Several well-studied medications and procedures can manage spasticity when baclofen is not the right fit, whether because of side effects, inadequate relief, or a clinical situation that calls for a different approach. The alternatives span oral drugs like tizanidine and dantrolene, injectable treatments like botulinum toxin, surgical interventions, and even non-invasive brain stimulation. Choosing among them depends on which muscles are affected, the underlying condition causing spasticity, and how much sedation or weakness a person can tolerate.
Tizanidine, the Closest Oral Substitute
If you are looking for a pill that works similarly to baclofen but with a different side-effect trade-off, tizanidine is the most frequently prescribed swap. Both drugs have roughly equivalent effectiveness at reducing spasticity, particularly in people with multiple sclerosis. A systematic review comparing skeletal muscle relaxants found fair evidence that baclofen and tizanidine are comparable for efficacy, though their side effects diverge: tizanidine is more likely to cause dry mouth, while baclofen more often causes muscle weakness.1PubMed. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review
That weakness issue matters more than it sounds. In a crossover study of people with MS-related spasticity, baclofen frequently caused muscle weakness severe enough to cause falls during walking and standing. Tizanidine, by contrast, actually appeared to improve mobility in some patients who had moderate-to-marked leg weakness alongside their spasticity.2PubMed. Tizanidine versus baclofen in the treatment of spasticity in multiple sclerosis patients This is a meaningful distinction: if your spasticity coexists with significant weakness in the same limbs, tizanidine may preserve your ability to move around better than baclofen does. On the other hand, a separate randomized trial found that clinicians and physiotherapists rated baclofen as superior overall in perceived efficacy and tolerance, though patients themselves did not show a statistically significant preference either way.3PubMed. Tizanidine versus baclofen in the treatment of spasticity in patients with multiple sclerosis Somnolence was also more common with tizanidine in that trial, so the choice often comes down to which side effects bother you more.
Diazepam and the Benzodiazepine Approach
Diazepam was one of the earliest drugs used for spasticity and remains an option, though its drawbacks limit its role. In a double-blind crossover study, both baclofen and diazepam produced overall improvement in spasticity with no significant difference in patient preference, but excessive daytime sedation was more common with diazepam.4PubMed. Baclofen versus diazepam for the treatment of spasticity and long-term follow-up of baclofen therapy A systematic review of oral spasticity treatments in MS confirmed that diazepam carries more side effects than either baclofen or tizanidine.5PubMed. Clinical effectiveness of oral treatments for spasticity in multiple sclerosis: a systematic review
Sedation is not the only concern. Benzodiazepines carry a risk of dependence with long-term use, and withdrawal can be dangerous. That makes diazepam a better fit for short-term flare-ups or nighttime spasms rather than ongoing daily management. Some clinicians use it as a low-dose add-on to another antispastic drug rather than as a standalone treatment. If you are already taking baclofen and it is not quite enough, a small bedtime dose of diazepam may help with overnight spasms without requiring a full drug switch.
Dantrolene, a Drug That Works at the Muscle
Every other oral option on this list works in the brain or spinal cord to calm overactive nerve signals. Dantrolene is different: it acts directly inside the muscle fibers to reduce the force of contraction.6PubMed Central. Tolperisone: a typical representative of a class of centrally acting muscle relaxants with less sedative side effects This peripheral mechanism means dantrolene does not cause the same drowsiness that plagues centrally acting drugs. The trade-off is that it weakens all muscles to some degree, not just the spastic ones, and it can cause liver toxicity in rare cases. Regular blood tests to monitor liver function are standard during treatment.
Evidence supports dantrolene’s effectiveness against placebo in spasticity, but there is not enough head-to-head data to say whether it is better or worse than baclofen or tizanidine.1PubMed. Comparative efficacy and safety of skeletal muscle relaxants for spasticity and musculoskeletal conditions: a systematic review It tends to be favored when sedation from other drugs is intolerable, or in people with stroke or brain injury who already struggle with cognitive fog and cannot afford additional central nervous system depression.
Gabapentin and Pregabalin
Gabapentin and pregabalin were developed as anti-seizure drugs, but they have found a second life treating neuropathic pain and, to a lesser extent, spasticity. Their advantage is that they address two problems at once: if your spasticity comes packaged with nerve pain, as it often does after spinal cord injury or in MS, a gabapentinoid can target both symptoms with a single medication.
