What are the best medications for treating tremors and neuropathy?

Best Medications for Tremors and Neuropathy

For Neuropathic Pain

Start with either duloxetine 60 mg daily or pregabalin 150 mg daily, as these are the only two FDA-approved medications for diabetic neuropathic pain with the strongest evidence base. 1

First-Line Treatment Options

• Duloxetine (SNRI) is highly effective with a number needed to treat (NNT) of 5.2 for 60 mg/day and 4.9 for 120 mg/day, offering advantages including fewer anticholinergic effects than tricyclics and no ECG monitoring required 1

• Start duloxetine at 30 mg once daily for the first week, then increase to 60 mg once daily, with a maximum dose of 120 mg/day if needed 2

• Most common side effect is nausea, which can be minimized by starting at 30 mg daily for one week 2

• Pregabalin has an NNT of 5.99 for 300 mg/day and 4.04 for 600 mg/day 1

• Begin at 150 mg/day in 2-3 divided doses, increasing to 300 mg/day after 1-2 weeks, with a maximum dose of 600 mg/day 2

• Pregabalin provides faster pain relief than gabapentin due to linear pharmacokinetics 2

• Gabapentin is an alternative to pregabalin, starting at 100-300 mg at night and gradually increasing to 900-3600 mg/day in 2-3 divided doses 2

• Topical lidocaine 5% patches are excellent for well-localized peripheral neuropathic pain with allodynia, particularly effective in elderly patients due to minimal systemic absorption 2

Combination Therapy Strategy

• If partial response occurs after an adequate trial (at least 2-4 weeks at therapeutic dose), add another first-line agent from a different class 2
• The combination of gabapentin/pregabalin with an antidepressant (duloxetine or nortriptyline) provides superior pain relief compared to either medication alone by targeting different neurotransmitter systems 2

Second-Line Options

• Tramadol can be considered after documented failure of first-line agents, starting at 50 mg once or twice daily with a maximum of 400 mg/day 3, 2
• Tramadol has dual mechanism as a weak μ-opioid agonist and inhibits serotonin/norepinephrine reuptake, with lower abuse potential than strong opioids 3
• Avoid strong opioids for long-term management due to risks of dependence, cognitive impairment, and pronociception 2

Important Caveats for Neuropathy Treatment

• Tricyclic antidepressants (TCAs) like nortriptyline have excellent efficacy (NNT 1.5-3.5) but require screening ECG in patients over 40 years before starting and should be avoided in patients with cardiac disease 2
• In patients with renal impairment, adjust gabapentin and pregabalin doses based on creatinine clearance 1
• Allow at least 2-4 weeks at therapeutic dose to properly assess efficacy before switching or adding medications 2

For Essential Tremor

Initiate treatment with either propranolol or primidone as first-line therapy, as these medications are effective in up to 70% of patients with essential tremor. 3

First-Line Treatment Options

• Propranolol is the most commonly used and generally most effective medication for essential tremor 4, 5

• Propranolol at 120 mg/day has demonstrated improvement in tremor in all treated patients in controlled trials, with most pronounced effects in upper extremities 6

• Propranolol is useful for most types of tremors, though it can fail to provide adequate tremor control even in essential tremor 5

• Primidone is equally effective as first-line therapy and can be used as monotherapy or in combination with propranolol 3, 4

Combination and Alternative Strategies

• If either primidone or propranolol do not provide adequate control, use the medications in combination 7
• If patients experience adverse effects with propranolol, other beta-adrenoceptor antagonists such as atenolol or metoprolol can be tried 7, 4
• Gabapentin or topiramate may be helpful as second-line agents if propranolol and primidone fail 7, 4
• Benzodiazepines such as clonazepam can provide benefit, particularly in patients with associated anxiety 7, 4

Important Caveats for Tremor Treatment

• Propranolol is contraindicated in patients with chronic obstructive pulmonary disease and other medical comorbidities 3
• Currently available medications improve tremor in only approximately 50% of patients 3, 4
• Treatment should only be initiated when symptoms interfere with function or quality of life 3
• Avoid carbamazepine for tremor treatment, as it is not indicated and has significant drug interactions including induction of CYP3A4 that can decrease levels of many concomitant medications 8

Surgical Options When Medications Fail

• If medications fail to provide adequate tremor control, consider MRI-guided focused ultrasound (MRgFUS) thalamotomy, which provides tremor suppression maintained at 2-4 years with hand tremor improvement of 56% 3
• Deep brain stimulation and thalamotomy provide adequate tremor control in approximately 90% of patients, with deep brain stimulation preferred for bilateral procedures due to fewer complications 7