What are the treatment options for stiff person syndrome?

Treatment Options for Stiff Person Syndrome

Benzodiazepines should be used as first-line treatment for stiff person syndrome, with diazepam being the preferred agent due to its efficacy in relieving muscle rigidity and painful spasms. 1, 2, 3

First-Line Treatment

• Benzodiazepines: Diazepam is FDA-approved as an adjunct for relief of skeletal muscle spasm due to reflex spasm, local pathology, and specifically for stiff-man syndrome 1
  • Start with diazepam at moderate doses and titrate up as needed to control symptoms 3
  • High doses may be required for adequate symptom control 4
  • Clonazepam can be an alternative, particularly when anxiety-triggered spasms are prominent 4

Second-Line Treatments

• Anti-epileptic medications:

  • Pregabalin (150 mg three times daily) has shown satisfying response in controlling muscle spasms and rigidity 5
  • Levetiracetam can be added if symptoms persist despite benzodiazepine therapy 2

• Baclofen:

  • Oral baclofen is recommended as a second-line therapy for enhancing GABA neurotransmission 2, 3
  • For refractory cases, intrathecal baclofen can be considered 2

Immunotherapy Options

Since stiff person syndrome has an autoimmune pathogenesis with antibodies against glutamic acid decarboxylase (GAD65) 3, 6:

• Intravenous immunoglobulin (IVIG) is effective for patients with refractory symptoms 2, 3

• Rituximab can be considered before tacrolimus in the immunotherapy sequence 2

• Corticosteroids may provide partial relief and additional evidence supports their use in the autoimmune etiology of SPS 6

• Plasmapheresis is an option for refractory cases, though evidence suggests it may be less effective than intrathecal baclofen or IVIG 2, 3

Treatment Algorithm

1. Initial therapy: Start with benzodiazepines (diazepam) 1, 2

2. If inadequate response: Add pregabalin or levetiracetam 2, 5

3. Second-line therapy: Add oral baclofen if symptoms persist 2, 3

4. For refractory cases:

   • Consider intrathecal baclofen 2
   • Initiate immunotherapy with IVIG 2, 3
   • Consider rituximab before tacrolimus if further treatment needed 2
   • Plasmapheresis as a last resort for non-responders 2, 3

Special Considerations

• Psychiatric comorbidities: Common in SPS patients and may require specific management 4

  • For comorbid anxiety or panic disorder: Scheduled (not as-needed) benzodiazepines may provide better control 4
  • For bipolar disorder: Valproic acid has been used successfully 4
  • Caution with SSRIs as they may exacerbate SPS symptoms in some cases 4

• Propofol may be used as a bridge therapy before initiating permanent treatment in acute exacerbations 2

• Monitoring: Regular assessment of symptom control, functional status, and medication side effects is essential 2, 3

Common Pitfalls

• Misdiagnosis: SPS is often misdiagnosed as a psychiatric illness due to anxiety-like symptoms and emotional triggers for spasms 5, 4

• Delayed diagnosis: The average time to diagnosis can be years, leading to inappropriate treatments and worsening disability 5

• Inadequate dosing: Benzodiazepines often require higher doses than typically used for anxiety disorders 4

• Failure to recognize autoimmune basis: Testing for anti-GAD65 antibodies is crucial when SPS is clinically suspected 5, 6