Introduction
In the current psychiatric classifications, schizophrenia and obsessive-compulsive disorder (OCD) are regarded as distinct clinical entities characterized by specific diagnostic criteria, clinical presentations, prognosis, and treatment. Nevertheless, they share some demographic and clinical characteristics as well as underlying pathophysiologic mechanisms. The two disorders have similar prevalence estimates, gender distributions, age at onset, and course of illness. Neuropathologic and neuroimaging studies show a substantial overlap between schizophrenia and OCD in structural and functional brain abnormalities and in the involvement of dopamine, serotonin, and glutamate neurotransmitter systems in the pathophysiology underlying these disorders. Thus, it is not surprising that OCD occurs in a substantially higher proportion of schizophrenia patients than would be expected by chance ( Table 3.1 ).
| Schizophrenia | OCD | |
|---|---|---|
| Prevalence | ~ 1%, narrowly defined 2%–3%, broadly defined | 2%–3% |
| Gender ratio (M/F) | 1/1 | 1/1 |
| Age of onset | 2nd–3rd decade Men earlier than women | 2nd–3rd decade Men earlier than women |
| Course | Chronic with remissions | Chronic, wax and wane |
| Involved brain regions | Cortex: DLPC, temporal, ACC; thalamus, hippocampus, striatum | Cortex: OFC, ACC; thalamus, striatum |
| Neurotransmitter systems | Dopamine/serotonin/glutamate | Serotonin/dopamine/glutamate |
| Treatment | Antipsychotic agents (add-on serotonin reuptake inhibitors) | Serotonin reuptake inhibitors (add-on antipsychotic agents) |
This chapter focuses on the clinical characterization of the complex psychopathologic interface between schizophrenia and OCD, sometimes considered “obsessive-compulsive schizophrenia” (OC-SCZ). This chapter is a guide to improving early recognition, differential diagnosis, and treatment of this complex psychiatric disorder.
Schizophrenia
According to DSM-5 criteria, the diagnosis of schizophrenia is based on a constellation of positive, negative, and disorganized symptoms, illness duration (at least 6 months, including at least 1 month of active phase), and functional impairment, after exclusion of affective disorders, and psychotic disorders associated with substance abuse or general medical conditions. Psychopathologic symptoms of schizophrenia are differentially expressed among different patients and different phases of illness. Although various delusions might occur within the positive symptom dimension, a majority of patients exhibit a restricted set of typical delusional themes (e.g., reference, persecution, grandeur, somatic, guilt, jealousy). Hallucinations can occur in any of the sensory modalities, though auditory hallucinations, imperative voices commenting or conversing, are far more common. Formal thought disorders refer to disorganization of the logical and goal-directed thought process, and range in severity from mild circumstantiality, tangentiality, derailment, and neologisms to severe incoherence.
Negative symptoms are intrinsic to schizophrenia and include restricted and blunted affect, anhedonia, avolition, apathy, and alogia. Negative symptoms may be detected at every stage of illness, including prodromal, acute, and chronic, and are strongly associated with functional impairment. Motor symptoms of schizophrenia include slowness, complex stereotypic movements, mannerisms, and catatonic symptoms. Affective symptoms are common and may be part of the prodromal phase, follow an acute episode, or occur during remission from schizophrenia. Depressive symptoms substantially contribute to the disease burden and are strongly associated with suicidality in schizophrenia patients ( Table 3.2 ).
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Obsessive-Compulsive Disorder
According to DSM-5 criteria, and similar to schizophrenia, OCD is associated with disturbances of thoughts, affect, and motor function. According to DSM-5 criteria, a diagnosis of OCD requires either obsessions or compulsions that are time-consuming, cause distress, and substantially interfere with normal functioning. Typical obsessions and compulsions are repetitive and intrusive in nature, perceived as unwanted and excessive, and are not simply excessive worries about real-life issues.
Notably, the thoughts are recognized as products of patients’ own minds, in contrast to the phenomenon of mind reading in schizophrenia. In addition, the obsessive-compulsive (OC) symptoms are not attributable to the physiologic effects of a substance (e.g., a drug of abuse, a medication) or another medical condition (e.g., epilepsy, head trauma), and the disturbance is not better explained by the symptoms of another mental disorder (e.g., eating disorder, anxiety disorder). The content of obsessions differs substantially from patient to patient. However, similar to delusions (with their restricted set of distinctive themes), there are several typical themes of obsessions, namely contamination, symmetry, and forbidden thoughts (aggressive, sexual, religious). Specific obsessions are associated with corresponding compulsions and form psychopathologic dimensions that are relatively stable over time ( Table 3.3 ).
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Specify if:
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Near-Psychotic Symptoms in Obsessive-Compulsive Disorder
Despite clear-cut differences in psychopathology between schizophrenia and OCD, there is a substantial overlap, a “gray zone,” between the two disorders. Thus, unusual and “bizarre” obsessive themes exhibited by a subgroup of otherwise typical OCD patients might complicate the distinction between the obsessions and delusions. The difference between OCD-related pathologic slowness and the restrictive motor output associated with negative symptoms of schizophrenia or with catatonic motor disturbances is not straightforward. The differential diagnosis between OCD-related indecisiveness and pathologic doubt and schizophrenic ambivalence is also challenging. Patient insight into the senseless nature of OC symptoms is one of the hallmarks of the disorder. According to the DSM-5, at some point in the course of the illness, the patients must recognize that their obsessive beliefs are “definitely or probably not true.” Indeed, in typical OCD cases, patients readily acknowledge that their OC symptoms are illogical and pathologic.
