Strategies for managing sexual dysfunction induced by antidepressant medication

Lisa Rudkin; Matthew J Taylor; Keith KE Hawton

doi:10.1002/14651858.CD003382.pub2

Strategies for managing sexual dysfunction induced by antidepressant medication

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Referencias

References to studies included in this review

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Clayton AH, McGarvey EL, Warnock J, Kornstein S, Pinkerton RC. Bupropion SR as an antidote to SSRI‐induced sexual dysfunction. 40th Annual NCDEU Meeting. National Institute of Mental Health, 2000:Poster 169.

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Ginsberg DL, Adler L, McCullough A, Ying P, Wu K, Rotrosen J. Sildenafil treatment of serotonin‐reuptake inhibitor (SRI)‐induced sexual dysfunction. 41st Annual New Clinical Drug Evaluation Unit (NCDEU) Meeting, USA. 2001.

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Landen M, Eriksson E, Agren H, Fahlen T. Effect of buspirone on sexual dysfunction in depressed patients treated with selective serotonin reuptake inhibitors. Journal of Clinical Psychopharmacology 1999;19:268‐71.

Masand PS, Ashton AK, Gupta S, Frank B. Sustained‐release bupropion for selective serotonin reuptake inhibitor‐induced sexual dysfunction: a randomised, double‐blind, placebo‐controlled, parallel‐group study. American Journal of Psychiatry 2001;158:805‐7.

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Michelson D, Kociban K, Tamura R, Morrison MF. Mirtazapine, yohimbine or olanzapine augmentation therapy for serotonin reuptake‐associated female sexual dysfunction: a randomised, placebo controlled trial. Journal of Psychiatric Research 2002;36:147‐52.

Nelson EB, Shah VN, Welge JA, Keck PE. A placebo‐controlled, crossover trial of granisetron in SRI‐induced sexual dysfunction. Journal of Clinical Psychiatry 2001;62:469‐73.

Nurnberg HG, Gelenberg A, Hargreave TB, Harrison WM, Siegel RL, Smith MD. Efficacy of sildenafil citrate for the treatment of erectile dysfunction in men taking serotonin reuptake inhibitors. American Journal of Psychiatry 2001;158:1926‐8.

Nurnberg HG, Gelenberg AJ, Fava M, Hensley PL, Lauriello J, Harrison WM, et al. Sildenafil for sri‐associated sexual dysfunction: a three‐center, six‐week, double‐blind, placebo‐controlled study in 90 men. 155th Annual Meeting of the American Psychiatric Association; 2002 May 18‐23rd; Philadelphia, PA, USA. 2002. [CN‐00430097]

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Segraves RT, Stevenson RW, Lee J, Walker DJ, Wang W, Dickson R. Tadalafil Treatment of Erectile Dysfunction in Men on Antidepressants. 157th Annual Meeting of the American Psychiatric Association; 2004 May 01‐06; New York, NY. 2004.

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References to studies excluded from this review

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Aizenberg D, Weizman A, Barak Y. Sildenafil for selective serotonin reuptake inhibitor‐induced erectile dysfunction in elderly male depressed patients. Journal of Sex and Marital Therapy 2003;29:297‐303. [MEDLINE: 14504018]

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Berk M, Stein DJ, Potgieter A, Maud CM, Els C, Janet ML, et al. Serotonergic targets in the treatment of antidepressant induced sexual dysfunction: a pilot study of granisetron and sumatriptan. International Clinical Psychopharmacology 2000;15:291‐5.

Cohen AJ, Bartlik B. Gingko biloba for antidepressant‐induced sexual dysfunction. Journal of Sex and Marital Therapy 1998;24:139‐43.

Gelenberg AJ, Laukes C, McGahuey C, Okayli G, Moreno F, Zentner L, et al. Mirtazapine substitution in SSRI‐induced sexual dysfunction. Journal of Clinical Psychiatry 2000;61:356‐9.

Moore BE, Rothschild AJ. Treatment of antidepressant‐induced sexual dysfunction. Hospital Practice 1999;34(1):89‐96.

Hensley PL, Nurnberg HG, Slonimski C, Paine S. Responders and Nonresponders to Sildenafil Citrate Therapy for SRI‐FSD. 157th Annual Meeting of the American Psychiatric Association, May 01‐06, 2004, New York, NY. 2004.

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Salerian AJ, Motto H, Baum AL. Dronabinol for Antidepressant‐Induced Sexual Dysfunction. 155th Annual Meeting of the American Psychiatric Association; 2002 May 18‐23rd; Philadelphia, PA. 2002.

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Tignol JL, Benkert O. Sildenafil citrate effectively treats erectile dysfunction in men who have been successfully treated for depression. 155th Annual Meeting of the American Psychiatric Association; 2002 May 18‐23rd; Philadelphia, PA. 2002. [CN‐00429611]

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References to studies awaiting assessment

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References to ongoing studies

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Ginkgo biloba: antidepressant‐induced sexual dysfunction. Ongoing studyJune 2002.

Additional references

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estudios en curso

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Croft H, Settle E, Houser T, Batey SR, Donahue RM, Ascher JA. A placebo‐controlled comparison of the antidepressant efficacy and effects on sexual functioning of sustained‐release bupropion and sertraline. Clinical Therapeutics 1999;21:643‐58. [MEDLINE: 10363731]

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Montejo‐Gonzalez AL, Llorca G, Izquierdo JA. SSRI‐induced sexual dysfunction: fluoxetine, paroxetine, sertraline and fluvoxamine in a prospective, multicentre and descriptive clinical study of 344 patients. Journal of Sex and Marital Therapy 1997;23:176‐94.

