What alternative medication can I prescribe for depression with minimal sexual side effects?

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Last updated: June 30, 2025View editorial policy

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From the Guidelines

Bupropion (Wellbutrin) is often considered first-line for patients concerned about sexual dysfunction, typically started at 150mg daily and titrated to 300-450mg daily if needed. Several antidepressant medications have lower rates of sexual side effects compared to SSRIs. Some key points to consider when prescribing alternative medications for depression with minimal sexual side effects include:

  • Mirtazapine (Remeron) at 15-45mg daily is another option with minimal sexual side effects, though it may cause sedation and weight gain.
  • Vortioxetine (Trintellix) at 5-20mg daily has shown lower rates of sexual dysfunction in clinical trials.
  • Vilazodone (Viibryd) at 10-40mg daily may also have fewer sexual side effects than traditional SSRIs.
  • These medications work through different mechanisms - bupropion affects dopamine and norepinephrine, while mirtazapine has complex effects on serotonin and norepinephrine systems.
  • For patients already on an SSRI with good antidepressant response but experiencing sexual side effects, adding bupropion (150-300mg daily) as an adjunct can sometimes improve sexual function while maintaining mood benefits.
  • Treatment should be individualized based on the patient's specific symptoms, medical history, and other medications, as recommended by the American College of Physicians 1.

From the FDA Drug Label

The effect of TRINTELLIX on TESD induced by prior SSRI treatment in MDD patients whose depressive symptoms were adequately treated was evaluated in an eight-week, randomized, double-blind, active-controlled (escitalopram), flexible-dose study (Study 11) Improvement in TESD induced by prior SSRI treatment in subjects switched to TRINTELLIX was superior to the improvement observed in those subjects who switched to escitalopram In a randomized Healthy Volunteer study (Study 12) with 348 subjects aged 18 years to 40 years with normal sexual functioning without the confounding effect of depression, TESD with TRINTELLIX 10 mg, was statistically significantly less than with paroxetine 20 mg

Based on the studies, vortioxetine (TRINTELLIX) can be considered as an alternative medication for depression with minimal sexual side effects.

  • It has been shown to have less sexual dysfunction compared to some SSRIs, such as paroxetine and escitalopram, in certain studies 2.
  • The medication maintained antidepressant response while improving treatment-emergent sexual dysfunction (TESD) in patients who switched from SSRIs. However, it is essential to weigh the benefits and risks of each medication and consider individual patient factors when making prescribing decisions.

From the Research

Alternative Medications for Depression with Minimal Sexual Side Effects

  • Bupropion is an effective antidepressant with minimal sexual side effects, as shown in studies 3, 4, 5.
  • It is available in three oral formulations: immediate release, sustained release, and extended release, all of which are bioequivalent in terms of systemic exposure to bupropion 3.
  • Bupropion has been found to have a lower risk of sexual dysfunction compared to selective serotonin reuptake inhibitors (SSRIs) and venlafaxine XR 5.
  • Other medications that may have minimal sexual side effects include:
    • Mirtazapine, which has a unique mechanism of action and has been found to have a lower risk of sexual dysfunction compared to SSRIs 6.
    • Vilazodone, which is a selective serotonin reuptake inhibitor and 5-HT1A receptor partial agonist that has been found to have a lower risk of sexual dysfunction compared to other SSRIs 6.
    • Vortioxetine, which is a novel antidepressant that has been found to have a lower risk of sexual dysfunction compared to other antidepressants 6.

Key Findings

  • Bupropion has been found to be effective in treating depression with minimal sexual side effects in multiple studies 3, 4, 5, 7.
  • The prevalence of sexual dysfunction varies across antidepressants, with bupropion and nefazodone having the lowest risk and SSRIs and venlafaxine XR having a higher risk 5.
  • Physicians often underestimate the prevalence of antidepressant-associated sexual dysfunction, highlighting the need for greater recognition and education 5.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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