On the other hand, a significant majority of schizophrenia patients either do not believe that they are ill, or even if they do acknowledge symptoms, they misattribute them to other causes. Nevertheless, a significant subset of OCD patients can sometimes present without insight, or with conviction that their obsessions are true, thus complicating the differential diagnosis of obsessions from delusions.
Overall, from the psychopathologic perspective, schizophrenia and OCD are distinct, despite their partially overlapping characteristics. Some symptoms, such as delusions and obsessions, pathologic doubt and ambivalence, rituals and motor stereotypy, may represent a continuum of OCD impairments, while others, such as negative and disorganized symptoms, are more schizophrenia-specific ( Fig 3.1 ).
Obsessive-compulsive disorder as a risk factor for schizophrenia
Ample evidence of a close interrelationship between the two disorders comes from epidemiologic studies that convincingly indicate that a diagnosis of OCD confers a risk for later development of schizophrenia. In a study based on Danish registries, prior diagnosis of OCD was associated with an increased risk of developing schizophrenia (incidence rate ratio [IRR] = 6.90; 95% confidence interval [CI], 6.25–7.60) and schizophrenia spectrum disorders (IRR = 5.77; 95% CI, 5.33–6.22) later in life. Similarly, children of parents with OCD had an increased risk of schizophrenia (IRR = 4.31; 95% CI, 2.72–6.43) and schizophrenia spectrum disorders (IRR = 3.10; 95% CI, 2.17–4.27). A Swedish registry-based longitudinal cohort and multigenerational family study found that patients with OCD had a substantially higher risk of having a comorbid diagnosis of schizophrenia and schizoaffective disorder compared with individuals without OCD. Individuals first diagnosed with OCD had a three fold higher risk of receiving a later diagnosis of schizophrenia compared with individuals without OCD.
From the perspective of psychotic diagnoses, patients first diagnosed with schizophrenia and schizoaffective disorder had a seven- and five-times higher risk of receiving a later diagnosis of OCD, respectively, in comparison with individuals without schizophrenia. A recent large-scale Australian epidemiologic study supports a link between the two disorders by showing a considerably higher risk of schizophrenia in the OCD group compared to matched non-OCD controls (hazard ratio: 30.29, 95%, CI, 17.91–51.21). Notably, male gender, age of OCD onset before 20 years, and antipsychotic prescriptions were associated with schizophrenia. Overall, these well-designed large-scale epidemiologic investigations convincingly demonstrated that it is essential for psychiatrists to be aware that OCD may herald further development of schizophrenia as a pathophysiologically related comorbid disorder, or even as a unique entity, namely OC-SCZ.
Obsessive-compulsive disorder/symptoms in schizophrenia
Prevalence
Initially, OC symptoms were thought to occur in a minority of patients with schizophrenia (1.1%–3.5%), and were considered a positive prognostic sign. In contrast to these early studies, modern large-scale investigations using structured clinical interviews, and operationally defined diagnostic criteria for OCD and schizophrenia, revealed that obsessive-compulsive phenomena are prevalent and clinically significant in schizophrenia patients. Thus, based on an analysis of 34 studies with more than 3000 participants that explicitly focused on the assessment of OCD/OC symptoms in patients with schizophrenia, an estimated pooled prevalence of OCD in schizophrenia was 12.1%. This rate is significantly higher than the lifetime rate of OCD found in the general population (1.3%–2.3%). Importantly, when the diagnostic threshold is relaxed, the proportion of schizophrenia patients with obsessive-compulsive symptoms rises to 25%.
Several conclusions from this meta-analysis are relevant to clinical practice. For patients with acute psychosis, it is useful to reassess the presence of OCD after resolution of psychosis, since OCD symptoms might then be more easily detectable, which could explain the higher rates of OCD found in outpatients. Since there is a higher prevalence of OCD after repeated schizophrenia episodes, when compared to first-episode patients, it may be that OCD rates may increase over time. This could be due to temporal fluctuations, antipsychotic treatment, or other factors. Ongoing longitudinal evaluation of OCD symptoms is thus warranted during the course of schizophrenic illness.
Clinical Characteristics of Obsessive-Compulsive Symptoms in Schizophrenia
Notably, complexity of obsessive-compulsive phenomena in schizophrenia goes beyond the typical OC symptoms. Unique obsessive-compulsive psychopathologic complexes have been found exclusively in patients with OC-SCZ (e.g., compulsive handwashing due to command auditory hallucinations; ego-dystonic obsessions experienced as thought insertions or auditory hallucinations). In view of the fact that these complex psychopathologic features are not captured by currently used diagnostic instruments (e.g., Yale Brown Obsessive Compulsive Scale, YBOCS), it is plausible that the overall prevalence of obsessive-compulsive features in schizophrenia is underestimated at present.
