Evening primrose oil reducing serum lithium concentration

Introduction

Evening primrose oil (EPO), Oenothera biennis, is available over-the-counter (OTC) for treating a range of conditions. Its omega-6 essential fatty acid ingredients, particularly gamma-linolenic acid, are precursors to prostaglandins, the well-known anti-inflammatory mediators [Pariza et al. 2000]. Evidence exists for EPO efficacy in alleviating perimenopausal hot flushes [Farzaneh et al. 2013]. Dermatologically, EPO lacks strong evidence for effectiveness in the treatment of atopic dermatitis or acne vulgaris [Stonemetz, 2008].

Lithium carbonate has an established efficacy in treatment of bipolar disorder and recurrent depressive disorder [Bauer et al. 2014]. A serum lithium concentration of 0.4–1 mmol/l is considered within the therapeutic window for maintenance of patients during the remission period [Mišak, 2005].

EPO decreases seizure threshold for patients taking phenothiazines [Vaddadi, 1981]; however, there are no reported interactions between EPO and lithium carbonate.

Case report

A 38-year-old woman with an established diagnosis of treatment-resistant depression has achieved remission for 10 years on a combination of thyroxin 25 µg and nortriptyline 150 mg daily augmented with lithium carbonate at a daily dose of 800 mg. She has comorbid chronic acne vulgaris with acne scarring that was stabilized on a combination of topical preparations, namely adapalene gel 0.3% and clindamycin/benzoyl peroxide (Duac®) gel and Tetralysal 300 mg daily. Serum levels of lithium were within the therapeutic range (0.69 mmol/l). However, she noted deterioration in her acne and was commenced on EPO 500 mg daily capsules. Yet, on regular 3-monthly check-up of lithium levels, after taking EPO for 2 months, a reduction in serum lithium level was noted (0.37 mmol/l). As she reported no affective symptoms and was functioning optimally, no change in the dose of lithium was warranted and she remained on the daily 800 mg dose. After 3 months, serum lithium level fell to 0.23 mmol/l. The EPO capsules were discontinued. After a further 6 weeks, the lithium level was observed to have risen to the therapeutic window level at 0.73 mmol/l.

No other medication was altered during the 6-month period and no difficulties in terms of physical well-being or compliance noted. All the biochemical investigations were unremarkable. The total duration of EPO therapy was 5 months.

Discussion

Despite the established efficacy of lithium carbonate in augmenting antidepressants in treatment-resistant depressive disorder [Bauer et al. 2014], a range of potentially serious interactions have been documented. It is prudent not to combine lithium carbonate with phenothiazine antipsychotic medications [Bailine and Doft, 2014]. Also, diuretics can enhance reabsorption of lithium in the proximal renal tubules, therefore, they increase serum lithium concentration [Huang, 1990]. Conversely, medications such as theophylline, caffeine, and acetazolamide [Colussi et al. 1989] increase lithium urinary concentrations and, thereby, reduce serum lithium levels.

In our patient, lithium levels dropped following co-intake of EPO. They improved immediately following EPO cessation. There was no other change in terms of medications, compliance, or medical status of the patient to explain such a phenomenon. The temporality between the drop in lithium levels and administration of EPO indicates potential interaction between the two. This is the first report, to our knowledge, of such an interaction.

A potential mechanism, by which EPO could have led to a reduction in the serum level of lithium, is via increasing the production of renal prostaglandin that may have resulted in increased renal blood flow and decreased renal reabsorption of lithium. This is exactly the opposite of how nonsteroidal anti-inflammatory drugs cause lithium toxicity [Shelley, 1987].

The ingredients of the EPO capsule are omega-6 fatty acids, including linoleic acid, natural vitamin E, beef gelatin, humectant (vegetable glycerol), and D-alpha tocopherol. None of these ingredients was reported to have an effect on lithium carbonate metabolism.

Conclusion

One limitation is that case reports remain at the bottom of the mental health evidence-base; however, reporting such interactions is of crucial importance in shaping clinical practice and research. It remains important, when on lithium treatment, to exercise caution before prescribing EPO or taking it OTC.