The evidence for spasticity specifically is modest compared to the data behind baclofen or tizanidine. Case reports in MS patients have described satisfactory spasticity relief with gabapentin alongside meaningful functional improvement.7PubMed. Gabapentin for relief of spasticity associated with multiple sclerosis An animal study in spinal cord injury found that gabapentin significantly reduced both spasticity and autonomic dysreflexia, a dangerous blood-pressure response that can occur after severe spinal injuries.8PubMed Central. Gabapentin for spasticity and autonomic dysreflexia after severe spinal cord injury For pregabalin, a case series found that most patients perceived a definite reduction in spasticity symptoms, with the majority continuing the drug.9PubMed. Pregabalin in the treatment of spasticity: a retrospective case series These are encouraging but limited findings. Gabapentinoids are usually considered add-on options rather than first-line replacements for baclofen, and they come with their own sedation and dizziness risks.
Clonidine, Oral and Through the Skin
Clonidine is best known as a blood-pressure medication, but it also dampens spinal cord excitability in a way that reduces muscle tone. It belongs to the same alpha-2 agonist family as tizanidine, though its broader effect on the cardiovascular system makes hypotension a concern. A series of spinal cord injury patients treated with transdermal clonidine patches found that most had a beneficial response, and in the majority of responders, other antispasticity drugs were either reduced or discontinued. Persistent problematic hypotension was not observed with this delivery method.10PubMed. Clonidine transdermal system for treatment of spasticity in spinal cord injury
A separate study of clonidine in spinal cord injury found significant improvement in spasticity measures after doses of 0.3 mg or more, with no serious complications reported.11Annals of Rehabilitation Medicine. Effect of Clonidine on Spasticity in Patients with Spinal Cord Injury The patch delivery route is appealing because it provides a steady drug level throughout the day and avoids the peaks that cause drowsiness or blood-pressure drops. Clonidine tends to be a second-line or adjunctive choice, but it fills a niche for people who have not responded well to baclofen or tizanidine and who tolerate its cardiovascular effects.
Tolperisone, a Less Sedating Central Relaxant
Widely used in Europe and parts of Asia but less well known in North America, tolperisone is a centrally acting muscle relaxant that has been in clinical use for decades.6PubMed Central. Tolperisone: a typical representative of a class of centrally acting muscle relaxants with less sedative side effects Its main selling point is right there in the pharmacological literature: it causes less sedation than other centrally acting drugs.12PubMed Central. Basic aspects of the pharmacodynamics of tolperisone, a widely applicable centrally acting muscle relaxant For people who need to stay alert for work or driving but still require spasticity treatment, tolperisone is worth discussing with a clinician who is familiar with it. Its availability varies by country, and it does not appear in most North American spasticity guidelines, which limits practical access for many readers.
Botulinum Toxin for Targeted Muscles
When spasticity is concentrated in specific muscle groups rather than spread across the whole body, injecting botulinum toxin directly into those muscles can be far more effective than any pill. The toxin temporarily blocks nerve signals at the junction where the nerve meets the muscle, relaxing that muscle without affecting the rest of the body. This means you avoid the systemic sedation and weakness that come with oral medications.
Consensus dosing guidelines note that botulinum toxin doses for spasticity tend to be higher than those used for conditions like dystonia, because the goal is a robust antispastic effect and the risk of localized weakness is less concerning in already-paretic muscles.13PubMed Central. Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity Effects typically last three to four months, meaning repeat injections are needed. For upper-limb spasticity after stroke, low-quality evidence suggests that combining botulinum toxin with rehabilitation programs such as constraint-induced movement therapy can improve motor function and spasticity for up to six months.14PubMed Central. Multidisciplinary rehabilitation following botulinum toxin and other focal intramuscular treatment for post-stroke spasticity
Cost is a real consideration. A cost-effectiveness analysis of two botulinum toxin formulations in children with upper-limb spasticity found the cost per responder at one year ranged from roughly £39,000 to £55,000, depending on the formulation.15Physical Medicine and Rehabilitation Clinics of North America. Intrathecal Clonidine Insurance coverage varies widely, and the need for repeat sessions every few months adds up. Despite the expense, botulinum toxin fills a gap that oral drugs cannot: precise, focal treatment of the muscles that are actually causing problems.
