Lamotrigine

Lamotrigine
Lamotrigine

Systematic (IUPAC) name

6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine
Clinical data
Trade names

Lamictal

AHFS/Drugs.com monograph [1]

[2]

MedlinePlus

a695007

Licence data

USFDA:link

Pregnancy cat.
Legal status
Routes

[3]

D (AU) C (US)
Prescription Only (S4) (AU) -only (CA) POM (UK) -only (US)
Oral
Pharmacokinetic data

Bioavailability

98%

Protein binding

55%

Metabolism
Half-life
Excretion

Hepatic (mostly UGT1A4-mediated)

29 hours
Urine (65%), faeces (2%)
Identifiers

CAS number

84057-84-1

ATC code

N03AX09

PubChem

CID 3878

IUPHAR ligand
DrugBank
ChemSpider
UNII
KEGG

2622

[5]
[6]

[7]

DB00555
3741

[4]

[9]

[8]

U3H27498KS
D00354

[11]

[10]

Lamotrigine

2
[12]

ChEBI

CHEBI:6367

ChEMBL

CHEMBL741

[13]

Chemical data
Formula
Mol. mass

C9H7Cl2N5
256.091 g/mol

(what is this?) (verify)

[14]

Lamotrigine, marketed in the US and most of Europe as Lamictal /lmktl/ by GlaxoSmithKline, is an

anticonvulsant drug used in the treatment of epilepsy and bipolar disorder. It is also used off-label as an adjunct in
treating clinical depression. For epilepsy, it is used to treat focal seizures, primary and secondary tonic-clonic
seizures, and seizures associated with Lennox-Gastaut syndrome. Like many other anticonvulsant medications,
lamotrigine also seems to act as an effective mood stabiliser, and has been the first US Food and Drug
Administration (FDA)-approved drug for this purpose since lithium, a drug approved almost 30 years earlier. It is
approved for the maintenance treatment of bipolar type I. Chemically unrelated to other anticonvulsants (due to
lamotrigine's being a phenyltriazine), lamotrigine has many possible side-effects. Lamotrigine is generally accepted
to be a member of the sodium channel blocking class of antiepileptic drugs, but it could have additional actions since
it has a broader spectrum of action than other sodium channel antiepileptic drugs such as phenytoin and
carbamazepine and is effective in the treatment of the depressed phase of bipolar disorder, whereas other sodium
channel blocking antiepileptic drugs are not. In addition, lamotrigine shares few side-effects with other, unrelated
anticonvulsants known to inhibit sodium channels, which further emphasises its unique properties. Lamotrigine is
inactivated by hepatic glucuronidation.

Medical uses
Epilepsy and seizures
Lamotrigine is approved in the US for the treatment of partial seizures. It is considered a first-line drug for primary
generalised tonic-clonic (includes simple partial, complex partial and secondarily generalised seizures), and as an
adjuvant therapy in partial seizures (focal onset tonic-clonic, atypical absence,myoclonic, Lennox Gastaut
syndrome). As well, it is used as an alternative drug for absence seizure and atypical absence, myoclonic, atonic.
Lamotrigine is one of a small number of FDA-approved therapies for seizures associated with Lennox-Gastaut
syndrome, a severe form of epilepsy. Typically developing before four years of age, LGS is associated with
developmental delays. There is no cure, treatment is often complicated, and complete recovery is rare. Symptoms
include the atonic seizure (also known as a "drop attack"), during which brief loss of muscle tone and consciousness
cause abrupt falls. Lamotrigine significantly reduces the frequency of LGS seizures, and is one of two medications
known to decrease the severity of drop attacks. Combination with valproate is common, but this increases the risk of
lamotrigine-induced rash, and necessitates reduced dosing due to the interaction of these drugs.