Similar to their OCD counterparts, a majority of patients with OC-SCZ have both obsessions and compulsions, while a few patients having mono-symptomatic OCD. The most frequently observed obsessions are aggressive, contamination, somatic, and symmetry, and the most frequently observed compulsions are checking, cleaning/washing, ordering/arranging, and counting. Factor analytic studies exploring an underlying structure of OC symptoms in schizophrenia point toward the existence of five psychopathologic dimensions that resemble those found in “pure” OCD. The first factor (forbidden thoughts) includes aggressive, sexual, and religious obsessions and counting compulsions; the second factor (symmetry) includes symmetry obsessions and ordering compulsions; the third factor (cleaning) includes contamination obsessions and cleaning compulsions; the fourth factor (somatic) includes somatic obsessions and repeating compulsions; the fifth factor (hoarding) includes hoarding obsessions and checking and repeating compulsions. Temporal stability of these factors in patients with OC-SCZ has not yet been determined.
The mean severity of OC symptoms in OC-SCZ patients is substantial and ranges from moderate to severe (total Y-BOCS = 16 to 40). OC symptom severity seems to progress during the course of schizophrenia, and there is indeed a positive correlation between duration of schizophrenia and severity of OC symptoms. Notably, the relationship between OC symptoms and specific schizophrenia subtypes is less clear. Although there is some indication of more frequent OC symptoms in patients with paranoid, schizo-affective, or undifferentiated subtypes of schizophrenia, a majority of studies failed to reveal predominance association with any specific subtype of schizophrenia.
Likewise, reports concerning OC symptom effects on schizophrenia symptom severity are inconsistent. Some studies, primarily those investigating recent-onset schizophrenia, show lower severity of delusions, formal thought disorder, and anergia. At the same time, other studies have shown higher schizophrenia symptom severity in patients with chronic OC-SCZ. Most reports, however, do not reveal differences in schizophrenia symptom severity as a function of comorbid OCD. Differences in study design, sample sizes, and assessment instruments and the inclusion of diverse patient populations may account, at least in part, for these discrepancies.
A meta-analysis that aimed to clarify the effect of OCD/OC symptoms on the severity of schizophrenia symptoms found that the presence of OC symptoms was associated with higher global, positive, and negative symptoms. Overall, the finding of a greater severity of psychosis in OC-SCZ is in line with poorer social and vocational functioning and poorer prognosis in this subset of schizophrenia patients.
Insight in patients with obsessive-compulsive schizophrenia
Insight has consistently been considered one of the key distinguishing features between obsessive-compulsive and psychotic phenomena. Nevertheless, studies demonstrate that patients with OCD may exhibit varying degrees of insight into the validity of their beliefs ranging from lack of insight to full insight. Poor insight was found in a substantial proportion (up to 40%) of OCD patients. DSM-5 acknowledges this phenomenon and adds the following specifier: with good or fair insight : the individual recognizes that OCD beliefs are definitely or probably not true or that they may or may not be true; with poor insight : the individual thinks OCD beliefs are probably true; with absent insight/delusional beliefs : the individual is completely convinced that OCD beliefs are true.
Extensive research into the category of insight, using standardized instruments for the evaluation of awareness of schizophrenia (Scale to Assess Unawareness of Mental Disorder) and insight into OCD (The Brown Assessment of Beliefs Scale), shows that a majority of patients with OC-SCZ have good or fair insight into OC symptoms, which makes them distinguishable from psychotic symptoms. In some cases, however, OC symptoms are characterized not by insight, but rather by full conviction and belief. Moreover, during psychotic exacerbations, obsessions might transform into delusional content and form complex psychopathologic phenomena that incorporate both obsessive-compulsive and other psychotic elements.
These patients pose a particular diagnostic challenge. From clinical experience, poor insight obsessions can be differentiated from delusions based on the typical OCD content (e.g., contamination), accompanying compulsions (e.g., checking, ordering), intact perception, and lack of delusional affect. Importantly, high awareness of OC symptoms apparently does not translate into meaningful awareness of psychotic schizophrenia symptoms. In fact, multiple self-awareness indices found no difference between schizophrenia groups with and without OCD, implying that OC symptoms do not significantly modify patients’ awareness of psychosis. Considering that poor awareness of schizophrenia is often associated with poor treatment compliance and poorer outcome, improvement of general illness awareness is critical for improving the prognosis of schizophrenia patients with or without OCD.
Ages of Onset for Schizophrenia and Obsessive-Compulsive Disorder
Schizophrenia onset age ranges from mid-adolescence to late adulthood, and peaks in early adulthood. OCD age at onset appears to be earlier, with roughly half of all cases beginning in childhood and adolescence. The two disorders each have a remarkably similar earlier age at onset in men than in women. Extensive research on age at onset in schizophrenia and OCD clearly demonstrates its clinical and prognostic significance. Patients with earlier age at onset of schizophrenia are more likely to be male, have poor pre-morbid adjustment, lower educational achievement, more evidence of structural brain abnormalities, and greater cognitive impairments and treatment resistance. Correspondingly, early-onset OCD has been associated with male predominance, tic disorders, greater symptom severity, and treatment resistance. The finding that patients with early onset are more likely to have relatives with the same illness suggests that early age at onset may be related to greater genetic vulnerability.
