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Substituting bupropion, nefazodone, or mirtazapine is beneficial. (Grade of recommendation: B, randomized controlled trials [RCTs].) Augmentation therapy with amantadine, bupropion, and buspirone is no better than placebo. (Grade of recommendation: B, RCTs.) Augmentation therapy with multiple other agents may be beneficial. (Grade of recommendation: D, open-label nonrandomized studies, case series, and case reports.) SSRI “drug holidays” may also be effective (Table 1). (Grade of recommendation: D, open-label nonrandomized studies.)
TABLE
Summary of treatment options for SSRI-induced sexual dysfunction
| Strategy | Drugs considered | RCT data | Other data |
|---|---|---|---|
| Switch therapy | Bupropion SR, bupropion, mirtazapine, nefazodone | Nefazodone effective | All agents effective in nonrandomized open-label trials |
| Augmentation | Buspirone, amantadine, bupropion, cyproheptadine, dextroamphetamine, granisetron, ginkgo biloba, methylphenidate, mirtazapine, nefazodone, pemoline, sildenafil, yohimbine | Small, transient effect with high-dose buspirone. | Other RCT with buspirone, amantadine, and bupropion showed no difference vs placebo. Most agents effective in nonrandomized open-label trials, case-series, or case reports. Placebo effect unknown |
| Drug holiday | Fluoxetine, paroxetine, sertraline | None available | Improvement in 2 of 4 weekends for sertraline and paroxetine only |
Evidence summary
SSRI-related sexual dysfunction may be dose dependent and diminish with time, but these aspects have not been evaluated prospectively. Data suggest that bupropion, nefazodone, and mirtazapine have little to no effect on sexual functioning.1 Changing from SSRIs to one of these agents may alleviate SSRI-induced sexual dysfunction. In a randomized double-blind study, patients experiencing sexual dysfunction on sertraline improved when switched to nefazodone 400 mg daily.2 Additional open-label nonrandomized studies of all 3 agents suggest improved sexual functioning in 60% to 85% of patients with little to no loss of antidepressant efficacy.1,3,6 The potential for placebo effects makes interpreting these open-label trials more difficult.
Three augmentation therapies have been tested in double-blind placebo-controlled trials. In the first, buspirone augmentation resulted in a statistical improvement in sexual functioning at weeks 2 and 3 of therapy, but not at weeks 1 and 4 (mean dose 48.5 mg per day).7 In the second, adding buspirone 20 to 30 mg per day, amantadine 50 to 100 mg per day, or placebo resulted in equal improvement in women’s sexual function.8 Finally, in a third trial, adding bupropion or placebo showed equal improvement in sexual function.9 Multiple other agents have been tested in open-label nonrandomized studies, case series, and case reports. Most showed a beneficial effect, but results must be interpreted with caution. One open-label nonrandomized study of weekend “drug holidays” showed no benefit for fluoxetine and inconsistent results for paroxetine and sertraline.10
Recommendations from others
Tertiary literature sources recommend the strategies described above.11
Clinical Commentary by Michael Fisher, MD, additional references, search strategy, and detailed evidence table at http://www.fpin.org.
1. Zajecka J, Drouin MA, Yang WH, Horak F, et al. J Clin Psychiatry 2001;62(suppl 3):35-43.2.Allergy 1992;12(suppl):173.-
2. Ferguson JM, Shrivastava RK, Stahl SM, et al. J Clin Psychiatry. 2001;62:24-9.
3. Rosen RC, Lane RM, Menza M. J Clin Psychopharmacol 1999;19:67-85.
4. Gelenberg AJ, Laukes C, McGahuey C, et al. J Clin Psychiatry 2000;61:356-60.
5. Clayton AH, McGarvey EL, Abouesh AI, et al. J Clin Psychiatry 2001;62:185-90.
6. Walker PW, Cole JO, Gardner EA, et al. J Clin Psychiatry 1993;54:459-65.
7. Landen M, Eriksson E, Agren H, et al. J Clin Psychopharmacol 1999;19:268-71
8. Michelson D, Bancroft J, Targum S, et al. Am J Psychiatry 2000;157:239-43.
9. Masand PS, Ashton AK, Gupta S, et al. Am J Psychiatry 2001;158:805-7.
10. Rothschild AJ. Am J Psychiatry 1995;152:1514-6.
11. Marangell LB, Yudofsky SC, Silver JM. Psychopharmacology and electroconvulsive therapy. In: Hales RE, Yudofsky SC, Talbott JA, eds. Textbook of Psychiatry. 3rd ed. Washington, DC: American Psychiatric Press; 1999;1025-132.
