What medication can be given to a patient for whom a Selective Serotonin Reuptake Inhibitor (SSRI) was not effective?

Medication Options After SSRI Failure

For patients who have not responded to SSRIs, switching to a serotonin-norepinephrine reuptake inhibitor (SNRI) such as venlafaxine is recommended as the most effective next step. 1

First-Line Alternative Options

SNRIs

• Venlafaxine:

  • Start at 37.5 mg daily for 1 week, then increase to 75 mg daily 2
  • Can be titrated up to 225-375 mg daily if needed 3
  • Demonstrated 69-76% response rate in patients who failed previous SSRI trials 4
  • Requires gradual discontinuation to avoid withdrawal symptoms 2

• Duloxetine:

  • Start at 30 mg daily for 1 week, then increase to 60 mg daily 1
  • Effective for both depression and neuropathic pain 1
  • Simpler dosing than venlafaxine (60 mg once daily appears as effective as 60 mg twice daily) 1

Medication Selection Algorithm:

1. If patient has depression with anxiety or OCD: Venlafaxine is preferred (75-225 mg daily) 1, 4
2. If patient has depression with neuropathic pain: Duloxetine is preferred (60 mg daily) 1
3. If patient has depression with insomnia: Mirtazapine may be considered (starting at 15 mg at bedtime)

Second-Line Options

Tricyclic Antidepressants (TCAs)

• Consider nortriptyline or desipramine (secondary-amine TCAs) 1
• Start at 10-25 mg at bedtime, gradually increase to 75-100 mg daily 1
• Caution: Requires ECG monitoring in patients over 40 years or with cardiac history 1
• Contraindications: Cardiac conduction abnormalities, recent MI

Atypical Antidepressants

• Bupropion: Effective alternative with different mechanism (dopamine/norepinephrine)
  • Particularly useful when sexual dysfunction was a problem with SSRIs 5
  • Similar remission rates to venlafaxine and sertraline in SSRI non-responders (21.3%) 5

Special Considerations

For Specific Conditions:

• Neuropathic pain: Consider gabapentin (300 mg at bedtime, increase to 1800-3600 mg/day) 1
• Menopausal symptoms: Venlafaxine or gabapentin if SSRIs failed 1
• OCD: Venlafaxine has shown 76% response rate in SSRI-resistant OCD 1, 4

Important Monitoring Parameters:

• Blood pressure and heart rate (especially with venlafaxine)
• Suicidal ideation, particularly in first weeks of treatment
• Serotonin syndrome symptoms (confusion, agitation, tremors, hyperthermia)
• Sexual dysfunction

Potential Pitfalls to Avoid:

1. Inadequate dosing: Ensure adequate dose and duration (8 weeks at maximum tolerated dose) before declaring treatment failure 3
2. Abrupt discontinuation: Always taper SNRIs and TCAs to avoid withdrawal syndrome 2
3. Drug interactions: Avoid combining with MAOIs (14-day washout period required) 2
4. Serotonin syndrome: Caution when combining multiple serotonergic medications 1

Practical Implementation

• Allow 4-6 weeks at therapeutic doses to evaluate efficacy
• If partial response after 8 weeks, consider augmentation strategies
• If no response after 8 weeks on adequate dose, switch to another class of medication
• Consider referral to psychiatry if two medication trials have failed

Remember that approximately 25% of patients will achieve remission when switching to another antidepressant after SSRI failure 5, so persistence with finding the right medication is essential for successful treatment.