Revised
Jan 14, 2000
FAQ: Lamotrigine for Depression and/or
Mania.
NOTE: Lamotrigine is only approved for the
treatment of people with seizures. There are
very few studies that establish the safety
or efficacy of lamotrigine as a treatment
for people with mood disorders and/or Borderline
Personality Disorder. While such studies are
ongoing, most of what is currently known about the
use of lamotrigine for the control of psychiatric
disorders comes from uncontrolled case reports.
1. What
is lamotrigine (Lamictal)?
Lamotrigine
is an anticonvulsant that is chemically unrelated to any other
anticonvulsant
or mood regulating medication.
2. When
was lamotrigine approved for marketing in the USA and for what
indications
may it be promoted?
Lamotrigine
received final approval for marketing in the USDA on 27
December
1994 and is labeled for use as an anticonvulsant.
3. Is a
generic version of lamotrigine available?
There is
no generic lamotrigine as the manufacturer has patent protection.
4. How does
lamotrigine differ from other mood stabilizing drugs?
Lamotrigine
differs from other mood stabilizing drugs in two major ways:
1. Lamotrigine's
frequent effectiveness for patients who have failed to respond
to antidepressants
or mood stabilizers;
2. Lamotrigine's
relatively benign side-effect profile.
5. What,
if anything, uniquely distinguishes lamotrigine from carbamazepine
and valproate?
Lamotrigine
has had been successful in controlling rapid cycling and mixed
bipolar
states in people who have not received adequate relief from
carbamazepine
and/or valproate. It also appears that lamotrigine has
significantly
more antidepressant potency than either carbamazepine or
valproate.
6. People
with what sorts of mood disorders are candidates for treatment with
lamotrigine?
It is too
early to be very specific about which mood disorders are most likely
to respond
to treatment with lamotrigine. There are few published reports on
lamotrigine's
use in psychiatry. Patients with hard-to-treat bipolar syndromes
and with
schizoaffective disorder have been treated more often than patients
with "treatment-resistant"
unipolar disorders. Some people with such hard to
treat unipolar
depressions have been treated with good results. Some patients
diagnosed
with Borderline Personality Disorder, a disorder that many
psychiatrists
believe is a varient of Bipolar Disorder, have responded to
treatment
with lamotrigine.
7. Is lamotrigine
useful for the treatment of acute depressed, manic and mixed
states,
and can it also be used to prevent future episodes of mania and/or
depression?
The initial
use of lamotrigine was to treat people with depressed, manic and
mixed states
that did not respond to existing medications. Some patients are
now being
maintained on lamotrigine on a long term basis in an attempt to
prevent
future episodes. The effectiveness of lamotrigine as a long-term
prophylactic
agent is currently being established.
8. Are there
any laboratory tests that should precede the start of lamotrigine
therapy?
Before lamotrigine
is prescribed the patient should have a thorough medical
evaluation,
including blood and urine tests, to rule out any medical condition,
such as
thyroid disorders, that may cause or exacerbate a mood disorder.
9. How is
treatment with lamotrigine initiated?
In people
not taking carbamazepine or valproate, lamotrigine is usually
initially
prescribed at an initial dose of 25 mg once or twice a day and the
dose increased
by 25 or 50 mg every week or two.
In people
taking valproate the initial dose of lamotrigine is often 12.5 mg/day
and the
drug is increased by 12.5 or 25 mg every two weeks.
In people
taking carbamazepine somewhat larger initial doses and more rapid
increases
in dose are possible.
10. Are
there any special problems prescribing lamotrigine for people taking
lithium,
Tegretol, or Depakote?
An interaction
between lithium and lamotrigine has not been reported.
Carbamazepine
induced enzymes that facilitate the metabolism of
lamotrigine.
Because of that, blood levels of lamotrigine are somewhat lower
in people
taking carbamazepine than in those not taking carbamazepine.
Valproate
has the ability to double plasma levels of lamotrigine. Because of
that, when
lamotrigine is started in people taking valproate, the initial dose
should
be approximately one-half as much as is usually initially prescribed.
11. What
is the usual final dose of lamotrigine?