Substituting bupropion, nefazodone, or mirtazapine is beneficial. (Grade of recommendation: B, randomized controlled trials [RCTs].) Augmentation therapy with amantadine, bupropion, and buspirone is no better than placebo. (Grade of recommendation: B, RCTs.) Augmentation therapy with multiple other agents may be beneficial. (Grade of recommendation: D, open-label nonrandomized studies, case series, and case reports.) SSRI “drug holidays” may also be effective (Table 1). (Grade of recommendation: D, open-label nonrandomized studies.)
TABLE
Summary of treatment options for SSRI-induced sexual dysfunction
| Strategy | Drugs considered | RCT data | Other data |
|---|---|---|---|
| Switch therapy | Bupropion SR, bupropion, mirtazapine, nefazodone | Nefazodone effective | All agents effective in nonrandomized open-label trials |
| Augmentation | Buspirone, amantadine, bupropion, cyproheptadine, dextroamphetamine, granisetron, ginkgo biloba, methylphenidate, mirtazapine, nefazodone, pemoline, sildenafil, yohimbine | Small, transient effect with high-dose buspirone. | Other RCT with buspirone, amantadine, and bupropion showed no difference vs placebo. Most agents effective in nonrandomized open-label trials, case-series, or case reports. Placebo effect unknown |
| Drug holiday | Fluoxetine, paroxetine, sertraline | None available | Improvement in 2 of 4 weekends for sertraline and paroxetine only |
Evidence summary
SSRI-related sexual dysfunction may be dose dependent and diminish with time, but these aspects have not been evaluated prospectively. Data suggest that bupropion, nefazodone, and mirtazapine have little to no effect on sexual functioning.1 Changing from SSRIs to one of these agents may alleviate SSRI-induced sexual dysfunction. In a randomized double-blind study, patients experiencing sexual dysfunction on sertraline improved when switched to nefazodone 400 mg daily.2 Additional open-label nonrandomized studies of all 3 agents suggest improved sexual functioning in 60% to 85% of patients with little to no loss of antidepressant efficacy.1,3,6 The potential for placebo effects makes interpreting these open-label trials more difficult.
Three augmentation therapies have been tested in double-blind placebo-controlled trials. In the first, buspirone augmentation resulted in a statistical improvement in sexual functioning at weeks 2 and 3 of therapy, but not at weeks 1 and 4 (mean dose 48.5 mg per day).7 In the second, adding buspirone 20 to 30 mg per day, amantadine 50 to 100 mg per day, or placebo resulted in equal improvement in women’s sexual function.8 Finally, in a third trial, adding bupropion or placebo showed equal improvement in sexual function.9 Multiple other agents have been tested in open-label nonrandomized studies, case series, and case reports. Most showed a beneficial effect, but results must be interpreted with caution. One open-label nonrandomized study of weekend “drug holidays” showed no benefit for fluoxetine and inconsistent results for paroxetine and sertraline.10
Recommendations from others
Tertiary literature sources recommend the strategies described above.11
Clinical Commentary by Michael Fisher, MD, additional references, search strategy, and detailed evidence table at http://www.fpin.org.
Substituting bupropion, nefazodone, or mirtazapine is beneficial. (Grade of recommendation: B, randomized controlled trials [RCTs].) Augmentation therapy with amantadine, bupropion, and buspirone is no better than placebo. (Grade of recommendation: B, RCTs.) Augmentation therapy with multiple other agents may be beneficial. (Grade of recommendation: D, open-label nonrandomized studies, case series, and case reports.) SSRI “drug holidays” may also be effective (Table 1). (Grade of recommendation: D, open-label nonrandomized studies.)
TABLE
Summary of treatment options for SSRI-induced sexual dysfunction
| Strategy | Drugs considered | RCT data | Other data |
|---|---|---|---|
| Switch therapy | Bupropion SR, bupropion, mirtazapine, nefazodone | Nefazodone effective | All agents effective in nonrandomized open-label trials |
| Augmentation | Buspirone, amantadine, bupropion, cyproheptadine, dextroamphetamine, granisetron, ginkgo biloba, methylphenidate, mirtazapine, nefazodone, pemoline, sildenafil, yohimbine | Small, transient effect with high-dose buspirone. | Other RCT with buspirone, amantadine, and bupropion showed no difference vs placebo. Most agents effective in nonrandomized open-label trials, case-series, or case reports. Placebo effect unknown |
| Drug holiday | Fluoxetine, paroxetine, sertraline | None available | Improvement in 2 of 4 weekends for sertraline and paroxetine only |
Evidence summary
SSRI-related sexual dysfunction may be dose dependent and diminish with time, but these aspects have not been evaluated prospectively. Data suggest that bupropion, nefazodone, and mirtazapine have little to no effect on sexual functioning.1 Changing from SSRIs to one of these agents may alleviate SSRI-induced sexual dysfunction. In a randomized double-blind study, patients experiencing sexual dysfunction on sertraline improved when switched to nefazodone 400 mg daily.2 Additional open-label nonrandomized studies of all 3 agents suggest improved sexual functioning in 60% to 85% of patients with little to no loss of antidepressant efficacy.1,3,6 The potential for placebo effects makes interpreting these open-label trials more difficult.