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Characteristics of studies

Characteristics of included studies [ordered by study ID]

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estudios excluidos
estudios en curso

Clayton 2004

Methods	Double blind, parallel arm, multicentre (3 sites). 4 weeks
Participants	55 adults randomised (48 women, 7 men). Non‐psychotic depression, on SSRI for at least 2 months with therapeutic response (Hamilton Rating Scale for Depression less than 11), developed or worsened sexual problems on current SSRI treatment.
Interventions	Bupropion SR 150mg twice daily or placebo twice daily, in addition to SSRI
Outcomes	Changes in Sexual Functioning Questionnaire. Hamilton Rating Scale for Depression.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

DeBattista 2001

Methods	Double‐blind, parallel arm
Participants	42 adults randomised.
Interventions	Bupropion SR 150mg once daily or placebo; in addition to current SSRI
Outcomes	Sexual dysfunction measures unclear, Hamilton Rating Scale for Depression, Beck Depression Inventory
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Ferguson 2001

Methods	Double blind, parallel arm, multicentre (9 sites). 10 weeks
Participants	75 adults randomised (34 women, 38 men). DSM‐III‐R moderate or severe depressive episode, sexual dysfunction due to sertraline, judged clinically stable and able to discontinue sertraline.
Interventions	Nefazodone 100mg twice daily increasing to 200mg after one week or sertraline 50mg once daily increasing to 100mg after one week and placebo at night
Outcomes	Physician's rating of sexual dysfunction. Hamilton Rating Scale for Depression.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Ginsberg 2001

Methods	Double blind, parallel arm. 8 weeks. (Further 8 week single blind period)
Participants	23 men (ages 30‐64). clinically recovered mood or anxiety disorder and SRI associated sexual dysfunction
Interventions	Sildenafil 50‐100mg once daily or placebo for 8 weeks. After 8 weeks, all participants received sildenafil 50‐100mg.
Outcomes	International Index of Erectile Function. Arizona Sexual Experience Scale. Erectile Dysfunction Inventory of Treatment Satifsaction. Rigiscan.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Jespersen 2004

Methods	Double‐blind, parallel arm. 14 days.
Participants	12 women randomised. antidepressant‐induced sexual dysfunction, past diagnosis of depression. No change in psychotropic treatment in the last 2 months, no comorbid psychiatric or medical disorder, no past history of sexual dysfunction
Interventions	granisetron (dose not specified) or placebo
Outcomes	Feiger Sexual Function and Satisfaction Questionnaire. Arizona Sexual Experience Scale.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Kang 2002

Methods	Double blind, parallel arm, single centre. 2 months.
Participants	37 adults randomised (10 women, 27 men). DSM‐IV substance‐induced sexual dysfunction, depressive disorder (without psychotic features) or anxiety disorder treated with an anti‐depressant, regular sexual activity.
Interventions	Ginkgo biloba 120mg /day increasing to 160mg / day after two weeks, and increasing to 240mg / day after four weeks, or placebo.
Outcomes	Investigator‐developed questionnaire. Beck Depression Inventory (Korean version). State and Trait Anxiety Inventory.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Landen 1999

Methods	Double blind, parallel arm, multicentre (12 centres). 4 weeks
Participants	47 adults from randomised group (27 women, 20 men). DSM‐IV major depressive episode, failed to respond to citalopram or paroxetine treatment of over 4 weeks, reported sexual side effects
Interventions	Buspirone 20‐60mg od or placebo, in addition to fixed dose usual SSRI
Outcomes	Udvalg fur Kliniske Undersogelser side effects rating scale. Clinical Global Impression.
Notes	Subanalysis of a larger study (n=119) exploring the efficacy of buspirone as add‐on treatment for patients not responding to SSRI alone
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Masand 2001

Methods	Double blind, parallel arm. 3 weeks
Participants	31 adults randomised (breakdown by gender unknown). Receiving SSRI for at least six weeks, sexual dysfunction attributed to SSRI, Hamilton Rating Scale for Depression score <10
Interventions	Bupropion SR 150 mg or placebo, in addition to SSRI
Outcomes	Arizona Sexual Experiences Scale. Hamilton Rating Scale for Depression, Udvalg fur Kliniske Undersogelser side effects rating scale
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Meston 2004

Methods	Double blind, crossover design. 8 weeks
Participants	29 women randomised. SSRI for depression, at least 10 weeks treatment, treatment otherwise successful, sexual dysfunction distinctly different from any noticed during depressed phase.
Interventions	Ephedrine 50mg once daily or placebo
Outcomes	Brief Index of Sexual Functioning for Women. Beck Depression Inventory.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Michelson 2000

Methods	Double blind, parallel arm, multicentre (3 sites). 12 weeks
Participants	67 women randomised. Stable dose of fluoxetine with consequent impaired orgasm or arousal, Cinical Global Impression sexual function score of at least 3, Hamilton Rating Scale for Depression less than 11
Interventions	Buspirone 10mg twice daily increasing to 15mg, or amantadine 50mg once daily increasing to 50mg twice daily, or placebo twice daily, in addition to fluoxetine
Outcomes	Interviewer Rating of Sexual Function. Patient rated visual analogue scales for sexual function. Clinician rated global impression. Patient rated global impression. Hamilton Rating Scale for Depression. Beck Depression Inventory. State‐Trait Anxiety Inventory.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Michelson 2002

