Factors associated with the presence of obsessive-compulsive symptoms in patients diagnosed with bipolar I disorder

Fatores associados à presença de sintomas obsessivo-compulsivos em pacientes diagnosticados com transtorno bipolar tipo I

ABSTRACT

Introduction:  Bipolar Disorder (BD) often coexists with obsessive-compulsive symptoms, impacting quality of life and complicating treatment. Research on these symptoms in euthymic BD type I patients remains limited.

Methods:  A cross-sectional study was conducted at Hospital Universitário Lauro Wanderley, including 37 euthymic patients diagnosed with BD type 1. Euthymia was confirmed using the Montgomery-Åsberg Depression Rating Scale and the Young Mania Rating Scale. Obsessive-compulsive symptoms were assessed using the Obsessive Compulsive Inventory-Revised (OCI-R), and patients scoring ≥21 were classified as having a higher likelihood of comorbid Obsessive-Compulsive Disorder (OCD). Binary logistic regression analyzed predictors of belonging to this high-score group.

Results:  Of the sample, 35.1% scored ≥21 on the OCI-R, being classified as at higher risk for comorbid OCD. Belonging to this group was significantly associated with a greater frequency of healthcare visits due to mood elevation in the past year (p = 0.043). No significant associations were found with demographic factors, substance use, or previous suicide attempts.

Discussion:  Our findings suggest that patients with higher obsessive-compulsive scores require more frequent healthcare support due to mood instability, highlighting the need for targeted interventions in BD patients at risk of OCD. Early detection of these symptoms may improve treatment outcomes and quality of life in this population.

KEYWORDS
Bipolar Disorder; Obsessive-compulsive disorder; psychiatry; comorbidity

RESUMO

Introdução:  O transtorno bipolar (TB) frequentemente coexiste com sintomas obsessivo-compulsivos, impactando a qualidade de vida e complicando o tratamento. A pesquisa sobre esses sintomas em pacientes eutímicos com TB tipo I ainda é limitada.

Métodos:  Foi realizado um estudo transversal no Hospital Universitário Lauro Wanderley, incluindo 37 pacientes eutímicos diagnosticados com TB tipo I. A eutimia foi confirmada por meio da Montgomery-Åsberg Depression Rating Scale e da Young Mania Rating Scale. Os sintomas obsessivo-compulsivos foram avaliados utilizando o Obsessive Compulsive Inventory-Revised (OCI-R), e pacientes com pontuação ≥21 foram classificados como tendo maior probabilidade de comorbidade com transtorno obsessivo-compulsivo (TOC). A regressão logística binária analisou os preditores de pertencimento a esse grupo de alta pontuação.

Resultados:  Na amostra, 35,1% obtiveram pontuação ≥21 no OCI-R, sendo classificados como de maior risco para comorbidade com TOC. Pertencer a esse grupo foi significativamente associado a uma maior frequência de atendimentos médicos devido à elevação do humor no último ano (p = 0,043). Não foram encontradas associações significativas com fatores demográficos, uso de substâncias ou tentativas de suicídio prévias.

Discussão:  Nossos achados sugerem que pacientes com escores mais altos de sintomas obsessivo-compulsivos requerem suporte médico mais frequente devido à instabilidade do humor, destacando a necessidade de intervenções direcionadas em pacientes com TB sob risco de TOC. A detecção precoce desses sintomas pode melhorar os desfechos do tratamento e a qualidade de vida dessa população.

PALAVRAS-CHAVE
Transtorno bipolar; transtorno obsessivo-compulsivo; psiquiatria; comorbidade

INTRODUCTION

Bipolar disorder (BD) is a psychiatric condition characterized by manic episodes—defined as distinct periods of abnormally and persistently elevated, expansive, or irritable mood and increased activity or energy lasting at least one week—often interspersed with remission periods or depressive episodes¹,². Bipolar type I disorder involves, mandatorily, manic episodes interspersed with remission periods, without the requirement of depressive episodes during the course of the disease³.

