What is a good adjunct Selective Serotonin Reuptake Inhibitor (SSRI) medication to use in place of benzodiazepines?

Tricyclic Antidepressants (TCAs) Are the Best SSRI Alternative to Benzodiazepines

Tricyclic antidepressants, particularly secondary amines like desipramine and nortriptyline, are the most effective adjunct medication to use in place of benzodiazepines due to their proven efficacy in reducing anxiety symptoms with less potential for dependence and withdrawal. 1

Evidence-Based Rationale for TCAs

TCAs have been shown to be effective in treating anxiety-related conditions through both peripheral and central actions that affect motility, secretion, and sensation. According to the American Gastroenterological Association (AGA) guidelines, TCAs are recommended for treating irritable bowel syndrome and other conditions with anxiety components, while SSRIs are specifically recommended against 1.

Key advantages of TCAs over traditional SSRIs:

• TCAs demonstrate global symptom relief (RR, 0.67; 95% CI, 0.54–0.82) and abdominal pain relief (RR, 0.76–0.94) in anxiety-related conditions 1
• TCAs act as gut-brain neuromodulators with both peripheral and central effects 1
• TCAs have multiple mechanisms of action, including inhibition of serotonin and noradrenergic reuptake plus blockade of muscarinic, adrenergic, and histamine receptors 1

Specific TCA Recommendations

When selecting a TCA as a benzodiazepine alternative:

1. Start with secondary amines (desipramine or nortriptyline) due to their lower anticholinergic effects 1
2. Begin with low doses (10-25mg) at bedtime and titrate slowly
3. Target doses of 50-150mg daily, though clinical benefit has been shown even at lower doses (10mg of amitriptyline) 1
4. Allow 3-4 weeks for full therapeutic effect to develop

Why Not Traditional SSRIs?

The AGA specifically suggests against using SSRIs for anxiety-related conditions (conditional recommendation, low certainty in evidence) 1. Studies comparing SSRIs to placebo showed only possible improvement in symptom relief (RR, 0.74; 95% CI, 0.52–1.06) with the upper boundary suggesting potential worsening of symptoms 1.

Additionally, SSRIs:

• Can initially exacerbate anxiety symptoms during the first few weeks of treatment 2
• Have a delayed onset of therapeutic effect (several weeks) 2
• May destabilize mood or incite manic episodes in vulnerable patients 1

Cautions and Monitoring with TCAs

While TCAs are effective, they require careful monitoring:

• Higher rates of withdrawals due to adverse effects compared to placebo (RR, 2.11; 95% CI, 1.35–3.28) 1
• Common side effects include dry mouth, sedation, constipation, and orthostatic hypotension
• Avoid in patients with cardiac conduction abnormalities
• Monitor for anticholinergic effects, especially in elderly patients 3

Alternative Options When TCAs Are Contraindicated

If TCAs are not suitable, consider:

1. Buspirone - Non-benzodiazepine anxiolytic with no dependence potential 4
2. Beta blockers - For somatic symptoms of anxiety 4
3. Pregabalin - For anxiety with neuropathic pain components 1
4. Sertraline - If an SSRI is necessary, sertraline has a lower potential for drug interactions compared to other SSRIs, making it safer for elderly patients or those on multiple medications 3, 5

Implementation Strategy

1. Assess baseline symptoms and document specific anxiety manifestations
2. Select appropriate TCA based on symptom profile and comorbidities
3. Start low and go slow with dosing to minimize side effects
4. Monitor weekly for the first month for therapeutic response and adverse effects
5. Evaluate for full response at 4-6 weeks before considering dose adjustments or augmentation
6. Consider cognitive behavioral therapy as an adjunct to medication 4

Pitfalls to Avoid

• Avoid abrupt discontinuation of benzodiazepines when transitioning to TCAs; implement a gradual taper over several weeks 1
• Do not combine TCAs with MAOIs due to risk of serotonin syndrome 6
• Be cautious when using TCAs in patients with cardiac disease, glaucoma, or prostatic hypertrophy
• Avoid using TCAs in patients with a history of seizures or at risk for overdose

By following these evidence-based recommendations, clinicians can effectively transition patients from benzodiazepines to safer, non-addictive alternatives while maintaining effective symptom control.