Bipolar disorder
Lamotrigine is approved in the US for maintenance treatment of Bipolar I disorder. While traditional anticonvulsant
drugs are predominantly antimanics, lamotrigine is most effective for preventing the recurrent depressive episodes of
bipolar disorder. The drug seems ineffective in the maintenance of current rapid-cycling, mania, or depression
bipolar disorder; however, it is effective at prophylaxis or delaying the mania, depressive, or rapid cycle. According
to studies in 2007, lamotrigine may treat bipolar depression without triggering mania, hypomania, mixed states, or
rapid-cycling.

Lamotrigine
There is less evidence of therapeutic benefit when lamotrigine is used to treat a current mood episode. It has not
demonstrated effectiveness in treating acute mania, and there is controversy regarding the drugs effectiveness in
treating acute bipolar depression. While the 2002 American Psychiatric Association (APA) guidelines recommend
lamotrigine as a first-line treatment for acute depression in Bipolar II disorder, the APAs website notes that the
guidelines, being more than five years old, can no longer be assumed to be current." A paper written in 2008 by
Nasser et al. reviewed evidence from trials that were unpublished and not referenced in the 2002 APA guidelines,
and it concludes that lamotrigine has "very limited, if any, efficacy in the treatment of acute bipolar depression." A
2008 paper by Calabrese et al. examined much of the same data, and found that in five placebo controlled studies,
lamotrigine did not significantly differ from placebo in the treatment of bipolar depression. However, in a
meta-analysis of these studies conducted in 2008, Calabrese found that lamotrigine was effective in individuals with
bipolar depression, with a number needed to treat (NNT) of 11, or 7 in severe depression. A recent review about
lamotrigine concluded that it is recommended in bipolar maintenance when depression is prominent and that more
research is needed in regards to its role in the treatment of acute bipolar depression and unipolar depression. As well,
no information to recommend its use in other psychiatric disorders was found

Other uses
Off-label uses include the treatment of peripheral neuropathy, trigeminal neuralgia, cluster headaches, migraines, and
reducing neuropathic pain. Off-label psychiatric usage includes the treatment of depersonalization disorder,
hallucinogen persisting perception disorder, schizoaffective disorder, borderline personality disorder, and
post-traumatic stress disorder. Lamotrigine has been studied as an adjunctive therapy for treatment of refractory
unipolar depression, attaining efficacy on the secondary metric for treatment outcomes (Clinical Global
Impressions), but not the primary metrics (Montgomery-sberg Depression Rating Scale and Hamilton Rating Scale
for Depression).

Pharmacology
Lamotrigine is a member of the sodium channel blocking class of
antiepileptic drugs. It is a triazine derivate that inhibits
voltage-sensitive sodium channels, leading to stabilization of neuronal
membranes. It also blocks L-, N-, and P-type calcium channels and has
weak 5-hydroxytryptamine-3 (5-HT3) receptor inhibition. These
actions are thought to inhibit release of glutamate at cortical
projections in the ventral striatum limbic areas, and it has been pointed
out this neuroprotective and antiglutamatergic effects as promising
Lamotrigine, 150 mg tablet.
contributors to its mood stabilizing activity. Observations that
lamotrigine reduced -aminobutyric acid (GABA) A receptor-mediated
neurotransmission in rat amygdala, suggest that a GABAergic mechanism may also be involved, although this
concept is not without controversy.
Lamotrigine does not have pronounced effects on any of the usual neurotransmitter receptors (adrenergic, dopamine
D1 and D2, muscarinic, GABA, histaminergic H1, serotonin 5-HT2, and N-methyl-D-asparate). Inhibitory effects on
5-HT, norepinephrine, and dopamine transporters are weak. Lamotrigine is a weak inhibitor of dihydrofolate
reductase, but whether this effect is sufficient to contribute to a mechanism of action or increases risk to the fetus
during pregnancy is not known. Early studies of lamotrigine's mechanism of action examined its effects on the
release of endogenous amino acids from rat cerebral cortex slices in vitro. As is the case for antiepileptic drugs that
act on voltage-dependent sodium channels, lamotrigine inhibited the release of glutamate and aspartate evoked by
the sodium-channel activator veratrine and was less effective in the inhibition of acetylcholine or GABA release. At
high concentrations, it had no effect on spontaneous or potassium evoked amino acid release [citation needed]. These