Phenol and Alcohol Nerve Blocks
Before botulinum toxin became widely available, clinicians used phenol or alcohol injected near motor nerves to chemically block nerve conduction and reduce spasticity. These nerve blocks remain useful, particularly in the early period after traumatic brain injury or incomplete spinal cord injury, when muscle tone is often at its worst. Phenol nerve infiltration provides a temporary block lasting weeks to months, allowing passive limb mobilization and helping to prevent the fixed soft-tissue contractures that can develop when spastic muscles stay locked in one position.16PubMed. Treatment of acquired muscle spasticity using phenol peripheral nerve blocks
Phenol blocks are considerably cheaper than botulinum toxin and can treat larger muscle groups in a single session. The downsides include pain at the injection site, a small risk of sensory nerve damage causing burning or dysesthesia, and the need for experienced hands to perform the procedure safely. They are often considered when cost or availability rules out botulinum toxin, or when treating large proximal muscles where the toxin doses required would exceed safety limits.
Cannabis-Based Medicines
Nabiximols, an oromucosal spray containing roughly equal parts THC and CBD, is approved in several countries for MS-related spasticity that has not responded adequately to other treatments. A randomized controlled trial found that this cannabis-based medicine was significantly superior to placebo on the primary efficacy measure, with about 40% of participants achieving at least a 30% improvement.17PubMed. Randomized controlled trial of cannabis-based medicine in spasticity caused by multiple sclerosis A review of clinical studies across different delivery routes confirmed that nabiximols improved spasticity, pain, and quality of life with tolerable side effects, while oral cannabinoids also showed significant benefits for MS pain and spasticity.18PubMed Central. The Efficacy of Cannabis on Multiple Sclerosis-Related Symptoms
Cannabis-based treatments generally sit late in the treatment sequence, typically tried after conventional oral drugs have failed or caused unacceptable side effects. Regulatory access differs dramatically between countries and even between states or provinces. The most common side effects are dizziness, fatigue, and dry mouth. If you live somewhere that allows it and your MS spasticity is not well controlled on standard medications, nabiximols is one of the better-studied options in this category.
Intrathecal Delivery Beyond Baclofen
Intrathecal baclofen, delivered via a surgically implanted pump directly into the spinal fluid, is a well-established escalation for severe spasticity. But what happens when even that stops working, or when pump-delivered baclofen does not fully control symptoms? Intrathecal clonidine has emerged as a potent alternative or add-on. One review describes intrathecal clonidine as a powerful antispastic drug with a mechanism of action more selective than baclofen’s.15Physical Medicine and Rehabilitation Clinics of North America. Intrathecal Clonidine
A case study illustrated this potential: a patient whose spasticity was not fully controlled by intrathecal baclofen alone experienced immediate improvement when clonidine was added to the pump reservoir. The combination resolved sphincter spasms and pain that baclofen alone could not address.19PubMed. Intrathecal clonidine and baclofen in the management of spasticity and neuropathic pain following spinal cord injury: a case study For people with implanted pumps who are developing tolerance to baclofen or experiencing breakthrough symptoms, the option to combine agents within the same pump is a meaningful advantage.
Selective Dorsal Rhizotomy
Surgery enters the picture when spasticity is severe, chronic, and concentrated in the lower limbs. Selective dorsal rhizotomy (SDR) permanently reduces spasticity by cutting selected sensory nerve rootlets in the spinal cord that are feeding the overactive reflex loop. A minimally invasive version of the procedure uses a single-level approach at the bottom of the spinal cord and is effective in selected children with cerebral palsy when combined with ongoing physiotherapy.20PubMed Central. Single-level selective dorsal rhizotomy for spastic cerebral palsy
A systematic review and meta-analysis confirmed that SDR significantly improved spasticity scores and gross motor function in children with lower-limb spasticity, with benefits lasting at least 12 months after treatment.21PubMed. Efficacy of selective dorsal rhizotomy in the treatment of spasticity in children with cerebral palsy: a systematic review and meta-analysis The permanence of the procedure is both its strength and its risk: once the nerve rootlets are cut, the change cannot be reversed. Patient selection is critical, and SDR is typically reserved for children with specific patterns of spastic cerebral palsy who have enough underlying strength to benefit from reduced tone.