This psychiatric condition is commonly related to comorbidities, with a study indicating a prevalence of at least 41.5% of those in bipolar patients⁴. Among them, one of the most common is the Obsessive-Compulsive Disorder (OCD), with relevant nosological and therapeutic implications⁵. According to a systematic review conducted by Ferentinos et al. (2020), the lifetime prevalence of comorbid OCD in bipolar patients may reach 10.9% (95% CI: 7.8-14.14%), causing more often chronic symptoms than episodic ones, but data on the difference between BD subtypes are not well established yet⁶. Evidence shows that most OCD symptoms are limited to depressive episodes (about 50 to 75% of the cases), with remission occurring during manic episodes⁵. However, studies examining the presence of obsessive-compulsive symptoms exclusively in euthymic patients are not as explored.

Patients with comorbid BD and OCD have greater indicators of severity, such as a reduction in quality of life and a higher prevalence of OCD with poor insight⁷,⁸. Moreover, when comorbid with OCD, BD is associated with greater disability, higher prevalence of rapid cycling, substance abuse, and eating disorders⁹. From a therapeutic point of view, evidence suggests that patients with BD comorbid with OCD have a worse response to treatment with anticonvulsants used as mood stabilizers¹⁰. Furthermore, the treatment for OCD itself, like with selective serotonin reuptake inhibitors, may worsen the course of BD, inducing manic episodes¹¹.

Besides the mentioned consequences of comorbid OCD, it is important to emphasize that obsessive-compulsive symptoms may persist for long periods, and they are a risk factor for the development of obsessive-compulsive disorder¹². Therefore, diagnosing these symptoms helps in the early intervention, preventing their negative consequences on the patient's quality of life and the development of more severe conditions. Thus, the primary objective of this study was to analyze the presence and intensity of obsessive-compulsive symptoms in euthymic patients diagnosed with BD type I and identify potential associated factors.

METHODS

Descriptive cross-sectional study with quantitative methods of data collection. The research was conducted at the psychiatry outpatient clinic of the Hospital Universitário Lauro Wanderley (HULW), of the Universidade Federal da Paraíba (UFPB), located in the city of João Pessoa, Paraíba, during the period from November 2020 to September 2021.

The sample consisted of euthymic patients diagnosed with BD type I, regularly followed-up at HULW. The inclusion criteria were: patients aged 18 years or older and with a previously established diagnosis of BD Type I, based on DSM-5. As exclusion criteria, it was established that patients who refused to sign the consent form and/or who did not have preserved cognitive capacity to answer the test and/or were not euthymic during the time of the research, would not be included.

The diagnosis of type I BD was confirmed by reviewing medical records. In cases of doubts or ambiguity, the attending psychiatrist was questioned about the patients’ diagnosis.

Initially, patients were evaluated by a physician with expertise in mental health care. Once euthymia was certified by clinical evaluation, the Montgomery-Asberg Depression Rating Scale and the Young Mania Rating Scale were utilized. Those with scores lower than 9 in the first¹³ and lower than 13 in the second¹⁴ scales, were considered euthymic and included in the study.

After the mood evaluation, an epidemiological information form about the patient was applied and, subsequently, the brazilian portuguese version of the Obsessive Compulsive Inventory – Revised (OCI-R)¹⁵. In addition to the analysis of the scale's total score, the average scores of each of its subscales (mental neutralising, checking/doubting, hoarding, obsessing, ordering and washing) were also examined.

The collected data was registered and statistically analyzed using SPSS 25.0 (Statistical Package for the Social Sciences 25.0). Sociodemographic and clinical variables were categorized into binary groups and described in absolute and relative frequencies.

The individuals were also divided into two groups according to the OCI-R assessment, in which those with scores ≥21 were considered more likely to have comorbid OCD. This value was established based on the cut-off points recommended by Foa et al.'s research (2002), which was able to diagnose OCD with a sensitivity of 65.6% and a specificity of 63.9%.

After categorizing the variables, binary coding was used to convert the variables into numerical values (0 and 1). The dependent variable in the logistic regression model was the probability of having comorbid OCD, defined as high when OCI-R ≥ 21 points.