When used
as an antidepressant or as a mood-stabilizing agent the final dose
of lamotrigine
is most often between 100 and 200 mg/day. Some people
require
doses as high as 400 mg/day to achieve a good antidepressant effect.
Such doses
should avoided in patients taking valproate because of the
pharmacokinetic
effect of valproate that increases plasma levels of
lamotrigine,
and the accompanying increased risk of serious dermatological
side effects.
12. How
long does it take for lamotrigine to 'kick-in?'
While some
people notice the antimanic and antidepressant effects early in
treatment,
others have to take a therapeutic amount of lamotrigine for up to a
month before
being aware of a significant amount of improvement.
13. What
are the side-effects of lamotrigine?
Here is
a listing of lamotrigine's side effects that affected 10% or more of the
711 people
taking the drug during clinical trials and the frequency of those
side effects
in the 419 people treated with placebo in those trials:
Adverse Reactions (%)
Adverse Reaction Lamotrigine
Placebo
Dizziness
38
13
Headache
29
19
Double Vision
28
7
Unsteadiness
22
6
Nausea
19
10
Blurred Vision
16
5
Sleepiness
14
7
Rash
10
5
Vomiting
10
4
Side-effects
are most noticeable the few days after an increase in dose and
then usually
fade.
14. Which
side-effects are severe enough to force people to discontinue
lamotrigine?
The side-effect
of lamotrigine that most often causes the drug to be
discontinued
is a rash. Rashes can be mild, similar to a slight sunburn, or can
be quite
severe resembling a severe case of poison-ivy. The more severe the
rash the
less likely it is that the individual will be able to continue the
medication.
ALL rashes should be reported to the physicians prescribing the
lamotrigine.
A rash is
more likely to develop when the initial doses of lamotrigine are high
or when
lamotrigine is too rapidly started when someone is taking valproate.
It is important
that people taking lamotrigine who develop a rash immediately
contact
their physician as there have been a few deaths in people who have
developed
lamotrigine-induced rashes.
15. Does
lamotrigine have any psychiatric side effects?
Among the
rarely reported side effects of lamotrigine are agitation, anxiety,
concentration
problems, confusion, depression, emotional lability, irritability,
and mania.
16. How
does lamotrigine interact with prescription and over-the-counter
medications?
Only a few
interactions between lamotrigine and other drugs have been
identified.
Lamotrigine increases the plasma level of carbamazepine and its
metabolites.
Carbamazepine lowers the concentration of lamotrigine in the
blood.
Valproate
doubles the plasma level of lamotrigine, and the level of valproate
is decreased
by about 25% in people taking lamotrigine.
Phenobarbital
and primidone lower the plasma level of lamotrigine by about
40%.
Interactions
with other prescription and over-the-counter drugs are not
known at
this time.
17. Is there
an interaction between lamotrigine and alcohol?
Alcohol
may increase the severity of the side-effects of lamotrigine.
18. Is lamotrigine
safe for a woman who is about to become pregnant, pregnant
or nursing
an infant?
Lamotrigine
is has been placed in the FDA pregnancy Category C:
"Animal
studies have shown an adverse effect on the fetus but there are no
adequate
studies in humans; The benefits from the use of the drug in pregnant
women may
be acceptable despite its potential risks . . . ."
19. Is lamotrigine
safe for children and adolescents?
While lamotrigine
has been used with children and young adolescents in other
countries.
In the USA, because of the increased risk of fatal side-effects in the
young,
lamotrigine is only approved for use in those over the age of 16.
20. Can
lamotrigine be used in elderly people?
Older people
seem to handle lamotrigine similarly to younger ones. There is
little
experience using lamotrigine for the treatment of psychiatric disorders
in
the elderly.
21. Do symptoms
develop if lamotrigine is suddenly discontinued?
There are
no specific symptoms that have been described following the abrupt
discontinuation
of lamotrigine, other than the seizures that sometimes follow
the rapid
discontinuation of any anticonvulsant. Only when necessary because
of a serious
side effect, should lamotrigine be suddenly discontinued.
22. Is lamotrigine
toxic if taken in overdose?
Data on
overdoses are scarce. Two individuals who took over 4,000 mg of
lamotrigine
survived without sequelae.
23. Can
lamotrigine be taken along with MAO inhibitors?
