This case report discusses the importance of ODT olanzapine in the treatment of a patient presenting with bipolar I disorder plus psychotic symptoms, and diminished gastrointestinal absorption, secondary to anatomical variability or inflammation.

Pravesh Sharma, MD; Kyle A. Schmucker, MS3; Ankit Parmar, MD, MHA; Deepti Vats, MD; Manish Aligeti, MD, MHA

Texas Tech University Health Sciences Center, Department of Psychiatry, Lubbock, TX

Drs. Sharma, Parmar, and Vats are psychiatry residents; Dr. Aligeti is a clinical assistant professor; Kyle A. Schmucker is a medical student (MSIII).


Introduction

Over half of patients with bipolar disorder experience psychotic symptoms at some point during their lifetime.1 Antipsychotic medications are an important treatment in such cases as they not only treat psychotic symptoms but also aid in mood stabilization. Olanzapine, an atypical antipsychotic medication, is commonly used in bipolar disorder for this purpose.2 It is available in three forms of administration: standard oral tablets (SOT), orally disintegrating tablets (ODT), and an intramuscular injection.3

Olanzapine has linear and dose-dependent pharmacokinetics in both SOT and ODT forms, with an average half-life of around 33 hours, reaching peak serum concentration at 6 hours.4 In the SOT form, 85% of olanzapine is absorbed by the gut in a healthy patient, of which 40% is inactivated by first pass metabolism, yielding a 60% bioavailability.4 Compared to SOT olanzapine, ODT olanzapine appears to have more rapid bioavailability following administration because of the added absorption occurring sublingually.5

This case report discusses the importance of ODT olanzapine in the treatment of a patient presenting with bipolar I disorder plus psychotic symptoms, and diminished gastrointestinal absorption, secondary to anatomical variability or inflammation.

The Case

Ms. X, a 43-year-old white woman with prior diagnosis of bipolar I disorder, presented to the emergency department with worsening psychosis over the past month. The patient was receiving perphenazine, buproprion, topiramate, and lorazepam at the time of admission. She had previously failed trials of antipsychotic medications viz olanzapine, perphenerazine, ziprasidone, haloperidol, risperidone, and quetiapine; and mood stabilizers viz lithium, valproic acid, carbamazepine, and topiramate. All the medications were SOT preparations.

At the time of presentation, the patient demonstrated poor personal hygiene. Her thought process was illogical, with paranoid delusions, ideas of reference, and auditory hallucinations. Upon physical examination, her vitals signs were within normal range. Routine laboratory investigations were within reference limits, and her urinary drug screen was positive for benzodiazepines.

On reviewing the patient’s electronic medical records, it was noted that she had several abdominal surgeries, including a complete colectomy with ileorectal anastomosis at age 39 years due to Reiter’s Syndrome (also known as reactive arthritis). The patient continued to experience gastrointestinal distress. Collateral information from her parents and partner affirmed that the patient continued to maintain medication adherence but had progressive worsening of psychiatric symptoms.

Considering the patient’s severe, long-standing intestinal problems and malabsorption, she was started on oral disintegrating formulation of risperidone M-Tab 1mg daily. However, after a single dose she reported increased irritability and feeling “jittery,” and she refused to take the medication. She continued to exhibit hallucinations and paranoid delusions, such as her food being contaminated by the staff. Even though the patient’s earlier trial of olanzapine had failed, olanzapine ODT preparation was attempted at this time. She was scheduled on a nightly dose of 5mg, which was subsequently titrated up to 5mg BID. She was also started on lithium 300mg BID for mood symptoms. The patient’s other medications were all discontinued.

Two days after starting ODT olanzapine the patient reported improvement in auditory hallucinations but continued to exhibit paranoia. The dose was further increased from 5mg BID to 5mg in the morning and 10mg at nighttime to provide additional benefits. Over the course of the next several days, she exhibited alternate periods of fluctuating psychotic symptoms. This was the first time she had claimed to experience periods of a “clear mind” in several years.

On day 7 of her hospital stay, Prozac 10mg/daily was started. Lithium was continued, and blood plasma level of lithium was noted to be 0.5 mEq/L. The patient had improved noticeably, with a reactive affect and peer interaction. She denied having auditory hallucinations or paranoia. The patient was discharged on day 9 to the care of her partner, with a plan to follow up with an outpatient psychiatry clinic in one week.

Discussion

The patient’s medical condition (Reiter’s syndrome) predisposed her to bowel inflammation and extensive intestinal damage. As a result, the SOT antipsychotics may not have been absorbed to an optimal degree. Despite several trials of SOT antipsychotic medications in escalating dosages, and follow-up with a psychiatrist, the patient had continued to experience worsening psychosis.

Upon admission, the patient was started on an ODT antipsychotic. She had never used this modality of drug administration before. The patient’s psychotic symptoms improved noticeably, with cessation of hallucinations and delusions after initiating the ODT medication. Although a portion of the dose is absorbed in the gastrointestinal tract when using an ODT, Markowitz et al demonstrated that significant sublingual absorption occurs, perhaps diminishing the role of intestinal absorption for ODT formulations. In addition, the study noted that SOT and OTD olanzapine formulations did not differ significantly on Cmax, Tmax, and AUC parameters, but that ODT only had better bioavailability sooner than SOT.5

The patient’s clinical improvement was superior to previous treatments because of the unique absorptive qualities of orally disintegrating olanzapine, which may have greater bioavailability as compared to the standard oral tablet of olanzapine. This case demonstrates the potential importance of using ODT preparation in a patient with impaired gastrointestinal absorption. It also emphasizes the importance of careful evaluation of surgical and medical history before selecting the appropriate form of psychotropic medication.


References:

1. Dunayevich E, Keck PE Jr. Prevalence and description of psychotic features in bipolar mania. Curr Psychiatry Rep. 2000;2:286-90.

2. Kutzelnigg A, Kopeinig M, Chen CK, et al. Compliance as a stable function in the treatment course of bipolar disorder in patients stabilized on olanzapine: results from a 24-month observational study. Int J Bipolar Disord. 2014;2:13.

3. Montgomery W, Treuer T, Karagianis J, Ascher-Svanum H, Harrison G. Orally disintegrating olanzapine review: effectiveness, patient preference, adherence, and other properties. Patient Prefer Adherence. 2012;6:109-25.

4. Callaghan JT, Bergstrom RF, Ptak LR, Beasley CM. Olanzapine. Pharmacokinetic and pharmacodynamic profile. Clin Pharmacokinet. 1999;37:177-93.

5. Markowitz JS, DeVane CL, Malcolm RJ, et al. Pharmacokinetics of olanzapine after single-dose oral administration of standard tablet versus normal and sublingual administration of an orally disintegrating tablet in normal volunteers. J Clin Pharmacol. 2006;46:164-71.