Thanks to Ivan Goldberg MD - for permission to use this FAQ

FAQ: Lamotrigine for Depression and/or Mania.

Revised   Jan 14, 2000

   FAQ: Lamotrigine for Depression and/or

          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

6. People with what sorts of mood disorders are candidates for treatment with

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

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

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

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

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

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

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

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

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

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

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

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

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

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


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