Yes, the
combination has been used without any special problems.
24. What
does lamotrigine cost?
As of 3
October 1996, the per tablet cost of lamotrigine, when ordered in lots
of 100
tablets from a well-known mail-order pharmacy in the USA was:
25 mg - $1.94
100 mg - $1.94
150 mg - $2.04
200 mg - $2.14
25. Might
lamotrigine be effective in people who have failed to receive benefit
from other
psychopharmacologic agents?
The major
use of lamotrigine in psychiatry is with people who have mood
disorders
that have not been adequately controlled by other medications.
26. What
are the advantages of lamotrigine?
Lamotrigine
seems to be effective in about two-thirds of people with bipolar
mood disorders
that have not responded to lithium or other mood-stabilizers.
Some people
who have not been able to tolerate any antidepressant because of
switches
to mania or increased speed or intensity of cycling, or because of the
development
of mixed states, have been able to tolerate therapeutic doses of
anti- depressants
when taking lamotrigine.
For most
people, lamotrigine has minimal side effects and can be taken once a
day.
27. What
are the disadvantages of lamotrigine?
As lamotrigine
has only been available for a relatively short time, it was first
marketed
in 1990, there is no information about long term side-effects. As its
use with
people with mood disorders started even more recently, it is not
known is
people who initially do well on lamotrigine continue to do so after
many years
of treatment.
There is
a small chance of a serious, and in some cases life-threatening, rash
developing
in people taking lamotrigine. This side effect is more frequently
seen in
those under the age of 16 than in older persons.
28. Why
should physicians prescribe, and patients take, lamotrigine, when there
are mood
regulating medications that have been available for many years and
which have
been shown to be effective in double-blind placebo-controlled
studies?
There are
two major reasons why physicians prescribe and patients take
lamotrigine
rather than conventional, better established drugs. They are that
not everyone
benefits from treatment with the older, better known drugs, and
that some
patients find the side effects of the established drugs to be
unacceptable.
29. Is lamotrigine
available in countries other than the USA?
Lamotrigine
is currently available in about 60 countries.
30. Has
anything been published on the use of lamotrigine as a therapeutic
agent for
people with mood disorders?
Here are
some bibliographic references on the use of lamotrigine for the
treatment
of people with mood disorders:
Botts SR
& Raskind J
Amer J
Health Syst Pharm 1999, 56, 1939-1944. Gabapentin and lamotrigine
in bipolar
disorder.
Calabrese
JR, Bowden, CL, Sachs GS, et al.
Journal
of Clinical Psychiatry 1999, 60, 79-88.
A double-blind
placebo-controlled study of lamotrigine monotherapy in
outpatients
with bipolar depression.
Calabrese
JR, Bowden CL, Susan L. McElroy SL, et al.
American
Journal of Psychiatry 1999 156: 1019-1023.
Spectrum
of Activity of Lamotrigine in Treatment-Refractory Bipolar
Disorder.
Calabrese
JR, Fatemi SH, Woyshville MJ
American
Journal of Psychiatry 1996, 153, 1236.
Antidepressant
effects of lamotrigine in rapidly-cycling bipolar disorder.
Calabrese
JR, Rappoprt DJ, Shelton MD, et al.
Neuropsychobiolog
1998, 38, 185-191.
Clinical
studies on the use of lamotrigine in bipolar Disorder.
Erfurth
A, Walden J, Grunze H
Neuropsychobiology
1998, 38, 204-205.
Lamotrigine
in the treatment of schizoaffective disorder.
Ettinger
AB, Weisbrot DM, Saracco J, et al.
Epilepsia
1998, 39, 874-877.
Positive
and negative psychotropic effects of lamotrigine in patients with
epilepsy
and mental retardation.
Fatemi SH,
Rappoport DJ, Calabrese JR, Thuras P
Journal
of Clinical Psychiatry 1997, 58, 522-527.
Lamotrigine
in rapid cycling bipolar Disorder.
Ferrier
IN
Neuropsychobiology
1998, 38, 192-197.
Lamotrigine
and gabapentin. Alternatives in the treatment of bipolar
disorder.
