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 lancinating 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 control 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 lethargy
- Slightly less potent than Carbamazepine, 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 lethargy
- Slightly less potent than Carbamazepine, 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
Pregabalin (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 – arrhythmia
- McQuay – systematic review 1996 – NNT 3 in DN, NNH 2.8
- Tricyclic anti-depressants
- Amitriptyline (Endep)
- Nortripyline (Allegron)
- Doxepin (Deptran)
- Prothiaden
- Selective serotonin 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
- Odourless, 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
IV Phenytoin
- Blocks sodium channels and inhibits pre-synaptic glutamate release
- McCleane GJ. Anesth Analg 1999
- Randomised, D-B, P-C study of 20 patients with acute flare-ups of neuropathic pain
- 2h placebo infusion cf 15mg/kg Phenytoin (av. 1000mg)
- Slow infusion – given over 1 hour
- Reduced burning, shooting pain and sensitivity for 4 days
- Alkaline pH – burning pain and IV site irritation
IV Epilim
- Increases inhibitory neurotransmitter GABA by binding to GABA receptors
- Prolongs repolarisation of voltage-gated sodium channels
- Stillman MJ. Headache 2004
- 130 patients with headache with Valproate dose ranged from 300-1200mg
- 57.5% responded to the first treatment
- Schwartz TH. Headache 2002
- IV Valproate 15mg/kg followed by 5kg/kg every 8hr
- Improvement in headache in 80%
IV Keppra
- Hamza 2009
- Oral Keppra in lumbar radiculopathy pain
- Pain scores decreased from 7.1 at baseline to 4.2 at week 12
- Improvements in general activity, ability to walk and mood
- IV infusion – 1000 mg over 15 min
- SE: Dizziness, somnolence, fatigue, headache
IV Lignocaine
- Sodium channel blocker
- Reduces spontaneous and evoked responses in a variety of neuropathic pain conditions
- 2000mg (2 x 10 ml x 10% xylocard – lignocaine HCl)
- 40mg/ml given 1mg/kg/hr (monitor BP and HR)
- Relief maximum 20 minutes after end of infusion and persisted for over 10 hours
ACUTE PAIN MANAGEMENT - 2
Wind-Up
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- Prolonged response to a noxious stimulus
- Dramatic increase in duration and magnitude of cell responses, but input into spinal cord remains the same
- Activation of:
- Neurotransmitters (glutamate, substance P, NO), NDMA receptors,
- Inflammation and chemicals (neurotropin) and Genes (Cfos)
- Prolonged response to a noxious stimulus
Ketamine
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- 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
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Pain Clinics
Does not imply “Pain is not Real”
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- When pain persists beyond healing or with no cause, it is often assumed patient is willingly aggravating the pain
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This is rarely the case
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- 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
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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.