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 12.5 or 25 mg a day and the dose increased by 12.5 or 25 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 mg every ten days or 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 600 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.

Mania or hypomanic induced by lamotrigine responds well to treatment with topiramate.

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 5 March 2000, the per tablet cost of lamotrigine, when ordered in lots of 100 tablets from a well-known mail-order pharmacy (PlanetRx) was:

25 mg - $1.81
100 mg - $1.97
150 mg - $2.02
200 mg - $2.12

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, and other psychiatric, disorders:

Berk, M
European Neuropsychopharmacology, 1999, 9 (Suppl 4) S119-S123..
Lamotrigine and the treatment of mania in bipolar disorder.
[MEDLINE abstract]

Botts SR & Raskind J
Amer J Health Syst Pharm 1999, 56, 1939-1944..
Gabapentin and lamotrigine in bipolar disorder.
[MEDLINE abstract]

Bowden CL Neuropsychopharmacology, 1998, 19, 194-199.
New concepts in mood stabilization: evidence for the effectiveness of valproate and lamotrigine.
[MEDLINE abstract]

Bowden CL, Calabrese JR, McElroy SL et al.
Biological Psychiatry, 1999, 45, 953-958.
The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder.
[MEDLINE abstract]

Bowden CL, Mitchell P, Suppes T
European Neuropsychopharmacology, 1999, 9 (Suppl 4) S113-S117.
Lamotrigine in the treatment of bipolar depression.
[MEDLINE abstract]

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.
[MEDLINE abstract]

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.
[MEDLINE abstract]

Calabrese JR, Fatemi SH, Woyshville MJ
American Journal of Psychiatry 1996, 153, 1236.
Antidepressant effects of lamotrigine in rapidly-cycling bipolar disorder.
[MEDLINE abstract]

Calabrese JR & Gajwani P
American Journal of Psychiatry 2000, 157, 1523.
Lamotrigine and clozapine for bipolar disorder.
[No MEDLINE abstract available]

Calabrese JR, Rappoport DJ, Kimmel SE et al.
European Neuropsychopharmacology, 1999, 9 (Suppl 4) S109-S112.
Controlled trials in bipolar I depression: Focus on switch rates and efficacy.
[No MEDLINE abstract available]

Calabrese JR, Rappoprt DJ, Shelton MD, et al.
Neuropsychobiology 1998, 38, 185-191.
Clinical studies on the use of lamotrigine in Bipolar Disorder.
[MEDLINE abstract]

Calabrese JR, Suppes T Bowder CL et al,>
Journal of Clinical Psychiatry 2000, 61, 841-850.
A double-blind, placebo controlled, prophylaxis study of lamotrigine in rapidly cycling bipolar disorder.
[MEDLINE abstract]

Chaudron LH, Jefferson JW
Journal of Clinical Psychiatry 2000, 61, 79-90.
Mood stabilizers druing breastfeediung: A review.
[MEDLINE abstract]

Devarjan S, Dursun SM
American Journal of Psychiatry, 2000, 157, 1178.
Aggression ain dementia with lamotrigine treatment.
[No MEDLINE abstract available]

Dunn RT, Frye MS, Kimbrell TA, Denicoff KD, Leverich GS, Post RM
Clinical Neuropharmacology, 1998; 21, 215-235..
The efficacy and use of anticonvulsants in mood disorders.
[MEDLINE abstract]

Dursun SM, McIntosh D, Milliken H
Archives of Genral Psychiatry, 1999, 56, 950.
Clozapine plus lamotrigine in treatment-resistant schizophrenia.
[No MEDLINE abstract available]

Engle PM, Heck AM
Annals of Pharmacotherapy, 2000, 34, 258-262.
Laotrigine for the treatment of bipolar disorder.
[MEDLINE abstract]

Erfurth A, Walden J, Grunze H
Neuropsychobiology 1998, 38, 204-205.
Lamotrigine in the treatment of schizoaffective disorder.
[MEDLINE research]

