte abnormalities, drug interactions

c.       May use Aripiprazole, Valproate, Trazodone and Benzodiazepines

d.       Oral Loxapine (first generation, typical anti-psychotic) inhalable form.

e.       ? Perospirone (Japan)

f.        Discuss in interdisciplinary conferences

g.       Discuss in ethics committee – risk of self harm vs. QT prolongation/TdP.

h.       Discuss non-pharmacologic treatments: Family member stay nearby to calm patient, Music therapy.

Reference: Ries R, Sayadipour A. Management of psychosis andagitation in medical-surgical patients who have or are at risk for prolonged QTinterval. J Psychiatr Practice 2014;20:338-344.


Andexxa - Recombinant Factor Xa - Antidote for Apixaban and Rivaroxaban

 Andexxa (Recombinant Factor Xa) - Adnexa net alfa: Received accelerated FDA approval in (?2018)

Mechanism of Action:

Andexanet Alfa - genetically modified variant of human factor Xa (alanine substituted for serine).

Acts by binding to Factor Xa inhibitors and neutralizes their anticoagulant effect.

This is useful to reverse the anticoagulant effect caused by Apixaban (Eliquis) and Rivaroxaban (Xarelto).

This is the second antidote approved by FDA for Factor Xa inhibitors:

First one, approved in 2015, was Idarucizumab (Praxbind) - for reversal of direct thrombin inhibitor - Dabigatran etexilate (Pradaxa).

Above information was taken from this JAMA review article: JAMA 2018;320(4):399-400.