What are the next steps for a patient with depression who is not responding to venlafaxine (Effexor)

Treatment Options for Depression Not Responding to Venlafaxine

For patients with depression who are not responding to venlafaxine (Effexor), switching to another antidepressant such as bupropion, sertraline, or extended-release venlafaxine is recommended, with no significant difference in efficacy between these options. 1

Assessment of Current Treatment Response

• Clinicians should assess patient status, therapeutic response, and adverse effects of antidepressant therapy on a regular basis, beginning within 1-2 weeks of initiation of therapy 1
• Treatment modification is recommended if the patient does not have an adequate response to pharmacotherapy within 6-8 weeks of initiation of therapy for major depressive disorder 1
• Approximately 38% of patients do not achieve a treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 1

Treatment Options for Venlafaxine Non-Responders

Switching to Another Antidepressant

• The STAR*D (Sequenced Treatment Alternatives to Relieve Depression) study showed that 1 in 4 patients became symptom-free after switching medications from a failed initial therapy 1
• When switching from venlafaxine, the following options have similar efficacy:
  • Sustained-release bupropion (Wellbutrin) 1
  • Sertraline (Zoloft) 1
  • Extended-release venlafaxine (at a different dosage) 1
• For severely depressed patients (Hamilton Rating Scale for Depression score >31), venlafaxine ER may be more effective than switching to an SSRI like citalopram 2

Augmentation Strategies

• Low-dosage lithium augmentation (300-450 mg/day) may be effective for venlafaxine-resistant depression, with 51% of patients showing significant improvement after 5 weeks 3
• Bipolar patients showed a better response to lithium augmentation than unipolar patients (64.3% vs 45.5%) 3
• Most patients (76%) showed a rapid response to lithium augmentation (within 7 days) 3

Considerations Based on Patient Characteristics

• When selecting a second-generation antidepressant, consider:
  • Adverse effect profiles 1
  • Cost 1
  • Patient preferences 1
• For older patients with depression, preferred agents include citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion 1
• Patients with accompanying anxiety symptoms may benefit from venlafaxine, which has shown better efficacy for managing anxiety compared to fluoxetine 1
• Patients with melancholia or psychomotor agitation may benefit from sertraline 1

Monitoring and Safety Considerations

• Monitor patients closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of therapy or at times of dose changes 4
• Watch for symptoms such as anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania 4
• Be alert for signs of serotonin syndrome when combining venlafaxine with other serotonergic drugs 4
• Common adverse effects of second-generation antidepressants include diarrhea, dizziness, dry mouth, fatigue, headache, sexual dysfunction, sweating, tremor, and weight gain 1

Duration of Treatment

• For a first episode of major depression, treatment should last at least 4-9 months after a satisfactory response 1
• For patients who have had 2 or more episodes of depression, an even longer duration of therapy may be beneficial 1

Common Pitfalls to Avoid

• Failing to wait an adequate duration (6-8 weeks) before determining treatment failure 1
• Not considering medication adherence as a potential cause of treatment failure
• Overlooking the possibility of bipolar disorder in patients with treatment-resistant depression 4
• Inadequate dosing of venlafaxine (effective doses are often in the range of 260 mg/day for treatment-resistant depression) 5
• Not monitoring for serotonin syndrome when combining venlafaxine with other serotonergic medications 4