All collected sociodemographic and clinical variables (age, sex, marital status, race, occupation, education, therapy status, alcohol and cigarette consumption, history of hospitalization, history of suicide attempt, and frequency of seeking healthcare due to agitation) were entered as potential independent variables to control for confounders. Cigarette consumption was specifically included as a control variable given its association with impulsivity and illness severity in BD patients¹⁶,¹⁷.

A backward stepwise (conditional) selection procedure was then applied to identify the predictors independently associated with the dependent variable. The entry probability was set at 0.05 and the removal probability at 0.10. Variables with p-values < 0.05 in the final model were considered statistically associated with comorbid OCD.

The project was approved by the ethics committee of the Centro de Ciências Médicas of the Universidade Federal da Paraíba (UFPB), under CAAE 31291020.5.0000.8069.

RESULTS

A final sample of 37 patients met the inclusion criteria and was included in the analysis. The mean age was 38.22 years (± 11.2), and the sample consisted mostly of women (64.9%). Most patients had a level of education equal to or greater than complete high school (78.4%). The other descriptive statistics of the variables are demonstrated in detail in tables 1 and 2.

Table 1
Relative and absolute frequencies of the sociodemographic and clinical variables.

Variable		Absolute frequency	Relative frequency
Sex
	Male	13	35.1%
	Female	24	64.9%
Marital status
	Married or common-law marriage	18	48.6%
	Divorced or single	19	51.4%
Self-declared race/skin color
	White	16	45.9%
	Pardo (mixed or brown skin) and black	21	56.8%
Occupation status
	Active	18	48.6%
	Non-active (unemployed or retired)	19	51.4%
Level of education
	< Complete high school	8	21.6%
	≥ Complete high school	29	78.4%
"Do you go to therapy?"
	No	32	86.5%
	Yes	5	13.5%
Alcoholic beverage consumption
	No	27	73.0%
	Yes	10	27.0%
Cigarette consumption
	No	33	89.2%
	Yes	4	10.8%
History of hospitalization in a mental health service
	No	14	37.8%
	Yes	23	62.2%
History of suicide attempt
	No	26	70.3%
	Yes	11	29.7%
More likely to have comorbid OCD (OCI-R score ≥ 21)
	No	24	64.9%
	Yes	13	35.1%

Table 2
Mean and standard deviation of the continuous variables

Variable		Mean (± SD)
Age		38.22 (± 11.2)
OCI-R score		17.54 (± 11.1)
OCI-R subscales’ scores
	Neutralizing	1.49 (± 2.46)
	Checking/doubting	2.86 (± 3.05)
	Hoarding	2.81 (± 2.79)
	Obsessing	4.76 (± 3.87)
	Ordering	3.78 (± 2.75)
	Washing	1.84 (± 2.50)
How many times, in the past year, did you seek a healthcare service due		0.78 (± 1.08)

A significant portion of the sample (29.7%) reported a history of suicide attempts.

The mean score of OCI-R was 17.5 (± 11.1) points. The subscale with the highest mean score was obsession (4.76 points) and the lowest was mental neutralising (1.49 points).

Approximately 35.1% of the patients had a score greater than or equal to 21 points on the OCI-R, a score that was used by this study as a cutoff point for identifying patients who are more likely to have OCD.

The model resulting from the binary logistic regression is represented in Table 3. The only factor associated with a higher probability of having OCD was the number of visits to a healthcare service in the past year due to episodes of agitation/mood expansion (OR: 2.90; p-value = 0.043; 95% CI: 1.03-8.12), showing that, in this sample, higher number of visits to a healthcare service was associated to a higher probability of having comorbid OCD.

