What are the next steps for managing low mood and low energy while taking Trintellix (vortioxetine)?

Managing Low Mood and Low Energy on Trintellix (Vortioxetine)

If you are experiencing persistent low mood and low energy despite taking Trintellix, the most appropriate next step is to optimize the vortioxetine dose to 20 mg daily (if not already at this dose), as this provides superior efficacy for both depressive symptoms and energy levels, with forced up-titration demonstrating good tolerability and clinically meaningful improvements within 8 weeks. 1

Dose Optimization Strategy

• Increase vortioxetine to 20 mg daily if currently on lower doses (5-10 mg), as higher doses show significantly better response rates for depression and associated symptoms including low energy 1
• The therapeutic trial requires at least 4-8 weeks at the target dose before concluding the medication is ineffective 2
• Dose increases should use increments of the initial dose every 5-7 days until therapeutic benefits become apparent 2
• Vortioxetine reaches steady-state plasma concentrations within 2 weeks of dosing, with a terminal half-life of approximately 66 hours 3

When Standard Dosing Is Insufficient

• Supratherapeutic doses (30-40 mg daily) may be considered for treatment-resistant cases, showing significant improvement in Clinical Global Impressions scores with relatively good tolerability 4
• At supratherapeutic doses, weight gain and nausea are the most common side effects, but no severe adverse events have been reported 4
• This approach should only be attempted after adequate trials at standard therapeutic doses (up to 20 mg) have proven insufficient 4

Augmentation Strategies if Monotherapy Fails

For Persistent Low Energy (Activating Agents)

• Bupropion (Wellbutrin) 37.5 mg every morning, increasing by 37.5 mg every 3 days to a maximum of 150 mg twice daily is activating with possible rapid improvement of energy level 2
• Give the second bupropion dose before 3 p.m. to minimize insomnia risk 2
• Avoid bupropion in agitated patients or those with seizure disorders 2
• Note that bupropion is a strong CYP2D6 inhibitor, which may increase vortioxetine exposure and require dose adjustment 3

For Comorbid Anxiety Contributing to Low Mood

• Vortioxetine demonstrates effectiveness in reducing both depression and anxiety symptoms when comorbid generalized anxiety disorder is present 1
• At week 8, 61% achieved depression response and 55% achieved anxiety response, with 52% responding on both measures simultaneously 1

Critical Monitoring Parameters

• Reassess symptoms at 4 weeks and 8 weeks using standardized measures to determine if adequate response is occurring 1
• If little improvement occurs after 8 weeks despite good adherence, consider adding augmentation therapy or switching medications 1
• Monitor for nausea, which is the most common side effect leading to dose reduction, though it typically improves with continued treatment 4

Important Caveats and Pitfalls

• Do not prematurely discontinue vortioxetine before completing an adequate 8-week trial at therapeutic doses, as full benefits may not manifest for several weeks 2
• When discontinuing any antidepressant, taper over 10-14 days to limit withdrawal symptoms 2
• Vortioxetine requires no dose adjustment for sex, age, race, body size, or renal/hepatic function in most patients 3
• Dose reduction is recommended for CYP2D6 poor metabolizers due to increased drug exposure 3
• Avoid combining with rifampin (broad CYP inducer), which significantly reduces vortioxetine exposure 3

Alternative Considerations if Vortioxetine Optimization Fails

• Desipramine (Norpramin) 10-25 mg in the morning, up to 150 mg tends to be activating and specifically reduces apathy, with lower risk for cardiotoxic effects 2
• Mirtazapine (Remeron) 7.5 mg at bedtime, up to 30 mg is potent and well-tolerated but promotes sleep and weight gain, making it less suitable for low energy complaints 2