Obsessive-compulsive (OC) symptoms comprise obsessions (recurrent, intrusive, unwanted thoughts, images, or urges causing anxiety or distress) and compulsions, which are repetitive behaviors or mental acts performed in response to these obsessions to reduce distress or prevent feared outcomes (1,2). These symptoms are understood to be distributed along a right-skewed continuum, with subclinical manifestations common in the general population, and individuals at the extreme end of the spectrum meeting criteria for obsessive compulsive disorder (OCD) (3-5). The pathophysiology of OC symptoms involves the cortico-striato-thalamo-cortical loop and modulatory inputs from limbic regions (6,7). The integrity and functioning of the circuits, which in turn shape susceptibility and symptom expression, could be influenced by multiple interacting factors, including genetic, perinatal and neurodevelopmental liability, as well as subsequent interactions with biopsychosocial circumstances (8-12). Pharmacological agents capable of disrupting the delicate neurotransmitter balance of the systems may, in susceptible individuals, precipitate new-onset OC symptoms or exacerbate pre-existent ones (13,14). Well-documented clinical examples include dopaminergic agonists used in Parkinson's disease, such as pramipexole and ropinirole, which have been associated with dose-dependent emergence of impulsive-compulsive behaviors, which phenomenologically overlap with the OC spectrum (15-17). Another agent widely recognized to precipitate or aggravate classical OC symptoms is clozapine, the first second-generation antipsychotic, which exerts complex effects on dopaminergic and serotonergic neurotransmissions (18). Among other second-generation antipsychotics, a small number of case reports have described the precipitation or aggravation of OC symptoms with olanzapine, risperidone and quetiapine (19-22). Notably, conflicting evidence also exists regarding potential therapeutic effects of some of these agents in OCD (23-25).

Cariprazine is an atypical antipsychotic approved for the treatment of schizophrenia and bipolar disorder, and is increasingly utilized in bipolar depression and mixed presentations (26-30). The agent acts as a partial agonist at the serotonin 1A (5-HT_1A) receptor and at dopamine D₂ and D₃ receptors, with a high affinity for the dopamine D₃ receptor (28,31). Cariprazine also acts as an antagonist at serotonin 2A (5-HT_2A) and serotonin 2B (5-HT_2B) receptors (27,28). Cariprazine is generally well tolerated, with commonly reported adverse effects including akathisia, insomnia, and extrapyramidal symptoms (32,33). However, as with other second-generation antipsychotics, unexpected neuropsychiatric adverse effects have been observed, although specific reports on worsening or emergence of OC symptoms remain limited (34-37). An analysis of post-marketing data has also suggested that its adverse effect profile may be more diverse than that observed in clinical trials (38). The present report describes a patient with bipolar II disorder who developed marked exacerbation of OC symptoms shortly after a medication switch to cariprazine.

A 28-year-old female patient with bipolar II disorder presented with marked emergence of OC symptoms shortly after cariprazine was added to her treatment regimen. All clinical encounters described in this case report were under the care of the same treating psychiatrist and took place in 2025 at HRH Princess Maha Chakri Sirindhorn Medical Center, a university-affiliated hospital in Nakhon Nayok Province, Thailand. A summary of the clinical timeline is provided in Table I.

The patient reported premorbid OC symptoms characterized by urges to count during goal-directed activities, such as counting steps while walking or counting numbers while preparing food, accompanied by a compulsion to restart the activity if the counting was not performed correctly. These symptoms were reportedly infrequent, occurring approximately once per week since the age of 14 years, remained stable in frequency and intensity over time, and did not cause significant distress or functional impairment. Consequently, the patient never sought treatment. The patient reported no childhood history of attention-deficit/hyperactivity disorder or tic disorder, and displayed no features suggestive of intellectual disability or autism spectrum disorder.

Eight months prior to the index visit, at the age of 27 years, the patient first sought psychiatric care at HRH Princess Maha Chakri Sirindhorn Medical Center (Nakhon Nayok, Thailand) for depressed mood, and was diagnosed with major depressive disorder. The symptoms responded poorly to fluoxetine (no partial response at 20 mg/day after 1.5 months) and sertraline (minimal response at doses of 50-100 mg/day after 3 months). Aripiprazole was later added as augmentative agent to sertraline at a dose of 2.5 mg/day for 1 month. A hypomanic episode subsequently emerged, prompting diagnosis revision to bipolar II disorder, discontinuation of sertraline, up-titration of aripiprazole to 5 mg/day, and initiation of clonazepam at 0.5 mg/day to control aripiprazole-related akathisia. The regimen adequately controlled the hypomanic symptoms but not depressive symptoms. Augmentation with lamotrigine was briefly attempted at doses of 25-50 mg/day over a 1-month period; however, a generalized allergic skin reaction occurring a week after dose titration to 50 mg/day led to its discontinuation. As aripiprazole-induced akathisia, first observed 3 months earlier at doses between 2.5-5 mg/day and required adjunctive clonazepam for symptom control, limited further dose titration, a switch in antipsychotic treatment was considered. The patient declined quetiapine because of metabolic concerns, and cariprazine was selected. Notably, throughout the 7 months of treatment prior to cariprazine initiation, the counting compulsion of the patient remained at baseline.