Methods	Double blind, parallel arm. Multicentre (12 centres) 10 weeks
Participants	148 women randomised. Stable dose fluoxetine leading to reduced lubrication and/or orgasmic dysfunction, condition for which fluoxetine prescribed responded satisfactorily.
Interventions	Mirtazapine 15mg once daily increasing to 30mg, or yohimbine 5.4mg once daily increasing to 10.8mg, or olanzapine 2.5mg once daily increasing to 5mg, or placebo, in addition to fluoxetine.
Outcomes	Patient assessment of sexual function. Daily diary visual analog scales. Kinsey Ratings of Sexual Function ‐ computer assisted structured interview.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Nelson 2001

Methods	Double blind, crossover design. 6 weeks
Participants	38 adults randomised (18 women, 2 men, 18 not described). Sexual dysfunction begun whilst taking SSRI, Hamilton Rating Scale for Depression score less than 10.
Interventions	Granisetron 1‐2mg as required or placebo, in addition to SSRI.
Outcomes	Sexual Side Effects Scale. Hamilton Rating Scale for Depression.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Nurnberg 2001

Methods	Double blind, parallel arm. Duration of treatment from 12 to 26 weeks
Participants	98 men, from randomised group. Erectile dysfunction for at least 6 months, no uncontrolled psychiatric illness.
Interventions	Sildenafil 5 ‐ 200mg once daily or placebo once daily
Outcomes	International Index of Erectile Function.
Notes	Retrospective subanalysis of 10 phase II/III trials (total n=3414) analysing outcomes of those also taking SSRI (n=98).
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Nurnberg 2003

Methods	Double blind, parallel arm. Multicentre (3 centres) 6 weeks
Participants	90 men randomised. Taking stable dose of an SSRI with substance‐induced sexual dysfunction for more than four weeks, DSM‐IV major depressive disorder in remission, Hamilton Rating Scale for Anxiety score less than 11, Hamilton Rating Scale for Depression score less than 11.
Interventions	Sildenafil 50mg as required increasing to 100mg as required or placebo. in addition to SSRI
Outcomes	International Index of Erectile Function. Arizona Sexual Experiences Scale. Massachusetts General Hospital‐Sexual Function Questionnaire. Hamilton Rating Scale for Depression.
Notes
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

Segraves 2004

Methods	Double blind. Multicentre (174 centres). 12 weeks.
Participants	111 men randomised. Receiving antidepressants
Interventions	tadalafil 10 mg or 20 mg or placebo
Outcomes	International Index of Erectile Dysfunction. Sexual Encounter Profile diary. Global Assessment Question.
Notes	retrospective subanalysis of 11 trials (involving 2102 men) analysing outcomes of those receiving antidepressants
*Risk of bias*
Bias	Authors' judgement	Support for judgement
Allocation concealment?	Unclear risk	B ‐ Unclear

SSRI ‐ Selective Serotonin Reuptake Inhibitor; SRI ‐ Serotonin Reuptake Inhibitor; DSM ‐ Diagnostic and Statistical Manual of American Psychiatric Association

Characteristics of excluded studies [ordered by study ID]

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Study	Reason for exclusion
Aizenberg 2003	Non‐randomised
Ashton 1998	Case series
Berk 2000	Case Series
Cohen 1999	Case Series
Gelenberg 2000	Case Series
Moore 2002	Review article
Nurnberg 2002	Non‐randomised
Salerian 2000	Case series
Salerian 2002	Case series
Tignol 2004	Not antidepressant induced sexual dysfunction
Walker 1993	Case series
Worthington 2002	Non‐randomised

Characteristics of ongoing studies [ordered by study ID]

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estudios excluidos

Meston 2002

Trial name or title	Ginkgo biloba: antidepressant‐induced sexual dysfunction
Methods
Participants	110 women (age 18‐65) stabilised on antidepressant medication and free of a current Axis I disorder
Interventions	8 weeks of 200mg Ginkgo biloba extract or placebo
Outcomes	daily patient diary, patient‐rating scales, blind independent evaluator ratings, vaginal photoplethysmography
Starting date	June 2002
Contact information	Alessandra Rellini, MA (512) 232‐4805 [email protected]
Notes	estimated completion date September 2004

Data and analyses

Open in table viewer

Comparison 1. nefazodone vs sertraline

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 re‐emergence antidepressant induced sexual dysfunction (physician rated) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.1 Comparison 1 nefazodone vs sertraline, Outcome 1 re‐emergence antidepressant induced sexual dysfunction (physician rated).
1.1 week one	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 endpoint	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 overall degree of sexual satisfaction (patient rated) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.2 Comparison 1 nefazodone vs sertraline, Outcome 2 overall degree of sexual satisfaction (patient rated).
2.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 week 8	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 last rating recorded	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.3 Comparison 1 nefazodone vs sertraline, Outcome 3 dropouts.
3.1 overall	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 due to adverse effects	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Hamilton Rating Scale for Depression score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 1.4 Comparison 1 nefazodone vs sertraline, Outcome 4 Hamilton Rating Scale for Depression score.
4.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 week 8	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Open in table viewer

