Early Markers in Resistant Schizophrenia: Effect of the First Antipsychotic Drug

Abstract

Background: Schizophrenia is a mental illness with a multifactorial etiology and clinical presentation. Treatment is mainly with antipsychotic drugs. Despite the increasing number of antipsychotic drugs, there has been no significant change in the percentage of resistant cases. These data gave us reason to look for a link between the effect of the first individually selected antipsychotic drug and the established resistance to therapy. Method: An assessment has been made of 105 patients with chronic schizophrenia with consecutive psychotic episodes. The choice of antipsychotic has been made on the basis of clinical features, history of efficacy of previously used neuroleptics, anthropometric features, as well as somatic comorbidities. Accidental use of benzodiazepines in anxiety conditions as well as correctors in indications for extrapyramidal problems have been reported. Assessment was made based on clinical observation as well as on changes in PANSS score. Results: Of the 105 observed patients, the effectiveness of the first antipsychotic effect was found in 46.7% of patients. Follow-up of patients for a period of 12 weeks revealed that 45 (42.8%) of them had resistant schizophrenia, while the remaining 60 (57.2%) achieved clinical remission and initial functional recovery. The effect of the first antipsychotic drug was established in 9 (20%) of the patients with resistant schizophrenia and in 40 (66.57%) of the patients in clinical remission. Conclusion: The evaluation of the first antipsychotic medication is significant for the prognosis of patients with schizophrenia. Its lack of effectiveness indicates a high probability of resistance and can be a good indicator of earlier change and a possible search for more “aggressive” measures to prevent future resistance and possible disability.

Treatment resistance in schizophrenia: a meta-analysis of prevalence and correlates

“…In the meta-regression analyses, there were significant associations between higher TRS prevalence, older age (0.0066, p = 0.0436), 7 , 25 - 31 , 33 - 38 , 40 , 42 - 47 , 49 - 51 , 53 , 55 , 56 , 58 - 61 , 65 - 68 , 70 higher percentage of clozapine users (0.0056, p = 0.0003), 25 , 30 , 31 , 33 , 34 , 38 , 39 , 41 , 43 , 45 , 46 , 50 , 54 , 56 , 59 - 61 , 64 - 68 lower Global Assessment of Functioning score (-0.0260, p = 0.0324), 45 , 55 , 60 , 61 and lower total TRRIP score (-0.0143, p = 0.0059), 7 , 8 , 16 , 25 - 71 as well as three specific TRRIP criteria: less fulfillment of current symptom severity threshold (-0.0641, p = 0.00462), 7 , 8 , 16 , 25 - 71 less fulfillment of minimum functional impairment (-0.0439, p = 0.0376), 7 , 8 , 16 , 25 - 71 and time course (-0.0634, p = 0.0326) 7 , 8 , 16 , 25 - 71 ( ).…”

“…Studies that only included patients with FES found a lower TRS prevalence (22%, 95%CI 18.4-25.8; n = 10,579) 16 , 25 , 27 , 38 , 39 , 62 , 64 , 66 , 69 than those that only included multi-episode patients (39.5%, 95%CI 32.2-57.0; n = 4,685) 8 , 29 , 31 , 34 , 36 , 40 , 43 , 49 , 70 (Q = 17.7, p < 0.0001).…”

“…The 50 independent studies 7 , 8 , 16 , 25 - 71 included in the quantitative synthesis were published between 1975 and 2022 and were from every continent, although 35 7 , 8 , 16 , 25 , 27 , 28 , 31 , 34 - 44 , 46 , 47 , 50 - 53 , 56 - 65 , 70 were from high-income countries and only 10 26 , 30 , 45 , 48 , 49 , 54 , 55 , 66 , 68 , 69 were from upper-middle-income countries. The five multicenter studies were from high- and upper-middle-income countries.…”

Clozapine Suppresses the Gene Expression and the Production of Cytokines and Up-Regulates Cyclooxygenase 2 mRNA in Human Astroglial Cells

“…The first line of treatment is the use of typical and atypical antipsychotics, but when this approach fails, clozapine is the last resort for treatment-resistant schizophrenia (TRS) [ 1 ]. It was suggested that failure of the first typical or atypical antipsychotic already justifies switching to clozapine [ 2 ] There is strong evidence that the immune system and neuroinflammation play a central role in the pathophysiology of SCZ [ 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Epidemiological studies have demonstrated that various infections and autoimmune disorders in the prenatal period or in early childhood, as well as chronic stress and genetic susceptibility, are associated with increased risk of developing SCZ later in life.…”

Comparative Analysis of Combination Therapy Regimens in Patients with Paranoid Schizophrenia with Non-Suicidal Auto aggression and Identified Signs of Resistance to Ongoing Neuroleptic Monotherapy

“…A special place among the clinical predictors of therapeutic resistance is occupied by psychopathic disorders with auto aggressive tendencies, traditionally considered within the framework of heboid states. At the same time, until recently, the main drug from the group of neuroleptics used to overcome resistance was clozapine [8,9,10,11,12,13]. In practice, up to 30% of patients remain intact to its action, which dictates the need for combination therapy [14,15,16].…”