At 14 days before the index visit, aripiprazole dose was reduced to 2.5 mg/day for four days before discontinuation. On the same day that the dose of aripiprazole was reduced, cariprazine treatment was initiated at 1.5 mg/day. After 3 days on cariprazine, two new forms of OC symptoms emerged. The first consisted of intrusive thoughts involving desecration of, or uttering profanities toward, religious objects. The second involved recurrent intrusive, fear-provoking mental images of catastrophic accidents affecting the family of the patient, in the absence of any relevant traumatic or separation-threatening events. Concurrently, the preexistent counting compulsion worsened in frequency and intensity, along with a development of a new undoing compulsion (engaging in self-pinching when the counting was not properly conducted). In contrast to its previously benign nature, the exacerbated counting compulsion started to become distressing and functionally impairing. However, insights into the irrationality of these OC phenomena were preserved. Focused clinical assessment did not identify any recent psychosocial stressors. There were no concurrent symptoms of infection, other clinical features suggestive of an immune-mediated exacerbation of OC symptoms, concurrent medical illnesses, or other new psychiatric symptoms. The patient was not concurrently on any other medications.

At the index visit, the patient reported these OC symptoms and additionally complained of weight gain. The treatment regimen was switched back to aripiprazole at a dose of 5 mg/day, and sertraline was reinitiated at 25 mg/day to manage the persistent depressive symptoms. Within 7 days after discontinuing cariprazine, the two newly emerged OC symptom clusters that had appeared 3 days after cariprazine initiation were completely resolved, while the counting compulsion returned to its baseline, subclinical severity. Rechallenge with cariprazine was not pursued due to the patient's refusal.

At subsequent follow-up visits up to 1.5 months later, the counting compulsion remained at baseline. Persistent akathisia was reported at the 2-week follow-up visit, while minor work-related stress was reported at the 1.5-month follow-up visit. Clonazepam was switched to propranolol (30 mg/day) to manage aripiprazole-associated akathisia, and sertraline was increased to 50 mg/day for depressive symptom control.

The present report describes marked exacerbation of OC symptoms in a patient with bipolar II disorder undergoing a medication switch. No proximal psychosocial stressors were identified based on clinical assessment at the time of symptom onset, reducing the likelihood of acute stress-related symptom exacerbation, although unrecognized or unreported stressors cannot be entirely excluded as assessment could have been limited in routine clinical settings. Nevertheless, the temporal association with cariprazine, including symptom emergence 3 days after its initiation and resolution 7 days after its discontinuation, was suggestive of a medication-related phenomenon.

The patient had been on aripiprazole for 4 consecutive months, without any sign of OC symptom fluctuation. Therefore, direct aripiprazole-induced phenomena were considered relatively unlikely. However, symptom onset occurred on the third day after the dose was reduced from 5 to 2.5 mg/day. While a classical withdrawal effect appears less consistent given aripiprazole's long elimination half-life and the low tapering dose (39), a transient change in net dopaminergic signaling could have occurred as cariprazine and aripiprazole possessed different dopaminergic receptor affinities (27,40). The overlapping exposure therefore represents a limitation in attributing causality in the present case.

The patient was also concurrently taking clonazepam (0.25 mg/day). The onset of OC symptoms did not coincide with either clonazepam initiation (3 months prior) or dose reduction (2 months prior), making a direct temporal association less likely. However, as relatively prolonged benzodiazepine use can lead to tolerance or inter-dose withdrawal that may theoretically influence anxiety symptom fluctuations (41,42), clonazepam's contributory role cannot be definitively excluded.

Sertraline was initiated at the time of cariprazine discontinuation at a dose of 25 mg/day. However, because complete remission of the OC symptoms occurred within 7 days, contributory therapeutic effect of sertraline was considered unlikely given both the low dose and the timeframe preceding sertraline's typical onset of action in OCD (43,44).

Given the evidence that premorbid or subclinical OC symptoms confer increased vulnerability to the later development of clinically significant OCD (45-47), cariprazine exposure in the current case may have acted as a precipitating factor that shifted the patient's preexisting OC-related pathology from a subclinical to a clinically manifestable level.

