Clozapine administration ameliorates disrupted long-range synchrony in a neurodevelopmental animal model of schizophrenia.

Dickerson DD, Restieaux AM, Bilkey DK. Clozapine administration ameliorates disrupted long-range synchrony in a neurodevelopmental animal model of schizophrenia. Schizophrenia Res. 2012;135(1-3):112-5. DOI: 10.1016/j.schres.2011.12.016. PubMed PMID: 22260963.

Sleep propensity at daytime as assessed by Multiple Sleep Latency Tests (MSLT) in patients with schizophrenia increases with clozapine and olanzapine.

Kluge M, Himmerich H, Wehmeier PM, Rummel-Kluge C, Dalal M, Hinze-Selch D, et al. Sleep propensity at daytime as assessed by Multiple Sleep Latency Tests (MSLT) in patients with schizophrenia increases with clozapine and olanzapine. Schizophrenia Res. 2012;135(1-3):123-7. DOI: 10.1016/j.schres.2011.12.017. PubMed PMID: 22257975.

Evaluation of clinical outcomes in patients who continued clozapine therapy despite moderate to severe leukopenia or neutropenia

The rare, but potentially fatal, side effect of agranulocytosis has caused the use of clozapine to be regulated more than any other antipsychotic medication. All patients must be registered in the Clozapine National Registry and frequent monitoring of WBC (white blood cell) count and ANC (absolute neutrophil count) must be performed every 7-28 days depending on the current duration of treatment. According to the clozapine monitoring guidelines provided by the Clozapine National Registry, a WBC count less than 3000/mm³ or ANC less than 1500/mm³ requires interruption of clozapine therapy. However, some physicians and patients are reluctant to discontinue clozapine. There are limited published reports in which clozapine was continued and the neutropenia was managed by adding lithium or granulopoiesis stimulating factors (GSFs), changing concomitant medications that might also be implicated in neutropenia, or observing to see if neutropenia is transient.

HEMATOLOGIC IMPACT OF ANTIBIOTIC ADMINISTRATION IN PATIENTS TAKING CLOZAPINE

Clozapine is an atypical antipsychotic with proven efficacy in a psychiatric patient population with treatment-resistant schizophrenia. The prescribing of clozapine in this population is limited in part by its side effect profile, which includes the risk of agranulocytosis and other adverse hematological outcomes. Since successful clozapine therapy requires the maintenance of specific blood counts, care must be taken to avoid confounding factors that may precipitate reductions in WBC or ANC. It is known that the resolution of an infection produces an accompanying decrease in antibody production and WBC/ANC. Antibiotics have been implicated as a confounding factor of decreased blood cell counts when administered concomitantly with clozapine. However, these drops in the WBC and ANC have been noted to be related to the resolution of infection and not to a drug induced dyscrasia.

"Closing-in" on clozapine dosing: a case warranting therapeutic drug monitoring

Clozapine is an atypical antipsychotic used in the treatment of schizophrenia. The typical daily dose is 300-600mg divided twice daily with a maximum daily dose of 900mg. There is a wide variation in serum levels for patients on a fixed dose of clozapine. An eight-fold inter-individual and a large intra-individual variation have been previously reported. Accepted standards of clinical practice do not include obtaining routine clozapine serum levels. However, certain clinical situations may warrant therapeutic drug monitoring (TDM) of clozapine levels. One indication for TDM is poor clinical response at typical doses. The medical literature postulates that the therapeutic range is between 350-400 ng/mL and one reference suggests a target of >504 ng/ml.

NEUROLEPTIC MALIGNANT SYNDROME WITH CONCOMITANT LAMOTRIGINE-INDUCED RASH: A CASE REPORT

Neuroleptic malignant syndrome (NMS) is a known potential adverse effect of antipsychotics, including clozapine. Characteristic signs and symptoms of NMS include altered mental status, fever, autonomic instability, and muscle rigidity. Lamotrigine is associated with dermatologic reactions ranging from a benign rash to Stevens-Johnson syndrome. Adverse reactions to clozapine or lamotrigine can be life threatening if unrecognized or untreated. We present a case of clozapine-induced NMS diagnosed on the same day as a lamotrigine drug rash.

Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT(1A) Receptor-Dependent Mechanism.

Kargieman L, Riga MS, Artigas F, Celada P. Clozapine Reverses Phencyclidine-Induced Desynchronization of Prefrontal Cortex through a 5-HT(1A) Receptor-Dependent Mechanism. Neuropsychopharmacology. 2012;37(3):723-33. DOI: 10.1038/npp.2011.249. PubMed PMID: 22012474; PubMed Central PMCID: PMC3260989.

Probabilistic classification and gambling in patients with schizophrenia receiving medication: comparison of risperidone, olanzapine, clozapine and typical antipsychotics.

Wasserman JI, Barry RJ, Bradford L, Delva NJ, Beninger RJ. Probabilistic classification and gambling in patients with schizophrenia receiving medication: comparison of risperidone, olanzapine, clozapine and typical antipsychotics. Psychopharmacology. 2012;222(1):173-83. DOI: 10.1007/s00213-011-2634-4. PubMed PMID: 22237855.

Acute Colonic Pseudo-obstruction: A Rare but Dangerous Complication of Clozapine Therapy

Constipation is a well-known and usually benign side effect of antipsychotic therapy; however, clozapine-induced gastrointestinal hypomotility can be associated with significant morbidity. Acute colonic pseudo-obstruction (ACPO), or Ogilvie’s syndrome, is a functional obstruction of the colon leading to decreased intestinal motility due to autonomic dysregulation.

Implementation of a clinician administered bowel movement questionnaire for the assessment of clozapine-induced constipation (CIC)

Clozapine, an atypical antipsychotic, is known to cause severe constipation, which can lead to bowel impaction, ischemic bowel, fecal vomitus, and even death. Monitoring suggestions for constipation caused by clozapine are minimal. The intent of this study is to evaluate the possible benefit of implementing a routine monitoring questionnaire to assess for clozapine-induced constipation (CIC).