This article reports on 18- to 80-year-old patients with symptomatic major depression disorder (MDD) defined by conventional criteria (⁴) and type 2 diabetes mellitus treated with extended-release BU in an open-label fashion over a 10-week study period (³). The protocol was approved by the institutional review board, and all subjects provided informed consent.

Ninety subjects (mean age 51.4 years, 63.3% were female, 46.7% were Caucasian) were initiated on BU therapy. Eighteen subjects (19.3%) failed to complete the study. Baseline rates of sexual dysfunction were similar between protocol completers and noncompleters (P = 0.48). Of the 72 participants who completed treatment, 61 (84.7%) met criteria for MDD remission. Sexual dysfunction was evident at baseline in 64 (71.1%) of the 90 study participants. Of these, 50 completed BU therapy and 28 (56%) experienced improved SF.

At baseline, participants with sexual dysfunction were older (52.8 vs. 48.0 years, P = 0.04) and had longer duration of MDD (25.5 vs. 18.3 years, P = 0.03). There were no significant between-group differences in depression or A1C. A trend toward longer duration of type 2 diabetes existed in those with sexual dysfunction (7.8 vs. 5.6 years, P = 0.14).

Those with persistent sexual dysfunction after therapy were older (55.1 vs. 52.0 years, P = 0.11) and had higher A1C (8.5 vs. 7.1%, P = 0.02). In contrast with baseline measures, significantly higher BDI scores after therapy were observed in those with persistent sexual dysfunction (9.0 vs. 4.9, P = 0.007).

SES improved significantly during treatment (SES mean pre- and posttreatment: 3.4–5.6, P < 0.0001), with 51 (70.8%) free of sexual dysfunction per established SES thresholds. This represented a significant improvement in rates of satisfactory SF (50/72, 69.4% vs. 23/72, 31.9%; χ² = 10.9, P = 0.001). Although improvement in SF was greatest in those with gains in depression and glycemic measures, it was also observed in two of 11 subjects (18.2%) who did not achieve depression remission and in seven of 27 subjects (25.9%) who had persistently elevated A1C levels (Fig. 1). Nominal improvements in SES after BU therapy (mean SES change of 0.6 ± 1.3) were experienced by those without improvement in SF. By comparison, those who had improved SF had a sevenfold change in SES (4.3 ± 1.7, P < 0.001).

We found a high rate (71.1%) of sexual dysfunction in patients with type 2 diabetes and MDD despite a modest rate of neuropathy (22.2%). SF improved significantly during BU therapy of MDD, with 58% of subjects experiencing substantial gains in SF during this interval. This effect was more robust in those with greater improvements in depression and glycemic control, but was still observed in approximately 20% of those with persistent MDD or hyperglycemia.

Diabetes may negatively influence SF though multiple pathophysiologic pathways, that is, vascular, neurologic, and hormonal effects (⁷–¹⁰). Hyperglycemia also impairs SF and may have been a factor in this sample (mean A1C >8%) (¹¹). MDD imposes additional risk of hyperglycemia (¹²), and indeed, A1C and BDI scores were positively correlated both at baseline and after BU therapy. Although depression, A1C, and SF tended to improve in concert, SF also improved significantly in 25% of those with persistent hyperglycemia.

In persons without diabetes, the risk of treatment-related sexual dysfunction is four to six times higher with selective serotonin- and norepinephrine-reuptake inhibitors compared with BU (¹³), possibly because of BU’s lack of influence on serotonergic presynaptic reuptake. Our findings add to evidence suggesting low sexual side effects with BU; indeed, new onset of sexual dysfunction occurred in only one subject. BU augmentation of dopamine effects regarded as important to arousal and orgasm may account for observed improvements in SF (¹⁴).

In summary, this study is the first to report on the high rate of sexual dysfunction in persons with diabetes and depression. Significant improvements in mood, glycemic control, and SF were observed during BU treatment of MDD. However, improvement in SF was still seen in approximately 20% of those with persistent depression or hyperglycemia. Limitations of the study relate to its small sample size, short-term treatment period, open treatment design, and use of a global measure of SF, the latter precluding comment on the specific nature of experienced sexual difficulties or improvements. Our findings support the need for routine assessment of SF in patients with type 2 diabetes and MDD, and affirm the importance of mood and glycemic control in SF. Selection of antidepressants with lower sexual side effects, such as BU, should yield the greatest potential for sexual and mental well-being in patients with type 2 diabetes and depression.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

No potential conflicts of interest relevant to this article were reported.

G.S.S. researched data, contributed to discussion, wrote the article, and reviewed and edited the article. B.M.G. researched data, contributed to discussion, and reviewed and edited the article. B.D.N. researched data. P.J.L. contributed to discussion, wrote the article, and reviewed and edited the article.