The present study adds to the limited literature regarding OC symptomatology attributed to cariprazine. One previous report has described a 65-year-old female patient with bipolar disorder who developed repetitive door checking, excessive cloth washing, fear of physical illness, and chanting ritual shortly after the initiation of cariprazine monotherapy at 1.5 mg/day. The patient's symptoms gradually improved during a 6-week taper, and complete remission was observed ~2 months after cariprazine discontinuation (37). Another report described a 19-year-old male patient with schizophrenia who developed ritualistic and intrusive cleanliness-related compulsions while receiving cariprazine (3 mg/day) in combination with olanzapine (5 mg/day), although the emergence of OC symptoms coincided with the patient's exposure to extensive news coverage of the coronavirus disease 2019 pandemic. Nevertheless, as the cariprazine dose was reduced to 1.5 mg/day while olanzapine was maintained at the same dose, the OC symptoms improved within 1 week and continued to improve substantially over the subsequent 2 months (48). These observations were broadly consistent with the emergence of OC symptoms after cariprazine exposure in the present case.

Multiple mechanisms across glutamatergic, serotonergic, and dopaminergic systems could be relevant in explaining antipsychotic-induced OC symptoms. Within the serotonergic system, the 5-HT_2A receptor is of particular interest because it is highly expressed in the prefrontal cortex and modulates cortical glutamatergic output, while dysregulated glutamatergic signaling has been implicated in OCD (49-52). A positron emission tomography study in OCD has reported low postsynaptic 5-HT_2A receptor availability at the orbitofrontal and dorsolateral prefrontal cortices, which was associated with symptom severity (53). Increased receptor binding in the caudate nucleus in untreated patients, interpreted as a possible compensatory response to altered serotonergic tone, was also reported (54). Antagonism of 5-HT_2A receptors, shared by a number of antipsychotic agents, including cariprazine (40), may therefore contribute to disturbances in neurotransmitter systems implicated in OC symptoms. Notably, it has been remarked that the 5-HT_2A antagonistic potency of the antipsychotic agent tended to mirror the frequency of reported drug-induced OC symptoms (55).

Heterogeneity in the relationship between antipsychotic doses and the emergence of OC symptoms across different agents has been observed (13,18-22,36,55-59). Remarkably, clozapine was consistently reported to be capable of inducing OC symptoms at a wide dose range (36,18). Risperidone, in contrast, has been reported to trigger OC symptoms at moderate to high weight-adjusted doses (56,58,59), at levels associated with relatively greater D₂ receptor occupancy (60). These observations led to the hypothesis that the relative balance between 5-HT_2A and D₂ receptor antagonism may be another relevant factor contributing to the emergence of drug-related OC symptoms (57), although whether high degrees of D₂ antagonism contribute to the development of OC symptoms remains unclear (56,59,61,62). In the present case, cariprazine, a partial D₂ agonist, appeared to trigger OC symptoms at a low dose, at which strong net D₂ antagonism is less likely (27,40). Therefore, pathophysiological mechanisms involving marked D₂ receptor blockade are unlikely to be relevant to our patient.

Cariprazine also exhibits partial agonism at the 5-HT_1A receptor (27), a receptor more commonly implicated in mood and anxiety regulation than in OC symptom domains (63). In animal models, agonism at this receptor has been shown to facilitate repetitive and compulsive behaviors (64,65), whereas human studies on OCD have yielded inconsistent findings (66-68). Nonetheless, a pharmacovigilance analysis of antipsychotics found that higher 5-HT_1A receptor affinity was positively associated with increased reporting of OC symptoms, and that the 5-HT_1A/D₂ receptor affinity ratio may be relevant to this signal (69).

To the best of our knowledge, antagonism at the 5-HT_2B receptor, another serotonergic effect of cariprazine (27,40), has not been systematically implicated in the development of OC symptoms.

The partial agonism of cariprazine at the dopamine D₃ receptor may also be relevant. Preclinical and human studies have indicated that dopamine D₃ receptor activation modulates reward-related learning and reinforcement processes (70,71), which can influence the persistence of learned or conditioned behaviors. Although findings are limited and mixed, genetic studies have also reported associations between dopamine D₃ receptor variations and OCD (72-74). Despite being described separately and differing in underlying mechanisms, impulsive-compulsive behaviors observed in Parkinson's disease share some clinical features with obsessive-compulsive symptoms, such as repetitiveness, difficulty of controlling, and persistence despite apparent maladaptation and negative consequences (72-75). Such behaviors have been associated with antiparkinsonian agents possessing high dopamine D₃ receptor selectivity (such as pramipexole and ropinirole), and less frequently with levodopa; proposed mechanisms similarly involve dysregulated reward processing and decision-making (76-79).