Lamotrigine
studies suggested that lamotrigine acts presynaptically on voltage-gated sodium channels to decrease glutamate
release. Several electrophysiological studies have investigated the effects of lamotrigine on voltage-dependent
sodium channels. For example, lamotrigine blocked sustained repetitive firing in cultured mouse spinal cord neurons
in a concentration-dependent manner, at concentrations that are therapeutically relevant in the treatment of human
seizures. In cultured hippocampal neurons, lamotrigine reduced sodium currents in a voltage-dependent manner, and
at depolarised potentials showed a small frequency-dependent inhibition. These and a variety of other results indicate
that the antiepileptic effect of lamotrigine, like that of phenytoin and carbamazepine, is at least in part due to useand voltage-dependent modulation of fast voltage-dependent sodium currents. However, lamotrigine has a broader
clinical spectrum of activity than phenytoin and carbamazepine and is recognised to be protective against generalised
absence epilepsy and other generalised epilepsy syndromes, including primary generalised tonicclonic seizures,
juvenile myoclonic epilepsy, and Lennox-Gastaut syndrome. The basis for the broader spectrum of activity of
lamotrigine is unknown, but could relate to actions of the drug on voltage-activated calcium channels. Lamotrigine
blocks T-type calcium channels weakly, if at all. However, it does inhibit native and recombinant
high-voltageactivated calcium channels (N- and P/Q/R-types) at therapeutic concentrations. Whether this activity
on calcium channels accounts for lamotrigine's broader clinical spectrum of activity in comparison with phenytoin
and carbamazepine remains to be determined.
It antagonises the following receptors with the following IC50 values:
5-HT3, IC50=18M
receptors, IC50=145M

Pharmacokinetics
The pharmacokinetics of lamotrigine follow first-order kinetics, with a half-life of 13.5 hours and volume of
distribution of 1.36 L/kg. Lamotrigine is rapidly and completely absorbed after oral administration. Its absolute
bioavailability is 98% and its plasma Cmax occurs from 1.4 to 4.8 hours. Available data indicate that its
bioavailability is not affected by food. Estimate of the mean apparent volume of distribution of lamotrigine following
oral administration ranges from 0.9 to 1.3 L/kg. This is independent of dose and is similar following single and
multiple doses in both patients with epilepsy and in healthy volunteers.
Lamotrigine is metabolised predominantly by glucuronic acid conjugation. Its major metabolite is an inactive
2-n-glucuronide conjugate. Lamotrigine has fewer drug interactions than many anticonvulsant drugs, although
pharmacokinetic interactions with carbamazepine, phenytoin and other hepatic enzyme inducing medications may
shorten half-life. Dose adjustments should be made on clinical response, but monitoring may be of benefit in
assessing compliance.(CITATION NEEDED)

Side Effects
Lamotrigine prescribing information has a black box warning about life-threatening skin reactions, including
StevensJohnson syndrome, DRESS syndrome and toxic epidermal necrolysis. The manufacturer states that nearly
all cases appear in the first 2 to 8 weeks of therapy and if medication is suddenly stopped then resumed at the normal
dosage. Patients should seek medical attention for any unexpected skin rash, as its presence is an indication of a
possible serious or even deadly side-effect of the drug. Not all rashes that occur while taking lamotrigine progress to
SJS or TEN. Between 5 to 10% of patients will develop a rash, but only one in a thousand patients will develop a
serious rash. Rash and other skin reactions are more common in children, so this medication is often reserved for
adults.
There is also an increased incidence of these eruptions in patients who are currently on, or recently discontinued a
valproate-type anticonvulsant drug, as these medications interact in such a way that the clearance of both is
decreased and the effective dose of lamotrigine is increased.

