Psychosomatics 48:179-180, April 2007
doi: 10.1176/appi.psy.48.2.179
© 2007 Academy of Psychosomatic Medicine
An Acute Attack of Porphyria in a Patient Taking Duloxetine
Tracy Loper, M.D., and
Bryan Touchet, M.D., Dept. of Psychiatry Univ. of Oklahoma College of Medicine Tulsa, OK
TO THE EDITOR: Variegate porphyria shares with other acute porphyrias the symptom triad of red rash, abdominal pain, and neuropsychiatric disturbances.1 It also shares exhaustive lists of "safe" and "unsafe" medications.2 To our knowledge, this is the first report of a porphyria patient who suffered a severe adverse reaction typical of an acute porphyria exacerbation shortly after exposure to duloxetine.
A white woman in her sixth decade, with a history of back pain and fibromyalgia, also experienced episodes of red rash with severe abdominal pain. Depression and anxiety followed. After several years, variegate porphyria was established by identifying porphyrins in a 24-hour urine sample, with coproporphyrin quantities greater than aminolevulinic acid and porphobilinogen, with coproporphyrin present in fecal samples, and with these same porphyrins present in serum assays. After tolerating a seemingly unsuccessful trial of extended-release venlafaxine for treatment of depression and anxiety and for pain prophylaxis, she was tapered from venlafaxine and prescribed another serotonin- and norepinephrine-reuptake inhibitor antidepressant, duloxetine. No other medication changes were made. After 4 days of duloxetine therapy, she experienced her "worst attack in years," with a painful and ulcerating red rash, severe abdominal pain with constipation and vomiting, paresthesias, and worsening depression and anxiety, along with hallucinations, paranoia, and suicidality. Delirium ensued. These symptoms rapidly abated with cessation of duloxetine, opioid analgesia, and Panhematin® therapy.
When heme-biosynthesis is disordered by pathway enzyme deficiencies, porphyrins or their precursors can accumulate and result in dangerous toxicity.3 Since heme is an essential component in cytochrome P450 enzymes, induction of this system in the liver increases heme-synthesis, thus exaggerating the existing heme genetic pathway block. Although there is no documented in-vitro induction by duloxetine of the P450 system, in-vivo induction by duloxetine is not yet definite. Thus, porphyria exacerbation by duloxetine in this patient through P450 induction is still possible. Although not proving causality, this case does suggest that duloxetine may be a significant factor in acute porphyria exacerbation. If so, it also demonstrates the relative ease with which an acute episode can be precipitated by a drug with a proposed mechanism of action similar to that of another safe medication. At minimum, this case demonstrates the caution required when prescribing for porphyria patients.
This report was presented as a poster at the Tulsa Health Research Forum, 2006, at The University of Oklahoma–Tulsa; Tulsa, OK, April 19–20, 2006.
This letter and the work it represents were supported by the Dept. of Psychiatry at the Univ. of Oklahoma College of Medicine, Tulsa, OK.
REFERENCES
- Anderson KE, Bloomer JR, Bonkovsky HL, et al: Recommendations for the diagnosis and treatment of the acute porphyrias. Ann Intern Med 2005; 142:439–450[Abstract/Free Full Text]
- American Porphyria Foundation at http://www.porphyriafoundation.com/index.html; accessed May 31, 2006
- Anderson K, Sassa S, Bishop D, et al: Disorders of heme biosynthesis: X-linked sideroblastic anemia and the porphyrias, in Metabolic and Molecular Bases of Inherited Disease. Edited by Scriver C, Beaudet A, Sly W, et al. New York, McGraw-Hill, 2001, pp 2991-3062
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