Comparative evaluation of age at onset of first schizophrenia and OC symptoms in patients with OC-SCZ found that the mean age of OCD onset was earlier than the mean age of schizophrenia onset (mean difference 1.04 years; 95% CI: 0.67–2.15). One study employed a systematic assessment of age at onset of schizophrenic and OC symptoms among 133 patients (97 men, 36 women; mean age 31.1 ± 8.7 years, mean number of hospitalizations 2.9 ± 2.6) who were consecutively hospitalized at Tirat Carmel Mental Health Center (Israel) and who met DSM-IV criteria for both schizophrenic or schizoaffective disorder and OCD. Briefly, age at onset of the first OC symptoms preceded age of onset of first psychotic symptoms (19.1 ± 7.7 years vs. 20.4 ± 5.9 years; P < .05). When gender was considered, there was a significantly earlier age of onset of OC symptoms than schizophrenic symptoms in men (18.3 ± 6.5 vs. 19.8 ± 4.8 years, P < .05), but not in women (21.2 ± 9.2 vs. 22.1 ± 7.9 years, P = .55).
A secondary analysis revealed that in first-episode predominantly drug-naïve schizophrenia patients ( n = 55) OC symptoms emerged approximately 3 years earlier than psychotic symptoms (18.2 ± 6.2 vs. 21.6 ± 6.2; P < .05). Notably, the average age at onset of first psychotic symptoms was significantly earlier in OC-SCZ patients than in their non-OCD schizophrenia counterparts (20.4 ± 5.9 vs. 23.4 ± 6.7 years; P < .001). Overall, the earlier age at onset of OC symptoms than schizophrenia symptoms in OC-SCZ patients suggests that they are independent of psychosis and are not subsequent to schizophrenia-related factors (e.g., antipsychotic treatment). If replicated in larger independent samples of OC-SCZ patients, these findings may indicate an accentuated neuro-developmental origin of OC-SCZ disorder, with earlier onset in men.
Course of Illness
OC symptoms may present across the life span in adolescent, adult, and elderly patients with schizophrenia. The course of OC-SCZ is chronic, and the possibility of full remission is relatively low. Symptom severity fluctuates over time, and there are several patterns of onset and progression of the illness. Studies have shown that in a majority of patients with OC-SCZ, OC symptoms precede initial psychotic symptoms in about 40% of patients, may succeed psychosis in 40%, and occur concurrently with psychotic symptoms in around 20%. In a 5-year follow-up of 172 patients admitted with first-episode schizophrenia, 49% had no OC symptoms anytime during the course, 15% had OC symptoms only during the first assessment, 13% had persistent OC symptoms, 7% developed OC symptoms subsequently, and 16% had intermittent OC symptoms, suggesting that the course of OC symptoms is variable. 21
Based on clinical experience, Hwang et al. described some potential OC symptom trajectories in schizophrenia. OC symptoms may occur during the prodromal phase, preceding the acute phase of schizophrenia, and may resolve or attenuate after the onset of psychosis. Alternatively, OCD that predates the onset of schizophrenia may persist or worsen regardless of schizophrenic illness progression, as an independent but coexisting disorder. Patients in this category may have initially met criteria for OCD, and subsequently developed psychosis that meets criteria for schizophrenia. Finally, OC symptoms that may develop as part of an acute psychosis will typically resolve with overall improvement in psychosis. The diminished OC symptoms may then present as obsessive rumination or obsessive doubt.
Three Obsessive-Compulsive Disorder Onset Patterns in Relationship to Schizophrenia
Several patterns of onset sequence of obsessive-compulsive and schizophrenia symptoms point toward the existence of more than one underlying mechanism of their temporal interrelationship. OC symptoms may co-occur with attenuated psychotic symptoms during a prodromal phase of schizophrenia. These subthreshold OCD symptoms can be considered early symptoms of schizophrenia. Alternatively, OC symptoms may precede schizophrenia in the form of full-scale OCD. From the clinical perspective it is important to note that at least some of these patients will be treated with selective serotonin reuptake inhibitors (SSRIs) and might be susceptible to the development of psychosis. Personal and/or family history of schizophrenia-spectrum disorders in patients with primary diagnosis of OCD should alert psychiatrists to increased risk for psychosis.
When OC symptoms follow the occurrence of schizophrenia, they can be associated with the pathophysiologic and psychological changes of schizophrenia. During the continuing course of schizophrenia, psychotic experiences may become a “focus of obsessive preoccupation,” giving rise to the appearance of complex psychopathologic phenomena psychotic in content and obsessive in form. These cases, though rare, further support the presence of a psychopathologic continuum between obsessive-compulsive and psychotic phenomena.
Finally, OC symptoms in schizophrenia may be a consequence of antipsychotic treatment, given that there are many reports that atypical antipsychotic agents can induce de novo, or exacerbate preexisting OC symptoms in schizophrenia patients.