Lamotrigine
As of December 2010, lamotrigine carries an FDA black box warning for aseptic meningitis.[15]
Side-effects such as rash, fever, and fatigue are very serious, as they may indicate incipient StevensJohnson
syndrome, toxic epidermal necrolysis, DRESS syndrome or aseptic meningitis.
Other side-effects include loss of balance or coordination, double vision, crossed eyes, pupil constriction, blurred
vision, dizziness and lack of coordination, drowsiness, insomnia, anxiety, vivid dreams or nightmares, dry mouth,
mouth ulcers, memory and cognitive problems, mood changes, runny nose, cough, nausea, indigestion, abdominal
pain, weight loss, missed or painful menstrual periods, and vaginitis. The side-effect profile is different for different
patient populations.
Lamotrigine has been associated with a decrease in white blood cell count (leukopenia). Lamotrigine does not
prolong QT/QTc in TQT studies in healthy subjects [16]
Cases of lamotrigine-induced neuroleptic malignant syndrome (NMS a condition characterised by muscle
rigidity, tremors, autonomic dysregulation [tachycardia (high heart rate), hypertension (high blood pressure),
diarrhoea, diaphoresis (profuse sweating), etc.], mental status change [e.g. hallucinations, agitation, delusions,
stupor, coma, etc.] and hyperthermia [elevated body temperature]; in patients that had been stabilised on atypical
antipsychotics for several months without NMS symptoms) have been reported.

Effects in women
In clinical trials women were more likely than men to have side-effects[citation needed]. This is the opposite of most
other anticonvulsants.
There is evidence showing interactions between lamotrigine and female hormones, which can be of particular
concern for women on estrogen-containing hormonal contraceptives. Ethinyl estradiol, the ingredient of such
contraceptives, has been shown to decrease serum levels of lamotrigine. Women starting an estrogen-containing oral
contraceptive may need to increase the dosage of lamotrigine to maintain its level of efficacy. Likewise, women may
experience an increase in lamotrigine side-effects upon discontinuation of the pill. This may include the "pill free"
week where lamotrigine serum levels have been shown to increase twofold. Another study showed a significant
increase in follicle stimulating hormone (FSH) and luteinizing hormone (LH) in women taking lamotrigine with oral
contraceptive compared to women taking oral contraceptives alone. However, these increases were not in
conjunction with increased progesterone, indicating that oral contraceptives maintained suppression of ovulation.

Pregnancy and breastfeeding

Lamotrigine is rated Pregnancy Category Risk C. Use during pregnancy is recommended only if benefits outweigh
potential risks. In September 2006, the FDA issued a warning stating that taking lamotrigine during the first trimester
of pregnancy may increase the risk for cleft lip and palate malformation in newborns.[17] Since then, review studies
have found that overall rates of congenital malformations in infants exposed to lamotrigine in utero are relatively
low (1-4%). This compares to a typical 3% rate in the untreated population. A prospective study on cognition in
children (mean age = 4.2 years) exposed to lamotrigine in utero did not indicate any adverse effects.
Lamotrigine is found in breast milk; the manufacturer does not recommend breastfeeding during treatment. In
"Medications and Mothers' Milk," a frequently updated review of scientific literature, lamotrigine is rated as L3:
moderately safe.

Lamotrigine

Other types of effects

Lamotrigine binds to melanin-containing tissues such as the iris of the eye. The long-term consequences of this are
unknown.
Some patients have reported experiencing a loss of concentration, even with very small doses. Lamotrigine has been
implicated in the apoptotic neurodegeneration of the developing brain. GlaxoSmithKline investigated lamotrigine for
the treatment of ADHD with inconclusive results. No detrimental effects on cognitive function were observed;
however, the only statistical improvement in core ADHD symptoms was an improvement on a test, PASAT (Paced
Auditory Serial Addition Test), that measures auditory processing speed and calculation ability.
Lamotrigine is known to affect sleep. Studies with small numbers (10-15) of patients reported that lamotrigine
increases sleep stability (increases the duration of REM sleep, decreases the number of phase shifts and decreases the
duration of slow-wave sleep), and that there was no effect on vigilance, and daytime somnolence and cognitive
function. However, a retrospective study of 109 patients' medical records found that 6.7% of patients experienced an
'alerting effect' resulting in intolerable insomnia, for which the treatment had to be discontinued.
Lamotrigine can induce a type of seizure known as a myoclonic jerk, which tends to happen soon after the use of the
medication.[18] When used in the treatment of myoclonic epilepsies such as juvenile myoclonic epilepsy, lower doses
(and lower plasma levels) are usually needed, as even moderate doses of this drug can lead to induction of seizures,
including tonic-clonic seizures, which can develop into status epilepticus, which is a medical emergency. It can also
cause myoclonic status epilepticus.[citation needed]
In overdose, lamotrigine can cause uncontrolled seizures in most people.

