Psychosomatics 40:444-445, October 1999
© 1999 The Academy of Psychosomatic Medine
Use of Olanzapine in Hereditary Coproporphyria
John Strauss, M.D., and
Andrea DiMartini, M.D.
Received March 22, 1999; accepted April 7, 1999. From the Western Psychiatric Institute and Clinic, Pittsburgh, PA. Address correspondence and reprint requests to Dr. Strauss, Western Psychiatric Institute and Clinic, 3811 O'Hara St., Pittsburgh, PA 15213; e-mail: straussj @msx.upmc.edu
Key Words: Olanzapine • Coproporphyria
Although it is well known that porphyrias present with psychiatric symptoms, it is less well known that psychiatric symptoms may be the only manifestation of acute hepatic porphyrias. Acute porphyrias include acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria.1 The full triad of mental status changes, abdominal pain, and peripheral neuropathy2 is not present in a significant proportion of those with porphyria: up to 15 percent of acute porphyrias will present without abdominal pain; up to 48 percent will lack muscle weakness.3 Because this disorder imitates so many conditions, clinical diagnosis of acute porphyria is vexing.4 Psychiatric presentation may vary in the same individual during different exacerbations.5
Moreover, the laboratory diagnosis of acute porphyrias is problematic. Samples of blood, stool, and urine must be taken early in the course of an attack: porphyrin precursors may only be detectable in the first days of an acute exacerbation. Porphyrins are light-sensitive and vulnerable to oxidation; they may be absent when the sample arrives at the laboratory. Current assays have high false-positive and false-negative rates. The diagnosis is difficult to exclude because of these complex clinical and laboratory features.3
Compounding diagnostic uncertainties are limited therapeutic possibilities. Following the standard approaches of administering high-dose intravenous glucose and hematin or heme arginate, psychiatric deficits may persist.
Treatment of such symptoms in acute porphyria is complicated by evidence that many psychotropics are porphyrogenic, including amphetamines, amitriptyline, barbiturates, carbamazepine, imipramine, tranylcypromine, and valproate.5 Antipsychotics believed to be safe in the acute hepatic porphyrias include droperidol and phenothiazines such as chlorpromazine and trifluoperazine.2,3 To date, there is no information in the porphyria literature on the use of novel antipsychotics such as olanzapine or risperidone in the treatment of psychiatric manifestations of acute porphyria.
Case Report
Mr. F., a 23-year-old, single, Caucasian man, was admitted to an academic medical center for acute changes in mental status. The presenting complaint was a 5-day history of mumbling, wandering, and visual hallucinations of animals, and 1 day of gait ataxia. Although abdominal pain had previously accompanied his psychiatric symptoms, there was none with this presentation.
He had a history of repeated psychotic episodes, two of which had resulted in psychiatric admissions. His mother stated that some of these episodes were precipitated by taking sulfonamides; on this occasion there were no obvious precipitants such as starvation, sedatives, stimulants, nonsteroidal anti-inflammatories, or alcohol. Three months before the current admission, a diagnosis of acute porphyria had been confirmed by his internist. His past medical history was significant only for mitral valve prolapse. The family history was remarkable for an acute porphyria in his father.
His past psychiatric history was significant for several psychotic episodes. Three years before the present admission, he developed paranoia and racing thoughts, which resolved spontaneously after 1 week; no medical attention was received at that time. Ten months before this admission, he again became symptomatic, with psychosis and abdominal pain. This resulted in his first psychiatric admission. During the evaluation of his acute psychosis, a diagnosis of porphyria was investigated. His coproporphyrinogen oxidase was marginally low (0.06 relative units; reference range: 0.10–0.30), which is compatible with hereditary coproporphyria. He responded rapidly to olanzapine but was discharged on no medications.
Four months before this admission, he had had a second psychiatric admission for acute psychosis; he was paranoid and anxious. His brother had found him walking in circles outside, allegedly "tracking bears." Urine drug screen was negative. Urinary porphobilinogen was elevated (4.1 mg/24h; reference: 0–2.7 mg/24h) and thus consistent with an acute porphyria. Olanzapine was started for the second time, and the psychosis ameliorated in 24 to 48 hours. His discharge diagnosis was Brief Psychotic Disorder and "rule out Psychotic Disorder due to Porphyria." He was discharged on olanzapine 5 mgqhs. Three months before the current admission, his internist had made a diagnosis of hereditary coproporphyria. The olanzapine was discontinued at that time.
In the first 24 hours of the present admission, he was treated with the usual antiporphyric regimen of high-dose intravenous glucose followed by hematin because of lack of response to glucose. A hematology consult confirmed a diagnosis of hereditary coproporphyria.
