Practice Points
- Sexual dysfunction can arise from environmental, social, medical, or drug effects and requires a multifaceted approach to treatment.
- When possible, take a baseline sexual dysfunction measurement to assess if selective serotonin reuptake inhibitor use is correlated with onset or worsening of sexual dysfunction.
- Nonpharmacologic options should be considered before and during pharmacotherapy.
- Sildenafil may be useful for treating anorgasmia in women taking serotonergic antidepressants.
- Phosphodiesterase type 5 inhibitors are not FDA-approved for sexual dysfunction in women.
Mrs. L, age 27, has a history of major depressive disorder with symptoms of anxiety. She was managed successfully for 2 years with bupropion XL, 300 mg/d, but was switched to venlafaxine, titrated to 225 mg/d, after she developed seizures secondary to a head injury sustained in a car accident. After the switch, Mrs. L’s mood deteriorated and she was hospitalized. Since then, she’s received several medication trials, including paroxetine, 30 mg/d, a selective serotonin reuptake inhibitor (SSRI), and the tricyclic antidepressant (TCA) nortriptyline, 75 mg/d, but she could not tolerate these medications because of severe xerostomia.
After taking sertraline, 150 mg/d, for 8 weeks, Mrs. L improves and has a Patient Health Questionnaire score of 6, indicating mild depression. Her initial complaints of diarrhea and nausea have resolved, but Mrs. L now reports that she and her husband are having marital difficulties because she cannot achieve orgasm during sexual intercourse. She did not have this problem when she was taking bupropion. Her husband occasionally takes the phosphodiesterase type 5 (PDE5) inhibitor sildenafil before intercourse, and Mrs. L asks you if this medication will help her achieve orgasm.
DSM-IV-TR defines sexual dysfunction as disturbances in sexual desire and/or in the sexual response cycle (excitement, plateau, orgasm, and resolution) that result in marked distress and interpersonal difficulty.1 Sexual dysfunction can occur with the use of any antidepressant with serotonergic activity; it affects an estimated 50% to 70% of patients who take SSRIs.2 Sexual dysfunction can occur with all SSRIs; however, higher rates of sexual dysfunction are found with citalopram, fluoxetine, paroxetine, and sertraline.3 Studies have suggested there may be a dose-side effect relationship with SSRI-induced sexual dysfunction.4
Several factors can increase a patient’s risk of sexual dysfunction and should be considered before prescribing an antidepressant or when a patient presents with new or worsening sexual dysfunction (Table 1).5 In general, nonserotonergic agents such as bupropion, mirtazapine, and nefazodone are associated with lower rates of sexual dysfunction. The pharmacology of these agents explains their decreased propensity to cause sexual dysfunction. These agents increase levels of dopamine in the mesolimbic dopaminergic system either by blocking reuptake (bupropion) or antagonizing the serotonin subtype-2 receptor and facilitating disinhibition of decreased dopamine downstream (nefazodone and mirtazapine).
Table 1
Risk factors for sexual dysfunction
| Sex | Risk factors |
|---|---|
| Women | History of sexual, physical, or emotional abuse, physical inactivity |
| Men | Severe hyperprolactinemia, smoking |
| Both sexes | Poor to fair health, genitourinary disease, diabetes mellitus, cardiovascular disease, hypertension, increasing age, psychiatric disorders, relationship difficulties |
| Source: Reference 5 | |
One option for treating antidepressant-induced sexual dysfunction in women is PDE5 inhibitors, which are used to treat erectile dysfunction (ED). These medications ameliorate ED by inhibiting degradation of cyclic guanosine monophosphate by PDE5, which increases blood flow to the penis during sexual stimulation. Although these medications are not FDA-approved for treating sexual dysfunction in women, adjunctive PDE5 inhibitor treatment may be beneficial for sexual dysfunction in females because similar mediators, such as nitric oxide and cyclic guanosine monophosphate, involved in the nonadrenergic-noncholinergic signaling that controls sexual stimulation in men also are found in female genital tissue.6
When treating a woman with SSRI-induced sexual dysfunction, consider nonpharmacologic treatments both before and during pharmacotherapy (Table 2).7,8 See Table 3 for a comparison of pharmacokinetics, side effects, and drug interactions of the 4 FDA-approved PDE5 inhibitors—avanafil, sildenafil, tadalafil, and vardenafil.
Table 2
Management strategies for SSRI-induced sexual dysfunction
| Intervention | Comments |
|---|---|
| Nonpharmacologic | |
| Lifestyle modifications | Encourage healthy eating, weight loss, smoking cessation, substance abuse treatment, or minimizing alcohol intake to improve patient self-image and overall health |
| Cognitive-behavioral therapy | Patients can identify coping strategies for reducing symptom severity and preventing worsening sexual dysfunction |
| Sex therapy | May benefit patients with relationship difficulties |
| ‘Watch and wait’ | Spontaneous resolving (or ‘adaptation’) of sexual dysfunction with antidepressants can take ≥6 months. Studies have found adaptation rates generally are low (~10%) |
| Pharmacologic | |
| Drug holiday | May be an option for patients taking antidepressants with shorter half-lives and patients taking lower doses. Be cautious of empowering patients to stop their own medications as needed |
| Dosage reduction | Serotonergic antidepressant-induced sexual dysfunction may be related to dose. Little research has been conducted on this method and the patient’s clinical status must be considered |
| Dose timing | Instructing a patient to take the antidepressant after his or her usual time of sexual activity (eg, patients who engage in sexual activity at night should take the antidepressant before falling asleep). This may allow the drug level to be lowest during sexual activity |
| Switching medications | Case reports, retrospective studies, and RCTs suggest switching to a different antidepressant with less serotonergic activity may be appropriate, particularly if the patient has not responded to the current antidepressant |
| Adjunctive therapy | RCTs support adjunctive bupropion (≥300 mg/d) or olanzapine (5 mg/d) as treatment for SSRI-induced sexual dysfunction in women Studies have found no improvement in sexual functioning with adjunctive buspirone, granisetron, amantadine, mirtazapine, yohimbine, ephedrine, or ginkgo biloba in women |
| RCTs: randomized controlled trials; SSRI: selective serotonin reuptake inhibitor Source: Reference 7,8 | |