Is terazosin an appropriate disease-modifying therapy for amyotrophic lateral sclerosis (ALS), and what dosing and safety monitoring should be used if considered?

Terazosin is NOT an Appropriate Disease-Modifying Therapy for ALS

Terazosin should not be used for ALS treatment—there is no evidence supporting its efficacy as a disease-modifying therapy, and it is not approved or recommended for this indication. The only FDA-approved disease-modifying therapies for ALS are riluzole, edaravone, and sodium phenylbutyrate/taurursodiol, with tofersen recently receiving accelerated approval for specific genetic subtypes 1, 2, 3.

Why Terazosin is Not Appropriate for ALS

Lack of Evidence Base

• Terazosin is an alpha-1 adrenergic blocker approved exclusively for benign prostatic hyperplasia (BPH) and hypertension 4
• No clinical trials, guidelines, or published evidence support terazosin use in ALS patients 5, 1, 2, 3, 6, 7
• The comprehensive ALS management guidelines make no mention of terazosin as a therapeutic option 5

Established ALS Disease-Modifying Therapies

The only evidence-based disease-modifying treatments are:

• Riluzole: Reduces glutamate-mediated motor neuron damage; remains the foundational therapy for two decades 1, 2, 3
• Edaravone: Acts as a free radical scavenger preventing oxidative stress damage 1, 2, 3
• Sodium phenylbutyrate/taurursodiol (PB/TURSO): Recently approved to slow ALS progression 2
• Tofersen: Accelerated approval for SOD1-mutation ALS, pending confirmatory trials 2

Potential Harm from Inappropriate Use

Using terazosin in ALS patients carries significant risks without benefit:

• Orthostatic hypotension and dizziness: Primary adverse effects that could increase fall risk in patients already experiencing progressive weakness and mobility impairment 4, 8
• Asthenia (tiredness): Would worsen the profound fatigue already experienced by ALS patients 4
• Delayed appropriate treatment: Pursuing unproven therapies delays initiation of evidence-based disease-modifying agents that modestly slow progression 1, 2, 3

What Should Be Done Instead

Implement Evidence-Based ALS Management

Disease-modifying therapy:

• Initiate riluzole as first-line therapy for all appropriate ALS patients 1, 2, 3
• Consider edaravone for patients meeting specific criteria 1, 2, 3
• Evaluate eligibility for PB/TURSO or genetic-specific therapies like tofersen 2, 7

Multidisciplinary palliative care from diagnosis:

• Integrate palliative care at diagnosis to optimize quality of life and survival—this is a Level A recommendation 5
• Establish advance care planning early, before communication becomes limited 5
• Implement structured caregiver support, as caregiver burden is substantial 5

Nutritional management:

• Perform videofluoroscopy at diagnosis to detect silent aspiration, which occurs without clinical signs in many patients 5
• Monitor BMI and weight closely—each 5% weight loss increases mortality risk by 34% 5
• Consider gastrostomy placement before severe respiratory compromise or >10% weight loss (which increases mortality risk 4-fold) 5

Respiratory support:

• Offer non-invasive ventilation (NIV) when appropriate, as it improves quality of life and prolongs survival 5, 6
• Screen for cognitive impairment before recommending NIV, as 40% of ALS patients have cognitive dysfunction that reduces compliance 5

Critical Pitfall to Avoid

Do not delay evidence-based ALS therapies by pursuing unproven treatments. ALS has a mean survival of only 3-5 years from symptom onset, making early initiation of riluzole, edaravone, or PB/TURSO essential 5, 1, 2, 3. The modest benefits these agents provide are maximized when started early in the disease course 1, 2, 3.