Comparison 2. sildenafil vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 endpoint International Index of Erectile Function scores Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.1 Comparison 2 sildenafil vs placebo, Outcome 1 endpoint International Index of Erectile Function scores.
1.1 total score	2	112	Mean Difference (IV, Fixed, 95% CI)	19.36 [15.00, 23.72]
1.2 erectile function	1	89	Mean Difference (IV, Fixed, 95% CI)	10.0 [7.39, 12.61]
1.3 orgasmic function	1	89	Mean Difference (IV, Fixed, 95% CI)	2.5 [1.36, 3.64]
1.4 sexual desire	1	89	Mean Difference (IV, Fixed, 95% CI)	0.5 [‐0.38, 1.38]
1.5 intercourse satisfaction	1	89	Mean Difference (IV, Fixed, 95% CI)	3.50 [2.48, 4.52]
1.6 overall satisfaction	1	89	Mean Difference (IV, Fixed, 95% CI)	1.80 [0.86, 2.74]
1.7 ability to acheive erection	2	182	Mean Difference (IV, Fixed, 95% CI)	1.15 [0.71, 1.60]
1.8 ability to maintain erection	2	182	Mean Difference (IV, Fixed, 95% CI)	1.27 [0.81, 1.73]
1.9 ejaculation frequency	1	92	Mean Difference (IV, Fixed, 95% CI)	0.78 [0.01, 1.55]
1.10 orgasm frequency	1	92	Mean Difference (IV, Fixed, 95% CI)	0.81 [0.04, 1.58]
1.11 desire frequency	1	93	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐0.46, 0.66]
2 endpoint Arizona Sexual Experience Scale scores Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only
Open in figure viewer Analysis 2.2 Comparison 2 sildenafil vs placebo, Outcome 2 endpoint Arizona Sexual Experience Scale scores.
2.1 Total score	2	112	Mean Difference (IV, Fixed, 95% CI)	‐4.62 [‐6.29, ‐2.95]
2.2 Sexual desire	1	89	Mean Difference (IV, Fixed, 95% CI)	‐0.60 [‐1.08, ‐0.12]
2.3 Arousal	1	89	Mean Difference (IV, Fixed, 95% CI)	‐0.60 [‐1.06, ‐0.14]
2.4 Erectile function	1	89	Mean Difference (IV, Fixed, 95% CI)	‐1.20 [‐1.66, ‐0.74]
2.5 Orgasm (ability)	1	89	Mean Difference (IV, Fixed, 95% CI)	‐1.40 [‐1.90, ‐0.90]
2.6 Orgasm (satisfaction)	1	89	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐1.58, ‐0.42]
3 endpoint MGH‐Sexual Functioning Questionnaire scores Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.3 Comparison 2 sildenafil vs placebo, Outcome 3 endpoint MGH‐Sexual Functioning Questionnaire scores.
3.1 Total score	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Sexual desire	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Arousal	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.4 Erectile function	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.5 Orgasm (ability)	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.6 Overall satisfaction	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 endpoint Erectile Dysfunction Inventory of Treatment Satisfaction scores Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.4 Comparison 2 sildenafil vs placebo, Outcome 4 endpoint Erectile Dysfunction Inventory of Treatment Satisfaction scores.
5 Clinical Global Impression ‐Sexual Function not "much/very much improved" by 6 weeks Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.5 Comparison 2 sildenafil vs placebo, Outcome 5 Clinical Global Impression ‐Sexual Function not "much/very much improved" by 6 weeks.
6 Sexual dysfunction defined by Arizona Sexual Experience Scale at trial endpoint Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.6 Comparison 2 sildenafil vs placebo, Outcome 6 Sexual dysfunction defined by Arizona Sexual Experience Scale at trial endpoint.
7 dropouts Show forest plot	2	113	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.28, 1.86]
Open in figure viewer Analysis 2.7 Comparison 2 sildenafil vs placebo, Outcome 7 dropouts.
8 endpoint Hamilton Rating Scale for Depression score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 2.8 Comparison 2 sildenafil vs placebo, Outcome 8 endpoint Hamilton Rating Scale for Depression score.

Open in table viewer

Comparison 3. bupropion vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 less than 50% improvement in Arizona Sexual Experiences Scale at 3 weeks Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 3.1 Comparison 3 bupropion vs placebo, Outcome 1 less than 50% improvement in Arizona Sexual Experiences Scale at 3 weeks.
2 less than 25% improvement in Arizona Sexual Experiences Scale at 3 weeks Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 3.2 Comparison 3 bupropion vs placebo, Outcome 2 less than 25% improvement in Arizona Sexual Experiences Scale at 3 weeks.
3 mean Changes in Sexual Functioning Questionnaire desire/frequency score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 3.3 Comparison 3 bupropion vs placebo, Outcome 3 mean Changes in Sexual Functioning Questionnaire desire/frequency score.
3.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 week 4	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 dropouts Show forest plot	2	86	Risk Ratio (M‐H, Fixed, 95% CI)	2.10 [0.78, 5.72]
Open in figure viewer Analysis 3.4 Comparison 3 bupropion vs placebo, Outcome 4 dropouts.
5 mean Hamilton Rating Scale for Depression score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 3.5 Comparison 3 bupropion vs placebo, Outcome 5 mean Hamilton Rating Scale for Depression score.
5.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 week 4	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Open in table viewer

Comparison 4. buspirone vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 no remission of sexual dysfunction symptoms at four weeks Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	0.60 [0.35, 1.01]
Open in figure viewer Analysis 4.1 Comparison 4 buspirone vs placebo, Outcome 1 no remission of sexual dysfunction symptoms at four weeks.
1.1 male	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.25, 1.74]
1.2 female	1	26	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.31, 1.05]
2 change in patient‐rated 'overall function' (sexual) visual analogue scale Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 4.2 Comparison 4 buspirone vs placebo, Outcome 2 change in patient‐rated 'overall function' (sexual) visual analogue scale.
3 dropouts Show forest plot	2	89	Risk Ratio (M‐H, Fixed, 95% CI)	2.09 [0.32, 13.59]
Open in figure viewer Analysis 4.3 Comparison 4 buspirone vs placebo, Outcome 3 dropouts.

