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Olanzapine for the treatment of hemiballismus: A case report

      Abstract

      Mukand JA, Fitzsimmons C, Wennemer HK, Carrillo A, Cai C, Bailey KM. Olanzapine for the treatment of hemiballismus: a case report.
      Hemiballismus is a rare movement disorder characterized by involuntary, large amplitude movements of the limbs of 1 side of the body. We describe the case of a man in his late sixties with slurred speech, agitation, and right-sided hemiballismus resulting from a left thalamic hemorrhagic stroke. Treatment with haloperidol was unsuccessful, but both the hemiballismus and agitation diminished significantly after initiation of olanzapine (Zyprexa). The improvement in the hemiballismus was quantified by recording the number of hemiballistic movements that occurred while the patient performed standardized 30-minute sessions (daily for 5d). With the first task (reaching within the base of support while seated), the average number of hemiballismic movements per session decreased from a baseline of 23.5 to 3.0 in the upper extremity and from 20.5 to 7.0 in the lower extremity. With the second task (catching a ball while seated), the abnormal movements decreased from 52 to 6.3 in the upper extremity and from 34.5 to 2.7 in the lower extremity. This case suggests that olanzapine may be a valuable pharmacologic alternative for patients with hemiballismus.

      Key words

      HEMIBALLISMUS IS A forceful and flailing movement of 1 side of the body usually caused by destructive lesions of the contralateral subthalamic nucleus.
      • Klawans H.L.
      • Moses 3rd, H.
      • Nausieda P.A.
      • Bergen D.
      • Weiner W.J.
      Treatment and prognosis of hemiballismus.
      • Whittier J.R.
      • Mettler F.A.
      Studies on subthalamus of rhesus monkey: hyperkinesia and other physiologic effects of subthalamic lesions, with special reference to the subthalamic nucleus of Luys.
      • Martin J.P.
      Hemichorea resulting from a local lesion of the brain (the syndrome of the body of Luys).
      The term is derived from the Greek word ballismos, which means to throw. These flinging movements are usually centered on the shoulder and hip joints of the hemibody and may be strong enough to injure the affected limbs.
      • Nath A.
      • Jankovic J.
      • Pettigrew L.C.
      Movement disorders and AIDS.
      The movement disorder may be suppressed to some degree by concentration or voluntary motions of the limbs. It is typically absent during sleep and is increased by stress.
      • Dewey R.B.
      • Jankovic J.
      Hemiballismus-hemichorea: clinical and pharmacologic findings in 21 patients.
      It is believed that the subthalamic nucleus has a tonic inhibitory influence on the thalamus via inhibitory neurons in the medial globus pallidus. These inhibitory fibers also travel to the ventrolateral thalamic nucleus, and excitatory pathways originating from this nucleus project to the cortex.
      • Whittier J.R.
      • Mettler F.A.
      Studies on subthalamus of rhesus monkey: hyperkinesia and other physiologic effects of subthalamic lesions, with special reference to the subthalamic nucleus of Luys.
      • Martin J.P.
      Hemichorea resulting from a local lesion of the brain (the syndrome of the body of Luys).
      • Kotter R.
      Postsynaptic integration of glutaminergic and dopaminergic signals in the striatum.
      Therefore, a lesion in the subthalamic nucleus may disinhibit these excitatory pathways, resulting in hemiballistic movements.
      • Provenzale J.M.
      • Schwarzschild M.A.
      Hemiballismus.
      The neurochemical basis of hemiballismus is thought to be increased presynaptic synthesis and release of dopamine, which produces an imbalance between inhibitory and excitatory fibers in the motor circuit between the basal ganglia, thalamus, and cortex.
      • Kotter R.
      Postsynaptic integration of glutaminergic and dopaminergic signals in the striatum.
      • Kimura M.
      Physiological bases of involuntary movement.
      • Carlos M.
      • Carlson A.
      Interactions between glutaminergic and monoaminergic systems within the basal ganglia.
      The most common causes of hemiballismus are vascular events affecting the subthalamic nucleus, which is supplied by branches of the anterior choroidal, posterior cerebellar, and posterior communicating arteries.
      • Dewey R.B.
      • Jankovic J.
      Hemiballismus-hemichorea: clinical and pharmacologic findings in 21 patients.
      Hemiballismus may also be caused by systemic lupus erythematosus, metabolic disorders (eg, nonketotic hyperglycemia), medications (oral contraceptives, phenytoin), trauma, arteriovenous malformations, neoplasm, or infectious diseases (tuberculosis, toxoplasmosis, meningitis, acquired immune deficiency virus).