Three augmentation therapies have been tested in double-blind placebo-controlled trials. In the first, buspirone augmentation resulted in a statistical improvement in sexual functioning at weeks 2 and 3 of therapy, but not at weeks 1 and 4 (mean dose 48.5 mg per day).7 In the second, adding buspirone 20 to 30 mg per day, amantadine 50 to 100 mg per day, or placebo resulted in equal improvement in women’s sexual function.8 Finally, in a third trial, adding bupropion or placebo showed equal improvement in sexual function.9 Multiple other agents have been tested in open-label nonrandomized studies, case series, and case reports. Most showed a beneficial effect, but results must be interpreted with caution. One open-label nonrandomized study of weekend “drug holidays” showed no benefit for fluoxetine and inconsistent results for paroxetine and sertraline.10
Recommendations from others
Tertiary literature sources recommend the strategies described above.11
Clinical Commentary by Michael Fisher, MD, additional references, search strategy, and detailed evidence table at http://www.fpin.org.
1. Zajecka J, Drouin MA, Yang WH, Horak F, et al. J Clin Psychiatry 2001;62(suppl 3):35-43.2.Allergy 1992;12(suppl):173.-
2. Ferguson JM, Shrivastava RK, Stahl SM, et al. J Clin Psychiatry. 2001;62:24-9.
3. Rosen RC, Lane RM, Menza M. J Clin Psychopharmacol 1999;19:67-85.
4. Gelenberg AJ, Laukes C, McGahuey C, et al. J Clin Psychiatry 2000;61:356-60.
5. Clayton AH, McGarvey EL, Abouesh AI, et al. J Clin Psychiatry 2001;62:185-90.
6. Walker PW, Cole JO, Gardner EA, et al. J Clin Psychiatry 1993;54:459-65.
7. Landen M, Eriksson E, Agren H, et al. J Clin Psychopharmacol 1999;19:268-71
8. Michelson D, Bancroft J, Targum S, et al. Am J Psychiatry 2000;157:239-43.
9. Masand PS, Ashton AK, Gupta S, et al. Am J Psychiatry 2001;158:805-7.
10. Rothschild AJ. Am J Psychiatry 1995;152:1514-6.
11. Marangell LB, Yudofsky SC, Silver JM. Psychopharmacology and electroconvulsive therapy. In: Hales RE, Yudofsky SC, Talbott JA, eds. Textbook of Psychiatry. 3rd ed. Washington, DC: American Psychiatric Press; 1999;1025-132.
1. Zajecka J, Drouin MA, Yang WH, Horak F, et al. J Clin Psychiatry 2001;62(suppl 3):35-43.2.Allergy 1992;12(suppl):173.-
2. Ferguson JM, Shrivastava RK, Stahl SM, et al. J Clin Psychiatry. 2001;62:24-9.
3. Rosen RC, Lane RM, Menza M. J Clin Psychopharmacol 1999;19:67-85.
4. Gelenberg AJ, Laukes C, McGahuey C, et al. J Clin Psychiatry 2000;61:356-60.
5. Clayton AH, McGarvey EL, Abouesh AI, et al. J Clin Psychiatry 2001;62:185-90.
6. Walker PW, Cole JO, Gardner EA, et al. J Clin Psychiatry 1993;54:459-65.
7. Landen M, Eriksson E, Agren H, et al. J Clin Psychopharmacol 1999;19:268-71
8. Michelson D, Bancroft J, Targum S, et al. Am J Psychiatry 2000;157:239-43.
9. Masand PS, Ashton AK, Gupta S, et al. Am J Psychiatry 2001;158:805-7.
10. Rothschild AJ. Am J Psychiatry 1995;152:1514-6.
11. Marangell LB, Yudofsky SC, Silver JM. Psychopharmacology and electroconvulsive therapy. In: Hales RE, Yudofsky SC, Talbott JA, eds. Textbook of Psychiatry. 3rd ed. Washington, DC: American Psychiatric Press; 1999;1025-132.
Evidence-based answers from the Family Physicians Inquiries Network