Augmentation of Clozapine with Lurasidone in Resistant Schizophrenia in Real Practice
Treatment-resistant schizophrenia remains a clinical and pharmacological challenge. Clozapine remains the gold standard in these cases. Unfortunately, a significant portion of patients respond only partially to it. The solution is often an augmentation strategy with another atypical antipsychotic. According to current findings, adjunctive therapy with lurasidone appears promising — two recently published studies have brought interesting data.
Italian Observational Study
Lurasidone is a second-generation antipsychotic that, in addition to its antagonistic effect on dopamine D2 receptors, also acts as a partial agonist on the serotonin 5-HT1A receptor and an antagonist on the 5-HT2A and 5-HT7 receptors. According to the authors of the pilot study, these properties may explain its procognitive effect documented by several published preclinical researches.
In this work by authors from Pavia, Italy, usual therapy (i.e., clozapine + another atypical antipsychotic) was compared with a strategy involving the augmentation of clozapine with lurasidone in patients with treatment-resistant schizophrenia.
Methods and Course
This was an observational study involving 20 patients diagnosed with treatment-resistant schizophrenia according to DSM-5 criteria and psychopharmacological history. The choice of therapy was left independently to the treating physicians of each patient. Ten participants received lurasidone augmentation of clozapine, while the remaining ten received usual therapy. PANSS (Positive and Negative Syndrome Scale) and BPRS (Brief Psychiatric Rating Scale) scales were used to assess general psychopathology at study entry and during monitoring. Additionally, the UKU scale (named after the Udvalg for Kliniske Undersøgelser Scandinavian Psychopharmacology Society working group) was used to assess side effects.
Results
All patients in the group receiving adjunctive lurasidone achieved clinically significant alleviation of both positive and negative symptoms, with a good tolerance profile and no significant side effects reported. Lurasidone did not exhibit any adverse effects on metabolic parameters or EKG, including the QTc interval. Improvements in the scales assessing psychopathology appeared bigger in patients who received lurasidone compared to those treated as usual, particularly in cognitive domains.
Polish Retrospective Study
The effectiveness of clozapine augmentation with lurasidone in patients with treatment-resistant schizophrenia in real practice was also evaluated in a retrospective study conducted at a university hospital in Krakow, Poland.
Methods and Course
From the medical records of 916 patients with this diagnosis treated between 2018 and 2022, 16 individuals treated with the combination of clozapine and lurasidone were identified, forming the study sample. These were patients aged 27–45 years (median 37.5 years), 7 women and 9 men, with a median total schizophrenia treatment duration of 12.5 years (7–16 years) and a median number of previous ineffective pharmacotherapies of 5 (3.6–6.75).
The authors compared CGI-S (Clinical Global Impression – Severity) scores achieved before treatment and 1 and 2 months after its initiation, and based on their improvement, they assessed the response to treatment. They evaluated CGI-S scores after 3 months from the start and then every 3 months but assessed the score differences for the shortest monitoring period common to all patients, which was 2 months. They also analyzed changes in CGI-S scores during the first 6 months of observation. Additionally, CGI-I (Clinical Global Impression – Improvement) scores were determined to assess the response to treatment between the first and last monitoring points.
Results
The majority of patients (87.5%, i.e., 14 out of 16) responded to lurasidone augmentation of clozapine (achieving a CGI-I score of 1–2). Therapeutic effects were observed within 3–12 weeks of treatment (median 6 weeks). After the first month, a decrease in CGI-S scores, alleviation of positive symptoms (10 patients), depressive and anxiety symptoms (alleviation of anxiety in 7 patients), and improvement in psychosocial functioning (in 9 patients; 4 returned to work) were observed. Affective symptoms improved in 7 individuals and sexual dysfunction in 2. For 2 patients who started lurasidone instead of haloperidol or risperidone, a beneficial effect on body weight (stabilization or reduction) was noted. In 2 patients switched from risperidone and amisulpride to lurasidone, prolactin levels normalized, and in 1 patient switched from risperidone to lurasidone, blood sugar levels stabilized. According to the authors, lurasidone augmentation of clozapine can lead to improvements in a wide range of schizophrenia symptoms.
Three patients discontinued treatment; two due to side effects (hyperprolactinemia with galactorrhea or extrapyramidal symptoms), and one patient stopped treatment without prior consultation with a doctor.
Conclusion
Both of the studies described above showed that augmentation of clozapine with lurasidone can offer significant benefits for patients with treatment-resistant schizophrenia. Results from prospective clinical studies with more participants will be essential for a definitive confirmation of the effect of lurasidone.
(esr)
Sources:
1. Arienti V., Civardi S. C., Besana F. et al. Lurasidone augmentation to clozapine in treatment resistant schizophrenia: a pilot study. Eur Psychiatry 2023; 66 (S1): S306–S307, doi: 10.1192/j.eurpsy.2023.684.
2. Siwek M., Chrobak A. A., Gorostowicz A. et al. Lurasidone augmentation of clozapine in schizophrenia – retrospective chart review. Brain Sci 2023 Mar; 13 (3): 445, doi: 10.3390/brainsci13030445.
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