Sorry, here's the more clearly stated question: Has anyone had any experiences, good or bad, with trying to combine SSRIs with TRT? Or in your case doc, in any of your patients?
There are no contraindications of TRT with SSRIs. In many studies, use of T supplementation with SSRIs for depression has shown benefit. I have included a number of abstracts on its use in depression. The single attachment is from Pope et al. following. As far as TRT being effective in eugonadal patients, I believe the evidence is far from definitive.
Pope HG, Jr., Cohane GH, Kanayama G, Siegel AJ, Hudson JI.
Testosterone gel supplementation for men with refractory depression: a randomized, placebo-controlled trial. Am J Psychiatry 2003;160(1):105-11.
OBJECTIVE: Testosterone supplementation may produce antidepressant effects in men, but until recently it has required cumbersome parenteral administration. In an 8-week randomized, placebo-controlled trial, the authors administered a testosterone transdermal gel to men aged 30-65 who had refractory depression and low or borderline testosterone levels. METHOD: Of 56 men screened, 24 (42.9%) displayed morning serum total testosterone levels of 350 ng/dl or less (normal range=270-1070). Of these men, 23 entered the study. One responded to an initial 1-week single-blind placebo period, and 22 were subsequently randomly assigned: 12 to 1% testosterone gel, 10 g/day, and 10 to identical-appearing placebo. Each subject continued his existing antidepressant regimen. Ten subjects receiving testosterone and nine receiving placebo completed the 8-week trial. RESULTS: The groups were closely matched on baseline demographic and psychiatric measures. Subjects receiving testosterone gel had significantly greater improvement in scores on the Hamilton Depression Rating Scale than subjects receiving placebo. These changes were noted on both the vegetative and affective subscales of the Hamilton Depression Rating Scale. A significant difference was also found on the Clinical Global Impression severity scale but not the Beck Depression Inventory. One subject assigned to testosterone reported increased difficulty with urination, suggesting an exacerbation of benign prostatic hyperplasia; no other subject reported adverse events apparently attributable to testosterone.
CONCLUSIONS: These preliminary findings suggest that testosterone gel may produce antidepressant effects in the large and probably underrecognized population of depressed men with low testosterone levels.
Orengo CA, Fullerton L, Kunik ME.
Safety and efficacy of testosterone gel 1% augmentation in depressed men with partial response to antidepressant therapy. J Geriatr Psychiatry Neurol 2005;18(1):20-4.
The current study evaluates the efficacy and safety of testosterone (T) gel 1% augmentation on depressive symptoms and quality of life in treatment-resistant, depressed, hypogonadal men older than 50 years of age who are receiving antidepressants. The authors hypothesized that T augmentation would improve depressive symptoms and quality of life. Eighteen hypogonadal men entered the study who had had an adequate trial of antidepressant therapy and had significant depressive symptoms. Participants were continued on their antidepressant and were randomized to receive either placebo or active T gel (5 g) to be applied once a day. Participants were tested on 6 occasions: screening visit, an initial session (pretreatment), at 6 and 12 weeks during the first treatment condition, and at 18 and 24 weeks during the crossover condition. The authors found a significant improvement in depressive symptoms from baseline to 12 weeks of testosterone treatment. However, a statistical difference between placebo and testosterone treatment phases was not demonstrated. The limitations of the study, including the chronicity and severity of patients' depression, variability in T levels, and a small sample size, probably influenced the ability to detect a discernable difference. Nevertheless, the study shows that T gel augmentation may be helpful in hypogonadal males with depression.
Seidman SN, Miyazaki M, Roose SP.
Intramuscular testosterone supplementation to selective serotonin reuptake inhibitor in treatment-resistant depressed men: randomized placebo-controlled clinical trial. J Clin Psychopharmacol 2005;25(6):584-8.
BACKGROUND: Treatment-resistant depression is a persistent clinical problem. Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant supplement, although this strategy has received limited systematic study. OBJECTIVE: The aim of the study was to examine the mood effects of testosterone supplementation to a serotonergic antidepressant in men with treatment-resistant depression. METHOD: Twenty-six healthy adult men with major depressive disorder, partial or nonresponse to 2 adequate antidepressant trials during the current episode, and currently using a selective serotonin reuptake inhibitor were randomized under double-blind conditions to receive intramuscular injections of escalating doses of testosterone or placebo, in addition to their existing selective serotonin reuptake inhibitor regimen, for 6 weeks. The main outcome measure was the Hamilton Rating Scale for Depression score. RESULTS: The mean age was 46.4 +/- 10.8 years; mean total testosterone level, 417.5 +/- 197 ng/dL; mean baseline Hamilton Rating Scale for Depression score, 22.2 +/- 5.2; and median duration of the current depressive episode, 6.3 +/- 10.6 years. Hamilton Rating Scale for Depression scores decreased significantly in both testosterone (8.4) and placebo (7.4) groups. Antidepressant response, defined as a 50% decline in Hamilton Rating Scale for Depression score, was achieved by 53.8% (7/13) in the testosterone group and 23.1% (3/13) in the placebo group (P = 0.226). CONCLUSION: Both injectable testosterone and placebo supplementation to selective serotonin reuptake inhibitor were associated with improvement in mood; group differences were not distinguishable in this small sample of predominantly eugonadal men with treatment-resistant depression.
