Psychosomatics 41:69-71, February 2000
© 2000 The Academy of Psychosomatic Medicine
Low-Dose Risperidone for the Irritable Medically Ill Patient
Darin M. Lerner, M.D.,
Laura Schuetz, M.D.,
Steven Holland, M.D.,
David R. Rubinow, M.D., and
Donald L. Rosenstein, M.D.
Received June 14, 1999; accepted July 28, 1999. From the National Institutes of Health (NIH), National Institute of Mental Health, Bethesda, Maryland. Address correspondence and reprint requests to Dr. Rosenstein, Chief, NIH Psychiatry-Consultation Liaison Service, Office of the Clinical Director, Intramural Research Program, National Institute of Mental Health, 10 Center Drive, MSC 1276, Room 3N238, Bethesda, MD 20892-1276.
Key Words: Medical-Surgical Patients • Clinical Management • Neuroleptics
One of the most difficult clinical management challenges for the consultation–liaison psychiatrist is the hostile, irritable, and uncooperative medical or surgical patient. Ill and physically uncomfortable patients characteristically express feelings of mild irritability and frustration. However, overt hostility, threats of aggression, and noncompliance with medical treatment frequently result in psychiatric consultation. These mood and behavioral dyscontrol syndromes, which do not meet diagnostic criteria for psychosis or delirium, can reflect longstanding character pathology or central nervous system effects of systemic illness and polypharmacy. Typically, management of such patients includes behavioral interventions and pharmacotherapy. Unfortunately, benzodiazepines can disinhibit these patients further, conventional neuroleptics can cause dysphoria and akathisia,1 and antidepressants require several weeks for beneficial mood effects.
One pharmacological approach to the management of the medically ill and pathologically irritable patient is the use of the atypical neuroleptic risperidone. Several studies demonstrate beneficial effects of risperidone on hostility, aggression, agitation, and affective lability in various clinical populations.2–8 Although one report describes the efficacy of risperidone for the treatment of delirium,9 there are no published observations on the use of risperidone for other behavioral syndromes in medical inpatients. We report three patients who demonstrated rapid improvement in symptoms of irritability, hostility, and behavioral disinhibition after treatment with low-dose risperidone.
Case Reports
Case 1. A 46-year-old man with multiple-drug–resistant tuberculosis and antisocial personality traits was enrolled in a research protocol requiring a 6-month hospitalization under respiratory isolation. The psychiatry consultation–liaison service was asked to evaluate the patient on several occasions for angry outbursts and disruptive behavior, including persistent smoking in his room, making sexually explicit and provocative comments to the female nursing staff, and failing to follow infectious-disease precautions. On examination, the patient was guarded and only minimally cooperative. He attributed his dysphoric and irritable affect to insomnia and poor nursing care. The patient showed no evidence of psychosis, cognitive impairment, or delirium.
Treatment with oral lorazepam (0.5 mg twice/day) and a behavioral contract resulted in modest benefit in sleep and only minimal behavioral improvement. The psychiatric consultant was later called to see the patient on an emergency basis because of escalating hostility that led some nurses to refuse care for him. When reexamined, the patient was agitated and combative and threatened to leave the hospital against medical advice. He reluctantly agreed to stay and try a new medication for alleviation of his mood and behavioral symptoms.
Two days after starting risperidone (0.5 mg twice/day), the patient reported improved sleep and feeling less angry and "short-fused." The nursing staff noted that he was substantially less irritable and confrontational. Upon follow-up 1 month later, his mood, behavior, and compliance remained markedly improved. His only complaint was a return of insomnia that was responsive to the addition of trazodone (50 mg at bedtime). He had a few further mildly contentious interactions with the staff and was discharged after completion of the protocol.
Case 2. A 42-year-old man with Hodgkin's disease, nodular sclerosing type, had experienced multiple relapses since his initial diagnosis in 1980. He had undergone a previous bone marrow transplantation but had refused follow-up treatment for several years. His current hospitalization was for a second bone marrow transplantation. The psychiatry consultation–liaison service was called to evaluate this patient after he displayed an angry, defiant, and aggressive attitude toward the nurses and physicians caring for him. The medical staff considered canceling the bone marrow transplantation because of concerns about the patient's compliance.
The patient stated that he was irritated not only with the staff, but also with himself for treating the staff rudely. He reported feeling "snappy" and "sarcastic" and stated that he did not like feeling so "on edge." He made little eye contact, answered with one-word responses, and displayed a rigid demeanor and irritable affect. He noted a loss of appetite and difficulty sleeping but denied sadness or hopelessness.
