How Does Clozapine Affect Checking Behaviors in People with Schizophrenia?

What you need to know

• Obsessive-compulsive symptoms (OCS) are common in people with schizophrenia treated with clozapine, with checking behaviors being especially prevalent
• Psychosis severity indirectly leads to checking behaviors by first causing obsessive thoughts
• After psychosis remission, higher clozapine doses are associated with more severe checking behaviors in some patients
• Understanding this process may help clinicians better manage symptoms in patients with schizophrenia

The Complex Relationship Between Psychosis, Medication, and Compulsive Behaviors

Many people with schizophrenia experience obsessive-compulsive symptoms (OCS) alongside their psychotic symptoms. These can include intrusive thoughts (obsessions) and repetitive behaviors (compulsions) like excessive checking. While the antipsychotic medication clozapine is often effective for treating schizophrenia, it may also play a role in the development or worsening of OCS in some patients. This complex relationship has puzzled researchers and clinicians for years.

A new study published in The British Journal of Psychiatry sheds light on how psychosis, clozapine treatment, and obsessive-compulsive symptoms interact over time in people with schizophrenia. The research team, led by Dr. Emilio Fernandez-Egea, followed 196 patients treated with clozapine for an average of 2.7 years, assessing their symptoms multiple times.

Psychosis Severity Linked to Obsessive Thoughts

The study found that the severity of a person’s psychotic symptoms was strongly associated with how many obsessive thoughts they experienced. This suggests that as psychosis worsens, it may directly lead to more intrusive and distressing thought patterns.

Dr. Fernandez-Egea explains: “We saw that when patients’ psychotic symptoms like delusions or hallucinations became more severe, they also reported more obsessive thoughts. This makes sense, as the distorted thinking in psychosis may fuel worry and repetitive thoughts.”

From Obsessive Thoughts to Checking Behaviors

Interestingly, the researchers found that psychosis severity didn’t directly cause an increase in compulsive checking behaviors. Instead, it led to checking indirectly by first increasing obsessive thoughts. In other words, as people experienced more intrusive thoughts due to their psychosis, they became more likely to engage in repetitive checking as a way to cope.

“Patients often described their checking behaviors as attempts to manage their psychotic fears,” says Dr. Fernandez-Egea. “For example, one person explained they needed to check everything was in place because they believed their neighbor was stealing from them.”

This finding highlights how compulsive behaviors in schizophrenia may initially serve as a way for patients to feel safer or more in control when experiencing psychotic symptoms.

The Role of Clozapine After Psychosis Remission

The study also explored what happens to checking behaviors after a patient’s psychotic symptoms improve with clozapine treatment. Among patients whose psychosis was in remission, the researchers found a significant correlation between clozapine dose and the severity of checking behaviors.

Dr. Fernandez-Egea elaborates: “In patients who were no longer actively psychotic, those on higher doses of clozapine tended to have more severe checking compulsions. This suggests clozapine might play a role in maintaining these behaviors even after the original psychotic trigger has resolved.”

This finding may help explain why some patients continue to struggle with OCS even when their schizophrenia symptoms are well-controlled. It also raises important questions about how to balance the benefits of clozapine in treating psychosis with its potential to exacerbate or maintain compulsive behaviors in some individuals.

A Two-Phase Model of OCS Development

Based on their findings, the researchers propose a two-phase model to explain how OCS develop and persist in people with schizophrenia:

1. Initial Phase: Psychosis leads to obsessive thoughts, which in turn cause checking behaviors as a way to cope with psychotic fears.

2. Maintenance Phase: After psychosis remission, clozapine treatment may contribute to the persistence of checking behaviors in some patients, possibly through its effects on brain chemistry.

This model helps explain why OCS can fluctuate over time in people with schizophrenia and why they may persist even when psychotic symptoms are well-controlled.

The Potential Role of Genetics

The study also explored whether certain genetic variations might make some people more susceptible to developing OCS when taking clozapine. While the sample size was too small to draw firm conclusions, the researchers found preliminary evidence that variations in genes involved in serotonin and glutamate signaling in the brain might play a role.

Dr. Fernandez-Egea notes: “This is an exciting area for future research. If we can identify genetic factors that predict who is more likely to develop OCS with clozapine treatment, it could help us personalize treatment approaches.”

Implications for Treatment

Understanding the complex relationship between psychosis, clozapine, and OCS has important implications for treating people with schizophrenia:

• Clinicians should be aware that severe psychosis may lead to an increase in obsessive thoughts and checking behaviors.
• After psychosis remission, persistent checking behaviors may be related to clozapine dose in some patients.
• For patients struggling with significant OCS, adjusting clozapine dose or adding medications that target the serotonin system (similar to those used to treat OCD) might be helpful.

Dr. Fernandez-Egea emphasizes: “It’s crucial to remember that clozapine is often a life-changing medication for people with treatment-resistant schizophrenia. The goal isn’t to avoid using it, but to understand its effects better so we can optimize treatment for each individual.”

Looking to the Future

While this study provides valuable insights, the researchers acknowledge that more work is needed. Future studies with larger sample sizes and longer follow-up periods could help confirm these findings and further explore the genetic factors involved.

Additionally, research into potential treatments specifically targeting clozapine-associated OCS is an important next step. This could include investigating the effectiveness of adding selective serotonin reuptake inhibitors (SSRIs) or other medications used to treat OCD in this population.

Conclusions

• Obsessive-compulsive symptoms in schizophrenia are complex, with both psychosis and clozapine treatment playing roles at different stages.
• Clinicians should monitor for OCS in patients with schizophrenia, especially during periods of severe psychosis and after starting clozapine treatment.
• Individualizing treatment approaches, potentially including clozapine dose adjustments or additional medications, may help manage OCS in people with schizophrenia.
• Further research is needed to better understand the genetic and neurobiological factors underlying the development of OCS in schizophrenia and to develop targeted treatment strategies.