Table 3
Summary of the model resulting from the binary logistic regression

Covariable	Coefficient	Standard-Deviation	Wald	Sig.	Odds Ratio	CI95%
						Lower limit	Upper limit
Cigarette consumption	2.122	1.326	2.558	0.11	8.344	0.620	112.309
Number of times, in the past year, the patient sought a healthcare service due to agitation/expansive mood	1.064	0.526	4.094	0.043	2.898	1.034	8.124
Coefficient	-1.659	0.589	8.296	0.004	0.184	-------------------

DISCUSSION

In the present study, a high prevalence of individuals with an higher probability of having OCD comorbid with BD type I was observed, corresponding to approximately 35% of the sample. In a systematic review conducted by Pavlova et al. (2016), which analyzed the comorbidity of anxiety disorders with BD in euthymia, without distinguishing the specific anxiety disorders, a prevalence of 7.1% (95%CI: 4.0-10.2%) of comorbid OCD was attested¹⁸. Despite the difference between our findings and those found in that study, it should be noted that we did not focus on diagnosing comorbid OCD, since to do so would require a detailed clinical evaluation and, possibly, in multiple appointments, which would make this research unfeasible (considering our limited resources) and increase the risks of losing follow-up. Therefore, our percentage does not mean prevalence of comorbid OCD, but an indication of those patients who should be evaluated by a psychiatrist for proper diagnosis.

In addition, the focus of this study was on euthymic patients, since this is the mood state presented by patients during most of the time, especially in the cases of those regularly followed up in mental healthcare reference services, as is the case of our sample. Therefore, understanding these symptoms outside the periods of mood decompensation is essential for an adequate management of those with stable euthymic mood for long periods.

We found a mean of 17.5 points in the total OCI-R score in our sample. In our literature review, we did not identify other studies that used the OCI-R as a scale for assessing obsessive-compulsive symptoms in bipolar patients, our study being the first to do so. Despite this scarcity of data, we chose to use the OCI-R because it is a self-administered scale, which reduces the risk of the interviewer's interpretation of the questions interfering in the patients’ answers, in addition to being a scale that has already been translated, adapted and validated in Brazil¹⁵.

As for the OCI-R subscales, the symptoms of obsession were the ones with the highest average score among the patients. As already mentioned, no other studies were found using the OCI-R in bipolar patients. However, literature data dealing with the comorbidity between OCD and BD indicate that obsessions are more common than compulsions¹⁹,²⁰. In a study conducted by Mahasuar et al. (2011), the obsessions of contamination and aggression in bipolar patients with OCD was noted, but there was no statistical difference in comparison with the patients only diagnosed with OCD²⁰.

Data indicates that obsessive-compulsive symptoms in bipolar patients are more common in younger patients⁵,²¹. However, in our study, we did not observe an association between age and the intensity of obsessive-compulsive symptoms. Furthermore, data on the distribution of obsessive-compulsive symptoms between genders are varied and not very consistent²²,²³. In the present study, there was no association of these symptoms with the patient's gender.

Although the question asked in the present study was "Do you currently use psychoactive substances?", no patient reported the use of illicit substances, reporting only the use of alcohol or cigarettes, and the consumption of these substances was not significantly associated with the intensity of obsessive-compulsive symptoms. It is important to note that prevarication bias may have interfered in data collection, as patients may feel embarrassed or afraid to claim use of illegal drugs in the first contact with the evaluator.

The only statistically significant variable associated with a higher risk of having OCD was the number of agitation/mood expansion episodes in the past year. Data from other studies indicate a higher risk of hospitalizations and a higher prevalence of rapid cycling¹¹, revealing a possible relationship between this comorbidity and the severity of BD. These factors can significantly worsen the patient's quality of life, especially in their social sphere, in addition to making their therapeutic management more difficult.

The non-association between a history of suicide attempts and a higher probability of having comorbid OCD was a finding consistent with similar studies, which compared the difference between the groups of bipolar patients with and without OCD regarding suicide attempts²²,²³, although their sample did not include euthymic patients only. On the other hand, older data indicated an association of comorbid OCD with a higher prevalence of suicidal ideation, thoughts of death and suicide attempts²⁴. In a study conducted by Di Salvo et al. (2020), bipolar patients with comorbid OCD had more violent suicide attempts compared to the ones without OCD²².

Limitations of the study

Due to the need of good reading and textual comprehension to answer the OCI-R, the sample consisted mostly of patients with higher education (i. e. complete high school). It can be considered a selection bias, although it was difficult to control it, since including patients who does not understand the questions would compromise the findings.

