Should a patient taking 150 mg of Effexor (venlafaxine) extended release, 300 mg of bupropion, and 7.5 mg of mirtazapine, and experiencing insomnia, decreased sleep quality, anorgasmia, and sexual dysfunction, discontinue venlafaxine?

Should Venlafaxine Be Discontinued?

Yes, venlafaxine should be discontinued in this patient, as it is the most likely culprit for both the insomnia and sexual dysfunction, and the patient is already on two other antidepressants (bupropion and mirtazapine) that have significantly better sexual tolerability profiles and could provide adequate antidepressant coverage. 1, 2, 3

Rationale for Discontinuing Venlafaxine

Sexual Dysfunction Profile

• Venlafaxine has one of the highest rates of sexual dysfunction among antidepressants, with studies showing 67.3% incidence of sexual dysfunction including anorgasmia, compared to only 24.4% with mirtazapine and 22-25% with bupropion. 2, 3

• The patient is already taking two medications (bupropion 300 mg and mirtazapine 7.5 mg) that have significantly lower sexual side effect profiles than venlafaxine. 2, 4, 3

• In prospective studies, venlafaxine showed sexual dysfunction rates of 62.9-73%, comparable to SSRIs, while bupropion and mirtazapine had rates of 6.9-24.4%. 3

Insomnia and Sleep Quality

• Venlafaxine is specifically associated with treatment-emergent insomnia, occurring in 18% of patients versus 10% with placebo, and is a common reason for discontinuation. 1

• The FDA label explicitly lists insomnia as a common adverse effect that led to drug discontinuation in 3% of venlafaxine-treated patients. 1

• Mirtazapine, which the patient is already taking, has sedating properties and improves sleep, making it counterproductive to combine it with an insomnia-inducing agent like venlafaxine. 5, 6

Existing Medication Coverage

• The patient is already on 300 mg of bupropion (at maximum recommended dose for depression) and 7.5 mg of mirtazapine. 7

• This combination provides dual antidepressant coverage through different mechanisms (norepinephrine-dopamine reuptake inhibition with bupropion and noradrenergic/specific serotonergic activity with mirtazapine). 6, 8

• Mirtazapine at 7.5 mg is a relatively low dose; if additional antidepressant effect is needed after discontinuing venlafaxine, increasing mirtazapine to 15-30 mg would be more appropriate than continuing triple therapy. 5, 6

Discontinuation Protocol

Tapering Strategy

• Venlafaxine requires gradual tapering due to high risk of discontinuation syndrome, which includes dizziness, sensory disturbances (electric shock sensations), insomnia, anxiety, and confusion. 1

• The FDA label specifically warns that abrupt discontinuation leads to withdrawal symptoms, with frequency increasing with dose level and duration of treatment. 1

• Recommended taper: Reduce by 37.5-75 mg every 4-7 days, monitoring for discontinuation symptoms. If intolerable symptoms occur, resume the previous dose and taper more gradually. 5, 1

Monitoring During Discontinuation

• Watch for discontinuation symptoms including: agitation, anxiety, dizziness, sensory disturbances, insomnia worsening, nausea, and mood changes. 1

• If severe discontinuation symptoms occur, temporarily resume the previous dose and implement a slower taper schedule. 1

Expected Outcomes After Discontinuation

Sexual Function Improvement

• Sexual dysfunction from venlafaxine typically improves within 2-4 weeks of discontinuation, as the serotonergic effects resolve. 2, 3

• The combination of bupropion and mirtazapine remaining in the regimen is associated with improved sexual function compared to baseline depression, with mirtazapine showing 41-52% improvement in desire and arousal in women and 10-23% in men. 8

Sleep Quality Improvement

• Insomnia should improve within 1-2 weeks of venlafaxine discontinuation, allowing mirtazapine's sedating properties to predominate. 1, 6

• Mirtazapine has been specifically shown to rapidly resolve insomnia in depressed patients through its 5-HT2 and 5-HT3 receptor blockade. 6

Critical Caveats

• Do not abruptly stop venlafaxine - the discontinuation syndrome can be severe and includes potentially dangerous symptoms like confusion and seizures in rare cases. 1

• If depressive symptoms worsen during or after venlafaxine taper, increase mirtazapine to 15-30 mg rather than continuing venlafaxine, as this addresses the depression without perpetuating sexual dysfunction and insomnia. 5, 6

• Monitor blood pressure during venlafaxine discontinuation, as rebound hypotension can occasionally occur. 5