TCPR: What is schizo-obsessive disorder?
Dr. Poyurovsky: Schizo-obsessive disorder (schizo-OCD) is not a DSM diagnosis. The term is used to refer to patients with schizophrenic disorders that have comorbid features of OCD. We see these obsessive-compulsive symptoms in schizophrenia more often than would be expected by chance. About one in four patients have them, although only about half of those patients actually meet the full DSM-5 criteria for OCD. Often the OCD symptoms decrease during acute psychosis, so you are more likely to see them between psychotic episodes. It’s important to recognize schizo-OCD since functional outcomes are worse for these patients (Poyurovsky M. Schizo-Obsessive Disorder. New York, NY: Cambridge University Press; 2013).

TCPR: How does the presentation differ from classic OCD?
Dr. Poyurovsky: Many of these patients have classic OCD symptoms, but there is a subgroup of around 10%–20% whose obsessions and ­compulsions are intertwined with their psychotic symptoms. For example, compulsive behaviors are driven by psychotic delusions, such as voices telling them to wash their hands. These patients might not complain of the compulsions because they are not aware of them. This differs from classic OCD, where patients usually have some awareness that their obsessions and compulsions are irrational.

The Antipsychotic-OCD Controversy

TCPR: I’ve heard that antipsychotics can cause OCD, and I’ve also heard that they can treat OCD. What is going on there?
Dr. Poyurovsky: Yes—this goes both ways. We have many controlled trials where antipsychotics improved OCD, but they can also cause or exacerbate it, particularly clozapine and to a lesser extent olanzapine. My best estimate is that clozapine causes OCD in 10%–15% of cases, and this risk may be dose dependent. We published open-label reports of clozapine improving schizo-OCD in the 150–300 mg/day dose range, but when titrated beyond that, clozapine has the opposite effect of provoking OCD (Poyurovsky M, Isr J Psychiatry Relat Sci 2008;45(3):219–220; Poyurovsky M et al, Clin Neuropharmacol 1996;19(4):305–313).

TCPR: Is it just in schizophrenia that we see this effect, or can antipsychotics trigger OCD in anyone?
Dr. Poyurovsky: It seems to be a drug effect rather than an association with schizophrenia itself. Antipsychotics can cause obsessive-compulsive symptoms in schizophrenia, bipolar disorder, and some other psychotic disorders.

TCPR: Which antipsychotics are less likely to cause OCD?
Dr. Poyurovsky: There are some data on aripiprazole, as well as amisulpride, but that medication is only available in Europe. Both of these antipsychotics have limited 5-HT2A serotonergic antagonism, which suggests they have a low potential for causing OCD (Schirmbeck F et al, J Psychopharmacol 2013;27(4):349–357).

TCPR: Is 5-HT2A antagonism the mechanism through which antipsychotics cause OCD?
Dr. Poyurovsky: We don’t have the evidence, but the impression is that the more 5-HT2A serotonin antagonism you have with an increased dose, the more of an OCD-provoking effect.

TCPR: So serotonin 5-HT2A antagonism might cause OCD. Can dopamine antagonism treat OCD?
Dr. Poyurovsky: Yes. The most solid evidence is the therapeutic efficacy of augmentation with low-dose D2 dopamine receptor antagonists in patients with severe, classic OCD, primarily with risperidone and haloperidol. By low dose, I would say 2.5 mg of haloperidol and 2–3 mg for risperidone. Other antipsychotics have positive trials in OCD as well, like aripiprazole, olanzapine, paliperidone, and quetiapine, and these have broader effects beyond the dopamine system that might explain their benefits (Zhou DD et al, J Psychiatr Res 2019;111:51–58). On the other hand, dopamine agonists like pramipexole can trigger OCD symptoms.

TCPR: Are there other 5-HT2A antagonists that we should worry about in schizo-OCD?
Dr. Poyurovsky: Mirtazapine, for example, is a very important 5-HT2A antagonist. There are some cases where it seems to provoke OCD, and at a minimum, mirtazapine is not going to treat OCD.

Other Treatments

TCPR: Do patients with schizo-OCD respond to SSRIs?
Dr. Poyurovsky: In general, schizo-OCD is difficult to treat. I would consider an SSRI in schizophrenia only when the symptoms are typical for OCD and their severity reaches a threshold for clinical significance. SSRIs should be added only in stabilized antipsychotic-treated patients during remission, not during acute psychosis. My impression is that lower doses are often sufficient, as opposed to the high doses we typically use in “pure” OCD. However, the evidence base is still lacking.

TCPR: Why not start SSRIs during acute psychosis? What is the risk?
Dr. Poyurovsky: Clinical experience suggests that antidepressants may cause psychotic exacerbation and manic symptoms, especially when there is concurrent bipolarity, such as in schizoaffective disorder. Patients with a history of impulsivity and aggressiveness may also be at risk for psychotic exacerbation on SSRIs. Akathisia is another concern. Patients with schizo-OCD are more vulnerable to this side effect, which can happen on SSRIs as well as antipsychotics. The bottom line is that we should use the lowest effective dose, only add an SSRI when the patient’s active psychotic symptoms are in remission, and continuously monitor for risks like akathisia and psychosis.

