Can mirtazapine mitigate the sexual side effects of Selective Serotonin Reuptake Inhibitors (SSRIs)?

Mirtazapine for Mitigating SSRI-Induced Sexual Dysfunction

Mirtazapine is effective in mitigating sexual side effects of SSRIs and can be used as a substitution therapy for patients experiencing SSRI-induced sexual dysfunction. 1

Mechanism and Effectiveness

• Mirtazapine works through a different mechanism than SSRIs, acting as an alpha2-adrenoceptor antagonist and serotonin 5-HT2/5-HT3 receptor blocker, which contributes to its lower incidence of sexual side effects 1, 2
• In a clinical study of patients with SSRI-induced sexual dysfunction who were switched to mirtazapine, 58% experienced a return to normal sexual functioning, and an additional 11% reported significant improvement in sexual function 1
• Unlike SSRIs, which commonly cause sexual dysfunction (erectile dysfunction, delayed ejaculation, anorgasmia), mirtazapine has been shown to improve sexual desire, arousal, and orgasm satisfaction in both men and women 3

Dosing and Administration

• Mirtazapine can be initiated at 7.5-15 mg at bedtime and titrated up to 30-45 mg daily as needed 1, 4
• When switching from an SSRI to mirtazapine to address sexual dysfunction, a short washout period (4-14 days) is typically recommended to avoid serotonin syndrome 5
• Mirtazapine is typically administered as a single evening dose due to its sedative properties at lower doses 2

Clinical Considerations

• Sexual dysfunction is a common side effect of SSRIs that can lead to treatment discontinuation and poor compliance 5
• Mirtazapine maintains antidepressant efficacy while improving sexual function, with studies showing patients maintain their antidepressant response after switching from SSRIs 1
• Mirtazapine has been shown to improve sexual functioning in both men and women, though improvements may be more pronounced in women (41-52% improvement in various aspects of sexual function in women vs. 10-23% in men) 3

Potential Side Effects and Limitations

• The most common side effects of mirtazapine include initial sedation, irritability, and potential weight gain 1, 4
• Somnolence is more common at lower doses (less than 15 mg) and tends to decrease at therapeutic doses 2
• Weight gain of 4.5-9 kg has been reported in some patients taking mirtazapine 1
• While mirtazapine promotes sleep and appetite, which can be beneficial in depression, these effects may be undesirable for some patients 4

Alternative Approaches for SSRI-Induced Sexual Dysfunction

• Other approaches to managing SSRI-induced sexual dysfunction include dose reduction of the SSRI, drug holidays, or switching to another antidepressant with a lower incidence of sexual side effects 4
• Bupropion has also been shown to have a significantly lower rate of sexual adverse events compared to SSRIs like fluoxetine and sertraline 4

Monitoring and Follow-up

• When switching to mirtazapine, patients should be monitored for both resolution of sexual dysfunction and maintenance of antidepressant effect 1
• Improvement in sexual function may be observed within the first few weeks of mirtazapine treatment 6
• Regular assessment of weight and sedation is important, as these are the most common side effects that may affect treatment adherence 1, 2

Mirtazapine represents a valuable option for patients experiencing SSRI-induced sexual dysfunction while still requiring antidepressant therapy, with evidence supporting both its efficacy in maintaining mood improvement and resolving sexual side effects.