Treatment Protocol for Major Depressive Disorder Using Trazodone
Trazodone is FDA-approved for the treatment of major depressive disorder (MDD) in adults and should be considered as a second-generation antidepressant option, particularly for patients with comorbid insomnia or anxiety. 1
Initial Treatment Approach
- Select trazodone based on its unique adverse effect profile, cost considerations, and patient preferences, as efficacy is comparable to other second-generation antidepressants 2
- Trazodone should be taken shortly after a meal or light snack to improve tolerability 1
- Begin with a dosage of 150 mg/day for adults with MDD, which can be increased based on clinical response 3, 4
- For elderly or debilitated patients, start with lower doses and titrate more cautiously 5
- Maximum tolerated doses are typically 300-400 mg/day for elderly patients and up to 600 mg/day for younger adults 5
Monitoring and Follow-up
- Assess patient status, therapeutic response, and adverse effects within 1-2 weeks of initiating therapy 2
- Monitor closely for increases in suicidal thoughts and behaviors, especially during the first 1-2 months of treatment 2
- Watch for emergence of agitation, irritability, or unusual changes in behavior that could indicate worsening depression 2
- Evaluate response to treatment (typically defined as ≥50% reduction in measured severity) using validated tools such as the Patient Health Questionnaire-9 (PHQ-9) or Hamilton Depression Rating Scale (HAM-D) 2
Treatment Modification
- If adequate response is not achieved within 6-8 weeks, modify the treatment plan 2
- Consider increasing the dose if partial response is observed without significant side effects 3
- For patients with persistent sleep disturbances despite adequate antidepressant effect, trazodone may be particularly beneficial due to its sedating properties 6, 3
- If trazodone is ineffective after an adequate trial, switch to another second-generation antidepressant with a different mechanism of action 2
Treatment Duration
- Continue treatment for 4-9 months after achieving a satisfactory response for patients with a first episode of MDD 2
- For patients who have experienced two or more episodes of depression, longer duration of therapy (maintenance phase) is recommended 2
- Treatment phases include acute (6-12 weeks), continuation (4-9 months), and maintenance (≥1 year) 2
Advantages of Trazodone for MDD
- Effective for a range of depression symptoms, particularly beneficial for patients with comorbid insomnia 6, 3
- Shows early improvement in depressive symptoms, with significant reduction in HAM-D17 scores within one week of starting treatment 4
- Avoids common side effects associated with SSRIs such as sexual dysfunction, weight gain, and activation 6, 3
- Available in a once-daily formulation that maintains effective blood levels for 24 hours while avoiding concentration peaks associated with side effects 3, 4
Common Side Effects and Management
- Most common adverse effects: drowsiness/sedation, headache, dizziness, and dry mouth 6, 3
- Less common but important side effects: orthostatic hypotension (particularly in elderly patients or those with heart disease), minimal anticholinergic activity, QT interval prolongation, cardiac arrhythmias, and rare occurrences of priapism 6, 3
- If drowsiness is problematic, adjust the timing of administration or consider dose reduction 1
- For patients experiencing orthostatic hypotension, advise slow position changes and adequate hydration 5
Special Considerations
- Trazodone has minimal anticholinergic activity compared to tricyclic antidepressants, making it potentially safer for elderly patients 5
- Low-dose trazodone (50-100 mg) may be used for insomnia in patients with MDD who are taking another antidepressant 2, 7
- Avoid concurrent use with MAOIs; allow at least 2 weeks after stopping an MAOI before starting trazodone 1
- Use with caution in patients with cardiac disease due to potential for QT prolongation 3