TCPR: Are there other risks with SSRIs?
Dr. Poyurovsky: Yes. You also have to look at the pharmacokinetic interactions between antipsychotics and SSRIs. Fluvoxamine (Luvox), fluoxetine (Prozac), and paroxetine (Paxil) can raise some antipsychotic levels two- to 10-fold. Escitalopram (Lexapro) is not FDA approved for OCD, but it may be considered as an off-label choice in schizo-OCD patients because it lacks those drug-drug interactions (Stryjer R, Int Clin Psychopharmacol 2013;28(2):96–98).

TCPR: And what about clomipramine?
Dr. Poyurovsky: Clomipramine should be reserved for the next step—after failure of an SSRI—because it produces prominent hallucinogenic serotonergic effects and cardiotoxicity. One combination I would avoid in particular is clomipramine and clozapine, because both can cause cardiac arrhythmias, lower seizure threshold, and—in rare cases—paralytic ileus (Margeti´c B et al, Psychopharmacol Bull 2008;41(2):9–11).

TCPR: Are there other pharmaceutical options for schizo-OCD?
Dr. Poyurovsky: In 2008 we published a small trial of lamotrigine in patients who had schizophrenia and schizoaffective disorder with OCD. We found it efficacious for OCD as well as depressive symptoms after titrating to a dose of 200 mg/day (Poyurovsky M et al, J Psychopharmacol 2010;24(6):861–866). That was an open-label study, but the concept was later supported by two randomized controlled trials of lamotrigine in classic, pure OCD where it augmented SSRIs (Bruno A et al, J Psychopharmacol 2012;26(11):1456–1462).

TCPR: What are some challenges to using cognitive behavioral therapy (CBT) in schizo-OCD?
Dr. Poyurovsky: CBT should be considered in schizo-OCD only when the psychosis has stabilized and the patient has typical OCD symptoms. CBT would be particularly appropriate for patients who are compliant with treatment, who have good insight into their OCD symptoms, and who are capable of understanding cognitive therapy and ready to be involved with it, which is not easy for a lot of patients with schizo-OCD.

Diagnostic Tips

TCPR: How do you screen for OCD in schizophrenia?
Dr. Poyurovsky: I start with the typical questions used to identify OCD, screening for common dimensions of OCD. I’ll ask questions like “Do you keep checking things over and over again?”, “Do you repeatedly wash your hands?”, and “Do you have repetitive intrusive thoughts that you perceive as unwanted and would like to get rid of?”

TCPR: Do you run into things that obscure the diagnosis?
Dr. Poyurovsky: Yes. There are a few areas where symptoms of schizophrenia and OCD overlap and it can be difficult to tell them apart. For example, psychotic content may take an obsessive-compulsive form, as when a patient said to me, “It seems like my neighbors are watching my every move when I smoke on the balcony, so I am very conscious of this and try to handle myself perfectly. When I am doing something different, like moving my body too much in one direction, I then have to look at my neighbors’ windows and blink my eyes 10 times. Otherwise the paranoia gets worse.” In a case like that, I would not diagnose OCD because it is exclusively related to delusional content. I would wait and reassess after the psychosis resolves. There are other areas where we see overlap.

TCPR: Such as?
Dr. Poyurovsky: Obsessional doubt may be mistaken for schizophrenic ambivalence. OCD-related compulsions can resemble the manneristic, stereotypical behaviors that are common in schizophrenia. Akathisia can also be associated with repetitive OCD-like behaviors. For example, if your patient starts to ask you repetitive questions despite your repetitive answers, it might be akathisia. Then again, patients with schizo-OCD are also more prone to extrapyramidal symptoms and akathisia.

TCPR: DSM-5 recognizes OCD “with poor insight.” How do we tell the difference between that and schizophrenia?
Dr. Poyurovsky: One of the most important things is to identify the primary disorder. Is it primary OCD with some schizophrenia spectrum components like schizotypal disorder? Or is schizophrenia the primary disorder with OCD as a comorbidity? This is extremely challenging because in most patients the OCD symptoms begin before the psychotic symptoms. OCD tends to begin in childhood, but if it progresses to schizophrenia during adolescence, I would see schizophrenia as the primary diagnosis.

TCPR: I would also imagine that negative symptoms are more prominent in schizo-OCD than in pure OCD with poor insight.
Dr. Poyurovsky: Yes. Amotivation, flat affect, and other negative symptoms, as well as disorganized behavior and cognitive dysfunction, help to establish the correct diagnosis of schizophrenia. Family history can help too. We conducted a study on this and found higher rates of OCD, obsessive-compulsive personality disorder, and schizo-OCD in the family histories of patients with schizo-OCD, but not in the families of patients with pure schizophrenia (Poyurovsky M et al, Am J Med Genet B Neuropsychiatr Genet 2005;133B(1):31–36).

TCPR: Do you also see an association of OCD with other disorders?
Dr. Poyurovsky: Yes. In the past my impression was that due to pathophysiological and clinical linkage between OCD and schizophrenia, there is some “affinity” between the two disorders. Now I have a different impression—the prevalence of OCD in bipolar disorder is very substantial, around 10%–20%, particularly in bipolar depression (Ferentinos P et al, J Affect Disord 2020;263:193–208; Braverman L et al, Psychiatry Res 2021;302:114010).

TCPR: Thank you for your time, Dr. Poyurovsky.