      • Klawans H.L.
      • Moses 3rd, H.
      • Nausieda P.A.
      • Bergen D.
      • Weiner W.J.
      Treatment and prognosis of hemiballismus.
      • Dewey R.B.
      • Jankovic J.
      Hemiballismus-hemichorea: clinical and pharmacologic findings in 21 patients.
      • Tams L.S.
      • Cohen M.G.
      • Li E.K.
      Hemiballismus in systemic lupus erythematosus: possible association with antiphospholipid antibodies.
      • Lietz T.E.
      • Huff J.S.
      Hemiballismus as a presenting sign of hyperglycemia.
      • Shannon K.M.
      Hemiballismus.
      • Kant R.
      • Zeiler D.
      Hemiballismus following closed head injury.
      • Tamaoka A.
      • Sakuta M.
      • Yamada H.
      Hemichorea-hemiballism caused by arteriovenous malformation in the putamen.
      • Glass J.
      • Jankovic J.
      • Borit A.
      Hemiballismus and metastatic brain tumor.
      These conditions may directly affect the subthalmic nucleus or may compromise its vasculature.
      Many patients with hemiballismus caused by stroke have spontaneous and gradual improvement over weeks or months as edema around the infarct resolves and there is reperfusion of the affected tissue.
      • Johnson W.G.
      • Fahn S.
      Treatment of vascular hemiballism and hemichorea.
      • Ristic A.
      • Marinkovic J.
      • Dragasevic N.
      • Stanisavlejevic D.
      • Kostic V.
      Long-term prognosis of vascular hemiballismus.
      Persistent or severe hemiballismus requires neuropharmacologic therapy.
      • Dewey R.B.
      • Jankovic J.
      Hemiballismus-hemichorea: clinical and pharmacologic findings in 21 patients.
      Pharmacologic agents that have been used to control ballistic movements include haloperidol, clozapine, valproic acid, progabide, risperidone, chlorpromazine, butyrophenone, tetrabenazine, chloral hydrate, barbiturates, paraldehyde, bromides, phenothiazines, and pimozide.
      • Bashir K.
      • Manyam B.V.
      Clozapine for the control of hemiballismus.
      • Gilbert G.J.
      Response of hemiballismus to haloperidol.
      • Lenton R.J.
      • Cofti M.
      • Smith R.G.
      Hemiballismus treated with sodium valproate.
      • Chandra V.
      • Wharton S.
      • Spunt A.L.
      Amelioration of hemiballismus with sodium valproate.
      • Gonce M.
      • Schoenen J.
      • Charlier M.
      • Delwaide P.J.
      Successful treatment of hemiballismus with progabide, a new GABA-mimetic agent.
      • Evident V.G.
      • Gwinn-Hardy K.
      • Caviness J.N.
      • Alder C.H.
      Risperidone is effective in severe hemichorea/hemiballismus.
      • Pearce J.
      Reversal of hemiballismus by tetrabenazine.
      Hemiballismus is usually treated with antipsychotics, such as haloperidol and clozapine, but thalamic ablation is considered in severe cases if there is no response to medical therapies.
      • Cardoso F.
      • Jankovic J.
      • Grossman R.G.
      • Hamilton W.J.
      Outcome after stereotactic thalamotomy for dystonia and hemiballismus.
      • Martin J.P.
      • McCaul I.R.
      Acute hemiballismus treated by ventrolateral thalamolysis.
      • Rosengarten H.
      • Schweitzer J.W.
      • Friedhoff A.J.
      The effect of novel antipsychotics in rat oral dyskinesia.
      Olanzapine (Zyprexa) is chemically similar to clozapine, a medication known to be effective in treating movement disorders such as hemiballismus, Huntington’s chorea, and tardive dyskinesia.
      • Bashir K.
      • Manyam B.V.
      Clozapine for the control of hemiballismus.
      • van Vugt J.P.
      • Siesling S.
      • Vergeer M.
      • van der Velde E.A.
      • Roos R.A.
      Clozapine versus placebo in Huntington’s disease: a double blind randomised comparative study.
      • Simson G.M.
      The treatment of tardive dyskinesia and tardive dystonia.
      A literature search revealed that olanzapine has not been used to treat hemiballismus, but it has been shown to decrease abnormal movements in patients with Huntington’s disease, Tourette’s syndrome, and tardive dyskinesia.
      • Bengi Semerci Z.
      Olanzapine in Tourette’s disorder.
      • Jiminez-Jiminez F.J.
      • de Toledo M.
      • Puertas I.
      • Baron M.
      • Zurdo M.
      • Barcenilla B.
      Olanzapine improves chorea in patients with Huntington’s disease.
      • Dipple H.C.
      The use of olanzapine for movement disorder in Huntington’s disease: a first case report.
      • Lucetti C.
      • Bellini G.
      • Nutti A.
      • et al.
      Treatment of patients with tardive dystonia with olanzapine.
      We report the case of a patient with hemiballismus caused by a left thalamic hemorrhage who did not benefit from haloperidol but who responded well to olanzapine.