Open in table viewer

Comparison 5. granisetron vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change from baseline on Sexual Side Effects Scale score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 5.1 Comparison 5 granisetron vs placebo, Outcome 1 change from baseline on Sexual Side Effects Scale score.
2 Feiger Sexual Function and Satisfaction Questionnaire score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 5.2 Comparison 5 granisetron vs placebo, Outcome 2 Feiger Sexual Function and Satisfaction Questionnaire score.
2.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 week 2	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Arizona Sexual Experience Scale score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 5.3 Comparison 5 granisetron vs placebo, Outcome 3 Arizona Sexual Experience Scale score.
3.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 week 2	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 5.4 Comparison 5 granisetron vs placebo, Outcome 4 dropouts.

Open in table viewer

Comparison 6. tadalafil vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in International Index of Erectile Function scores Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 6.1 Comparison 6 tadalafil vs placebo, Outcome 1 change in International Index of Erectile Function scores.
1.1 erectile function	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 failure to report improvement in erections at trial endpoint Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 6.2 Comparison 6 tadalafil vs placebo, Outcome 2 failure to report improvement in erections at trial endpoint.

Open in table viewer

Comparison 7. olanzapine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.1 Comparison 7 olanzapine vs placebo, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).
2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.2 Comparison 7 olanzapine vs placebo, Outcome 2 change in 'overall sexual function' (diary ratings).
3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 7.3 Comparison 7 olanzapine vs placebo, Outcome 3 dropouts due to adverse effects.

Open in table viewer

Comparison 8. mirtazapine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 8.1 Comparison 8 mirtazapine vs placebo, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).
2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 8.2 Comparison 8 mirtazapine vs placebo, Outcome 2 change in 'overall sexual function' (diary ratings).
3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 8.3 Comparison 8 mirtazapine vs placebo, Outcome 3 dropouts due to adverse effects.

Open in table viewer

Comparison 9. yohimbine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 9.1 Comparison 9 yohimbine vs placebo, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).
2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 9.2 Comparison 9 yohimbine vs placebo, Outcome 2 change in 'overall sexual function' (diary ratings).
3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 9.3 Comparison 9 yohimbine vs placebo, Outcome 3 dropouts due to adverse effects.

Open in table viewer

Comparison 10. amantadine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in patient‐rated 'overall function' (sexual) visual analogue scale Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 10.1 Comparison 10 amantadine vs placebo, Outcome 1 change in patient‐rated 'overall function' (sexual) visual analogue scale.
2 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 10.2 Comparison 10 amantadine vs placebo, Outcome 2 dropouts.

Open in table viewer

Comparison 11. Ginkgo biloba vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 sexual function ratings at week 8 (questionnaire) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 11.1 Comparison 11 Ginkgo biloba vs placebo, Outcome 1 sexual function ratings at week 8 (questionnaire).
1.1 sexual desire	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 overall sexual function	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 erection maintenance time	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 orgasm frequency	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 satisfaction to orgasm	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 11.2 Comparison 11 Ginkgo biloba vs placebo, Outcome 2 dropouts.

Open in table viewer

Comparison 12. ephedrine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Brief Index of Sexual Functioning for Women at end of treatment phase Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 12.1 Comparison 12 ephedrine vs placebo, Outcome 1 Brief Index of Sexual Functioning for Women at end of treatment phase.
1.1 sexual desire	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 sexual arousability	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 lack of vaginal lubrication	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 orgasm ability	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 orgasm intensity/pleasure	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.6 sexual dissatisfaction	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Open in table viewer

Comparison 13. amantadine vs buspirone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in patient‐rated 'overall function' (sexual) visual analogue scale Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 13.1 Comparison 13 amantadine vs buspirone, Outcome 1 change in patient‐rated 'overall function' (sexual) visual analogue scale.
2 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 13.2 Comparison 13 amantadine vs buspirone, Outcome 2 dropouts.

Open in table viewer

Comparison 14. olanzapine vs mirtazapine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 14.1 Comparison 14 olanzapine vs mirtazapine, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).
2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 14.2 Comparison 14 olanzapine vs mirtazapine, Outcome 2 change in 'overall sexual function' (diary ratings).
3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 14.3 Comparison 14 olanzapine vs mirtazapine, Outcome 3 dropouts due to adverse effects.

Open in table viewer

Comparison 15. olanzapine vs yohimbine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 15.1 Comparison 15 olanzapine vs yohimbine, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).
2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 15.2 Comparison 15 olanzapine vs yohimbine, Outcome 2 change in 'overall sexual function' (diary ratings).
3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 15.3 Comparison 15 olanzapine vs yohimbine, Outcome 3 dropouts due to adverse effects.

Open in table viewer

Comparison 16. mirtazapine vs yohimbine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 16.1 Comparison 16 mirtazapine vs yohimbine, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).
2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 16.2 Comparison 16 mirtazapine vs yohimbine, Outcome 2 change in 'overall sexual function' (diary ratings).
3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected
Open in figure viewer Analysis 16.3 Comparison 16 mirtazapine vs yohimbine, Outcome 3 dropouts due to adverse effects.