We did not find any studies applying the OCI-R in bipolar patients, a fact that compromised the comparative discussion with other literatures. However, we chose to use it since it is a self-administered scale, so it would not make data collection dependent on the subjective interpretation of the questions and answers by the interviewer.

The COVID-19 pandemic reduced the number of patients at the outpatient clinic during the initial months of the research, which limited data collection and the reach of a larger sample. In addition, the initial project included collecting data in two Centro de Atenção Psicossocial (CAPS). However, also due to the pandemic, researches were not allowed at these locations.

Finally, a critical limitation was the inability to control for medication class in the regression model due to sample size constraints. Current literature indicates that second-generation antipsychotics (e.g., clozapine, olanzapine, risperidone, and even aripiprazole) may induce or exacerbate obsessive-compulsive symptoms through serotonergic and dopaminergic modulation mechanisms²⁵-³³. Since patients with higher service utilization due to agitation might be more likely to receive these medications to stabilize mood, we cannot rule out that the observed association is partially mediated by pharmacological treatment rather than being solely intrinsic to the bipolar pathophysiology.

CONCLUSIONS

In conclusion, our study demonstrated a significant association between the presence of obsessive-compulsive symptoms and a higher frequency of seeking healthcare services due to mood elevation. While our cross-sectional design precludes determining causality—whether OC symptoms contribute to mood instability or vice versa— these findings suggest that patients with greater mood instability may present a higher burden of comorbid OC symptoms, highlighting the importance of screening for these symptoms in clinical practice.

ACKNOWLEDGMENTS

The authors thank all the medical residents and supervisors of the Psychiatry Residency Program at Hospital Universitário Lauro Wanderley (HULW) for their availability, attention, and assistance.

• FINANCIAL STATEMENT
  This work was supported by the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for one year, between 2020 and 2021, through the payment of a scientific initiation scholarship under the Institutional Scientific Initiation Scholarship Program (PIBIC) to the main author (BRL 400.00 per month).

DATA AVAILABILITY STATEMENT

The data that support this study are available from the authors upon request.