      Case description

      A right-handed, Hispanic man in his late sixties was admitted with the acute onset of slurred speech, confusion, and sudden flailing movements of the right arm. A computed tomography scan showed an acute left thalamic hemorrhage and 2 old infarctions in the left occipital and right frontal lobes. His medical history was significant for hypertension, tobacco abuse (10 cigarettes a day for >40y), alcohol abuse, and a history of a stroke 10 years previously, with no residual functional deficits. Premorbidly, he was independent with all activities of daily living (ADLs). Medications on admission for inpatient rehabilitation included aspirin, lorazepam, haloperidol, metoprolol, folate, thiamine, and multivitamins.
      The initial examination revealed a confused, moderately dysarthric, agitated man with sudden involuntary movements of his right hemibody. These flailing movements increased with attempts to perform functional tasks, such as feeding and grooming. The patient had severe ataxia and decreased coordination on the right side. His strength was 4/5 (muscle contraction was possible against gravity and with less than the normal amount of resistance) in the right upper and lower extremities. His sensation was difficult to assess because of his confusion, but it appeared to be intact for pressure and pain. Strength on the left side was 5/5 (normal strength), and there were no involuntary movements. Reflexes were symmetric but slightly diminished (1/4) in all extremities, and bilateral plantar responses were downgoing.
      Functional assessment revealed severe cognitive deficits, especially with attention, memory, and comprehension. He was not oriented to person, place, or time and was unable to follow commands or answer questions. He had mild dysphagia but was able to tolerate pureed solids and thin liquids. He was unable to stand or ambulate because of poor balance. He was incontinent of both bowel and bladder. He required moderate to maximal assistance for feeding and grooming, and he was dependent for bathing, dressing, and toileting.
      The patient’s agitation was difficult to control and was the primary focus of early interventions. Initially, he became very agitated during therapy sessions and at night. He required a safety belt in the wheelchair, as well as safety pads for the bed and wheelchair, at all times due to agitation and hemiballismus. Behavioral techniques were implemented to help control his agitation but were only minimally effective.
      The agitation did not respond to higher doses of haloperidol and lorazepam, and the increased sedation interfered with his rehabilitation. After 1 week, these psychiatric medications were reduced, and his sedation lessened. A brief trial of quetiapine (Seroquel) resulted in daytime sedation that interfered with therapies and did not improve the insomnia or agitation.
      During this medication regimen and behavioral treatments, the hemiballismus continued to be a significant problem. The abnormal movements were exacerbated during functional tasks, adversely affecting his mobility and ADLs. It was believed that olanzapine might improve both the agitation and hemiballismus. For this reason, after obtaining informed consent from the patient’s wife, a therapeutic trial of olanzapine (2.5mg at night) was initiated on day 11, and the dose was held constant during the remainder of the patient’s stay. The patient continued to take a low oral dose (0.5mg) of haloperidol at night, but lorazepam was discontinued before the initiation of olanzapine.
      Hemiballistic movements were recorded during 2 standardized, half-hour therapy sessions at the same time each day by the treating physical and occupational therapists, who were blind to the initiation of olanzapine. The movement disorder data were collected daily for 2 days before and 3 days after initiation of olanzapine. Additionally, FIM instrument scores were obtained on admission, day 7, day 13, and at discharge.
      For the first functional task (reaching within the base of support while seated), 2 days of baseline data showed an average of 23.5 upper- and 20.5 lower-extremity movements during the therapy sessions. The day after the first dose of olanzapine, there was a dramatic reduction in the number of hemiballistic movements, with an average of only 3.0 upper- and 7.0 lower-extremity movements during 3 therapy sessions (fig 1).
      Figure thumbnail gr1
      Fig 1Hemiballistic movements while seated and reaching within the base of support.
      The second standardized therapeutic activity involved the patient catching a ball while seated, a more dynamic and challenging activity than the previous one. As expected, the total number of hemiballistic movements was higher. The average of 2 days of baseline data was 52 upper- and 34.5 lower-extremity movements. After initiation of olanzapine, there was an average of 6.3 upper- and 2.7 lower-extremity movements (fig 2). The hemiballistic movements continued at these much lower levels for the rest of the patient’s stay.
      Figure thumbnail gr2
      Fig 2Hemiballistic movements while seated and catching a ball.
      The FIM score on admission was 25, and it increased to 32 by day 7 (28% gain). Notably, 2 days after initiation of olanzapine, the patient’s score improved from 32 to 47 (46.9% gain). The rate of change in the FIM was considerably better after olanzapine (2.5 FIM points per day), in contrast with the baseline gain of 1 FIM point per day. Although he continued to make progress in the remaining week of his stay, the gains were not as dramatic, and his final FIM score was 52 (10.6% gain). The FIM scores over the course of the admission are shown in figure 3.
      Figure thumbnail gr3
      Fig 3FIM scores. Note that the first dose of olanzapine was given on day 11.
      After initiation of olanzapine, the patient’s participation in therapies improved, and there was a marked reduction in both daytime and nighttime agitation. Additionally, he required only 2 doses of haloperidol and only 3 doses of lorazepam for severe agitation during the remaining 10 days of his admission.
      At discharge, the patient required contact guard for transfers, ambulation, and dynamic balance; minimal assistance for grooming and bathing; moderate assistance for lower-body dressing; and maximal assistance for toileting. He remained incontinent of bowel and bladder. Cognition, communication, and orientation were essentially unchanged from admission. He was still unable to identify pictures of family members and required maximum verbal cues to attend to tasks such as eating.

