Techniques for switching antipsychotics

Converting patients from one antipsychotic to another requires great care in order to ensure that they do not develop withdrawal symptoms, rebound or breakthrough psychosis, or aggravation of side effects

Generally, as shown in Figure 9.1, this means not precipitously discontinuing the first antipsychotic, therefore not allowing a true washout where subtherapeutic dosing gaps may occur between the administration of the two antipsychotics

This approach was never utilized in this case

When switching from one antipsychotic to another, it is frequently prudent to “cross-titrate”; that is, to lower the dose of the first drug while building up the dose of the other in equal proportions or rations over a few days to a few weeks (Figure 9.2)

This leads to transient administration of two drugs (polypharmacy) but is justified in order to reduce side effects and the risk of rebound symptoms, and to accelerate the successful transition to the second drug

This approach was utilized initially for the first three monotherapies in this case

When switching from one atypical antipsychotic to another, the patient may improve in the middle of cross-titration

Polypharmacy results if cross-titration is stopped at this point and the patient continues on both drugs indefinitely (Figure 9.3)

It is generally better to complete the cross-titration ending with a solid monotherapy approach. This allows for the discontinuation of the first antipsychotic and use of an adequate monotherapy trial of the second antipsychotic before trying long-term polypharmacy

One method for switching from one antipsychotic to another is to maintain the full dose of the initial failing antipsychotic agent until the second (new) antipsychotic agent is at its therapeutic dose

This switching method may be best for patients who are switching due to lack of adequate control of symptoms on their initial antipsychotic rather than for those who are switching due to intolerability, as the temporary use of two fully dosed antipsychotic agents concomitantly may cause more side effects

This approach was utilized later in this case when symptom control was minimal and even more breakthrough psychotic symptoms were feared

Figure 9.1. How not to switch antipsychotics.

Figure 9.2. Switching from one antipsychotic to another.

Figure 9.3. Getting caught in cross-titration.

What are usual doses of the atypical antipsychotics in schizophrenia?

Risperidone (Risperdal)

1–8 mg/d approved dosing

Usual dosing 4–6 mg/d

Super-dosing up to 12 mg/d

Olanzapine (Zyprexa)

5–10 mg/d

Usual dosing 15–20 mg/d

Super-dosing up to 40+ mg/d

Quetiapine (Seroquel-XR)

50–800 mg/d

Usual dosing 400–800 mg/d

Super-dosing up to 1500 mg/d

Ziprasidone (Geodon)

40–160 mg/d

Usual dosing 120–180 mg/d

Super-dosing up to 320 mg/d

Aripiprazole (Abilify)

2–30 mg/d

Usual dosing 15–30 mg/d

Super-dosing 45–60 mg/d

Paliperidone (Invega)

3–12 mg/d

Usual dosing 6–12 mg/d

Super-dosing up to 18 mg/d

Asenapine (Saphris)

5–20 mg/d

Usual dosing 10–20 mg/d

Super-dosing up to 30+ mg/d

Iloperidone (Fanapt)

2–24 mg/d

Usual dose 12–24 mg/d

Super-dosing is poorly studied/reported

Lurasidone (Latuda)

40–120 mg/d

Usual dosing 40–80 mg/d

Super-dosing up to 240 mg/d in ongoing studies

Brexpiprazole (Rexult)

2–4 mg/d

Cariprazine (Vraylan)

1.5–6 mg/d

Posttest self-assessment question and answer

Which of the following is true regarding QTc prolongation and antipsychotics?

A. Thioridazine (Mellaril) has a warning

B. Ziprasidone (Geodon) has a warning

C. Iloperidone (Fanapt) has a warning

D. EKG monitoring should occur in cardiac risk patients, or those on antipsychotic polypharmacy, or those on super-dosed monotherapies

E. Only the antipsychotics in A, B, C should have EKG monitoring

F. All antipsychotics should have EKG monitoring

G. B and C

H. A, B, C, and D

Answer: H

Agents in A, B, C have QTc prolongation warnings from 9–90 ms and are true. D is accurate in that, clinically, this approach is warranted to prevent sudden cardiac death in at-risk patients. Therefore, A–D are correct, making H the best answer. G is false in that it leaves out thioridazine’s 90 ms QTc warning that was levied some 40+ years after its approval. E and F are false in that more than A–C should be monitored, but that all patients treated with any antipsychotic should have an EKG every time is too stringent.

References

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Patient file

The Case:

It worked this time, but with a hitch

The Question:

Can clozapine (Clozaril) work for patients without side effects?

The Dilemma:

Using this medication in treatment-resistant schizophrenia frequently requires measures to make the drug better tolerated. Sialorrhea is often a stumbling block