The patient agreed to a trial of risperidone (0.5 mg twice/day). After two doses, the patient appeared excessively sedated, and the dose was reduced to 0.5 mg at bedtime. Two days later, the patient reported feeling calmer and less frustrated. The medical and nursing staff noted his improved mood and increased cooperation and compliance. This improvement continued for the duration of his hospitalization, and he presented no further behavioral problems.
Case 3. A 23-year-old woman with chronic granulomatous disease had been hospitalized for several months for treatment of disseminated Nocardia asteroides (including two small brain lesions). The psychiatry consultation–liaison service was called to evaluate her escalating diphenhydramine requirements, sleep difficulty, progressive irritability, verbal outbursts, and uncooperativeness with staff.
On mental status examination, she exhibited no cognitive deficits or evidence of delirium. The patient was convinced that she was experiencing an adverse reaction to the antibiotic amphotericin, characterized by extreme nervousness, tremulousness, and neck pain. She felt too agitated to eat and had lost 4.4 kilograms over the preceding 4 weeks. As part of a regimen that included up to 15 medications, the patient received intravenous diphenhydramine (up to 400 mg/day) to treat her symptoms of insomnia, anxiety, irritability, and shaking. She stated that she desired improved sleep and less need for diphenhydramine.
Initial trials of lorazepam and trazodone to aid with sleep and anxiety failed. She did not tolerate the subjective experience of benzodiazepines, and trazodone was ineffective for her insomnia. The patient refused antidepressant medication. She agreed to a trial of risperidone in an effort to reduce her anxiety and escalating need for diphenhydramine. The patient was begun on risperidone (0.5 mg at bedtime), which was subsequently increased to 0.5 mg twice daily and then to 1 mg twice daily. She displayed a rapid response to risperidone: resolution of irritability and insomnia within 48 hours. She remained on risperidone throughout her hospitalization and continued to do well.
DISCUSSION
In each of these cases, symptoms of irritability, dysphoria, or uncooperativeness responded rapidly and in a sustained fashion to low-dose risperidone. Compared with other neuroleptic agents commonly used in this clinical setting, risperidone was well tolerated. Conventional neuroleptics can cause extrapyramidal symptoms (including dystonia, akathisia, and tardive dyskinesia) and dysphoria. Although benzodiazepines are useful for alleviating anxiety, they carry risks of tolerance, dependence, withdrawal, and behavioral disinhibition. Antidepressants have been effective for the irritability and rage associated with depression,10 but require several weeks to provide benefit and may precipitate delirium in medically ill patients.
Data from clinical trials for a broad spectrum of psychiatric disorders suggest that risperidone has a specific therapeutic effect on symptoms of irritability and aggression. Three open-label, prospective studies using risperidone in childhood autism and pervasive developmental disorder demonstrated significant reduction in aggression, self-injury, overactivity, and poor sleep hygiene.5,8,11 In one of these studies, improvement occurred within 24–48 hours.8 Furthermore, in a double-blind, placebo controlled study of adults with autistic spectrum disorders, risperidone was associated with decreases in physical aggression, property destruction, and self-injury.6
Similar anti-aggressive effects of risperidone, compared with haloperidol and placebo, were observed in a placebo-controlled, double-blind study in patients with schizophrenia.2 Also, recent evidence suggests that risperidone may have thymoleptic and anxiolytic effects in patients with schizophrenia, affective disorder, and borderline personality disorder.3,12–14 Another report suggests that risperidone may be useful in the treatment of agitation and social withdrawal in geriatric patients.4
The pharmacologic mechanisms that mediate reductions in irritability and hostility are not known. Risperidone has a unique profile of pharmacodynamic properties that include dopamine type-2 receptor and serotonin type-2A receptor antagonism as well as blocking effects on alpha-adrenergic and histaminergic receptors. The nucleus accumbens is an anatomical site thought to mediate aggressive behaviors; it is known to be rich in functionally interactive dopaminergic and serotonergic innervation. In this context, it has been suggested that the joint action on dopaminergic and serotonergic systems by risperidone underlies a selective effect on hostility.2 An extensive literature implicates low turnover of central nervous system serotonin in aggression.15 Risperidone's potent blockade of alpha-1 and alpha-2 adrenoceptors, along with effects on several 5HT-receptor types, may selectively lead to increased 5HT1A neurotransmission and turnover, and thus mediate antiaggressive effects.16
The preliminary clinical observations reported here suggest that risperidone may be effective in reducing hostility, dysphoria, irritability, and uncooperative behavior observed in hospitalized medical patients. The use of other atypical neuroleptics for these symptoms in this population has not been reported. Published accounts describing similar therapeutic benefit in other populations lend support to the notion that risperidone may have selective anti-aggressive effects. Given its rapid onset of action, favorable side-effect profile at low doses, and few clinically problematic drug interactions, risperidone may be a particularly effective medication to use in this select group of medical patients.
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