Analysis 1.1

Comparison 1 nefazodone vs sertraline, Outcome 1 re‐emergence antidepressant induced sexual dysfunction (physician rated).

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Analysis 1.2

Comparison 1 nefazodone vs sertraline, Outcome 2 overall degree of sexual satisfaction (patient rated).

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Analysis 1.3

Comparison 1 nefazodone vs sertraline, Outcome 3 dropouts.

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Analysis 1.4

Comparison 1 nefazodone vs sertraline, Outcome 4 Hamilton Rating Scale for Depression score.

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Analysis 2.1

Comparison 2 sildenafil vs placebo, Outcome 1 endpoint International Index of Erectile Function scores.

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Analysis 2.2

Comparison 2 sildenafil vs placebo, Outcome 2 endpoint Arizona Sexual Experience Scale scores.

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Analysis 2.3

Comparison 2 sildenafil vs placebo, Outcome 3 endpoint MGH‐Sexual Functioning Questionnaire scores.

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Analysis 2.4

Comparison 2 sildenafil vs placebo, Outcome 4 endpoint Erectile Dysfunction Inventory of Treatment Satisfaction scores.

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Analysis 2.5

Comparison 2 sildenafil vs placebo, Outcome 5 Clinical Global Impression ‐Sexual Function not "much/very much improved" by 6 weeks.

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Analysis 2.6

Comparison 2 sildenafil vs placebo, Outcome 6 Sexual dysfunction defined by Arizona Sexual Experience Scale at trial endpoint.

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Analysis 2.7

Comparison 2 sildenafil vs placebo, Outcome 7 dropouts.

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Analysis 2.8

Comparison 2 sildenafil vs placebo, Outcome 8 endpoint Hamilton Rating Scale for Depression score.

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Analysis 3.1

Comparison 3 bupropion vs placebo, Outcome 1 less than 50% improvement in Arizona Sexual Experiences Scale at 3 weeks.

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Analysis 3.2

Comparison 3 bupropion vs placebo, Outcome 2 less than 25% improvement in Arizona Sexual Experiences Scale at 3 weeks.

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Analysis 3.3

Comparison 3 bupropion vs placebo, Outcome 3 mean Changes in Sexual Functioning Questionnaire desire/frequency score.

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Analysis 3.4

Comparison 3 bupropion vs placebo, Outcome 4 dropouts.

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Analysis 3.5

Comparison 3 bupropion vs placebo, Outcome 5 mean Hamilton Rating Scale for Depression score.

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Analysis 4.1

Comparison 4 buspirone vs placebo, Outcome 1 no remission of sexual dysfunction symptoms at four weeks.

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Analysis 4.2

Comparison 4 buspirone vs placebo, Outcome 2 change in patient‐rated 'overall function' (sexual) visual analogue scale.

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Analysis 4.3

Comparison 4 buspirone vs placebo, Outcome 3 dropouts.

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Analysis 5.1

Comparison 5 granisetron vs placebo, Outcome 1 change from baseline on Sexual Side Effects Scale score.

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Analysis 5.2

Comparison 5 granisetron vs placebo, Outcome 2 Feiger Sexual Function and Satisfaction Questionnaire score.

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Analysis 5.3

Comparison 5 granisetron vs placebo, Outcome 3 Arizona Sexual Experience Scale score.

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Analysis 5.4

Comparison 5 granisetron vs placebo, Outcome 4 dropouts.

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Analysis 6.1

Comparison 6 tadalafil vs placebo, Outcome 1 change in International Index of Erectile Function scores.

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Analysis 6.2

Comparison 6 tadalafil vs placebo, Outcome 2 failure to report improvement in erections at trial endpoint.

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Analysis 7.1

Comparison 7 olanzapine vs placebo, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).

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Analysis 7.2

Comparison 7 olanzapine vs placebo, Outcome 2 change in 'overall sexual function' (diary ratings).

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Analysis 7.3

Comparison 7 olanzapine vs placebo, Outcome 3 dropouts due to adverse effects.

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Analysis 8.1

Comparison 8 mirtazapine vs placebo, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).

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Analysis 8.2

Comparison 8 mirtazapine vs placebo, Outcome 2 change in 'overall sexual function' (diary ratings).

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Analysis 8.3

Comparison 8 mirtazapine vs placebo, Outcome 3 dropouts due to adverse effects.

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Analysis 9.1

Comparison 9 yohimbine vs placebo, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).

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Analysis 9.2

Comparison 9 yohimbine vs placebo, Outcome 2 change in 'overall sexual function' (diary ratings).

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Analysis 9.3

Comparison 9 yohimbine vs placebo, Outcome 3 dropouts due to adverse effects.

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Analysis 10.1

Comparison 10 amantadine vs placebo, Outcome 1 change in patient‐rated 'overall function' (sexual) visual analogue scale.

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Analysis 10.2

Comparison 10 amantadine vs placebo, Outcome 2 dropouts.

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Analysis 11.1

Comparison 11 Ginkgo biloba vs placebo, Outcome 1 sexual function ratings at week 8 (questionnaire).

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Analysis 11.2

Comparison 11 Ginkgo biloba vs placebo, Outcome 2 dropouts.

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Analysis 12.1

Comparison 12 ephedrine vs placebo, Outcome 1 Brief Index of Sexual Functioning for Women at end of treatment phase.

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Analysis 13.1

Comparison 13 amantadine vs buspirone, Outcome 1 change in patient‐rated 'overall function' (sexual) visual analogue scale.

