Akathisia in Multiple Sclerosis: Management Approach
Akathisia in MS patients is not a recognized manifestation of the disease itself, but rather a drug-induced adverse effect from medications used to treat MS symptoms or comorbid psychiatric conditions. The management principles follow those established for antipsychotic-induced akathisia, with careful attention to the underlying cause.
Identifying the Causative Agent
The first critical step is determining which medication is causing akathisia:
- Antipsychotic medications are the most common culprits, with prevalence rates of 20-30% in patients using classical antipsychotics and lower rates (5-36.8%) with atypical agents 1, 2, 3
- Antiemetic agents with dopamine-blocking properties can also induce akathisia 3
- MS patients may be prescribed these medications for psychiatric comorbidity, nausea, or behavioral symptoms 4
Clinical Recognition
Akathisia consists of both subjective and objective components that must be assessed:
- Subjective symptoms: Inner restlessness, urge to move, emotional unease, anxiety, and inability to tolerate inactivity 1, 5
- Objective signs: Rocking while standing or sitting, lifting feet as if marching on the spot, crossing and uncrossing legs while sitting, and restless leg movements 1, 6
A critical pitfall is misdiagnosing akathisia as psychiatric agitation or anxiety, which often leads to inappropriate increases in antipsychotic dosage that worsen the condition 5. Assessment must include direct patient reporting of symptoms 5.
Treatment Algorithm
First-Line Approach: Medication Adjustment
If clinically feasible, the first intervention is dose reduction or discontinuation of the offending agent 2, 6, 3. If the medication cannot be stopped:
- Switch to atypical antipsychotics (clozapine, olanzapine, or quetiapine) which have lower akathisia rates 3
- Lower the dose of the current agent if discontinuation is not possible 2, 6
Second-Line: Pharmacological Treatment
When medication adjustment is insufficient or not feasible, propranolol or other lipophilic beta-blockers are the most consistently effective treatment for acute akathisia 1, 2. The American Psychiatric Association guidelines support this approach for antipsychotic-induced akathisia 4.
Third-Line: Alternative Agents
If beta-blockers fail or are contraindicated:
- Benzodiazepines are the sensible next choice, especially if subjective distress persists 1, 2
- Anticholinergic medications can be effective, though evidence is less robust than for beta-blockers 2, 6, 3
- Mianserin has been suggested as an alternative option 3
Fourth-Line: Refractory Cases
For treatment-resistant akathisia, consider:
- Amantadine or clonidine 1, 2
- Other agents with limited evidence include opiates, buspirone, piracetam, and amitriptyline 2
MS-Specific Considerations
MS patients requiring psychiatric medication management should be referred to mental health providers for appropriate care 4. This is particularly important given that:
- Psychiatric disability may be present after MS diagnosis and requires specialized management 4
- Cognitive dysfunction in MS patients requires careful medication selection 4
- The risk-benefit profile of dopamine-blocking agents must be carefully weighed against MS-related symptoms 4
Monitoring and Prevention
Prevention is superior to treatment 1. For MS patients requiring antipsychotic therapy:
- Use standardized titration protocols 1
- Prefer novel (atypical) antipsychotics when possible 1, 3
- Monitor closely for early signs of akathisia using standardized assessment scales 2
- Assess iron status, as it may play a role in akathisia pathophysiology 2
Critical Risk Factors
Be aware that certain factors increase akathisia risk:
- High antipsychotic dosages 3
- Previous history of akathisia 3
- Diabetes mellitus 3
- Rapid dose escalation 1
Complications to Prevent
Non-compliance and impulsive or suicidal behavior are serious complications of untreated akathisia 2, 6. Early recognition and treatment are essential to prevent these outcomes 6.