Conversely, cariprazine has also been reported to be an effective augmenting agent in treatment-resistant OCD, predominantly in adolescent-onset patients, at a dose of 1.5 mg/day (80,81). Cariprazine has also been reported to be effective in a case of OCD comorbid with schizophrenia, as well as in another case of OCD comorbid with autism, as an augmentative agent at doses between 1.5 and 3 mg/day (82,83). Mirroring the conflicting reports regarding the OC-inducing potential and treatment efficacy observed in other antipsychotics (19-25), it could be hypothesized that cariprazine's combination of mechanisms of action may confer benefit in certain subgroups of OCD, given the heterogeneity of the biological underpinnings of OC symptoms (84,85). Nevertheless, direct comparative data on pathophysiological differences across various OC and OCD phenotypes remain limited (86).

OCD is recognized to have a bimodal age-at-onset, at which point the symptoms can emerge at subclinical levels (3). Although the precise age cutoffs remain inconsistent across studies (3,87,88), childhood-onset (or early-onset) OCD is more commonly linked with comorbidity such as tic disorders and neurodevelopmental disorders, whereas adult-onset (or late-onset) OCD more frequently co-occurs with mood and anxiety disorders (87,89-92). Structural and functional neurological differences across these groups have been characterized (93-95). These two phenotypes also appear to respond differently to pharmacotherapy, with early-onset groups showing lower response rates to selective serotonin reuptake inhibitors (SSRIs), while responding more favorably to antipsychotics when comorbid tic disorder is present or when the disease is resistant to SSRIs (86,96-98). As their biological underpinnings and response profiles to serotonergic and dopaminergic agents differ, it can be inferred that the propensity for preexisting OC symptoms to be exacerbated by antipsychotics (especially ones that possess both serotonergic and dopaminergic mechanisms of action) may also vary by age-at-onset phenotypes. Numerous case reports and association studies of antipsychotic-associated OC symptoms have not systematically evaluated patient age at onset or the presence of premorbid symptoms (13,18-22,36,55-59). The observation that the same antipsychotic can both induce and alleviate OC symptoms at similar doses may be partly attributable to differences in age-at-onset OC phenotypes. This represents an important knowledge gap, and future case reports and observational studies would benefit from more detailed phenotypic characterization. Improved patient characteristic delineation may enhance the understanding of who may be at greater risk of OC symptom exacerbation or, alternatively, who may benefit from cariprazine treatment.

The present case should be considered as a probable case of cariprazine exacerbating preexisting adolescent-onset OC symptoms. The patient's age at onset (14 years) lies within the gray zone of commonly suggested age cutoffs (3,87,88), and the symptoms likely remained unevaluated because of their mild severity and sociocultural barriers related to emotion suppression, avoidant coping tendency, and mental health-related stigma (99-105). Clinicians should remain attentive to emerging reports of OC symptoms associated with cariprazine, particularly with regard to patient characteristics that may indicate vulnerability, to help inform treatment selection.

The present case report has several limitations. Symptom assessment was based on clinical interview and patient reports, without the use of standardized psychometric instruments such as the Yale-Brown Obsessive Compulsive Scale or structured interview (106), limiting objective quantification. Due to constraints inherent to real-world clinical practice, drug washout was not implemented. Rechallenge with cariprazine was not pursued due to patient refusal. Cross-titration was implemented in a relatively short period. Contributory effects of concurrently administered medications, including aripiprazole (either drug-related effects or withdrawal phenomena) and clonazepam, cannot be definitively excluded. All of these factors limited the ability to establish a confirmatory causal relationship, and the observed association between cariprazine and OC symptom exacerbation should be interpreted as suggestive rather than definitive. Alternative strategies, such as a slower cross-titration or more gradual exposure to cariprazine, were not explored in the present patient and may be considered in similar cases in the future.

The presence of premorbid, subclinical OC symptoms limited generalizability. The small possibility that the OC pathology worsened independent of pharmacological effects cannot be fully excluded.

The present report described the case of a 28-year-old female patient with premorbid, subclinical adolescent-onset OC symptoms, whose OC symptoms were exacerbated to the clinical level after cariprazine was introduced into the treatment regimen for bipolar II disorder. Mechanistic considerations involving serotonergic and dopaminergic systems have been discussed. Clinicians are advised to be cautious regarding the ability of cariprazine to induce OC symptoms in vulnerable cases. In particular, patients with pre-existing subclinical OC symptoms may benefit from close monitoring during the first week of treatment.