Treatment of Depression with Comorbid Anxiety

Introduction to Treatment Options

The American College of Physicians and other guideline societies recommend optimizing the current antidepressant regimen by increasing the dose to therapeutic levels or switching to augmentation with another agent, such as bupropion, for patients with depression and increasing anxiety, as evidenced by the patient's escalating gabapentin use while on venlafaxine 37.5 mg, mirtazapine 30 mg, and Vyvanse 1
Increasing venlafaxine to 75-225 mg daily is recommended, as 37.5 mg is considered a subtherapeutic dose for treating depression or anxiety, according to the Annals of Internal Medicine 2
The patient's current venlafaxine dose is subtherapeutic, which likely explains the lack of perceived benefit and potentially the worsening anxiety, as supported by the Annals of Internal Medicine 2

Increasing venlafaxine ER to 75-225 mg daily is recommended, as the current 37.5 mg dose is inadequate for treating either depression or anxiety, with high strength of evidence from the Annals of Internal Medicine 2
Venlafaxine has demonstrated superior efficacy compared to fluoxetine specifically for treating anxiety symptoms in patients with comorbid depression and anxiety, with moderate strength of evidence from the Annals of Internal Medicine and Praxis Medical Insights 2, 1
An adequate antidepressant trial requires a minimum licensed dosage for at least 4 weeks before determining treatment failure, as recommended by Praxis Medical Insights 1
Adding bupropion to the existing mirtazapine (discontinuing venlafaxine if not effective at higher doses) is a recommended augmentation strategy, with moderate strength of evidence from Praxis Medical Insights 1
Bupropion augmentation decreases depression severity more than buspirone augmentation, with lower discontinuation rates due to adverse events, as supported by Praxis Medical Insights 1

Switching from venlafaxine to sertraline or another SSRI at therapeutic doses (sertraline 50-200 mg) is a recommended alternative strategy, with high strength of evidence from the Annals of Internal Medicine 2, 3
The STAR*D trial showed that switching to sustained-release bupropion, sertraline, or extended-release venlafaxine resulted in 1 in 4 patients becoming symptom-free, with no difference among the three drugs, as reported in the Annals of Internal Medicine 3
SSRIs show similar efficacy to SNRIs for treating depression with accompanying anxiety symptoms, with moderate strength of evidence from the Annals of Internal Medicine 2
Adding aripiprazole (2-15 mg) or quetiapine (50-300 mg) to the current antidepressant regimen is a recommended augmentation strategy, with moderate strength of evidence from Praxis Medical Insights 1
Lithium augmentation is one of the best-documented treatments for treatment-resistant depression, requiring careful monitoring of blood levels, thyroid function, and renal function, as supported by Praxis Medical Insights 1

The first step in the treatment algorithm is to increase venlafaxine ER to 150 mg daily (therapeutic dose) and reassess after 4-6 weeks, with high strength of evidence from the Annals of Internal Medicine and Praxis Medical Insights 2, 1
If there is an inadequate response, either switch to bupropion augmentation (add bupropion SR 150-300 mg to mirtazapine) or switch to an SSRI like sertraline 100-200 mg, with moderate strength of evidence from the Annals of Internal Medicine and Praxis Medical Insights 3, 1
Ensuring adequate trial duration (minimum 4 weeks at therapeutic dose) before declaring treatment failure is crucial, as recommended by Praxis Medical Insights 1
Monitoring for serotonin syndrome when combining multiple serotonergic agents (venlafaxine + mirtazapine) is essential, although the strength of evidence for this recommendation is not specified 2

The American Academy of Sleep Medicine recommends against using trazodone for sleep or depression treatment, and it is likely contributing to cognitive impairment, balance problems, and potentially inadequate depression control 4
The American Family Physician suggests that antipsychotics, such as olanzapine, commonly cause cognitive impairment symptoms, including forgetfulness and poor concentration, especially when combined with other CNS-active medications 5
Venlafaxine monotherapy at 150-225mg daily has demonstrated comparable or superior efficacy to combination regimens and avoids the polypharmacy risks currently present, according to the Annals of Internal Medicine 6, 7
If psychotic features are absent, the American Family Physician recommends considering tapering and discontinuing olanzapine while optimizing venlafaxine, as patients with depression without psychosis do not require concomitant antipsychotic medication 5
The Annals of Internal Medicine suggests that switching to sertraline 100-200mg daily as monotherapy may result in remission in 25% of treatment-resistant patients, with no difference between bupropion, sertraline, and venlafaxine 7