Testosterone has long been considered effective for treatment of depression (Altschule and Tillotson 1948). Recent studies have shown that blood testosterone concentrations are lower in older men with dysthymia or major depression compared with non-depressed controls (Seidman et al. 2002). This effect may also be modulated by androgen receptor polymorphisms, since blood testosterone concentrations predict depression, but only in the subgroup of men with shorter CAG repeats (Seidman etal. 2001a), a putative genetic marker of higher tissue androgen sensitivity (Zitzmann and Nieschlag 2003). So far, however, androgen therapy has not been convincingly shown to improve mood in depressed men. Whether this is due to inappropriate targeting of subjects (blood testosterone concentrations) or dose (Perry etal. 2002) is not clear.

Oral mesterolone was the first androgen studied for anti-depressive effects. Laboratory evidence that a single dose of mesterolone (1-25 mg) mimics the effects of tricyclic antidepressants on the electroencephalogram led to a patent predicting that androgens might have beneficial effects on clinical depression (Itil etal. 1974). This was, however, refuted in a double-blind clinical trial which randomised 52 depressed men to treatment with mesterolone (150-450 mg daily) or placebo for six weeks (Itil etal. 1984). Both groups improved equally in scores for global clinical impression, physician's checklist for depression, self-rating and Hamilton depression rating. There were no differences in electroencephalogram measures or plasma monoamine oxidase levels. Another study of 34 depressed men randomly assigned to receive either mesterolone (150-550 mg/day) or amitriptyline (75-300 mg/day), the two treatments were equally effective in 26 subjects who continued treatment

(Vogel etal. 1985). However, the small sample size and lack ofaplacebo (rather than an active treatment) control limit the interpretation of this study. More recently, intramuscular testosterone has also been examined. In a well controlled study of 30 older depressed men selected on the basis of low-normal blood testosterone concentration, weekly intramuscular injections of 200 mg testosterone enanthate for 6 weeks did not improve mood significantly compared with placebo (Seidman et al. 2001b). Observational studies of older men with low-normal blood testosterone concentrations (but not clinically depressed) reported that weekly injections of 100 mg testosterone cypionate had no effect on depression scores in 32 men treated for 12 months (Sih etal. 1997) or 14 men treated forthree months (Morley et al. 1993). However, the lack of proper masking limits the interpretation of these studies.

A potential role for androgen therapy as an adjunct to antidepressant therapy was suggested following a report evaluating potential benefit as salvage therapy when conventional antidepressant therapy is failing (Seidman and Rabkin 1998). After a 1 week run-in period, 22 men with major treatment-resistant depression and low serum testosterone were randomised to receive transdermal testosterone gel (1%, initial dose 10 g/d, downwardly dose-titrated) or placebo gel for eight weeks in addition to their current antidepressant therapy (Pope et al. 2003). Testosterone treatment significant improved the Hamilton depression rating and clinical global impression severity score, but not the Beck depression inventory score. Further studies would clearly be of great interest.

Anxiety and Depression 101

Anxiety and Depression 101

Everything you ever wanted to know about. We have been discussing depression and anxiety and how different information that is out on the market only seems to target one particular cure for these two common conditions that seem to walk hand in hand.

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