      Discussion

      Olanzapine, like clozapine, is a dopamine and serotonin receptor antagonist and has little or no effect on other receptors.
      • Bymaster F.P.
      • Rasmussen K.
      • Calligaro D.O.
      • et al.
      In vitro and in vivo biochemistry of olanzapine: a novel antipsychotic drug.
      It should theoretically treat hemiballismus by counteracting the increased synthesis and release of dopamine. Animal studies show that olanzapine, like clozapine, inhibits oral dyskinesias induced by both serotonergic (5-HT2) and dopaminergic (D1) agonists.
      • Rosengarten H.
      • Schweitzer J.W.
      • Friedhoff A.J.
      The effect of novel antipsychotics in rat oral dyskinesia.
      Additionally, olanzapine has been effective in treating movement disorders, such as Huntington’s chorea, tardive dyskinesia, and Tourette’s syndrome.
      • Bengi Semerci Z.
      Olanzapine in Tourette’s disorder.
      • Jiminez-Jiminez F.J.
      • de Toledo M.
      • Puertas I.
      • Baron M.
      • Zurdo M.
      • Barcenilla B.
      Olanzapine improves chorea in patients with Huntington’s disease.
      • Dipple H.C.
      The use of olanzapine for movement disorder in Huntington’s disease: a first case report.
      • Lucetti C.
      • Bellini G.
      • Nutti A.
      • et al.
      Treatment of patients with tardive dystonia with olanzapine.
      Reported side effects with olanzapine include dry mouth, constipation, postural hypotension, dizziness, akathisia, weight gain, and transient elevation in liver enzymes.
      • Conley R.R.
      • Meltzer H.Y.
      Adverse events related to olanzapine.
      The incidence of agranulocytosis is much lower with olanzapine. The incidence with clozapine is approximately 1%, and there have been only 12 cases of olanzapine-induced agranulocystosis reported in the literature.
      • Alvir J.M.
      • Lieberman J.A.
      • Safferman A.Z.
      • Schwimmer J.L.
      • Schaaf J.A.
      Clozapine-induced agranulocytosis: Incidence and risk factors in the United States.
      • Tolosa-Vilella C.
      • Ruiz-Ripoll A.
      • Mari-Alfonso B.
      • Naval-Sendra E.
      Olanzapine-induced agranulocytosis: a case report and review of literature.
      Haloperidol is an effective therapy for hemiballismus, but its use is limited by side effects, including extrapyramidal reactions, tardive dyskinesia, sedation, and a lowered seizure threshold.
      • Bashir K.
      • Manyam B.V.
      Clozapine for the control of hemiballismus.
      Therefore, olanzapine may be preferable in some cases to clozapine or haloperidol for the treatment of hemiballismus.