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Analysis 13.2

Comparison 13 amantadine vs buspirone, Outcome 2 dropouts.

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Analysis 14.1

Comparison 14 olanzapine vs mirtazapine, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).

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Analysis 14.2

Comparison 14 olanzapine vs mirtazapine, Outcome 2 change in 'overall sexual function' (diary ratings).

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Analysis 14.3

Comparison 14 olanzapine vs mirtazapine, Outcome 3 dropouts due to adverse effects.

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Analysis 15.1

Comparison 15 olanzapine vs yohimbine, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).

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Analysis 15.2

Comparison 15 olanzapine vs yohimbine, Outcome 2 change in 'overall sexual function' (diary ratings).

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Analysis 15.3

Comparison 15 olanzapine vs yohimbine, Outcome 3 dropouts due to adverse effects.

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Analysis 16.1

Comparison 16 mirtazapine vs yohimbine, Outcome 1 change in 'overall satisfaction' (patient rated assessment of sexual function).

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Analysis 16.2

Comparison 16 mirtazapine vs yohimbine, Outcome 2 change in 'overall sexual function' (diary ratings).

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Analysis 16.3

Comparison 16 mirtazapine vs yohimbine, Outcome 3 dropouts due to adverse effects.

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Comparison 1. nefazodone vs sertraline

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 re‐emergence antidepressant induced sexual dysfunction (physician rated) Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

1.1 week one	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 endpoint	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 overall degree of sexual satisfaction (patient rated) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 week 8	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.3 last rating recorded	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3.1 overall	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 due to adverse effects	1		Risk Ratio (M‐H, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 Hamilton Rating Scale for Depression score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

4.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4.2 week 8	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 1. nefazodone vs sertraline

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Comparison 2. sildenafil vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 endpoint International Index of Erectile Function scores Show forest plot	3		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

1.1 total score	2	112	Mean Difference (IV, Fixed, 95% CI)	19.36 [15.00, 23.72]
1.2 erectile function	1	89	Mean Difference (IV, Fixed, 95% CI)	10.0 [7.39, 12.61]
1.3 orgasmic function	1	89	Mean Difference (IV, Fixed, 95% CI)	2.5 [1.36, 3.64]
1.4 sexual desire	1	89	Mean Difference (IV, Fixed, 95% CI)	0.5 [‐0.38, 1.38]
1.5 intercourse satisfaction	1	89	Mean Difference (IV, Fixed, 95% CI)	3.50 [2.48, 4.52]
1.6 overall satisfaction	1	89	Mean Difference (IV, Fixed, 95% CI)	1.80 [0.86, 2.74]
1.7 ability to acheive erection	2	182	Mean Difference (IV, Fixed, 95% CI)	1.15 [0.71, 1.60]
1.8 ability to maintain erection	2	182	Mean Difference (IV, Fixed, 95% CI)	1.27 [0.81, 1.73]
1.9 ejaculation frequency	1	92	Mean Difference (IV, Fixed, 95% CI)	0.78 [0.01, 1.55]
1.10 orgasm frequency	1	92	Mean Difference (IV, Fixed, 95% CI)	0.81 [0.04, 1.58]
1.11 desire frequency	1	93	Mean Difference (IV, Fixed, 95% CI)	0.10 [‐0.46, 0.66]
2 endpoint Arizona Sexual Experience Scale scores Show forest plot	2		Mean Difference (IV, Fixed, 95% CI)	Subtotals only

2.1 Total score	2	112	Mean Difference (IV, Fixed, 95% CI)	‐4.62 [‐6.29, ‐2.95]
2.2 Sexual desire	1	89	Mean Difference (IV, Fixed, 95% CI)	‐0.60 [‐1.08, ‐0.12]
2.3 Arousal	1	89	Mean Difference (IV, Fixed, 95% CI)	‐0.60 [‐1.06, ‐0.14]
2.4 Erectile function	1	89	Mean Difference (IV, Fixed, 95% CI)	‐1.20 [‐1.66, ‐0.74]
2.5 Orgasm (ability)	1	89	Mean Difference (IV, Fixed, 95% CI)	‐1.40 [‐1.90, ‐0.90]
2.6 Orgasm (satisfaction)	1	89	Mean Difference (IV, Fixed, 95% CI)	‐1.0 [‐1.58, ‐0.42]
3 endpoint MGH‐Sexual Functioning Questionnaire scores Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 Total score	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 Sexual desire	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.3 Arousal	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.4 Erectile function	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.5 Orgasm (ability)	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.6 Overall satisfaction	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 endpoint Erectile Dysfunction Inventory of Treatment Satisfaction scores Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5 Clinical Global Impression ‐Sexual Function not "much/very much improved" by 6 weeks Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

6 Sexual dysfunction defined by Arizona Sexual Experience Scale at trial endpoint Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

7 dropouts Show forest plot	2	113	Risk Ratio (M‐H, Fixed, 95% CI)	0.72 [0.28, 1.86]

8 endpoint Hamilton Rating Scale for Depression score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

Comparison 2. sildenafil vs placebo

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Comparison 3. bupropion vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 less than 50% improvement in Arizona Sexual Experiences Scale at 3 weeks Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

2 less than 25% improvement in Arizona Sexual Experiences Scale at 3 weeks Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

3 mean Changes in Sexual Functioning Questionnaire desire/frequency score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 week 4	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 dropouts Show forest plot	2	86	Risk Ratio (M‐H, Fixed, 95% CI)	2.10 [0.78, 5.72]

