Efficacy and Safety Study of Lamotrigine to Treat Trigeminal Neuralgia

Lamotrigine in Trigeminal Neuralgia: Efficacy and Safety in Comparison With Carbamazepine

The purpose of this study was to determine the efficacy and safety of lamotrigine in patients with trigeminal neuralgia (TGN).

Study Overview

• Status: Completed
• Conditions: Trigeminal Neuralgia
• Intervention / Treatment: Drug: Lamictal®; Drug: Tegretol®

Detailed Description

Trigeminal Neuralgia (TGN) is a rare form of chronic facial pain shrouded in mystery, although not life threatening, can be excruciating painful and extraordinarily debilitating. Its uniqueness and peculiarity can be ascertained by the fact that TGN may present to and be managed by dentists, neurologists, neurosurgeons, oral surgeons and ear, nose and throat surgeons.

The management of TGN is initially medical, with the "gold standard" drug of carbamazepine (CBZ). Whilst CBZ continues to be the treatment of choice, a substantial proportion of patients tolerate this drug poorly, predominantly because of side-effects that include drowsiness, accommodation disorders, hepatitis, elevation in liver enzymes, renal dysfunction, congestive heart failure, delayed multi-organ failure, leucopenia, thrombocytopenia etc. etc. If pain-relief is incomplete with CBZ or it produces adverse side-effects, options include using an alternative second-line medical agent. The drugs suggested to be considered as second-line agents for the treatment of TGN, include: lamotrigine, baclofen, phenytoin, oxcarbazepine, gabapentin, clonazepam, valproate, mexiletine, and topiramate.

Lamotrigine (LTG), a novel anticonvulsant, which has not been adequately assessed for its antineuralgic properties. It has a bimodal mechanism of action:

• inhibits the release of glutamate and aspartate by blocking voltage-sensitive sodium channels
• antagonistic at neuroexcitatory N-methyl-d-aspartate receptors.

It can also acts at and inhibits calcium channels to enhance the gamma- Aminobutyric acid (GABA) synthesis. GABA is an inhibitory amino acid neurotransmitter that decreases neural membrane action potentials and therefore decreases nerve excitability. Glutamate has been implicated in the mechanisms contributing towards phenomenon of chronic pain, such as sensitisation and wind up. LTG through its inhibition of pathological release of glutamate, has the potential towards management of chronic pain, particularly of neuropathic origin.

Lamotrigine, therefore has the potential to be a promising new treatment for TGN.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Malaysia
  • Kuala Lumpur, Malaysia, 50603
    • Dept. of OMOP, Faculty of Dentistry, University Malaya.
  • Kuala Lumpur, Malaysia, 50603
    • Dept. of Oral Medicine and Oral Pathology, Faculty of Dentistry, University Malaya.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Clinical diagnosis of Trigeminal Neuralgia
• Male; or non-pregnant/non-lactating female
• Must be willing to cooperate with and understands study instructions
• Signed informed consent prior to entering study

Exclusion Criteria:

• psychiatric illness
• severe liver or cardiovascular disease
• renal impairment, low white cell count
• malignancy
• pregnancy or lactation
• alcohol or recreational drug abuse
• and positive tests for human immunodeficiency virus or hepatitis B or C.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Lamictal®; Lamictal® was used as the "active" medication in this study.	Drug: Lamictal®; The regime of prescription for Lamictal® during the clinical trials was as follows: 50 mg twice daily for 10days, followed by,; 100 mg twice daily for the next 10days, followed by,; 100 mg thrice daily for the next10 days, followed by,; 100 mg four times daily for the final 10 days.; Other Names: Lamotrigine (generic name for Lamictal®); Carbamazepine (generic name for Tegretol®); Drug: Tegretol®; The regime of prescription for Tegretol® during the clinical trials was as follows: 150 mg twice daily for 10days, followed by,; 200 mg thrice daily for the next 10days, followed by,; 300 mg thrice daily for the next 10 days, followed by,; 300 mg four times daily for the final 10 days.; Other Names: Lamotrigine (generic name for Lamictal®); Carbamazepine (generic name for Tegretol®)
Active Comparator: Tegretol®; Tegretol® was employed as the "control" for comparative purposes in order to check and evaluate the efficacy (pain-relief) and occurrence of side- effects of Lamictal®.	Drug: Lamictal®; The regime of prescription for Lamictal® during the clinical trials was as follows: 50 mg twice daily for 10days, followed by,; 100 mg twice daily for the next 10days, followed by,; 100 mg thrice daily for the next10 days, followed by,; 100 mg four times daily for the final 10 days.; Other Names: Lamotrigine (generic name for Lamictal®); Carbamazepine (generic name for Tegretol®); Drug: Tegretol®; The regime of prescription for Tegretol® during the clinical trials was as follows: 150 mg twice daily for 10days, followed by,; 200 mg thrice daily for the next 10days, followed by,; 300 mg thrice daily for the next 10 days, followed by,; 300 mg four times daily for the final 10 days.; Other Names: Lamotrigine (generic name for Lamictal®); Carbamazepine (generic name for Tegretol®)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Pain-relief	3-6 months

Collaborators and Investigators

• Sponsor: University of Malaya
• Investigators: Principal Investigator: Dr. Sameer Shaikh, MDSc., Faculty of Dentistry, University Malaya

Publications and helpful links

General Publications

• Shaikh S, Yaacob HB, Abd Rahman RB. Lamotrigine for trigeminal neuralgia: efficacy and safety in comparison with carbamazepine. J Chin Med Assoc. 2011 Jun;74(6):243-9. doi: 10.1016/j.jcma.2011.04.002. Epub 2011 May 10.

Study record dates

Study Major Dates

• Study Start: September 1, 2007
• Primary Completion (Actual): February 1, 2008
• Study Completion (Actual): June 1, 2008

Study Registration Dates

• First Submitted: May 27, 2009
• First Submitted That Met QC Criteria: May 29, 2009
• First Posted (Estimate): June 3, 2009

Study Record Updates

• Last Update Posted (Estimate): June 29, 2010
• Last Update Submitted That Met QC Criteria: June 27, 2010
• Last Verified: June 1, 2010

More Information

Terms related to this study

• Keywords: Lamotrigine; Carbamazepine; Trigeminal Neuralgia; Lamictal®; Tegretol®
• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Neuromuscular Diseases; Stomatognathic Diseases; Mouth Diseases; Peripheral Nervous System Diseases; Cranial Nerve Diseases; Facial Nerve Diseases; Trigeminal Nerve Diseases; Facial Neuralgia; Neuralgia; Trigeminal Neuralgia; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Membrane Transport Modulators; Sodium Channel Blockers; Antimanic Agents; Cytochrome P-450 Enzyme Inducers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Cytochrome P-450 CYP3A Inducers; Lamotrigine; Anticonvulsants; Carbamazepine
• Other Study ID Numbers: PS287-2007B