      Conclusions

      The hemiballistic movements, agitation, and FIM scores all improved after treatment with olanzapine. Consequently, the olanzapine was not discontinued to prove a causal link between the improvements and the medication. We believed that discontinuing the olanzapine would have had adverse effects for the patient and therefore would have been unethical. This case report does not conclusively prove that olanzapine is responsible for the reduced hemiballismus and FIM gains in this patient. He did show some modest progress before treatment with olanzapine, but the rate of change in FIM scores was much greater after the medication. Olanzapine may be a valuable alternative treatment for patients with hemiballismus, but a large randomized controlled trial is needed to determine its efficacy.

      References

        • Klawans H.L.
        • Moses 3rd, H.
        • Nausieda P.A.
        • Bergen D.
        • Weiner W.J.
        Treatment and prognosis of hemiballismus.
        N Engl J Med. 1976; 295: 1348-1350
        • Whittier J.R.
        • Mettler F.A.
        Studies on subthalamus of rhesus monkey: hyperkinesia and other physiologic effects of subthalamic lesions, with special reference to the subthalamic nucleus of Luys.
        J Comp Neurol. 1949; 90: 319-372
        • Martin J.P.
        Hemichorea resulting from a local lesion of the brain (the syndrome of the body of Luys).
        Brain. 1927; 50: 637-651
        • Nath A.
        • Jankovic J.
        • Pettigrew L.C.
        Movement disorders and AIDS.
        Neurology. 1987; 37: 37-41
        • Dewey R.B.
        • Jankovic J.
        Hemiballismus-hemichorea: clinical and pharmacologic findings in 21 patients.
        Arch Neurol. 1989; 46: 862-867
        • Kotter R.
        Postsynaptic integration of glutaminergic and dopaminergic signals in the striatum.
        Prog Neurobiol. 1994; 44: 163-196
        • Provenzale J.M.
        • Schwarzschild M.A.
        Hemiballismus.
        Am J Neuroradiol. 1994; 15: 1377-1382
        • Kimura M.
        Physiological bases of involuntary movement.
        Neurology. 1994; 34: 1241-1242
        • Carlos M.
        • Carlson A.
        Interactions between glutaminergic and monoaminergic systems within the basal ganglia.
        Trends Neurosci. 1990; 13: 272-276
        • Tams L.S.
        • Cohen M.G.
        • Li E.K.
        Hemiballismus in systemic lupus erythematosus: possible association with antiphospholipid antibodies.
        Lupus. 1995; 4: 67-69
        • Lietz T.E.
        • Huff J.S.
        Hemiballismus as a presenting sign of hyperglycemia.
        Am J Emerg Med. 1995; 13: 647-648
        • Shannon K.M.
        Hemiballismus.
        Clin Neuropharmacol. 1990; 13: 413-425
        • Kant R.
        • Zeiler D.
        Hemiballismus following closed head injury.
        Brain Inj. 1996; 10: 155-158
        • Tamaoka A.
        • Sakuta M.
        • Yamada H.
        Hemichorea-hemiballism caused by arteriovenous malformation in the putamen.
        J Neurol. 1987; 234: 124-125
        • Glass J.
        • Jankovic J.
        • Borit A.
        Hemiballismus and metastatic brain tumor.
        Neurol. 1984; 34: 204-207
        • Johnson W.G.
        • Fahn S.
        Treatment of vascular hemiballism and hemichorea.
        Neurology. 1977; 27: 634-636
        • Ristic A.
        • Marinkovic J.
        • Dragasevic N.
        • Stanisavlejevic D.
        • Kostic V.
        Long-term prognosis of vascular hemiballismus.
        Stroke. 2002; 33: 2109-2115
        • Bashir K.
        • Manyam B.V.