Depressive symptoms and suicidality in obsessive-compulsive schizophrenia
Several studies note the impact of OC symptoms on the depressive dimension among schizophrenia patients. Thus, Szmulewicz et al. showed a positive correlation between suicidality and intensity of OC symptoms (YBOCS, r = 0.513, P = .01), and with both YBOCS obsession ( r = 0.444, P = .01) and compulsion subscales ( r = 0.433, P = .01) in a study of 65 schizophrenia patients. Moreover, the total YBOCS was also significantly correlated with depressive symptoms ( r = 0.389, P = .01) and with YBOCS score higher than 8, indicating that clinically significant OCD severity of OCD is an independent predictor of suicide attempts. The impact of OCD on suicidality has been confirmed in a study of 246 patients after first-episode psychosis, where presence of OCD ( N = 26, 10.6%) was associated with more suicidal plans and attempts in the month before hospitalization. In addition, a 5-year longitudinal follow-up of 176 patients with a first-episode psychosis showed that patients with OCD displayed more severe depressive symptoms at admission and during the follow-up.
Overall, OCD/OC symptoms appeared to be associated with depressive symptoms and suicidality among patients with schizophrenia. Even so, none of these studies evaluated depressive symptoms with the Calgary Depression Scale (a questionnaire validated for assessing depressive symptoms while differentiating them from schizophrenia negative symptoms). Clinicians’ awareness and repeated clinical assessments with particular focus on depressive dimensions and suicidality are warranted to ensure early recognition and adequate management of these symptoms in OC-SCZ patients.
Neuropsychological Profiles in Obsessive-Compulsive Schizophrenia
Neuropsychological studies suggest that patients with OC symptoms have diminished executive functioning, cognitive deficits, and increased negative symptoms, as compared to patients with non-OC schizophrenia. Hwang et al. showed that patients with OC symptoms completed fewer categories on the Wisconsin Card Sorting Test ( P < .05) with a greater perseverative error ( P < .01), as compared to the non-OC symptoms patients. In addition, OC-SCZ had higher negative symptom ratings on psychopathologic assessment with the Positive and Negative Symptoms Scale ( P < .05) compared to non-OC symptoms patients. Michalopoulou et al. showed that patients with OC schizophrenia had significantly lower processing speed measured by the reading condition of the Stroop test compared to non-OC schizophrenic patients. Overall, this neurocognitive profile suggests greater impairment of the frontal lobe structure and function.
Additional Comorbidities in Obsessive-Compulsive Schizophrenia
A substantial proportion of patients with both schizophrenia and OCD exhibit additional psychiatric disorders during the life span. Panic anxiety ( Chapter 4 ), social anxiety ( Chapter 5 ), major depressive disorders ( 6, 7 ), and substance use (see Chapter 8 ) are frequently diagnosed comorbidities in both schizophrenia and in OCD. In addition, OCD has also been strongly associated with such OCD-related DSM-5 disorders as body dysmorphic disorder, hypochondriasis, tic disorders, and eating disorders. Such OCD-comorbid psychiatric conditions as body dysmorphic disorder and tic disorders may share OCD etiologic pathways, while others (e.g., major depression) may represent secondary syndromes. Indeed, considerable overlap has been found in the clinical presentation, familial inheritance, basal ganglia dysfunction, and pharmacotherapy between body dysmorphic disorder, tic disorders, and OCD.
If OC symptoms represent a distinct dimension of psychopathology in schizophrenia, there might be a preferential aggregation of OCD-related disorders in patients with OC-SCZ compared to non-OCD schizophrenia. Indeed, comparing two relatively large schizophrenia patient groups with and without OCD (100 patients per group), over half of the patients had at least one additional psychiatric disorder, supporting the high comorbidity of schizophrenia. Major depression was most frequent, followed by anxiety disorders.
Comparing the two groups, there was a robust differentiation with respect to combined OCD-related disorders evaluated in the study. This difference was primarily due to a substantially higher rate of tic disorders and body dysmorphic disorder in the OC-SCZ group, as compared to the non-OCD schizophrenia group. There was also a higher rate of comorbid eating disorders and hypochondriasis in the OC-SCZ group, however this difference became nonsignificant after adjustment for illness age at onset. Overall, combining OCD-related disorders yielded a robust between-group difference in a number of patients with at least one OCD-spectrum disorder (OC-SCZ 30/100 vs. schizophrenia 8/100; OR = 4.35; 95% CI = 2.13 to 11.41; P = .001).
Moreover, patients with two comorbid OCD-spectrum disorders were found only in the OC-SCZ group (8/100 vs. 0/100, χ 2 = 8.33, P = .0039). These findings strongly suggest that there is a specific elevation in the rate of OCD-related disorders in OC-SCZ patients, rather than generally elevated psychopathology. From a clinical perspective, observation of either OCD or OCD-related symptoms supports careful evaluation for all OCD group syndromes.
Obsessive-Compulsive Symptoms in Prodromal Schizophrenia
Current criteria for individuals at ultra-high risk (UHR) of psychosis include one or more of: attenuated psychotic symptoms, brief limited intermittent psychotic symptoms (less than a week, with spontaneous resolution), or trait and state factors (e.g., presence of schizotypal personality traits). However, since most clinical investigations show substantial clinical heterogeneity, many researchers focus on other psychopathologic dimensions that might predict transition to psychotic disorders.