History
December 1994 Lamotrigine was approved for the treatment of partial seizures.
August 1998 for use as adjunctive treatment of Lennox-Gastaut syndrome in pediatric and adult patients, new
dosage form: chewable dispersible tablets.
December 1998 for use as monotherapy for treatment of partial seizures in adult patients when converting
from a single enzyme-inducing anti-epileptic drug (EIAED).
January 2003 for use as adjunctive therapy for partial seizures in pediatric patients as young as two years of
age.
June 2003 approved for maintenance treatment of Bipolar I disorder; the first such medication since lithium.[]
January 2004 for use as monotherapy for treatment of partial seizures in adult patients when converting from
the anti-epileptic drug valproate (including valproic acid (Depakene); sodium valproate (Epilim) and divalproex
sodium (Depakote)).

Availability
GlaxoSmithKline's trademarked brand of lamotrigine, Lamictal, is
manufactured in scored tablets (25mg, 50mg, 100mg, 150mg
and 200mg) and chewable dispersible tablets (2mg, 5mg and
25mg). Five-week sample kits are also available; these include
titration [19] instructions and scored tablets (25mg for patients
taking valproate, 25mg and 100mg for patients not taking
valproate). Lamotrigine is also available in un-scored tablet form.
In 2005, Teva Pharmaceutical Industries Ltd. began selling generic
lamotrigine in the United States, but only in 5mg and 25mg

Lamictal 200 mg tablets

Lamotrigine
chewable dispersible tablets. On 23 July 2008 Teva began offering the full line of generic lamotrigine in the US.[20]
Lamotrigine is also available in generic form in the United States, the United Kingdom, Canada and Australia. It
should be noted that brand name Lamictal is not available in 200mg tablets in Canada, at all registered pharmacies
(while 25, 100, and 150mg are all offered). Starter kits are also not available in Canada.
Lamotrigine is marketed as Lamotrine in Egypt, Lamitrin in Bangladesh [21], Lamictin in South Africa, '
(Lamogine) in Israel, and in South Korea and generally named as Lamitor.

Lamictal XR
In 2009 GlaxoSmithKline received FDA Approval for an extended-release version of lamotrigine branded Lamictal
XR. Lamictal XR tablets are a novel preparation of lamotrigine, delivered in a tablet with an enteric coating that
GlaxoSmithKline has branded DiffCORE. The extended release formulation is analogous to the instant release
version, such that treatment may begin without titration or recalibration of the dosage.

Chemistry
Lamotrigine can be prepared from 2,3-dichlorobenzoyl cyanide.

