treatment-resistant schizophrenia

Q: 34 years old male with an established diagnosis of schizophrenia is admitted to ICU with exacerbation of his symptoms. Patient's meds have been recently changed by his outpatient physician due to probable treatment-resistant schizophrenia. Spouse reports that lately, the patient has increased his smoking habit due to stress at work. Which medicine probably has been prescribed? (select one)

A) Carbamazepine 

B) Amisulpride

C) Paliperidone

D) Clozapine 

E) Risperidone

Answer: D

This question aims to cover two objectives. 

First, The drug of choice for treatment-resistant schizophrenia is clozapine. This is the only drug approved so far by the FDA for this indication.

Second: Tobacco smoking decreases the level/effect of olanzapine due to stimulation of cytochrome P450 1A2 enzyme that is involved in the antipsychotics’ metabolism.

Carbamazepine (choice A) is not used for treatment-resistant schizophrenia, though it has the potential to reduce the levels of all antipsychotics.

Amisulpride is excreted by the kidney (choice B), and levels can be affected in patients with renal insufficiency.

Paliperidone (choice C) does not undergo first-pass metabolism, and levels are usually unaffected.

Risperidone (choice E) is metabolized by the cytochrome P450 2D6 enzyme. Its level can be elevated by co-treatment with fluoxetine and paroxetine, which are metabolized by the same enzyme system.

#psychiatry

#pharmacology

References:

1. Potkin SG, Kane JM, Correll CU, Lindenmayer JP, Agid O, Marder SR, Olfson M, Howes OD. The neurobiology of treatment-resistant schizophrenia: paths to antipsychotic resistance and a roadmap for future research. NPJ Schizophr. 2020 Jan 7;6(1):1. doi: 10.1038/s41537-019-0090-z. PMID: 31911624; PMCID: PMC6946650.

2. Kane JM, Agid O, Baldwin ML, Howes O, Lindenmayer JP, Marder S, Olfson M, Potkin SG, Correll CU. Clinical Guidance on the Identification and Management of Treatment-Resistant Schizophrenia. J Clin Psychiatry. 2019 Mar 5;80(2):18com12123. doi: 10.4088/JCP.18com12123. PMID: 30840788.

3. Ying J, Chew QH, McIntyre RS, Sim K. Treatment-Resistant Schizophrenia, Clozapine Resistance, Genetic Associations, and Implications for Precision Psychiatry: A Scoping Review. Genes (Basel). 2023 Mar 10;14(3):689. doi: 10.3390/genes14030689. PMID: 36980961; PMCID: PMC10048540.