        Clozapine for the control of hemiballismus.
        Clin Neuropharmacol. 1994; 17: 477-480
        • Gilbert G.J.
        Response of hemiballismus to haloperidol.
        JAMA. 1975; 233: 535-536
        • Lenton R.J.
        • Cofti M.
        • Smith R.G.
        Hemiballismus treated with sodium valproate.
        BMJ. 1981; 283: 17-18
        • Chandra V.
        • Wharton S.
        • Spunt A.L.
        Amelioration of hemiballismus with sodium valproate.
        Ann Neurol. 1982; 12: 407-411
        • Gonce M.
        • Schoenen J.
        • Charlier M.
        • Delwaide P.J.
        Successful treatment of hemiballismus with progabide, a new GABA-mimetic agent.
        J Neurol. 1983; 229: 121-124
        • Evident V.G.
        • Gwinn-Hardy K.
        • Caviness J.N.
        • Alder C.H.
        Risperidone is effective in severe hemichorea/hemiballismus.
        Mov Disord. 1999; 14: 377-379
        • Pearce J.
        Reversal of hemiballismus by tetrabenazine.
        JAMA. 1972; 219: 1345-1347
        • Cardoso F.
        • Jankovic J.
        • Grossman R.G.
        • Hamilton W.J.
        Outcome after stereotactic thalamotomy for dystonia and hemiballismus.
        Neurosurgery. 1995; 36: 501-508
        • Martin J.P.
        • McCaul I.R.
        Acute hemiballismus treated by ventrolateral thalamolysis.
        Brain. 1959; 82: 104-108
        • Rosengarten H.
        • Schweitzer J.W.
        • Friedhoff A.J.
        The effect of novel antipsychotics in rat oral dyskinesia.
        Prog Neuropsychopharmacol Biol Psychiatry. 1999; 23: 1389-1404
        • van Vugt J.P.
        • Siesling S.
        • Vergeer M.
        • van der Velde E.A.
        • Roos R.A.
        Clozapine versus placebo in Huntington’s disease: a double blind randomised comparative study.
        J Neurol Neurosurg Psychiatry. 1997; 63: 35-39
        • Simson G.M.
        The treatment of tardive dyskinesia and tardive dystonia.
        J Clin Psychiatry. 2000; 61: 39-44
        • Bengi Semerci Z.
        Olanzapine in Tourette’s disorder.
        J Am Acad Child Adolesc Psychiatry. 2000; 39: 140-143
        • Jiminez-Jiminez F.J.
        • de Toledo M.
        • Puertas I.
        • Baron M.
        • Zurdo M.
        • Barcenilla B.
        Olanzapine improves chorea in patients with Huntington’s disease.
        Rev Neurol. 2002; 35: 524-525
        • Dipple H.C.
        The use of olanzapine for movement disorder in Huntington’s disease: a first case report.
        J Neurol Neurosurg Psychiatry. 1999; 67: 123-124
        • Lucetti C.
        • Bellini G.
        • Nutti A.
        • et al.
        Treatment of patients with tardive dystonia with olanzapine.
        Clin Neuropharmacol. 2002; 25: 71-74
        • Bymaster F.P.
        • Rasmussen K.
        • Calligaro D.O.
        • et al.
        In vitro and in vivo biochemistry of olanzapine: a novel antipsychotic drug.
        J Clin Psychiatry. 1997; 58: 28-36
        • Conley R.R.
        • Meltzer H.Y.
        Adverse events related to olanzapine.
        J Clin Psychiatry. 2000; 61: 26-29
        • Alvir J.M.
        • Lieberman J.A.
        • Safferman A.Z.
        • Schwimmer J.L.
        • Schaaf J.A.
        Clozapine-induced agranulocytosis: Incidence and risk factors in the United States.
        N Engl J Med. 1993; 329: 162-167
        • Tolosa-Vilella C.
        • Ruiz-Ripoll A.
        • Mari-Alfonso B.
        • Naval-Sendra E.
        Olanzapine-induced agranulocytosis: a case report and review of literature.
        Prog Neuropsychopharmacol Biol Psychiatry. 2002; 26: 411-414