Could an old antifungal open up a new way to tackle the problem when antidepressant drugs stop working?
The development of tolerance to antidepressant treatment is an important clinical problem affecting about one third of patients treated for depression. This can show up as a loss of clinical effect, for example an antidepressant, which was working becomes less effective. In some cases, patients may develop resistance after a period of time off treatment, failing to respond to an antidepressant which had been effective previously.
Until now there has been no satisfactory explanation nor a way to improve treatment of antidepressant intolerance or resistance. Now Nicoletta Sonino, endocrinologist at the Department of Mental Health in Padova working together with Giovanni A. Fava at the University of Bologna in Italy, have described a novel way to tackle the problem.
Their work was based on assessing the hypothalamic-pituitary-adrenal (HPA) axis in such patients -they found their HPA axis seemed to be overactive. The breakthrough came from using a treatment to bring down the level of steroids in the blood. One way to do this is by giving patients ketoconazole. This is an agent which is often used for treatment of systemic fungal infections, including thrush. Ketoconazole is also known to block adrenal steroid production. Sonino and Fava found that ketoconazole was effective in reversing the tolerance to antidepressants in two carefully studied cases.
Clearly, a larger scale investigation will be needed, but the pioneering work by Sonino and Fava opens up a new avenue for helping a large number of patients to overcome depression when tolerance or resistance to medication is a problem.
Peer reviewed publication and reference:
Sonino N, Fava GA: Tolerance to antidepressant treatment may be overcome by ketoconazole. Report of two cases. J Psychiat Res 2003 ; 37 : 171-173
Keywords : Antidepressant Tolerance Resistance Ketoconazole Antifungal agent Steroid biosynthesis inhibitor HPA axis Clinical reversal of tolerance
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