Orally disintegrating olanzapine for the treatment of psychotic and behavioral disturbances associated with dementia. (Case Report).

Abstract: Orally disintegrating olanzapine is a recently marketed form of olanzapine that dissolves rapidly on contact with saliva. We describe six demented patients resistant to treatment with common oral antipsychotic medications who were successfully treated with the formulation. The importance of these case reports is to make physicians aware that orally disintegrating olanzapine may be useful for the management of psychobehavioral disturbances in demented patients who resist or have difficulty taking standard oral medications.

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Various causes of dementia are commonly seen in the geriatric population, the most common being Alzheimer's disease and vascular dementia, which may account for up to 90% of all cases. (1) One of the greatest challenges facing caregivers is managing the psychotic and behavioral problems of patients with dementia. It is estimated that up to 70% of nursing home residents may have dementia, with 90% of these patients diagnosed with behavioral disturbances. (2,3) This may create an undue burden for caregivers, and reduction of psychobehavioral symptoms is often a treatment goal in the elderly patient with dementia.

Antipsychotic medications are the treatment of choice for psychosis, and are frequently part of the treatment regimen for behavioral disturbances, including agitation and aggression. Atypical antipsychotic agents (risperidone, olanzapine, quetiapine, and ziprasidone) have fewer side effects and are safer than older, typical antipsychotic medications in the elderly. Although these agents all show some degree of efficacy, problems may arise, complicating treatment. Demented patients may resist taking medications orally; as their behavior deteriorates because of not receiving medication, their resistance may increase. Parenteral typical antipsychotic medications, such as haloperidol, may be used in such cases but are often associated with side effects in the elderly. An atypical antipsychotic is not yet available in injectable form. Even if one were available, frequent injections of an elderly, demented patient would prove impractical in many settings.

Olanzapine (Zyprexa; Eli Lilly and Co., Indianapolis, IN) is an atypical antipsychotic agent effective for treatment of psychosis and behavioral conditions in the elderly. (4-6) Recently, an orally disintegrating olanzapine tablet (Zyprexa Zydis; Eli Lilly and Co.) that rapidly dissolves on contact with saliva has become available. The case reports below show, albeit anecdotally, that orally disintegrating olanzapine may be helpful for the treatment of psychobehavioral disturbances in demented patients resistant to the usual oral medications.

The cases described below were obtained by reviewing the medical records of patients with dementia who had exhibited behavioral disturbances severe enough to necessitate admission. Difficulty was encountered in giving each of them commonly used oral medications, either before or after admission, and for that reason they were treated with orally disintegrating olanzapine. Agitation was rated according to five directly observable Positive and Negative Syndrome Scale (7) items: excitement, hostility, hallucinatory behavior, uncooperativeness, and poor impulse control. Each item was rated on a scale ranging from 1 (absent) to 7 (extreme), with the agitation score being the sum of the scores for the five items.

Discussion

Although olanzapine is an effective atypical antipsychotic agent, benefits of the drug may not be fully realized in patients who do not swallow it properly. Because of the nature of dementia, patients may have difficulty taking medications dispensed in solid or liquid forms. Evidence from the six cases presented here suggests that orally disintegrating olanzapine may be useful for the treatment of psychobehavioral disturbances in patients with dementia who, for whatever reasons, are unwilling or unable to swallow commonly used oral medications.

Orally disintegrating olanzapine is intended to deliver the dose analogous to an oral tablet. At this time, the dosage forms approved for use in the United States are the 5- and 10-mg formulations. The tablets dissolve on contact with saliva; mean time to initial disintegration is reported to be 15.8 seconds, (9) although in our experience dissolution occurs much faster. Buccal absorption does not occur to a measurable extent. Orally disintegrating olanzapine does not have a faster onset of action than standard olanzapine. If desired, solutions or suspensions may be easily prepared by crushing or dispersing orally disintegrating olanzapine and serving it in a beverage to the patient.

It should be noted that during the time period of our review, attempted treatment of three other similarly demented patients with orally disintegrating olanzapine was unsuccessful. Thus, our success rate with the medication was 66.7%. The only side effect of the drug noted occurred in just one patient and was not serious (sedation in Patient 4). Further investigation of the use of orally disintegrating olanzapine in demented patients is clearly warranted. Initial studies have shown promise for the use of the medication in patients with schizophrenia, (9) so it may ultimately prove valuable in several psychiatric disorders. The prospect of being able to use an orally disintegrating medication instead of an injected anti-psychotic agent may be of particular value to both the staff and the patient.

