A search was conducted in the mentioned databases, yielding 613 results in PubMed, 160 results in LILACS, 699 results in Embase, and 0 results in Scielo, for a total of 1,472 results. These results were imported into the reference management program Rayyan, where the program detected 567 possible duplicates. Subsequently, 327 articles that were indeed duplicates were removed through manual review.

The remaining 1,145 articles were evaluated independently by two reviewers for selection based on title and abstract. As a result of this evaluation, 26 articles were selected for full review. During the full-text review, the authors of two selected articles from the title and abstract screening phase were contacted; however, both articles could not be obtained [44, 45], and ten were excluded for not meeting the inclusion and exclusion criteria, leaving a final count of 14 articles. It is noteworthy that no results were obtained in the complementary search by references (Fig. 1).

A total of 14 studies were included in this review, of which 13 were published in English and 1 in Spanish, with the oldest published in 1995 and the most recent in 2024 [28, 31, 46,47,48,49,50,51,52,53,54,55,56,57]. All studies included in the review had a cross-sectional design and were conducted in the countries of Germany (n = 1), Brazil (n = 1), China (n = 1), the United States (n = 1), Italy (n = 1), Ireland (n = 1), Peru (n = 1), the United Kingdom (n = 4), Singapore (n = 1), and Turkey (n = 2). The primary objective of half of the studies was to determine the prevalence of OCS in patients diagnosed with schizophrenia receiving clozapine treatment, while the remaining half reported it as part of their results (Table 2).

The data collection method in three of the 14 studies was solely through medical records [46, 50, 56], one study used only patient interviews [51], six studies utilized both medical records and interviews [28, 31, 47, 49, 52, 54], and finally, four studies used interviews, medical records, and blood sample analysis [48, 53, 55, 57], of which three aimed to determine plasma clozapine concentration and one to assess the genes of the sample [57]. It is noteworthy that two of the studies conducted interviews not only with patients but also with caregivers or family members [48, 53]. A total of ten studies evaluated medical records and/or outpatient patients [31, 47,48,49, 51,52,53,54,55,56], one study evaluated medical records of hospitalized patients only [46], two studies evaluated medical records of both outpatient and hospitalized patients [50, 57], and one study did not specify whether the medical records evaluated were from outpatient or hospitalized care [28].

The number of participants in the studies ranged from 49 to 196 participants, with an average age ranging from 30 to 47 years, and a higher proportion of male participants. Regarding the characteristics of clozapine treatment, the average dose ranged from 196 to 525 mg/day, and the duration of treatment ranged from five to 210 months.

The samples of the reviewed studies were diverse: seven of them included only patients diagnosed with schizophrenia receiving clozapine treatment [28, 47, 48, 53,54,55,56]; while in four other studies, in addition to patients with schizophrenia, patients with other diagnoses such as schizoaffective disorder, schizophreniform disorder, bipolar disorder, borderline personality disorder, psychotic depression, and undifferentiated psychosis were included [50, 52, 56, 57]. On the other hand, the remaining three studies included patients with a diagnosis of schizophrenia who were treated not only with clozapine but also with other atypical antipsychotics such as olanzapine, quetiapine, risperidone, etc., and classical antipsychotics such as haloperidol [31, 49, 51].

Two studies addressed family history in their results. The first, by Ertugrul et al. [47], reported no significant differences in the family history of mental illness between the groups. The second, by Mongenroth et al. [57], indicated that 57% of participants had a family history of psychiatric disorders; however, this finding was not further discussed in their analysis.

The prevalence of OCS was identified in seven of the 14 studies [47,48,49, 52, 54,55,56,57]. To evaluate the overall prevalence of OCS, a comparison was made between the prevalences reported in the seven studies. The observed prevalences ranged from 20 to 76%, with a mean of 36.86 ± 19.51. To provide a more robust measure of central tendency and dispersion against the variability of the data, the median was calculated at 38%, with an interquartile range (IQR) of 18%.

The scatter plot (Fig. 2) shows the prevalences from the eight studies. An outlier with a prevalence of 76% was reported by Ertugrul et al. [47], which is considerably higher than most of the other articles. Additionally, one of the eight studies used comparator groups of clozapine versus another antipsychotic in its methodology: Sa et al. [49], which, in addition to clozapine, evaluated the prevalence of OCS in patients treated with haloperidol, reporting prevalences of 20% and 25%, respectively.

Scatter plot of general prevalence rates of OCS across studies

The overall prevalence of OCD was reported in seven studies [28, 48, 49, 51, 55, 57] (Fig. 3). This was found to range from 6.9 to 47%. The mean was 27 ± 14.6, the median was 28.5%, and the IQR was 21%. A comparison between overall prevalences of OCS and OCD in studies that reported these results is shown in (Fig. 4).

Scatter plot of general prevalence rates of ocd across studies

Comparison of prevalence of OCS and OCD by study

When evaluating the seven studies that included only patients with schizophrenia treated with clozapine [28, 47, 48, 53,54,55,56], without considering studies with comparator groups using other drugs or different clinical diagnoses, a prevalence of OCS ranging from 21.4 to 76% was observed, with a median of 41% and an IQR of 7.6. Four of these reviewed studies reported the concomitant use of medication [28, 47, 48, 53]. Fernández-Egea et al. [28] evaluated the use of medications with potential effects on OCD, including aripiprazole, SSRIs, serotonin and norepinephrine reuptake inhibitors (SNRIs), and tricyclic antidepressants (TCAs), referred to in the study as “anti-OCD medication.” The results indicated that the prevalence of OCD and the mean OCI-R scores in patients using anti-OCD medication were significantly higher compared to those taking only clozapine (64% vs. 31%; p = 0.001) and (24.6 ± 13.2 vs. 16.2 ± 12.2; p = 0.001). In the study by Ertugrul et al. [47], with a sample of 50 patients, it was reported that ten were on adjunctive treatment with SSRIs, of which three received it for comorbid OCD and another three for comorbid major depression. On the other hand, Lin et al. [