Laboratory values were normal for hemoglobin, white blood cell count and differential, glucose, sodium, potassium, chloride, calcium, magnesium, phosphorus, creatinine, TSH, B12, and folate. Abnormal were an AST (121 IU/L) and a platelet count (99 x 10E+9).
A psychiatry consult was requested because of the patient's persistent disorganized thought. The consulting psychiatrist recommended olanzapine 5 mg po qhs because of his apparent robust responses during both previous psychiatric admissions. Olanzapine was restarted 5 days after admission. The patient showed some improvement in mental status but continued to display tangentiality, flight of ideas, suspiciousness, visual hallucinations, flat affect, concreteness, inattention, and visuospatial deficits. An electroencephalogram and a magnetic resonance imaging study of the brain were unremarkable.
By the 20th hospital day, he denied paranoia and hallucinations. His thoughts were more organized; attention was markedly better, and he was fully oriented. After 22 days, he was discharged on 7.5 mg of olanzapine.
Five weeks after discharge, he complained of sedation. He was sleeping 15 hours daily. The hypersomnia decreased when the olanzapine was briefly stopped and returned when the medication was restarted at 2.5 mg qhs.
Discussion
In this patient, olanzapine was used to treat three separate attacks of acute porphyria with psychiatric symptoms. The first two episodes were psychotic states; the most recent was consistent with delirium. Although data are lacking on the use of olanzapine in acute porphyria, there is some literature on the use of novel antipsychotics in the treatment of delirium. Both risperidone and olanzapine have been used with delirium patients in case reports6,7 and a small controlled study.8
Olanzapine is a novel antipsychotic with high receptor affinities for serotonin (5-HT2A/2C, 5-HT3, and 5-HT6), dopamine (D1–4), muscarinic (M1–5),  1 adrenergic and histamine H1 receptors.9 There is evidence that it is more selective for the mesolimbic (A10) tracts that may contribute to psychosis than the nigrostriatal (A9) tracts, which modulate extrapyramidal symptoms.9
Preliminary evidence has suggested that olanzapine may be helpful in the treatment of delirium; in a small, controlled, nonrandomized study, it was better tolerated than haloperidol.8 Although olanzapine appeared helpful for this case of porphyria-related delirium, the improvement was more gradual than in other deliria treated with olanzapine.8 It is also possible that this episode of porphyria was unaltered by the antipsychotic and simply followed its natural course. A third possibility is that the antipsychotic effects were obscured by central anticholinergic effects that may have prolonged his confusional state. Similarly, the apparent response of the first two episodes of psychosis may have been due to milder symptom attacks or may have been caused by removing the patient from an unidentified environmental trigger.
His sedation after the last discharge correlated well with his medication compliance. This known side effect of olanzapine seemed excessive for the 2.5 mg daily dose he was taking. We suspect it may be related to resolving porphyric symptoms and a resulting increased vulnerability to sedation.
This case history demonstrates the complexity of gauging response to a novel antipsychotic in an individual with hereditary coproporphyria; it underscores the need for further inquiry into the use of olanzapine in mental status changes due to acute porphyrias. The rareness3 and diagnostic elusiveness of this disorder will likely make such inquiry challenging.
REFERENCES
-
Kalman DR, Bonkovsky HL: Management of acute attacks in the porphyrias. Clin Dermatol 1998; 16:299–306[Medline]
-
Lishman WA: Endocrine diseases and metabolic disorders, in Organic Psychiatry: The Psychological Consequences of Cerebral Disorder, 3rd Edition. London, UK, Blackwell Science, 1998, pp 567–569
-
Crimlisk HL: The little imitator—porphyria: a neuropsychiatric disorder. J Neurol Neurosurg Psychiatry 1997; 62:319–328[Abstract/Free Full Text]
-
Burgoyne K, Swartz R, Ananth J: Porphyria: reexamination of psychiatric implications. Psychother Psychosom 1995; 64:121–130[Medline]
-
Santosh PJ, Malhotra S: Varied psychiatric manifestations of acute intermittent porphyria. Biol Psychiatry 1994; 36:744–747[Medline]
-
Sipahimalani A, Masand PS: Use of risperidone in delirium: case reports. Ann Clin Psychiatry 1997; 9:105–107[Medline]
-
Ravona-Springer R, Dolberg OT, Hirschman S, et al: Delirium in elderly patients treated with risperidone: a report of three cases. J Clin Psychopharmacol 1998; 18:171–172[Medline]
-
Sipahimalani A, Masand PS: Olanzapine in the treatment of delirium. Psychosomatics 1998; 39:422–429[Abstract/Free Full Text]
-
Owens MJ, Risch SC: Atypical antipsychotics, in The American Psychiatric Press Textbook of Psychopharmacology, 2nd Edition, edited by Schatzberg A, Nemeroff C. Washington, DC, American Psychiatric Press, 1998, pp. 338–340
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