Accepted April 8, 2002.

References

(1.) Yeager BF, Farnett LE, Ruzicka SA. Management of the behavioral manifestations of dementia. Arch Intern Med 1995;155:250-260.

(2.) Rovner BW, Kafonek S, Filipp L, Lucas MJ, Folstein ME. Prevalence of mental illness in a community nursing home. Am J Psychiatry 1986;143:1446-1449.

(3.) Tariot PN, Podgorski CA, Blazina L, Leibovici A. Mental disorders in the nursing home: Another perspective. Am J Psychiatry 1993;150:1063-1069.

(4.) Clark WS, Street JS, Feldman PD, Breier A. The effects of olanzapine in reducing the emergence of psychosis among nursing home patients with Alzheimer's disease. J Clin Psychiatry 2001;62:34-40.

(5.) Satterlee WG, Reams SG, Bums PR, Hamilton 5, Tran PV, Tollefson GD. A clinical update on olanzapine treatment in schizophrenia and in elderly Alzheimer's disease patients. Psychopharmacol Bull 1995;31:534 (abstr).

(6.) Street JS, Clark WS, Gannon KS, Cummings JL, Bymaster FP, Tamura RN, et al. Olanzapine treatment of psychotic and behavioral symptoms in patients with Alzheimer disease in nursing care facilities: A double-blind, randomized, placebo-controlled trial--The HGEU Study Group. Arch Gen Psychiatry 2000;57:968-976.

(7.) Kay SR, Opler LA, Fizbein A. The Positive and Negative Syndrome Scale (PANSS) Manual. North Tonawanda, NY, Multi-Health System, 1986.

(8.) Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.

(9.) Jones B, Chue P, Adams C. Use of olanzapine rapidly disintegrating tablet in schizophrenia. Schizophrenia Res 1999;36:283 (abstract).

RELATED ARTICLE: Key Points

* The orally disintegrating form of olanzapine dissolves rapidly on contact with saliva.

* Orally disintegrating olanzapine may be useful for the management of psychobehavioral disturbances in demented patients who resist or have difficulty taking standard oral medications.

* Orally disintegrating olanzapine is intended to deliver a dose analogous to regular olanzapine tablets.

* The onset of action of orally disintegrating olanzapine is not faster than that of standard olanzapine; the primary advantage is its ease of administration to patients who are difficult to medicate.

Case Reports

Patient 1

A 67-year-old black man with Alzheimer's disease had become progressively paranoid. His medical history included hypertension treated with verapamil hydrochloride, and he was receiving donepezil hydrochloride, 10 mg/d. He thought that the nurses were poisoning him and was observed to "cheek" his medications repeatedly. His paranoia and hostility increased, requiring hospitalization. His Mini-Mental State Examination (8) (MMSE) score was 10 of a possible 30 and his agitation score was 23 of a possible 35. Treatment with orally disintegrating olanzapine, 10 mg/d, was begun. Because of its rapid dissolution, no problems were encountered with administration of the medication, although the patient was observed "cheeking" verapamil hydrochloride 5 days after admission. After 8 days of treatment, his paranoia had subsided enough for him to return to his nursing home, where he continued to take orally disintegrating olanzapine, 10 mg/d. His MMSE score at discharge was 13 and his agitation score was 12.

Patient 2

A 79-year-old white man with Alzheimer's disease gradually became combative with the staff at his nursing home and began refusing some meals and medications. Medical history included hypertension treated with clonidine hydrochloride and chronic obstructive pulmonary disease treated with albuterol inhaler; he was also receiving donepezil hydrochloride, 5 mg/d. Eventually, he began threatening to kill nurses if they approached him. At admission he was agitated and told staff, "Just wait till I get my shotgun!" His MMSE score was 9 and his agitation score was 25. He could not be persuaded to swallow pills, but nurses were able to place orally disintegrating olanzapine, 5 mg, into his mouth. In the first 4 days of hospitalization, he required 5 mg olanzapine, four times daily; in the next 3 days, the dosage was reduced to 5 mg, twice daily, and he became agreeable to taking medications. At that point, his MMSE score was 9 and his agitation score was 12. He was able to return to his nursing home taking standard ol anzapine therapy, 2.5 mg each morning and 5 mg at bedtime.

