Medication Therapy
Medical Therapy for Trigeminal Neuralgia
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.
Variety of Medications Available
Carbamazepine (NNT to obtain 50% relief – 1.7)
Valproate, Phenytoin, Clonazepam
Gabapentin, Lamotrigine, Topiramate, Oxcarbazepine
Pregabalin, Levetiracetam, Lacosamide
Amitriptyline, Nortriptyline, Imipramine
Opioids –Tramadol, Oxycodone, Morphine, Norspan, Tapentadol
Baclofen, Mexilitene, Clonidine
Capsaicin cream
N-methyl-D-aspartate (NMDA) blockers – Ketamine
Botulinum Toxin
Vitamin B12
Anti-convulsants
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
Carbamezpine (Tegretol CR)
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
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
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
Anti-depressants
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.
Other Classes
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
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
Acute 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 Management - 2
Wind-Up
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)
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
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
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
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
To learn more about Trigeminal Neuralgia Association Australia, reach out today.