Fogelson
DL, Sternbach H
Journal
of Clinical Psychiatry 1997, 58, 271-273.
Lamotrigine
in treatment of refractory bipolar disorder.
Gelenberg
AJ
Biological
Therapies in Psychiatry Newsletter 1997, 20, 21-24.
New anticonvulsants
in bipolar and other psychiatric disorders.
Harmer RM
& Simpson PM
Biological
Psychiatry 1999, 46, 1711-1712. The efficacy of lamotrigine in rapid
cycling
and non-rapid cycling patients with bipolar disorder.
Kaufman
KR & Gerner R
Seizure
1998 7, 163-165.
Lamotrigine
toxicity secondary to sertraline.
Kock RJ
& Yerevanian BI
Pharmacopsyhciatry
1998, 31, 35.
Is lamotrigine
effective for treatment-refractory mania?
Kotler M
& Matar MA
Clinical
Neuropharmacology 1998, 21, 65-67.
Lamotrigine
in the treatment of resistant bipolar disorder.
Kusumakar
V, Yatham LN
American
Journal of Psychiatry 1997, 154, 1171-1172.
Lamotrigine
treatment of rapidly cycling bipolar disorder.
Kusumakar
V, Yatham LN
Psychiatry
Research 1997, 19, 145-148.
An open
study of lamotrigine in refractory bipolar depression.
Labbate
LA & Rubey RN
American
Journal of Psychiatry 1997, 154, 1317.
Lamotrigine
for treatment-refractory bipolar disorder.
Maidment
ID
Annals
of Pharmacotherapy 1999, 33, 864-867. Lamotrigine---An efective mood
stabilizer?
Maltese
TM
American
Journal of Psychiatry 1999, 156, 1833.
Adjunctive
lamtrigine treatment fro major depression.
Martin R,
Kuzniecky R, Ho S, et al.
Neurology
1999, 15, 321-327.
Cognitive
side effects of topiramate, gabapentin, and lamotrigine in healthy
young adults.
Pinto OC
& Akiskal HS Journal of Affective Disorders 1998, 51, 333-343.
Lamotrigine
as a promising approach to borderline personality: An open case
series
without concurrent DSM-IV major mood disorder.
Post RM,
Frye MA, Denicoff KD, et al.
Neuropsychopharmacology
1998, 19, 206-219.
Beyond
lithium in the treatment of bipolar illness.
Post RM,
Leverich GS, Denicoff KD, et al.
Depression
and Anxiety 1997, 5, 275-189.
Alternative
approaches to refractory depression in bipolar illness.
Preda A,
Fazeli A, McKay BG et al.
Journal
of Clinical Psychiatry 1999, 60, 708-709 Lamotrigine as prophylaxis
against
steroid-induced mania.
Rapport
DJ, Calabrese JR, Clegg K et al.
Primary
Psychiatry 1999, 6 (4), 41-42.
Lamotrigine
in unipolar major depression. <
Sporn J,
Sachs G
Journal
of Clinical Psychopharmacology 1997, 17, 185-189.
The anticonvulsant
lamotrigine in treatment-resistant manic-depressive illness.
Walden J,
Hesslinger B
Fortschr
Neurol Psychiat 1996, 63, 320-335.
Value of
old and new anticonvulsants in treatment of psychiatric diseases.
Walden J,
Hesslinger B, van Calker D, Berger M
Pharmacopsychiatry
1996, 29, 193-195.
Adddition
of lamotrigine to valproate may enhance efficacy in the treatment of
bipolar
affective disorder.
Xie X &
Hagan RM
Neuropsychobiology
1998, 38, 119-130.
Cellular
and molecular actions of lamotrigine: Possible mechanisms of efficacy
in bipolar
disorder.
Yathammm
LN, Kusumakar V, Parikh SV, et al.
Canadian
Journal of Psychiatry 1997, 42 (Suppl 2), 87S-91S.
Bipolar
depression: Treatment options.
31. Additions
and corrections?
Please address
additions and corrections to:
Ivan K.
Goldberg, M.D.
1556 Third
Avenue
New York,
NY 10128-3100
Voice: +
212 876 7800
Fax: +
914 362 9267
Email Psydoc@PsyCom.Net
Revised
1/14/00
