Tizanidine vs Baclofen RCT — Spasticity in Multiple Sclerosis
This double-blind crossover randomized controlled trial is the most directly cited evidence for pharmacotherapy decisions in UMN-driven spasticity — including PLS. It enrolled 66 patients with multiple sclerosis and significant spasticity, randomized them to tizanidine or baclofen, then crossed each patient over to the other drug. The result: both drugs work, they differ mainly in which side effects they cause, and clinician preference for one over the other depends almost entirely on which adverse effect profile the individual patient can best tolerate.
What they did
Sixty-six patients with multiple sclerosis and clinically significant spasticity entered the trial. Each medication was introduced over a three-week titration period and then maintained at the highest tolerated dose for five weeks. The two treatment phases were separated by a one-week drug withdrawal and a two-week washout period to prevent carryover effects.
At the end of each phase, three independent raters assessed outcomes: neurologists, physiotherapists, and the patients themselves. All three groups rated both perceived efficacy and tolerability for each drug. This three-perspective rating structure is one of the study's methodological strengths — it captures how physicians see the response, how rehabilitation specialists see it, and how the patient living with the drug actually experiences it.
The study design is a crossover, meaning each patient served as their own control. This reduces confounding from between-patient variation and increases statistical efficiency, particularly valuable in a 66-patient sample that might otherwise be underpowered to detect modest treatment differences.
What they found
Neurologists and physiotherapists judged baclofen superior to tizanidine on perceived efficacy and overall tolerance (p ≤ 0.05). Patient-rated efficacy, however, told a slightly different story: 39% of patients rated baclofen as good-to-excellent, versus 24% for tizanidine — a difference that did not reach statistical significance on its own.
The side-effect profiles diverged in clinically meaningful ways. Muscle weakness was the most common adverse effect overall, and it was significantly more troublesome in patients treated with baclofen than with tizanidine. Tizanidine, on the other hand, caused more somnolence (drowsiness) and xerostomia (dry mouth) than baclofen.
The study's conclusion is measured: both baclofen and tizanidine appear to be useful adjuncts in the treatment of spasticity. Preference for one over the other is driven principally by the side-effect profile — not by a large difference in efficacy.
Why it matters
For someone with PLS, this study is the closest thing to level-one evidence for the choice between the two most commonly prescribed antispasticity medications. PLS causes upper motor neuron dysfunction with a mechanism broadly comparable to the UMN component of MS — which is why this MS-population trial has been applied directly to PLS management by neurologists for decades.
The weakness finding is particularly important in PLS. Many people with PLS are still walking, still working, still driving — often for years longer than ALS patients — and preserving residual muscle strength is a high priority. If baclofen is significantly more likely to cause troublesome muscle weakness than tizanidine, that is a real consideration when choosing a first-line agent. Tizanidine's drowsiness and dry mouth are real too, but for many patients they are manageable in ways that worsening weakness is not.
The study also validates the clinical approach many PLS neurologists use: start with whichever agent fits the patient's specific situation, watch for the characteristic side effects, and switch or combine if necessary. Neither drug is universally superior. The evidence supports individualized selection.
Limitations and context
This trial enrolled patients with multiple sclerosis, not PLS. MS spasticity shares the UMN mechanism with PLS but differs in pathophysiology and natural history — MS is an inflammatory demyelinating condition, while PLS involves progressive upper motor neuron degeneration. The direct applicability to PLS is a reasonable extrapolation, not a proven equivalence.
The trial is also decades old, and dosing practices have evolved. Modern titration approaches tend to be more gradual, particularly in PLS patients where the disease trajectory makes preserving function a longer-term objective than in more rapidly progressive ALS. The side-effect profiles documented here remain valid, but individual dosing strategies may differ from what was used in this study.
No PLS-specific randomized controlled trial comparing tizanidine and baclofen has been conducted. This MS study remains the primary evidence base for the choice between these agents in PLS spasticity management.
How this connects
This trial is cited in the context of virtually every discussion of spasticity pharmacotherapy in PLS. It connects directly to the evidence reviewed on the Spasticity Research hub page, which covers the full landscape of studies informing PLS spasticity management. For the next step when oral agents fail, the ITB Long-Term Follow-Up 2004 study describes what the evidence shows for intrathecal baclofen pump implantation. The practical implications — how dosing works, what to watch for, when to consider escalation — are covered in the Spasticity management guide.
Citation
Tolosa E, Dorado R, Domercq M, et al. Tizanidine versus baclofen in the treatment of spasticity in patients with multiple sclerosis. PubMed PMID: 3345456. Randomized controlled trial.