OCD/OC symptoms has been one area of interest. Several studies estimated their prevalence at 8.4% to 20% in UHR populations. To date, though, no studies offer significant findings for OCD-related transition risk in UHR individuals. Thus, in a retrospective cohort of 64 UHR subjects, there was a lower risk of psychotic transition rate among the 20% of subjects with OCD (transition rate 0% in the OCD group vs. 22% in the non-OCD group, P > .05). Fontenelle et al. followed up 37 UHR subjects for 7 years and did not report differences in transition to psychosis based on the presence of OCD at baseline. Notably, incident OC symptoms were associated with greater risk of transition to delusional disorder, psychotic disorders not otherwise specified, depression, or bipolar disorder with psychotic features, but not with schizophrenia.
Overall, since OCD/OC symptoms are prevalent in UHR individuals at a rate comparable to that in first-episode and chronic schizophrenia patients, it appears that OCD persists over the full course of schizophrenia. Moreover, OC symptoms in the prodromal phase of schizophrenia have been associated with higher severity of positive symptoms, distress, depression, and suicidality. The association of obsessive-compulsive and negative symptoms of schizophrenia is particularly challenging in terms of differential diagnosis, treatment, and prognosis. In a vast majority of schizophrenia patients, OC symptoms continue beyond the prodromal phase of schizophrenia.
Interview and Assessment Guidelines for Obsessive-Compulsive Disorder Screening in Schizophrenia
Formal guidelines do not yet exist for assessment, identification, and management of obsessive-compulsive phenomena in high-risk individuals, or in prodromal or established schizophrenia patients. Based on clinical experience, the following recommendations can be considered:
- 1.
It is essential to screen individuals who are at high risk or in a prodromal stage of psychosis for OCD/OC symptoms owing to their high prevalence and clinical significance. Conversely, inquiry about attenuated psychotic experiences in patients who present with “full-blown” OCD is prudent, especially in individuals who have a family history of either schizophrenia-spectrum disorders or OCD related disorders.
- 2.
Organic causes for both psychotic and OC symptoms should be ruled out. Metabolic, endocrine, or neurologic factors (e.g., Sydenham’s chorea, Huntington’s disease) can account for both psychotic or OC symptoms and their co-occurrence.
- 3.
Close follow-up is crucial for obsessive-compulsive and attenuated psychotic components that present during a prodromal phase. The validity of the original diagnosis of prodromal syndrome is provisional, and determined over time. There can be progression to psychosis, to another disorder (e.g., affective), to continuing prodrome, or to remission.
- 4.
Assessment of OCD/OC symptoms after schizophrenia onset can be difficult. Patients may be focused on hallucinations and paranoid delusions, and may have impaired cognition or paranoid fears that frustrate even a very careful interview technique. Even so, many patients can describe OC symptoms in response to specific and carefully phrased questions.
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Some patients may have psychotic-like symptoms that suggest an OCD core. Awareness of these phenomenon, distress, and voluntary reporting suggest an OCD rather than a perceptual core. For example:
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Difficulty differentiating between repetitive thoughts and voices
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Repetitive handwashing, checking locked doors, compulsive rituals
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Other patients may have OCD symptoms so well incorporated into psychotic phenomenology that the degree of OCD contribution is at first inapparent. For example:
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Eccentric dress (i.e., all white clothing) to ward off feared persecutors
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Unusual diet (i.e., no tap water) for fear of poison
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Ritualized behaviors (i.e., eccentric repetitive movements) directed by voices
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Comorbid and premorbid OCD/OC symptom histories may be easier to assess after psychosis is diminished by medication. Full lifetime OC symptom history is essential for understanding the illness as a whole.
Treatment of Obsessive-Compulsive Schizophrenia
Patients with OC-SCZ represent a difficult-to-treat subgroup that requires a distinct therapeutic approach. Addition of an adjunctive SSRI can sometimes effect significant benefit. Escitalopram and sertraline may have more benign pharmacokinetic profiles than other SSRIs. SSRI doses are generally higher than for non-psychotic depression, but perhaps not as high as for non-psychotic OCD.
Even so, there are many treatment approaches and challenges to consider with these patients. When is monotherapy with an antipsychotic agent appropriate, and when is it more effective to add anti-obsessive agents (SSRIs or clomipramine)? At what point should anti-obsessive agents be initiated? What are the short- and long-term risks and benefits of antipsychotic-SSRI combinations? Which patients are susceptible to antipsychotic-induced OC symptoms? How should antipsychotic-induced OC symptoms be treated? What is the role of nonpharmacologic (e.g., cognitive-behavioral therapy [CBT]) intervention in the management of patients with OC-SCZ?
Monotherapy with atypical antipsychotics for obsessive-compulsive schizophrenia
Typical antipsychotic agents seem to be of limited therapeutic value for patients with OC-SCZ presumably due to their limited serotonergic properties. A majority of reports to date indicate that atypical antipsychotics with their serotonin/dopamine antagonism might induce de novo or aggravate preexisting OC symptoms in schizophrenia patients. Nevertheless, there is preliminary evidence indicating that monotherapy with some atypical antipsychotics may attenuate OC symptoms, pointing toward a potential bidirectional (alleviating vs. provoking) effect on OC symptoms in schizophrenia. Thus, olanzapine was efficacious in ameliorating both psychotic and OC symptoms in a large-scale randomized study in young patients with recent-onset schizophrenia-spectrum disorders. By the end of a 6-week trial, olanzapine (mean dose 11.3 mg/day) but not risperidone (mean dose 3.0 mg/day) was associated with a meaningful decrease in the severity of OC symptoms (YBOCS, -2.2 vs.-0.3, z = -2.651, P < .01).
