What is the next step in treating worsened depression in an elderly female patient with a history of paranoid schizophrenia and severe depression, currently on venlafaxine (Effexor) IR 75 mg 3 times daily and buspirone (Buspar) 10 mg 3 times daily, with well-controlled schizophrenia?

Optimizing Treatment for Worsened Depression in Elderly Patient with Schizophrenia

Increase the venlafaxine dose to the maximum FDA-approved range (up to 225 mg/day total) before considering other interventions, as the current dose of 225 mg/day is already at the upper limit and augmentation with an antidepressant is the next appropriate step.

Immediate Assessment and Dose Optimization

The patient is currently on venlafaxine IR 75 mg three times daily (225 mg/day total), which is at the maximum recommended dose for elderly patients. 1 Before adding additional agents, verify:

• Medication adherence - confirm the patient is actually taking all three daily doses 2
• Rule out secondary causes - assess for metabolic problems (particularly hyponatremia, which occurs in 0.5-12% of elderly patients on antidepressants), medication interactions, or worsening of schizophrenia symptoms that may present as depression 1, 3
• Evaluate antipsychotic burden - if the patient is on antipsychotics for schizophrenia, consider whether increased dopamine D2 receptor blockade is contributing to dysphoria or anhedonia 4

Recommended Next Step: Antidepressant Augmentation

Add mirtazapine 7.5-15 mg at bedtime to augment the current venlafaxine regimen. 2, 5 This recommendation is based on:

• Moderate-quality evidence showing that augmenting current antidepressant treatment with another antidepressant (specifically mianserin, which is pharmacologically similar to mirtazapine) improves depressive symptoms (MD on HAM-D -4.8,95% CI -8.18 to -1.42) 5
• High-quality evidence demonstrating mirtazapine augmentation is well-tolerated in elderly patients, with only 2% dropout rates compared to 3% in controls 5
• Mirtazapine is specifically recommended as a preferred antidepressant for older adults with favorable adverse effect profiles 1, 6
• Complementary mechanisms - mirtazapine's noradrenergic and specific serotonergic activity complements venlafaxine's SNRI mechanism 6

Alternative Augmentation Strategy: Buspirone Optimization

The patient is already on buspirone 10 mg three times daily (30 mg/day). While evidence for buspirone augmentation in treatment-resistant depression is limited and shows no clear benefit (MD on MADRS -0.30,95% CI -9.48 to 8.88), 5 the current dose is appropriate and should be continued given its established role in the regimen. 2

Critical Monitoring Requirements

Monitor sodium levels within the first month of any dose adjustment, as elderly patients are at substantially greater risk for SSRI/SNRI-induced hyponatremia due to age-related changes in renal function 1

Assess for serotonin syndrome when combining venlafaxine with mirtazapine, particularly monitoring for mental status changes, autonomic instability, and neuromuscular symptoms, though the risk is lower with this combination than with other serotonergic agents 7, 8

Evaluate treatment response at 4 weeks and 8 weeks using standardized depression scales (PHQ-9 or HAM-D) 1

What NOT to Do

Do not switch antipsychotics unless schizophrenia symptoms are poorly controlled, as the question states schizophrenia is well-controlled 2, 4

Do not add an antipsychotic for depression augmentation in this elderly patient, as antipsychotics increase dropout rates (RR 1.57-1.68) and adverse events, with dropout rates of 10-39% compared to 12-23% in controls 5. This strategy is only appropriate when depressive symptoms occur with psychotic features or treatment-resistant depression after multiple antidepressant trials 2, 9

Do not discontinue buspirone - while evidence for its efficacy in augmentation is limited, abrupt discontinuation may destabilize the patient 5

Do not use paroxetine or fluoxetine if considering a switch, as these are explicitly contraindicated as first-line agents in older adults due to anticholinergic effects and drug interactions 1

If Augmentation Fails After 8-12 Weeks

Consider switching to a different antidepressant monotherapy (such as escitalopram 10 mg daily or sertraline 25-50 mg daily, starting at 50% of standard adult doses) rather than continuing multiple augmentation strategies 1, 6

Reassess the diagnosis - ensure depressive symptoms are not actually negative symptoms of schizophrenia, which may require adjustment of antipsychotic therapy rather than antidepressant augmentation 2, 4

Consider electroconvulsive therapy (ECT) if depression becomes severe or psychotic features emerge, as this is a first-line option for psychotic depression in elderly patients 9

Duration of Treatment

Continue augmented treatment for at least 6-12 months after achieving remission for this episode, given the patient's history of severe depression 1, 9