Non-Invasive Brain Stimulation
Repetitive transcranial magnetic stimulation (rTMS) uses magnetic pulses delivered to the scalp to modulate activity in the brain’s motor cortex. A study of MS patients with lower-limb spasticity found that daily rTMS sessions over two weeks improved spasticity scores, with benefits maintained for at least a week after treatment ended.22PubMed Central. Outcomes in spasticity after repetitive transcranial magnetic stimulation and transcranial direct current stimulations A systematic review and meta-analysis of rTMS in patients with upper motor neuron injuries including stroke concluded that rTMS, whether used alone or alongside conventional rehabilitation, effectively reduced spasticity. Both high-frequency and low-frequency protocols showed benefits.23Frontiers in Neural Circuits. The effectiveness and safety of repetitive transcranial magnetic stimulation on spasticity after upper motor neuron injury: A systematic review and meta-analysis
The practical limitation is access. rTMS requires specialized equipment and repeated clinic visits, and it is not widely available outside academic medical centers. The effects also appear to be temporary, fading over days to weeks, which means it works better as a complement to other treatments than as a standalone solution. Still, for people who want to avoid or reduce medications, it represents a genuinely different approach to the problem.
Physical Therapies and Functional Electrical Stimulation
Physical therapy remains the foundation of spasticity management regardless of which drugs or procedures are used. Stretching, positioning, and strengthening exercises do not replace medications, but they can reduce the dose needed and prevent the secondary complications that spasticity causes, such as joint contractures and pressure injuries.
Functional electrical stimulation (FES) cycling, which uses electrical pulses to drive leg muscles through pedaling motions, has shown evidence of reducing lower-extremity spasticity in people with spinal cord injury across various injury levels. A systematic review found beneficial effects of FES cycling on spasticity in this population, suggesting it can serve as a useful non-pharmacological adjunct. The approach is appealing because it simultaneously addresses muscle conditioning and spasticity, two problems that often coexist after spinal cord injury.
Matching the Treatment to the Problem
One reason so many alternatives exist is that spasticity is not a single condition with a single solution. The underlying cause matters for treatment selection. In MS, where spasticity tends to be widespread and fluctuating, oral medications like tizanidine or baclofen are typical starting points, with nabiximols available for refractory cases. After stroke, where spasticity often localizes to one arm or leg, botulinum toxin injections targeting specific muscles tend to be more efficient than systemic pills that fog the whole brain. In cerebral palsy, where spasticity is lifelong and concentrated in the lower limbs, the calculus may shift toward more permanent solutions like SDR. After spinal cord injury, the combination of spasticity with neuropathic pain and autonomic dysfunction opens the door to gabapentinoids or clonidine, which address multiple symptoms simultaneously.
There is no universal ranking of these alternatives from best to worst. The right choice depends on whether your spasticity is localized or widespread, whether you also have pain or weakness in the affected limbs, how much sedation you can tolerate, what is available and affordable where you live, and whether the goal is to reduce tone enough to improve function or simply to make daily care and comfort manageable.
Spasticity Treatment During Pregnancy
Managing spasticity during pregnancy requires particular caution, since most antispastic medications have limited safety data in pregnant women. A review on managing spasticity in pregnant women with spinal cord injury noted that there are several case reports on the use of intrathecal baclofen and focal botulinum toxin injections during pregnancy, but no large controlled trials.24SpringerLink. Managing Spasticity in a Pregnant Woman with Spinal Cord Injury: a Review The general approach leans toward non-pharmacological strategies like stretching and positioning as much as possible, with intrathecal delivery preferred over oral medications when drugs are necessary, because the intrathecal route exposes the fetus to far lower systemic drug levels. Decisions in this situation are highly individualized and require close coordination between a spasticity specialist and the obstetric team.
Experimental Targets on the Horizon
Most existing treatments either dampen nerve signaling broadly or block muscle contraction locally. A newer line of research is pursuing drugs that target a specific chloride transporter called KCC2, which plays a role in how spinal cord neurons regulate their own excitability. In a recent study using animal models of chronic spinal cord injury, KCC2-enhancing compounds normalized reflex responses and improved locomotor function, revealing what the researchers described as substantial potential for KCC2 enhancers as a novel anti-spastic treatment.25PubMed Central. KCC2 enhancers normalize reflex responses and improve locomotor function after chronic spinal cord injury This approach is still in early-stage animal research, so no human treatments are available yet. But it represents a fundamentally different strategy from the drugs currently on the market, targeting the underlying imbalance in spinal cord excitability rather than simply suppressing the output.