Treatment resistance

Question 1

What is treatment resistance?

Answer 1

Inadequate response despite adequate treatment to two sequential trials of different antipsychotics

Lack of response for a correct treatment for a correct diagnosis

Question 2

What are some issues with assessing treatment resistance?

Answer 2

McCutcheon et al 2015
44% of patients have sub-therapeutic levels = they have no or partial adherence so they seam to be resistant but they are not

Base on guidelines def of “adequate” is different Howes et al., 2017

Question 3

Inadequate Response: TRRIP Consensus idea
Howes et al., 2017

Answer 3

At least moderate symptom severity
Persistent: most weeks
Frequent: at least 3 times/ day
Functional/ health impact
PANSS score of 4 or greater

Question 4

Adequate Trial: TRRIP Consensus idea
Howes et al., 2017

Answer 4

At least two different antipsychotic drugs
Each at BNF therapeutic dose
Each for at least 6 weeks
Evidence of adherence:
-check prescriptions, ask to see tablet boxes, check plasma levels
-in-patient treatment episodes, LAI

Question 5

Who and when is treatment resistant?

Answer 5

Common from first episode: some, but not much benefit from switching

The majority of TRS at FEP show little response to second drug

Some patients develop treatment resistance over course of illness

Question 6

What are the 3 steps for treatment resistance?

Answer 6

1. Assess reason for it (are they taking the drug? It the treatment correct? Are they comorbidities which interfere with treatment?)#
2. Discuss options with the patient + conference with other clinicians (engage patients to help with hopelessness)
3. Clozapine (superior to any other antipsychotic)
   [Contra-indications: Bone marrow disorders, uncontrolled epilepsy, severe renal/cardiac illness
   Relative contraindications: Ability to engage, Cardiometabolic illness (e.g. uncontrolled diabetes, uncontrolled HTN), Elderly/young]
4. Review and optimize (if they don’t respond to clozapine) [check blood plasma levels + smoking increases clozapine metabolism]
5. Augmentation [Lithium; Carbamazepine; Sodium valproate; SSRI antidepressant; Benzodiazepine; Lamotrigine; Glycine]

Question 7

What not to do with someone who appears to be treatment resistant?

Answer 7

1. Do not do nothing - treatment resistance is a suicide risk
2. Combine antipsychotics
3. Increase the dose of the antipsychotic