Patient 3

A 59-year-old white man with dementia resulting from a head injury had severe episodes of agitation during which he would be aggressive toward the nursing staff. Medical history was otherwise unremarkable. He had been undergoing treatment for more than a year with valproic acid, 500 mg, three times daily, for behavioral control. His hostility became almost constant, requiring hospitalization. His MMSE score was 19 and his agitation score was 27. During the first 36 hours in the hospital, four injections of haloperidol, 5 mg, were given. He became agitated at the sight of needles but would not swallow tablets. Orally disintegrating olanzapine was given at doses of 10 mg at bedtime and 5 mg every 4 hours, as needed, for 8 days, at which time the doses being given on an as-needed basis were discontinued. His MMSE score at that time was 20 and his agitation score was 14. Eventually, he became calmer, and his medications at discharge were standard olanzapine, 10 mg/d, and valproic acid, 500 mg, three times daily.

Patient 4

A 72-year-old black man with vascular dementia was hospitalized under court commitment because of increasing paranoia, aggression, noncompliance with medication, and not attending to his personal hygiene and other activities of daily living. Medical history included prostatic hypertrophy treated with terazosin hydrochloride and ischemic heart disease treated with aspirin and isosorbide. His MMSE score was 7 and his agitation score was 26. He was difficult to approach and would spit out tablets or liquids placed in his mouth. Orally disintegrating olanzapine could be given, because it dissolved before he could spit it out; he was given 5 mg every 6 hours, as needed, for 2 days (five doses were given, with noticeable calming). On the third day, he appeared sedated, and the dose was decreased to 5 mg at bedtime. At this dosage, he was suitable for discharge a week later, with an MMSE score of 7 and an agitation score of 13.

Patient 5

An 81-year-old white man with Alzheimer' s disease was sent to the hospital from his nursing home because of increasing paranoia and hallucinations. Medical history included Type 2 diabetes treated with glyburide, and he was receiving donepezil hydrochloride, 10 mg/d. He was convinced that his deceased brother was trying to steal his money and complained of seeing waist-tall creatures who were giving him things to eat. He began refusing to swallow his medications, saying that he had already been given them. His MMSE score was 15 and his agitation score was 25. Orally disintegrating olanzapine, 5 mg/d, was easily given to him. Over 6 days, his psychotic symptoms improved and his medication was changed to standard olanzapine, 2.5 mg/d. At that point, his MMSE score was 16 and his agitation score was 14. He was discharged 3 days later.

Patient 6

An 82-year-old white man with vascular dementia was brought to the hospital by ambulance after 3 days of increasing behavioral problems. He had had a stroke 6 months previously, with residual right-sided weakness and mixed receptive and expressive aphasia. Other medical problems include hypertension treated with verapamil hydrochloride and ischemic heart disease treated with isosorbide; he also received ticlopidine hydrochloride and donepezil hydrochloride, 5 mg/d. His MMSE score was 5 and his agitation score was 19. He was easily agitated and was occasionally aggressive toward staff. He would become particularly frustrated when he could not communicate his ideas by speaking. At times he appeared not to comprehend nurses' instructions to take his medication. Evaluation revealed him to have difficulty swallowing because of effects of his stroke. Orally disintegrating olanzapine, 5 mg every 6 hours, was successfully given for 24 hours; afterward, he was given 5 mg/d. He improved gradually and 8 days later was d ischarged with an MMSE score of 5 and an agitation score of 10.

From the Departments of Psychiatry and Neurology, University of Mississippi School of Medicine, and the G.V. (Sonny) Montgomery Veterans Affairs Medical Center, Jackson, MS.

Supported in part by the South Central Veterans Affairs Health Care Network Mental Illness Research, Education, and Clinical Center.

Address reprint requests to Roy R. Reeves, DO, PhD, Department of Psychiatry (116A), VA Medical Center, 1500 E. Woodrow Wilson Drive, Jackson, MS 39216. Email: [e-mail]

Copyright [C] 2003 by The Southern Medical Association

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