References
[1] http:/ / www. drugs. com/ monograph/ lamotrigine. html
[2] http:/ / www. nlm. nih. gov/ medlineplus/ druginfo/ meds/ a695007. html
[3] http:/ / www. accessdata. fda. gov/ scripts/ cder/ drugsatfda/ index. cfm?fuseaction=Search. SearchAction& SearchTerm=Lamotrigine&
SearchType=BasicSearch
[4] http:/ / www. nlm. nih. gov/ cgi/ mesh/ 2009/ MB_cgi?term=84057-84-1& rn=1
[5] http:/ / www. whocc. no/ atc_ddd_index/ ?code=N03AX09
[6] http:/ / pubchem. ncbi. nlm. nih. gov/ summary/ summary. cgi?cid=3878
[7] http:/ / www. iuphar-db. org/ DATABASE/ LigandDisplayForward?ligandId=2622
[8] http:/ / www. drugbank. ca/ drugs/ DB00555
[9] http:/ / www. chemspider. com/ Chemical-Structure. 3741
[10] http:/ / fdasis. nlm. nih. gov/ srs/ srsdirect. jsp?regno=U3H27498KS
[11] http:/ / www. kegg. jp/ entry/ D00354
[12] https:/ / www. ebi. ac. uk/ chebi/ searchId. do?chebiId=CHEBI:6367
[13] https:/ / www. ebi. ac. uk/ chembldb/ index. php/ compound/ inspect/ CHEMBL741
[14] http:/ / en. wikipedia. org/ w/ index. php?title=Special:ComparePages& rev1=420280917& page2=Lamotrigine
[15] http:/ / www. drugs. com/ monograph/ lamotrigine. html
[16] Lamotrigine does not prolong QTc in a thorough QT/QTc study in healthy subjects (http:/ / www. richmondpharmacology. com/ downloads/
Publications/ Lamotrigine does not prolong QTc in a thorough QTQTc study in healthy subjects. pdf)
[17] FDA: Safety Alerts: Lamotrigine (http:/ / www. fda. gov/ Safety/ MedWatch/ SafetyInformation/ SafetyAlertsforHumanMedicalProducts/
ucm150637. htm)
[18] http:/ / www. ehealthme. com/ ds/ lamictal/ myoclonic+ jerks Retrieved August 19, 2010. Myoclonic Jerk in the use of Lamictal.
[19] In medicine, titration is the process of gradually adjusting the dose of a medication until optimal results are reached.
[20] http:/ / www. tevapharm. com/ pr/ 2008/ pr_779. asp
[21] http:/ / www. bddrugs. com/ product5. php?idn=244& prev=99& prev1=& prev2=

Lamotrigine

External links
FAQ: Psychiatric Uses of Lamotrigine (Lamictal) (http://www.psycom.net/depression.central.lamotrigine.
html), by Ivan K. Goldberg, MD. Includes many references from the medical literature.
Center for Drug Evaluation and Research: Lamictal (http://www.accessdata.fda.gov/scripts/cder/drugsatfda/
index.cfm?fuseaction=Search.Label_ApprovalHistory) documents related to the FDA approval process,
including medical reviews and correspondence letters.
Epilepsy South Africa: MEDICATION FOR EPILEPSY (http://www.epilepsy.org.za/faq.php) an
Epilepsy FAQ with a list of medicines for treatment thereof, includes Lamotrigine with South African trade
name Lamictin.
Adverse Reactions (http://www.druglib.com/adverse-reactions_side-effects/lamictal/) Reported adverse
reactions and side-effects.
U.S. National Library of Medicine: Drug Information Portal Lamotrigine (http://druginfo.nlm.nih.gov/
drugportal/dpdirect.jsp?name=Lamotrigine)