Similarly, in a 6-week, open-label, flexible-dose trial, monotherapy with aripiprazole (10–30 mg/day) resulted in a meaningful clinical improvement of OC symptoms in schizophrenia patients who were partially responsive to a prior exposure to either typical or atypical antipsychotic agents. Even modest improvement of functioning, due to improvement in OC symptoms, as in this study, might be clinically meaningful for schizophrenia patients. In addition, amisulpride (not currently available in the United States) may effect amelioration of OC symptoms in schizophrenia patients. Although the underlying mechanism of this positive effect of antipsychotics on OC symptoms is unclear, it could be related to differing serotonergic effects. Notably, aripiprazole is distinguished by its partial dopamine agonism coupled with a low 5-HT 2 to D 2 affinity ratio and a low 5-HT 1A receptor occupancy. Amisulpride is distinguished by its highly selective dopamine D 2 /D 3 receptor antagonism and a minimal affinity for the 5-HT 2A receptor.
Addition of serotonin reuptake inhibitors for obsessive-compulsive schizophrenia
The independent nature of OC symptoms in a vast majority of patients with OC-SCZ and their clinical similarity with “pure” OCD prompted evaluation of adjunctive anti-obsessive agents for antipsychotic-treated schizophrenia patients. Adjunctive escitalopram (10–40 mg/day), a common SSRI, showed a beneficial effect on OC symptoms in several open-label prospective trials in schizophrenia patients. The drug’s well-tolerated side effect profile and paucity of drug-drug interactions was substantiated. No clinically significant side effects or worsening of psychosis were observed.
On the other hand, while adjunctive fluvoxamine (100–200 mg/day) has been evaluated in several small studies and demonstrated its potential to reduce the severity of OC symptoms and associated pathologic slowness and doubt, side effect concerns remain. Fluvoxamine may exacerbate psychosis and increase aggressiveness in those OC-SCZ patients with prior impulsivity or aggressive behavior.
Adjunctive clomipramine, a tricyclic antidepressant and a nonselective SRI, was also evaluated as a putative therapeutic option, but with important side effect concerns. A small placebo-controlled crossover study and a number of case reports revealed that clomipramine (dose range 50–300 mg/day) was associated with a beneficial effect on OC symptoms, reduction of anxiety accompanied by compulsive rituals, and improvement of positive and negative schizophrenia symptoms in some OC-SCZ patients. However, lack of therapeutic effect of clomipramine and exacerbation of psychosis were also reported. In addition, the anticholinergic properties of clomipramine, its cardiovascular side effects, and associated weight gain limit its utility in schizophrenia patients, particularly those who are treated with low-potency typical antipsychotic agents, anticholinergic agents, or clozapine.
Overall, the SSRIs exert a favorable effect on OC symptoms in certain schizophrenia patients. Therapeutic dose ranges for adjunctive SSRIs while treating schizophrenia patients are not well established. Indeed, a sizeable proportion of OC-SCZ patients do not respond or are intolerant to SSRI addition. Predictors of response and long-term treatment outcomes are not yet known. Limited clinical experience suggests that some OC-SCZ patients can better tolerate therapeutic SSRI doses if they also receive clonazepam q12h at an adequate dose.
An additional concern about of SSRI-antipsychotic drug combinations is the potential for clinically significant pharmacokinetic drug interactions. Fluvoxamine, fluoxetine, and paroxetine may elevate plasma concentrations of antipsychotics 2- to 10-fold. This in turn may increase the likelihood of antipsychotic drug-induced side effects (e.g., extrapyramidal side effects, decreased seizure threshold, excessive sedation).
Clozapine is currently the most effective available antipsychotic. However, due to a high burden of adverse effects (e.g., potentially life-threatening agranulocytosis, paralytic ileus, seizures), clozapine is reserved for treatment-resistant schizophrenia patients. In contrast to apparent efficacy in schizophrenia patients, clozapine was found ineffective in patients with OCD. There is compelling evidence that links clozapine with precipitating or worsening obsessions and compulsions in individuals with schizophrenia. However, there is also preliminary data indicating that clozapine in a relatively low-dose range with or without SSRIs may exert a beneficial effect at least in some OC-SCZ individuals. Undoubtedly, more controlled investigations are warranted to elucidate predictors and risk factors of bidirectional (OC symptom-attenuating vs. OC symptom-provoking) effect of clozapine in patients with OC-SCZ.
Overall, it seems that for some patients with OC-SCZ, monotherapy with atypical antipsychotics may improve both schizophrenic and obsessive-compulsive dimensions of psychopathology without running the risk of OC symptom exacerbation. The identification of clinical and biological predictors of such a positive response is a major unmet need in pharmacologic management of patients with OC-SCZ.
