Abstract
Several open trials and one placebo-controlled investigation suggest ketoconazole may relieve symptoms of major depressive disorder (MDD) by lowering cortisol levels. Manic, depressed and mixed states of bipolar disorder (BPD) are also associated with hypercortisolemia. The use of cortisol synthesis inhibitors (e.g. ketoconazole) has not been examined in BPD. Three wOrnen and one man with BPD were given ketoconazole beginning at 200 mg/d titrated upward to 600 mgld, based on clinical response and side-effects, in an open fashion for five weeks for symptoms of mania, depression or mood lability. One subject discontinued the medication after four days secondary to abdominal pain, distention and flatus. The other three subjects all had greater than 50% reductions in the Hamilton Depression Rating Scale (31-item version). All three also had reductions on the Brief Psychiatric Rating Scale. One subject was discontinued due to a very mild and transient elevation of liver enzymes at a 600 mg dose. The preliminary data suggest ketoconazole may be useful for mood symptoms, particularly depression, in persons with BPD.
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