Seidman SN, Roose SP.
The sexual effects of testosterone replacement in depressed men: randomized, placebo-controlled clinical trial. J Sex Marital Ther 2006;32(3):267-73.
Symptoms of male hypogonadism such as low libido and erectile dysfunction (ED) respond to testosterone (T) replacement. In hypogonadal men with major depressive disorder (MDD), the extent to which T replacement alleviates sexual symptoms of hypogonadism is not known. We conducted 6 week double-blind placebo-controlled clinical trial in men with low and low-normal T levels (i.e., total T <or= 350 ng/dl) and MDD. Men were randomized to receive weekly intramuscular injections of either T enanthate 200 mg or sesame-seed oil (placebo). The primary outcome measure was self-reported sexual functioning. We randomized 30 patients. The mean age was 52(SD +/- 8) years, mean T level 262.5(SD +/- 8) ng/dl, and mean baseline Hamilton Rating Scale for Depression (HAM-D) score 21(SD +/- 8). At baseline, sexual function was low, with the majority reporting having had normal erectile and orgasmic functioning 0-1 time in the preceding month. All patients who received T achieved normalization of their T levels. The HAM-D scores decreased significantly in both T and placebo groups, and there were no significant between-group differences: reduction in mean HAM-D score from baseline to endpoint was 10.1 in patients who received T and 10.5 in those who received placebo. Self-reported sexual functioning improved slightly in both groups; a between-group difference was not detected. Both T replacement and placebo were associated with improvement in sexual function and mood, but differences between T and placebo were not distinguishable.
Seidman SN, Rabkin JG.
Testosterone replacement therapy for hypogonadal men with SSRI-refractory depression. J Affect Disord 1998;48(2-3):157-61.
BACKGROUND: Testosterone replacement therapy is an effective treatment of some depressive symptoms in hypogonadal men, and may be an effective augmentation treatment for SSRI-refractory major depression in such men. METHODS: We treated five depressed men who had low testosterone levels and had not responded to an adequate SSRI trial with 400 mg testosterone replacement biweekly for 8 weeks. Four patients underwent single-blind placebo discontinuation. Patients were assessed at baseline and biweekly thereafter using the Hamilton Depression Rating Scale (HAM-D) and the Endicott Quality of Life Enjoyment and Satisfaction Scale (Q-LES-Q). RESULTS: Patients' mean age was 40 years, and mean testosterone level 277 ng/dl. All had a rapid and dramatic recovery from major depression following testosterone augmentation: mean 21-item HAM-D decreased from 19.2 to 7.2 by week 2, and to 4.0 by week 8; mean Q-LES-Q increased from 45% to 68%. Three of four subjects who underwent discontinuation of testosterone under single-blind placebo treatment began to relapse. CONCLUSION: Testosterone replacement therapy may be an effective treatment of depressive symptoms in some men, and warrants further research.
Seidman SN, Spatz E, Rizzo C, Roose SP.
Testosterone replacement therapy for hypogonadal men with major depressive disorder: a randomized, placebo-controlled clinical trial. J Clin Psychiatry 2001;62(6):406-12.
BACKGROUND: Symptoms of male hypogonadism include low libido, fatigue, and dysphoria and are alleviated with testosterone replacement. The prevalence of major depressive disorder (MDD) in hypogonadal men is not known, nor is the antidepressant efficacy of testosterone replacement in depressed, hypogonadal men. METHOD: A 6-week double-blind, placebo-controlled clinical trial was conducted in 32 men with DSM-IV MDD and a low testosterone level, defined as total serum testosterone < or = 350 ng/dL. Patients were randomly assigned to receive weekly 1-mL intramuscular injections of either testosterone enanthate, 200 mg, or sesame seed oil (placebo). The primary outcome measure was the 24-item Hamilton Rating Scale for Depression (HAM-D). RESULTS: Thirty patients were randomly assigned to an intervention; 13 received testosterone, and 17 received placebo. Mean +/- SD age was 52+/-10 years, mean testosterone level was 266.1+/-50.6 ng/dL, and mean baseline HAM-D score was 21+/-8. All patients who received testosterone achieved normalization of their testosterone levels. The HAM-D scores decreased in both testosterone and placebo groups, and there were no significant between-group differences: reduction in group mean HAM-D score from baseline to endpoint was 10.1 in patients who received testosterone and 10.5 in those who received placebo. Response rate, defined as a 50% or greater reduction in HAM-D score, was 38.5% (5/13) for patients who received testosterone and 41.2% (7/17) for patients who received placebo. Patients receiving testosterone had a marginal but statistically significant improvement in sexual function (p = .02). CONCLUSION: In this clinical trial with depressed, hypogonadal men, antidepressant effects of testosterone replacement could not be differentiated from those of placebo.
