Clozapine and New-Onset Obsessions

Clozapine as a treatment option has many strengths. But it also has some weaknesses. This week I had a patient who has been stable on clozapine for ages, but now has a new problem related to this drug.

My patient has a well known problem associated with clozapine that is fortunately rare – obsessional phenomena. Till date, we do not know what makes some patients on clozapine to develop obsessions and compulsions.

Glutamate modulation, serotonergic 5-HT2C hypersensitivity and dopaminergic ‘escape’ after chronic blockade are all suspected but none of these mechanisms are proven to be causal (1).

So how can we manage this?

(1) Clozapine dose reduction is a popular strategy in practice, though this may not be always practical when the patient is still unwell with psychotic symptoms.

(2) Adding a serotonin reuptake inhibitor such as fluoxetine or sertraline may help, as long as clozapine/nor-clozapine levels are monitored.

(3) Adding aripiprazole, a 5-HT1A partial agonist, seems to be helpful in some studies.

(4) Other options include the popular anti-OCD treatment clomipramine as well as glutamatergic modulators such as lamotrigine.

Have you come across clozapine-induced obsessions in your practice? What worked for you? 

 

Post Contribution by Dr. Lena Palaniyappan

Attend our Psychiatry Education Forum’s Conference online for more information on Managing Clozapine Adverse Events:

(1) Hematologic Side Effects:

  • Types: Neutropenia, Eosinophilia, Thrombocytopenia, Thrombocytosis.
  • Relation to Dose and Duration.
  • Management.
  • When to discontinue clozapine?
  • When to re-challenge & when to avoid re-challenge?

(2) Cardiac Side Effects:

  • Types and Definition.
  • Relation to Dose and Duration.
  • Evaluation.
  • Monitoring Protocol.
  • Management.
  • When to discontinue clozapine?
  • When to re-challenge & when to avoid re-challenge?

(3) Neurologic Side Effects:

  • Types of Seizures.
  • Relation to Dose and Duration.
  • Risk Factors.
  • Role of EEG.
  • Management.
  • When to discontinue clozapine?
  • When to re-challenge & when to avoid re-challenge?

(4) Gastro-Intestinal Side Effects:

  • Types: Gastro-Intestinal Hypomotility.
  • Underlying Mechanism.
  • Clinical Signs & Symptoms.
  • Risk Factors.
  • Prevention strategies.
  • Management.
  • When to discontinue clozapine?
  • When to re-challenge & when to avoid re-challenge?

(5) Hyper-Salivation Side Effects:

  • Underlying Mechanism.
  • Management: Localized and Systemic Treatment.

Psychiatry Education Forum’s first CME online conference is dedicated to the essential and must-know clinical facts in psychiatry. This conference will offer a maximum of 10 AMA PRA Category 1 Credits™ for topics clinically relevant to your daily clinical practice.

  • Online conference: finish this conference at your own pace, and at any time with no need to spend money on travel-related expenses.

  • Peer-Reviewed: each presentation is reviewed by independent peer-reviewers.

  • No Disclosures: No pharmaceutical or non-pharmaceutical sponsors. All lectures are based on clinical data from literature with no influence from sponsors.

  • Conference Booklet: PDF version of reading material for each lecture will also be provided.

CONFERENCE TABLE OF CONTENT:

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of PeerPoint Medical Education Institute and the Psychiatry Education Forum LLC. PeerPoint Medical Education Institute is accredited by the ACCME to provide continuing medical education for physicians. PeerPoint Medical Education Institute designates the enduring material format for this educational activity for a maximum of 10.0 AMA PRA Category 1 Credits™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Reference:

  1. Kim DD, Barr AM, White RF, Honer WG, Procyshyn RM. Clozapine-induced obsessive–compulsive symptoms: mechanisms and treatment. Journal of psychiatry & neuroscience: JPN. 2019 Jan;44(1):71.

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