Is Trintellix (vortioxetine) a suitable next step for a patient with treatment-resistant depression, currently taking Wellbutrin XL (bupropion) and Buspar (buspirone), with a history of sexual side effects and weight gain with other antidepressants?

Trintellix (Vortioxetine) for Treatment-Resistant Depression

Yes, starting Trintellix is a reasonable next step for this patient with treatment-resistant depression who has failed multiple SSRIs (Paxil, Zoloft, Prozac, Lexapro, Citalopram) due to sexual side effects and weight gain, while currently on Wellbutrin and Buspar with inadequate response. 1, 2

Rationale for Trintellix in This Clinical Context

Treatment-Resistant Depression Criteria Met

• This patient meets criteria for treatment-resistant depression, having failed at least two adequate antidepressant trials of different mechanisms (multiple SSRIs), with significant functional impairment (increased sadness, emotional lability, sleep disturbance) despite current therapy with Wellbutrin XL 450mg and Buspar 30mg. 2
• After failure of two treatment trials, the chances of remission decrease significantly, making alternative strategies critical. 1

Why Trintellix is Appropriate Here

Favorable adverse effect profile for this patient's specific concerns:

• Sexual dysfunction: Vortioxetine has lower rates of sexual side effects compared to traditional SSRIs, addressing the patient's primary reason for discontinuing Citalopram. 3
• Weight neutrality: Unlike the SSRIs this patient previously failed (Paxil, Zoloft, Prozac, Lexapro), vortioxetine is not associated with significant weight gain, which is crucial given the patient's active weight loss efforts. 1
• The most common adverse effects are nausea (21-32% depending on dose), constipation (3-6%), and vomiting (3-6%), with nausea typically mild-to-moderate and resolving within two weeks. 3

Unique mechanism complementing current regimen:

• Vortioxetine combines serotonin transporter inhibition with modulation of multiple serotonin receptors (5-HT1A agonist, 5-HT3/5-HT7/5-HT1D antagonist, 5-HT1B partial agonist), providing a different mechanism than the patient's current Wellbutrin (norepinephrine-dopamine reuptake inhibitor) and Buspar (5-HT1A partial agonist). 4, 5
• This multimodal action may address residual depressive symptoms not covered by the current dopaminergic/noradrenergic approach. 4

Alternative Strategies to Consider

FDA-Approved Augmentation Options

If you prefer augmentation over switching:

• Atypical antipsychotics have the most extensive evidence base for treatment-resistant depression, with aripiprazole, quetiapine, and olanzapine-fluoxetine combination being FDA-approved specifically for this indication. 2
• However, given this patient's weight concerns and history of weight gain with previous medications, atypical antipsychotics carry significant metabolic risks that make them less ideal. 2

Bupropion Augmentation

• The patient is already on maximum-dose Wellbutrin XL (450mg), which is appropriate as bupropion augmentation is an evidence-based strategy for treatment-resistant depression with lower sexual side effects. 1, 2
• The STAR*D trial showed that switching to or augmenting with bupropion achieved remission in 1 in 4 patients whose initial therapy failed. 1, 2

Dosing and Implementation Strategy

Starting Trintellix

• Initiate at 10mg once daily, taken with or without food. 3
• Titrate to 20mg daily if needed after assessing response at 2 weeks, as therapeutic effects are typically observed at 2 weeks with full efficacy at 4-6 weeks. 4
• Can reduce to 5mg daily if tolerability issues arise, though efficacy may be reduced. 3

Managing Current Medications

Critical consideration for serotonin syndrome risk:

• Buspar (buspirone) is a 5-HT1A partial agonist, and combining it with Trintellix (which also has 5-HT1A agonist activity plus serotonin transporter inhibition) increases serotonin syndrome risk. 3
• Monitor closely for serotonin syndrome symptoms: agitation, confusion, tachycardia, hypertension, hyperthermia, tremor, muscle rigidity, diaphoresis, diarrhea, or mydriasis. 3
• Consider tapering Buspar if adequate response to Trintellix is achieved, as their mechanisms partially overlap. 3

Wellbutrin can be continued safely as it has no serotonergic activity and the combination addresses different neurotransmitter systems. 4

Critical Safety Monitoring

First 4-8 Weeks

• Assess for nausea (most common side effect, typically resolves within 2 weeks). 3
• Monitor for discontinuation syndrome if stopping Citalopram recently: nausea, sweating, dysphoric mood, irritability, dizziness, paresthesias, anxiety, confusion, headache. 3
• Screen for bipolar disorder history before initiating, as antidepressants can precipitate manic episodes (though risk with vortioxetine is <0.1%). 3

Ongoing Monitoring

• Hyponatremia risk, particularly given the patient may be using OTC sleep aids (antihistamines can compound this risk): monitor for headache, confusion, weakness, unsteadiness. 3
• Sexual function: Specifically inquire about changes, as vortioxetine can cause sexual dysfunction (though less than traditional SSRIs), including delayed ejaculation, erectile dysfunction, decreased libido, or delayed/absent orgasm. 3
• Bleeding risk: Counsel about increased bleeding risk, especially if patient takes NSAIDs, aspirin, or anticoagulants. 3

Addressing Sleep Disturbance

The patient's 5-hour sleep duration with OTC sleep aids requires attention:

• Vortioxetine's effect on sleep is variable; some patients experience insomnia (reported in clinical trials). 3
• Consider adding mirtazapine 7.5-15mg at bedtime if sleep does not improve, as it has strong sedating properties via H1 antagonism and is evidence-based for depression. 1
• Alternatively, trazodone 50-100mg at bedtime is commonly used for insomnia in depression, though it has less antidepressant efficacy at these doses. 4

Common Pitfalls to Avoid

• Do not declare treatment failure before 4 weeks at adequate dosage (minimum 10mg for vortioxetine). 2
• Do not abruptly discontinue Trintellix if switching later; taper gradually to avoid discontinuation syndrome, particularly at doses of 15-20mg. 3
• Do not combine with MAOIs or use within 14 days of MAOI discontinuation due to serotonin syndrome risk. 3
• Do not ignore partial response; if some improvement occurs by 4-6 weeks but remission is not achieved, optimize the dose to 20mg before considering this a treatment failure. 4