Is lithium-induced aggravation of psoriasis a dose-dependent side effect?/nAre omega-3 fatty acids

Fråga: Is lithium-induced aggravation of psoriasis a dose-dependent side effect?

Are omega-3 fatty acids effective in the treatment of psoriasis?

What are the pharmacological alternatives to lithium and valproate in the treatment of bipolar disorder?

A 55-year-old male has been effectively treated with lithium for a bipolar disorder. Unfortunately, the treatment also caused an aggravation of his pre-existing psoriasis. Adding omega-3 fatty acids (capsule Picazol Forte 1000 mg BID) did not improve the psoriatic symptoms.

When switching to valproate the psoriatic symptoms resolved, but the psychiatric condition worsened.

Sammanfattning: Dose-reduction could theoretically be beneficial in cases of lithium-induced aggravation of psoriasis.

There are a few randomised studies indicating advantageous effects of systemically administered omega-3 fatty acids in psoriasis, but evidence is inconsistent.

Several adjuvant therapies could be tried in bipolar disorder non-responsive to lithium and valproate, eg atypical neuroleptics, lamotrigine, gabapentin or topiramate. However, manic or bipolar disorder are approved indications only in lithium, valproic acid and olanzapine. Several ongoing systematic reviews of pharmacological treatment of bipolar disorder will be published in the Cochrane Library during 2003.

Svar: Aggravation of psoriasis is a well-known side effect of lithium, thought to result from a local increase of cytokine and growth factor secretion in the affected skin (1). Unlike immunologic skin reactions, one would expect this effect to display some degree of dose-dependency. Such dose-dependent properties are implicated in a review article, where dose-reduction is recommended as a first measure (2).

A question regarding the use of omega-3 fatty acids in the treatment of psoriasis has previously been answered by the Drug Information Centre (3). The evidence then consisted of a few ecological (investigating correlations on population level) or un-controlled studies and two small randomised controlled trials indicating beneficial effects of orally administered omega-3 fatty acids in psoriasis.

An updated Medline search identified three new randomised studies addressing this question in patients with plaque psoriasis, using clinical outcome data (4-6). In 145 patients assigned to four months´ oral treatment with either omega-3 fatty acids 6 g per day or omega-6 fatty acids 5 g per day (controls), there was no difference between the groups with regard to psoriasis symptoms (4). More promising results were seen in a study in 83 patients treated with omega-3 or omega-6 fatty acids intravenously for 14 days. Here, omega-3 significantly reduced psoriatic symptoms as compared to omega-6 (controls) (5). Lastly, eight weeks´ topical treatment with omega-3 ointment was no better than placebo in 52 studied patients with plaque psoriasis (6).

Although lithium and valproic acid are the most well-documented remedies in bipolar disorder, several other substances have proven beneficial. When lithium or valproate is insufficient per se, adjuvant treatment with an atypical neuroleptic or lamotrigine could be taken under consideration (7-8). Add-on medication with gabapentin or topiramate could also be beneficial, but is less well-documented (8). Combining lithium and valproic acid is another possible alternative (7). When considering combination therapy, possible pharmacological interactions should be taken into account. 1 Ockenfels HM, Wagner SN, Keim-Maas C, Funk R, Nussbaum G, Goos M. Lithium and psoriasis: cytokine modulation of cultured lymphocytes and psoriatic keratinocytes by lithium. Arch Dermatol Res 1996;288:173-8. 2 Mantelet S, Feline A. Cutaneous effects of lithium. Ann Med Psychol 1997;155:664-8. 3 Drugline no 08564 (year 1991) (enclosed) 4 Soyland E, Funk J, Rajka G, Sandberg M, Thune P, Rustad L et al. Effects of dietary supplementation with very-long-chain n-3 fatty acids in patients with psoriasis. N Engl J Med 1993;328:1812-6. 5 Mayser P, Mrowietz U, Arenberger P, Bartak P, Buchvald J, Christophers E et al. Omega-3 fatty acid-based lipid infusion in patients with chronic plaque psoriasis: results of a double-lind, randomised, placebo-controlled, multicenter trial. J Am Acad Dermatol 1998;38:539-47. 6 Henneicke-von Zepelin HH, Mrowietz U, Farber L, Bruck-Borchers K, Schober C, Huber J et al. Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study. Br J Dermatol 1993;129:713-7. (abstract) 7 Ghaemi SN. New treatments for bipolar disorder: the role of atypical neuroleptic agents. J Clin Psychiatry 2000;61(suppl 14):33-42. 8 Nemeroff CB. An ever-increasing pharmacopoeia for the management of patients with bipolar disorder. J Clin Psychiatry 2000;61(suppl 13):19-25.