REFERENCES

• ¹ Bosaipo NB, Borges VF, Juruena MF. Bipolar disorder: a review of conceptual and clinical aspects. Med (Ribeirao Preto Online). 2017;50(supl1.):72.
• ² Sadock BJ, Sadock VA, Ruiz P. Compêndio de Psiquiatria: ciência do comportamento e psiquiatria clínica. Compêndio de Psiquiatria: Ciência do Comportamento e Psiquiatria Clínica. 2017.
• ³ American Psychiatry Association. DSM-V-TR - Manual diagnóstico e estatístico de transtornos mentais. Artmed. 2013.
• ⁴ Dell’Osso B, Buoli M, Bortolussi S, Camuri G, Vecchi V, Altamura AC. Patterns of Axis i comorbidity in relation to age in patients with Bipolar Disorder: A cross-sectional analysis. J Affect Disord [Internet]. 2011;130(1–2):318–22. Available from: http://dx.doi.org/10.1016/j.jad.2010.10.008
  » http://dx.doi.org/10.1016/j.jad.2010.10.008
• ⁵ Amerio A, Stubbs B, Odone A, Tonna M, Marchesi C, Ghaemi SN. The prevalence and predictors of comorbid bipolar disorder and obsessive-compulsive disorder: A systematic review and meta-analysis. J Affect Disord. 2015;186:99–109.
• ⁶ Ferentinos P, Preti A, Veroniki AA, Pitsalidis KG, Theofilidis AT, Antoniou A, et al. Comorbidity of obsessive-compulsive disorder in bipolar spectrum disorders: Systematic review and meta-analysis of its prevalence. J Affect Disord [Internet]. 2020;263:193–208. Available from: https://www.sciencedirect.com/science/article/pii/S0165032719312571
  » https://www.sciencedirect.com/science/article/pii/S0165032719312571
• ⁷ Khafif TC, Belizario GO, Silva M, Gomes BC, Lafer B. Quality of life and clinical outcomes in bipolar disorder: An 8-year longitudinal study. J Affect Disord [Internet]. 2021;278(July 2020):239–43. Available from: https://doi.org/10.1016/j.jad.2020.09.061
  » https://doi.org/10.1016/j.jad.2020.09.061
• ⁸ Kazhungil F, Mohandas E. Management of obsessive-compulsive disorder comorbid with bipolar disorder. Indian J Psychiatry [Internet]. 2016;58(3):259–69. Available from: https://pubmed.ncbi.nlm.nih.gov/28066002
  » https://pubmed.ncbi.nlm.nih.gov/28066002
• ⁹ Shashidhara M, Sushma BR, Viswanath B, Math SB, Janardhan Reddy YC. Comorbid obsessive compulsive disorder in patients with bipolar-I disorder. J Affect Disord [Internet]. 2015;174:367–71. Available from: http://dx.doi.org/10.1016/j.jad.2014.12.019
  » http://dx.doi.org/10.1016/j.jad.2014.12.019
• ¹⁰ Henry C, Den Bulke D Van, Bellivier F, Etain B, Rouillon F, Leboyer M. Anxiety disorders in 318 bipolar patients: Prevalence and impact on illness severity and response to mood stabilizer. J Clin Psychiatry. 2003;
• ¹¹ Sharma LP, Reddy YCJ. Obsessive-compulsive disorder comorbid with schizophrenia and bipolar disorder. Indian J Psychiatry [Internet]. 2019 Jan;61(Suppl 1):S140–8. Available from: https://pubmed.ncbi.nlm.nih.gov/30745688
  » https://pubmed.ncbi.nlm.nih.gov/30745688
• ¹² Alvarenga PG, do Rosario MC, Cesar RC, Manfro GG, Moriyama TS, Bloch MH, et al. Obsessive–compulsive symptoms are associated with psychiatric comorbidities, behavioral and clinical problems: a population-based study of Brazilian school children. Eur Child Adolesc Psychiatry. 2016;25(2):175–82.
• ¹³ Müller-Thomsen T, Arlt S, Mann U, Maß R, Ganzer S. Detecting depression in Alzheimer's disease: Evaluation of four different scales. Arch Clin Neuropsychol. 2005;20(2):271–6.
• ¹⁴ de Moraes PHP, Neves FS, Vasconcelos AG, Lima IMM, Brancaglion M, Sedyiama CY, et al. Relationship between neuropsychological and clinical aspects and suicide attempts in euthymic bipolar patients. Psicol Reflex e Crit. 2013;26(1):160–7.
• ¹⁵ De Souza FP, Foa EB, Meyer E, Niederauer KG, Raffin AL, Cordioli AV. Obsessive-compulsive inventory and obsessive-compulsive inventory-revised scales: Translation into Brazilian Portuguese and cross-cultural adaptation. Rev Bras Psiquiatr. 2008;30(1):42–6.
• ¹⁶ Heffner JL, Fleck DE, DelBello MP, Adler CM, Strakowski SM. Cigarette smoking and impulsivity in bipolar disorder. Bipolar Disord. 2012;14(7):735-42.
• ¹⁷ Ostacher MJ, LeBeau RT, Perlis RH, Nierenberg AA, Lund HG, Moshier SJ, et al. Cigarette smoking is associated with suicidality in bipolar disorder. Bipolar Disord. 2009;11(7):766-71.
