Medication

There is a variety of medications available for the treatment of Trigeminal Neuralgia. Initial treatment is usually in the form of anti-epileptic medications. Carbamazepine (Tegretol®) being the first drug of choice. When medication fails, surgery may be considered.

Medications Available for the treatment of Trigeminal Neuralgia

Anti-epileptics / Anticonvulsants
  • Used in treatment of pain since the 1960’s
  • Useful for neuropathic pain, especially if pain is lacinating or burning in nature
  • Specific mechanisms of action uncertain, but likely to stabilise the nerve membrane by blockade of voltage sensitive Na channels resulting in reduced ionic conductance of sodium and potassium

Carbamazepine (Tegretol) – NNT to obtain 50% relief – 1.7

  • Controlled release preparation better tolerated than immediate release usual tablet
  • 200mg nocte increasing slowly to 400mg bd
  • Response within a week in 65-80%
  • Minor SE: sedation, dizziness, nausea, unsteadiness, rash
  • Major SE: bone marrow suppression, liver function abnormalities, hyponatremia
  • Serum therapeutic ranges are irrelevant
  • 4 placebo controlled trials showing effectiveness

Sodium Valproate (Epilim)

  • Better tolerated than Tegretol
  • Increases activity of the inhibitory transmitter GABA
  • 200mg nocte increasing to 400mg bd
  • SE: GIT, weight gain, tremor
  • Hepatic dysfunction so LFT’s should be monitored
  • Serum therapeutic ranges are irrelevant
  • Oxcarbazepine (Trileptal)
  • Active metabolite of Tegretol therefore less side effects of effect on sodium, dizziness, drowsiness and lethergy
  • Slightly less potent than Carbazepine, so higher doses needed
  • 4 studies in Canada and Europe show it is as effective as Tegretol (70-80% response)
  • Not covered by PBS currently in Australia and costs approx $90 per month

Oxcarbazepine (Trileptal)

  • Active metabolite of Tegretol therefore less side effects of effect on sodium, dizziness, drowsiness and lethergy
  • Slightly less potent than Carbazepine, so higher doses needed
  • 4 studies in Canada and Europe show it is as effective as Tegretol (70-80% response)
  • Not covered by PBS currently in Australia and costs approx $90 per month

Pregablin (Lyrica)

  • Works on alpha-2-delta ligand
  • Analgesic, anxiolytic and anti-convulsant
  • SE’s: Dizziness, somnolence, blurred vision, weight gain and peripheral oedema
  • 25mg nocte increasing slowly to 300mg bd

Gabapentin

  • Used in a variety of neuropathic pain conditions such it prevents allodynia and hyperalgesia
  • Improves pain and sleep
  • Designed as an analogue of GABA, but also acts also on NMDA receptors
  • 100mg nocte titrating up to 1800mg/day
  • SE’s: ataxia, drowsiness, fatigue
Antidepressants
  • Also used for over 30 years for neuropathic pain
  • Direct analgesic effect and also relieve of other symptoms, such as sleep disorder
    • Lower doses (10-25mg) required c.f 100-150mg for mood
    • Occurs faster (3-4 days) than anti-depressant effects
    • SE’s: Anticholingeric effects – Sedation, dry mouth, blurred vision, urinary retention
    • Life-threatening cardiovascular effects – arrhthymias
  • McQuay – systematic review 1996 – NNT 3 in DN, NNH 2.8
  • Tricyclic anti-depressants
    • Amitriptyline (Endep)
    • Nortripyline (Allegron)
    • Doxepin (Deptran)
    • Prothiaden
  • Selective seretonin reuptake inhibitors (SSRI)
    • Paroxetine (Aropax)
    • Fluoxetine (Prozac / Lovan)
    • Citalopram (Cipramil)
    • Seretaline (Zoloft)
  • Mixed (SNRI)
    • Mirtazapine (Avanza)
    • Venlafaxine (Efexor)
    • Reboxetine (Edronax)
    • Duloxetine (Cymbalta)
    • Duloxetine
  • Selective serotonin and NAR reuptake inhibitor
  • 30 mg daily for 1 month then 60 mg daily
  • Increasing use and effect independent of mood effect
  • Recent diabetic PN study – within 1 week, 50% reduction in pain in 50% of patients
  • SE’s: Nausea, somnolence, constipation
Opioids
  • Beneficial in some patients
    • Demonstrated good efficacy outcomes with only moderate side effects and low risk of abuse or addiction
  • Longer acting opioids are better than short-acting
  • Patient selection and close follow-up important

Tramadol

  • CNS-active analgesic, synergistic action via:
    • Non-opioid by inhibition of noradrenaline reuptake and stimulation of serotonin release at the spinal level
    • Opioid with weak binding to mu-opioid receptors
  • Quick acting, slow release, extended release, IV or IM
  • Side effects: CNS (somnolence, confusion, dizziness) & GIT (nausea)
  • Small risk of seizures (use contraindicated if seizure history)
  • NNT for Tramadol 100mg 4.7

Buprenorphine (Norspan)

  • Transdermal patch – weekly
    • Partial opioid agonist
    • SE’s: Application site skin irritation (rotate sites), headaches , Dizziness, drowsiness, nausea
    • Doses: 5 mcg/hr / 10 / 20 /40 weekly