Article Sources and Contributors

Article Sources and Contributors

Lamotrigine Source: http://en.wikipedia.org/w/index.php?oldid=591578305 Contributors: A876, ABCD, Abcb336, Aetheling, Agjchs, Akb4, Albmont, Alchemagenta, Alexrexpvt, Allens,
Aneah, Ara6012, Arcadian, AssetBurned, Batamt, Beetstra, Bkell, Bllix, Bogwhistle, Bonhomie, Bradd, Bwilliams, Casforty, Casliber, Cfailde, Chemgirl131, Chowbok, Chronulator, Daevatgl,
Dagrrl, Danhash, Darklilac, David Hedlund, Dcirovic, Deepwatership, Deflective, Deli nk, Dfogelso, Dfxoreilly, Dhatfield, Dixto, Download, Drphilharmonic, Ecwp2, Edgar181, Edward, Elvey,
Enix150, Epicgenius, Epolk, FREvers, Facts707, Fortheloveofbacon, Fraggle81, Funandtrvl, Fuse809, Fvasconcellos, Gaius Cornelius, Gene Nygaard, Gigacephalus, GingerDemarque,
Giorgiogp2, GngstrMNKY, GoingBatty, Golbez, Gprobins, Graeme Bartlett, Grec3000, Ground Zero, Hoffmeier, Hohohahaha, Hopkapi, Hurricane111, I dream of horses, IDX, Indon, Inferior
Olive, Interestedperson, Ithacagorges, Jhaochen, Jimp, Jmh649, Joemorethanokman, Jonesey95, K-MUS, Karada, KaterGator, Katharine908, Katpra, Keziah, Khoikhoi, KirkCliff2, Koavf,
Kpstewart, Kwamikagami, Lada Guy, Lanulos, LeaMaimone, Letsgoridebikes, Levydav, Linberry, Lmatt, Loserduh, LuK3, Lucid, Lwnf360, Lyrl, Macaddct1984, Mailer diablo, Mandel, Marcel
Lavender, Mark D Hardy, Marnanel, Mc1998, Mcarrasco03, Memtgs, Metalhead94, Metaphoria, Mfourman, MichaK, Michael Ward, Mikael Hggstrm, Milliemchi, Mogism, Mohsenkazempur,
Motamot, Msvs, MusicNewz, Mykhal, Neonfuzz, NeuroGlossary, Ngubernator, Nihiltres, Nmg20, Nono64, Oaktree b, Oddity-, Ohnoitsjamie, OsamaBinLogin, PStrait, Panscient, Parhamr,
Pashihiko, Patter lake, Patxi lurra, Pentagron, PharmerDan, Pigkeeper, Poindexter Propellerhead, Ptavangar, Pztheron, Quale, RDBrown, Ramius, Rangoon11, Rckites, Rhombus, Riemann Zeta,
Risssa, Rjwilmsi, Rmky87, Ruby Murray, Rushiagr, Rybkovich, Rgis Dcamps, Sandkicker10, SarahEmm, Sburke, Sduibek, SelfishSeahorse, Selket, Siafu, Some guy, Spylab, St3vo, Staciabb,
SteveCrook, SteveLoughran, Stillwaterising, Substantiate, Sun Creator, Supbonkers, Superwawa66, Swelgemoed, Tatsundo h, Tea with toast, Testem, The Anome, TheDude2006, TimBuck2,
Tmallard, Tobycat, TomCat4680, Tomas e, Tomwac, Tonyfaull, Torqueing, Tristanb, Ur0pl, Useight, Vanished user kjdioejh329io3rksdkj, Verloren Hoop, VernoWhitney, Vokesk, Vytal,
W.F.Galway, Watermelon mang, Westewart, Wroughtirony, Xanzzibar, Xavierlives, Xwdl, Yandman, Yid, Ytcracker, , 276 anonymous edits

Image Sources, Licenses and Contributors

file:Lamotrigine2DACS.svg Source: http://en.wikipedia.org/w/index.php?title=File:Lamotrigine2DACS.svg License: Creative Commons Attribution-Sharealike 3.0 Contributors: Fuse809
File:Yes check.svg Source: http://en.wikipedia.org/w/index.php?title=File:Yes_check.svg License: Public Domain Contributors: Anomie
File:X mark.svg Source: http://en.wikipedia.org/w/index.php?title=File:X_mark.svg License: Public Domain Contributors: User:Gmaxwell
File:Lamotrigine 150 MG Oral Tablet.jpg Source: http://en.wikipedia.org/w/index.php?title=File:Lamotrigine_150_MG_Oral_Tablet.jpg License: Public domain Contributors: Unknown
Image:Lamictal200mgTablet.png Source: http://en.wikipedia.org/w/index.php?title=File:Lamictal200mgTablet.png License: Public Domain Contributors: Parhamr
File:Lamotrigine synth.png Source: http://en.wikipedia.org/w/index.php?title=File:Lamotrigine_synth.png License: Creative Commons Attribution-Sharealike 3.0 Contributors: Yid

License
Creative Commons Attribution-Share Alike 3.0
//creativecommons.org/licenses/by-sa/3.0/