• ¹⁸ Pavlova B, Perlis RH, Mantere O, Sellgren CM, Isometsä E, Mitchell PB, et al. Prevalence of current anxiety disorders in people with bipolar disorder during euthymia: A meta-analysis. Psychol Med. 2017;47(6):1107–15.
• ¹⁹ Krüger S, Cooke RG, Hasey GM, Jorna T, Persad E. Comorbidity of obsessive compulsive disorder in bipolar disorder. J Affect Disord. 1995;34(2):117–20.
• ²⁰ Mahasuar R, Janardhan Reddy YC, Math SB. Obsessive-compulsive disorder with and without bipolar disorder. Psychiatry Clin Neurosci. 2011;65(5):423–33.
• ²¹ Amerio A, Tonna M, Odone A, Stubbs B, Ghaemi SN. Commentaries: Comorbid bipolar disorder and obsessive-compulsive disorder in children and adolescents: Treatment implications. Aust N Z J Psychiatry. 2016;50(6):594–6.
• ²² Di Salvo G, Pessina E, Aragno E, Martini A, Albert U, Maina G, et al. Impact of comorbid obsessive-compulsive disorder on suicidality in patients with bipolar disorder. Psychiatry Res [Internet]. 2020;290(April):113088. Available from: https://doi.org/10.1016/j.psychres.2020.113088
  » https://doi.org/10.1016/j.psychres.2020.113088
• ²³ Jeon S, Baek JH, Yang SY, Choi Y, Ahn SW, Ha K, et al. Exploration of comorbid obsessive-compulsive disorder in patients with bipolar disorder: The clinic-based prevalence rate, symptoms nature and clinical correlates. J Affect Disord [Internet]. 2018;225:227–33. Available from: https://www.sciencedirect.com/science/article/pii/S0165032717308054
  » https://www.sciencedirect.com/science/article/pii/S0165032717308054
• ²⁴ Chen YW, Dilsaver SC. Comorbidity for obsessive-compulsive disorder in bipolar and unipolar disorders. Psychiatry Res. 1995;59(1–2):57–64.
• ²⁵ Scheltema Beduin AA, Swets M, Machielsen M, Korver N. Obsessive-compulsive symptoms in patients with schizophrenia: a naturalistic cross-sectional study comparing treatment with clozapine, olanzapine, risperidone, and no antipsychotics in 543 patients. J Clin Psychiatry. 2012;73(11):1395-402.
• ²⁶ Schirmbeck F, Rausch F, Englisch S, Eifler S, Esslinger C, Meyer-Lindenberg A, et al. Differential effects of antipsychotic agents on obsessive-compulsive symptoms in schizophrenia: a longitudinal study. J Psychopharmacol. 2013;27(4):349-57.
• ²⁷ Schirmbeck F, Esslinger C, Rausch F, Englisch S, Meyer-Lindenberg A, Zink M. Antiserotonergic antipsychotics are associated with obsessive-compulsive symptoms in schizophrenia. Psychol Med. 2011;41(11):2361-73.
• ²⁸ Burk BG, DiGiacomo T, Polancich S, Pruett BS, Sivaraman S, Birur B. Antipsychotics and obsessive-compulsive disorder/obsessive-compulsive symptoms: a pharmacovigilance study of the FDA adverse event reporting system. Acta Psychiatr Scand. 2023;148(1):32-46.
• ²⁹ Akbari M, Jamshidi S, Sheikhi S, Alijani F, Kafshchi P, Taylor D. Aripiprazole and its adverse effects in the form of impulsive-compulsive behaviors: a systematic review of case reports. Psychopharmacology (Berl). 2024;241(2):209-23.
• ³⁰ Grillault Laroche D, Gaillard A. Induced obsessive compulsive symptoms (OCS) in schizophrenia patients under atypical antipsychotics (AAPs): review and hypotheses. Psychiatry Res. 2016;246:119-28.
• ³¹ Kim SW, Shin IS, Kim JM, Youn T, Yang SJ, Hwang MY, et al. The 5-HT2 receptor profiles of antipsychotics in the pathogenesis of obsessive-compulsive symptoms in schizophrenia. Clin Neuropharmacol. 2009;32(4):224-6.
• ³² Kim JH, Ryu S, Nam HJ, Lim M, Baek JH, Joo YH, et al. Symptom structure of antipsychotic-induced obsessive compulsive symptoms in schizophrenia patients. Prog Neuropsychopharmacol Biol Psychiatry. 2012;39(1):75-9.
• ³³ Kim DD, Barr AM, Lu C, Stewart SE, White RF, Honer WG, et al. Clozapine-associated obsessive-compulsive symptoms and their management: a systematic review and analysis of 107 reported cases. Psychother Psychosom. 2020;89(3):151-60.

Edited by

• Handling Editor:
  Mariana Luz

Publication Dates

• Publication in this collection
  24 July 2026
• Date of issue
  2026

History

• Received
  29 May 2025
• Accepted
  25 Mar 2026