Tapentadol

  • Opiate agonist and noradrenaline reuptake inhibitor.
  • Used when there is mixed pain with elements of nociceptive and neuropathic pain.
  • Theoretical risk of confusion and serotonin toxicity if prescribed with SSRIs or serotonergic agents.
  • Start at 50 mg at night increasing slowly to 200mg twice a day.
  • Similar side effects to other opiates, but generally not as severe or frequent.
Baclofen, Mexilitene, Clonidine
Baclofen

  • GABA b receptor agonist
    • Lacinating pains primarily through inhibitory effect
    • Initiate slowly, 5mg bd (increase up to 40-60mg/day)
  • Side effects: CNS depression of sedation, confusion, dizziness and nausea and postural hypotension

Mexilitene

  • Blocks sodium channels and reduces abnormal baseline and inducible nerve discharges
    • Difficult to initiate. Start 50 mg daily increasing slowly to 200 mg tds
  • Poorly tolerated with anorexia, nausea, vomiting, drowsiness, confusion

Clonidine

  • Alpha 2 adrenergic agonist in dorsal horn and brainstem
    • Transdermal, intravenous, oral, and epidural
    • Suppress CNS noradrenergic activity and peripheral sympathetic tone
  • Opiate analgesia may be potentiate as it has a dual effects on opiate receptors
  • Non-addictive therefore useful for weaning opioid-dependent patients by blocking withdrawal
Capsaicin cream
  • Naturally occurring alkaloid
    • Works on small cutaneous c-fiber afferents by stimulating then blocking fibres
    • Depletes substance P and reduces membrane excitability and blocks axon transport
    • Low concentration, 0.075% topical cream
    • May burn for the first several weeks
N-methyl-D-aspartate (NMDA) blockers – Ketamine
  • Developed in 1963 as safer alternative to PCP
  • NMDA receptor inhibition in dorsal horn of spinal cord
  • Anaesthetic with:
    • Dissociative (separates perception from sensation)
    • Analgesic, sedative and amnesic properties
    • Used in veterinary medicine
    • Odorless, tasteless, undetectable in drinks
  • 80% hepatic metabolism to active Norketamine
    • Orally as only 1/3 analgesic potency of ketamine
    • Cognitive side effects and hallucinations at high doses
  • Ketamine infusion
    • 200mg in 50ml plus
    • Generally run at 2ml/hr initially over 3-5 days
    • If effective
      • Ketamine lozenges – 25mg three times a day initially
Vitamin B12
  • Used by the body in the production of myelin
  • Gross deficiencies lead to nerve damage (pain and inflammation)
  • Beef, lamb, eggs, liver, oysters
  • Parenteral B12 or oral 1000 micrograms daily (Methylcobalamin)
    • Help regenerate myelin and nerve cells, even in non-deficient
  • Initial studies (1940’s) -promising results
  • Recent study in TNA also promising
    • Talaei 2009
    • Parenteral vitamin B(12) vs nortriptyline in DPN – 100 patients
    • Pain decreased 3.6 on VAS in vitamin B12 and 0.8 in Nortriptyline
Botulinum Toxin
  • Turk 2005 – Clin NeuroPharm
    • 8 patients with TN 50u injected just above and below the zygomatic arch at a depth of 2 cm
  • Reduction in pain within hours or days in all after the injection – 3.2 +/- 2 days
  • Zuniga 2008
    • 12 patients with TN – 20-50 units into trigger zones – massester muscle if V2
    • 10/12 significant improvement for 60 days
Others
Topiramate (Topamax)

  • Modulation of voltage-gated Na and Ca channels
  • Potentiation of GABA and block AMPA receptors
  • 25 mg daily increasing very slowly to 100mg bd
  • Used in Migraine prophylaxis

Levetiracetam (Keppra)

  • Jorns 2009 – 10 week study in TN
  • 250mg twice a day increasing slowly to 1000mg twice a day – 40% improvement

Lacosamide (Vimpat)

  • Selectively enhances slow inactivation of Sodium channel, reducing hyperexcitability.
  • 50mg twice a day up to 200mg twice a day
  • SE’s – dizziness, headache, nausea and diplopia

Clonezapam

  • Benzodiazepine – drowsiness and addictive
  • Facilitates binding of GABA to its receptors
  • Very good for nocturnal symptoms, esp. burning pain

ACUTE PAIN MANAGEMENT - 1
ACUTE PAIN MANAGEMENT - 2

Pain Clinics

Does not imply “Pain is not Real”

  • When pain persists beyond healing or with no cause, it is often assumed patient is willingly aggravating the pain

This is rarely the case

  • Pain is a perception, which is filtered through the brain
  • Multidisciplinary treatment
    • 1st pain clinic to include psychological component –1976
    • Cognitive components are crucial to the treatment
      • Reduce pain but also improve mood and decrease disability
    • Medical, physical, behavioural, emotional, vocational, social
  • Investigations and referrals
  • Medications
    • Nociceptive or anti-neuropathic
  • Anaesthetic blocks or TENS
  • Physical therapy and exercise program
  • Occupational therapy
  • Psychiatric or D & A review
  • Psychological management
    • Meditation / relaxation or Pain Education Program
  • Implantable drug pump and spinal cord stimulation
Our mission is to provide support and encouragement to sufferers of Trigeminal Neuralgia and related facial pain. All material provided on the TNA Australia website is for information purposes only; to supplement a reader’s general knowledge.