5 mean Hamilton Rating Scale for Depression score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

5.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
5.2 week 4	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 3. bupropion vs placebo

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Comparison 4. buspirone vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 no remission of sexual dysfunction symptoms at four weeks Show forest plot	1	46	Risk Ratio (M‐H, Fixed, 95% CI)	0.60 [0.35, 1.01]

1.1 male	1	20	Risk Ratio (M‐H, Fixed, 95% CI)	0.65 [0.25, 1.74]
1.2 female	1	26	Risk Ratio (M‐H, Fixed, 95% CI)	0.57 [0.31, 1.05]
2 change in patient‐rated 'overall function' (sexual) visual analogue scale Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 dropouts Show forest plot	2	89	Risk Ratio (M‐H, Fixed, 95% CI)	2.09 [0.32, 13.59]

Comparison 4. buspirone vs placebo

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Comparison 5. granisetron vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change from baseline on Sexual Side Effects Scale score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 Feiger Sexual Function and Satisfaction Questionnaire score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2.2 week 2	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3 Arizona Sexual Experience Scale score Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3.1 baseline	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
3.2 week 2	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
4 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 5. granisetron vs placebo

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Comparison 6. tadalafil vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in International Index of Erectile Function scores Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.1 erectile function	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 failure to report improvement in erections at trial endpoint Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 6. tadalafil vs placebo

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Comparison 7. olanzapine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 7. olanzapine vs placebo

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Comparison 8. mirtazapine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 8. mirtazapine vs placebo

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Comparison 9. yohimbine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 9. yohimbine vs placebo

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Comparison 10. amantadine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in patient‐rated 'overall function' (sexual) visual analogue scale Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 10. amantadine vs placebo

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Comparison 11. Ginkgo biloba vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 sexual function ratings at week 8 (questionnaire) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.1 sexual desire	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 overall sexual function	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 erection maintenance time	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 orgasm frequency	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 satisfaction to orgasm	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
2 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 11. Ginkgo biloba vs placebo

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Comparison 12. ephedrine vs placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 Brief Index of Sexual Functioning for Women at end of treatment phase Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

1.1 sexual desire	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.2 sexual arousability	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.3 lack of vaginal lubrication	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.4 orgasm ability	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.5 orgasm intensity/pleasure	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]
1.6 sexual dissatisfaction	1		Mean Difference (IV, Fixed, 95% CI)	0.0 [0.0, 0.0]

Comparison 12. ephedrine vs placebo

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Comparison 13. amantadine vs buspirone

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in patient‐rated 'overall function' (sexual) visual analogue scale Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 dropouts Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 13. amantadine vs buspirone

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Comparison 14. olanzapine vs mirtazapine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 14. olanzapine vs mirtazapine

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Comparison 15. olanzapine vs yohimbine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 15. olanzapine vs yohimbine

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Comparison 16. mirtazapine vs yohimbine

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1 change in 'overall satisfaction' (patient rated assessment of sexual function) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

2 change in 'overall sexual function' (diary ratings) Show forest plot	1		Mean Difference (IV, Fixed, 95% CI)	Totals not selected

3 dropouts due to adverse effects Show forest plot	1		Risk Ratio (M‐H, Fixed, 95% CI)	Totals not selected

Comparison 16. mirtazapine vs yohimbine

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Referencias

References to studies included in this review

Clayton 2004 {published and unpublished data}

DeBattista 2001 {published data only}

Ferguson 2001 {published and unpublished data}

Ginsberg 2001 {published and unpublished data}

Jespersen 2004 {published data only}

Kang 2002 {published data only}

Landen 1999 {published data only}

Masand 2001 {published data only}

Meston 2004 {published data only}

Michelson 2000 {published data only}

Michelson 2002 {published and unpublished data}

Nelson 2001 {published data only}

Nurnberg 2001 {published data only}

Nurnberg 2003 {published and unpublished data}

Segraves 2004 {published and unpublished data}

References to studies excluded from this review

Aizenberg 2003 {published data only}

Ashton 1998 {published data only}

Berk 2000 {published data only}

Cohen 1999 {published data only}

Gelenberg 2000 {published data only}

Moore 2002 {published data only}

Nurnberg 2002 {published data only}

Salerian 2000 {published data only}

Salerian 2002 {published data only}

Tignol 2004 {published data only}

Walker 1993 {published data only}

Worthington 2002 {published data only}

References to studies awaiting assessment

Croft 2002 {published data only}

References to ongoing studies

Meston 2002 {published data only}

Additional references

Alderson 2004

Althof 1999

Angst 1998

Baldwin 1997

Balon 1993

Beck 1961

Carson 2004

Clayton 1997

Clayton 2003

Croft 1999

CUAGC 2002

DerSimonian 1986

Donoghue 1996

Feiger 1996

Fink 2002

Gregorian 2002

Guy 1976

Hamilton 1959

Hamilton 1960

Hawton 1995

Jick 1995

Labbate 2001

Lingjaerde 1987

McGahuey 2000

Moncrieff 2001

Montejo‐Gonzalez 97

Montgomery 2002

Philipp 1993

Rosen 1997

Sackett 1996

Sinclair 1994

Spielberger 1983

Taylor 1994

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Characteristics of excluded studies [ordered by study ID]

Characteristics of ongoing studies [ordered by study ID]

Data and analyses

Copiar o descargar referencia

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Instituciones a las que se accedió previamente

Usuarios institucionales