Nonpharmacologic treatment for obsessive-compulsive schizophrenia
Psychoeducation, stress management, and family support are important for patient management. CBT along with pharmacotherapy is a first-line treatment for OCD. In contrast, the role of CBT in treating OC symptoms in schizophrenia is uncertain. This reflects concerns that accentuated stress of exposure-based interventions may increase vulnerability to psychotic relapse. Nevertheless, one open-label study reported that schizophrenia patients with OC symptoms do adhere to CBT, and that adjunctive CBT may be an effective alternative to an SSRI for at least some patients without increasing the risk of psychosis.
On the positive side, CBT avoids drug-induced side effects and drug-drug interactions associated with adjunctive SSRIs, and may be beneficial to those where SSRIs are contraindicated or intolerable. Limitations include the need for an experienced therapist, cost, CBT treatment time span, and concerns about psychotogenic effects. A more graded approach for OC-SCZ patients than for patients with OCD alone seems reasonable. Close monitoring of mental state and regular assessments of symptoms are important for addressing all risks and benefits.
Electroconvulsive therapy for obsessive-compulsive schizophrenia
Electroconvulsive therapy (ECT) is not an approved therapy for OCD. ECT is indicated for schizophrenia patients for catatonia, treatment resistance, and when pharmacotherapy is contraindicated. There are a few case reports that suggest the utility of ECT for patients with OC-SCZ who did not respond to or could not tolerate side effects associated with psychotropic agents and in cases in which the severity of the symptoms poses a serious threat to the patient’s mental health and physical safety. Side effects (e.g., memory disturbance), perceived stigma, and patient preference need to be considered prior to ECT.
Treatment of obsessive-compulsive symptoms in high-risk individuals
Pharmacotherapy should be considered, in addition to psychoeducation, family support, and stress management. SSRIs can be used for clinically significant OCD, combined with rigorous monitoring of attenuated positive symptoms. Some UHR patients with OCD/OC symptoms may benefit from a low-dose antipsychotic medication trial, even though these are not currently recommended for ongoing treatment of attenuated prodromal symptoms. Long-term treatment with antipsychotic agents should be considered only after the established diagnosis of schizophrenia. All treatment approaches require scrupulous risk/benefit evaluations.
Antipsychotic-induced obsessive-compulsive symptoms
There are many reports that atypical antipsychotic agents with anti-serotonergic properties can induce or exacerbate OC symptoms. While schizophrenia patients with preexisting OC symptoms may be at particular risk of drug-induced exacerbation of obsessions and compulsions, the majority of reports deal with de novo emergence of OC symptoms.
In most patients with olanzapine-, risperidone-, and quetiapine-induced OC symptoms, the symptoms appeared during initial treatment weeks. A wide dose range is associated with the OCD-provoking effects of olanzapine (5–25 mg/day) and clozapine (150–900 mg/day), but only relatively high risperidone (> 4 mg/day) and quetiapine (450–1100 mg/day).
Dose reduction is a reasonable first step to control antipsychotic-induced OC symptoms. A combination of a dose reduction and SSRI co-administration is an appropriate next step. Clomipramine may be needed to ameliorate antipsychotic-induced OC symptoms. Pharmacokinetic and pharmacodynamic drug-drug interactions should be explored carefully. Discontinuation of the offending compound and a switch to an atypical antipsychotic with lower potential to induce OC symptoms, such as aripiprazole and amisulpride, should be considered.
Fictional Case: Prodromal Obsessive-Compulsive Disorder Preceding Schizophrenia Onset
A 28-year-old single white male began showing symptoms of OCD at age 12, including ritualistic touching before meals and prolonged handwashing many times each day. He was first brought to treatment at age 15, 7 months after he began to have paranoid delusions that his food had been poisoned, critical auditory hallucinations, and a slight reduction in obvious OC behaviors. He was diagnosed then with paranoid schizophrenia, and treated with a variety of antipsychotic medications over time. Each medication diminished but did not stop psychotic symptoms. He had several psychotic exacerbations over the years, each responding to temporarily increased antipsychotic medication.
His most recent hospitalization followed another acute exacerbation of paranoid delusion, auditory hallucinations with concurrent panic anxiety, accompanied by increased ritualistic behavior. In the hospital, he was noted as repetitively touching objects, opening and closing doors, and forcefully rubbing his eyes to the point of injury. Medical evaluation, including brain CT scan, was normal. His newly noted panic anxiety was treated with clonazepam titrated up to 1 mg q12h, while his newly diagnosed OCD was treated with fluoxetine, rapidly titrated up to 60 mg qd (clonazepam may have helped prevent potential fluoxetine-induced agitation). He was continued on fluphenazine decanoate (50 mg/2 weeks). After 4 weeks of fluoxetine 40 mg/day, his rituals became less frequent and intense, with improved socialization and therapy participation and a marked reduction in psychosis.
His family was happy with the level of improvement. Even so, there were brief episodes of noncompliance and ongoing non-psychotic emotional distress. Skillful psychotherapy was necessary to ensure medication compliance and to help him navigate the slow transition to a less symptomatic and more functional life.
Conclusions and future directions
Overall, a substantial body of evidence indicates that OCD and OC symptoms represent a clinically meaningful dimension of psychopathology in schizophrenia, and that OC-SCZ may have distinct clinical and neurobiological characteristics, treatment response, and prognosis, suggesting a possibly distinct diagnostic entity. Provisional diagnostic criteria for the identification of OC-SCZ have been suggested.
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