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.
[MEDLINE abstract]

Fatemi SH, Rapport DJ, Calabrese JR, Thuras P
Journal of Clinical Psychiatry 1997, 58, 522-527.
Lamotrigine in rapid cycling bipolar Disorder.
[MEDLINE abstract]

Ferrier IN
Neuropsychobiology 1998, 38, 192-197.
Lamotrigine and gabapentin. Alternatives in the treatment of bipolar disorder.
[MEDLINE abstract]

Fogelson DL, Sternbach H
Journal of Clinical Psychiatry 1997, 58, 271-273.
Lamotrigine in treatment of refractory bipolar disorder.
[No MEDLINE abstract available]

Frye MA, Ketter TA Dunn RT et al.
Journal of Clinical Psychopharmacology 2000, 20, 607-614.
A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders.
[MEDLINE abstract]

Gelenberg AJ
Biological Therapies in Psychiatry Newsletter 1997, 20, 21-24.
New anticonvulsants in bipolar and other psychiatric disorders.

Ghaemi SN, Gaughan S
Harvard Review of Psychiatry 2000, 8, 1-7.
Novel anticonvulsants: A new generation of mood stabilizers?
[MEDLINE abstract]

Hamer RM & Simpson PM
Biological Psychiatry 1999, 46, 1711-1712.
The efficacy of lamotrigine in rapid cycling and non-rapid cycling patients with bipolar disorder.
[MEDLINE abstract]

Hertzberg MA, Butterfield MI, Feldman ME, et al.
Biological Psychiatry, 1999, 45, 1226-1229.
A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder.
[MEDLINE abstract]

Ichim L, Berk M, Brook S
Annals of Clinical Psychiatry, 2000, 12, 5-10.
Lamotrigine compared with lithium in mania: A double blind randomized controlled trial.
[MEDLINE abstract]

Kaufman KR
Annals of Clinical Psychiatry, 1998, 10, :181-184.
Adjunctive tiagabine treatment of psychiatric disorders: three cases.
[MEDLINE abstract]

Kaufman KR & Gerner R
Seizure 1998 7, 163-165.
Lamotrigine toxicity secondary to sertraline.
[MEDLINE abstract]

Keck PE Jr, McElroy SL, Strakowski SM
Journal of Clinical Psychiatry 1998, 59 (Suppl 6),74-81.
Anticonvulsants and antipsychotics in the treatment of bipolar disorder.
[MEDLINE abstract]

Kock RJ & Yerevanian BI
Pharmacopsychiatry 1998, 31, 35.
Is lamotrigine effective for treatment-refractory mania?
[No MEDLINE abstract available]

Kotler M & Matar MA
Clinical Neuropharmacology 1998, 21, 65-67.
Lamotrigine in the treatment of resistant bipolar disorder.
[MEDLINE abstract]

Kusumakar V, Yatham LN
American Journal of Psychiatry 1997, 154, 1171-1172.
Lamotrigine treatment of rapidly cycling bipolar disorder.
[No MEDLINE abstract available]

Kusumakar V, Yatham LN
Psychiatry Research 1997, 19, 145-148.
An open study of lamotrigine in refractory bipolar depression.
[MEDLINE abstract]

Labbate LA & Rubey RN
American Journal of Psychiatry 1997, 154, 1317.
Lamotrigine for treatment-refractory bipolar disorder.
[No MEDLINE abstract available]

Lovell RW
American Journal of Psychiatry, 1999, 156, 980-981.
Mood stabilizer combinations for bipolar disorder.
[No MEDLINE abstract available]

Maidment ID
Annals of Pharmacotherapy 1999, 33, 864-867.
Lamotrigine---An effective mood stabilizer?
[MEDLINE abstract]

Maltese TM
American Journal of Psychiatry 1999, 156, 1833.
Adjunctive lamotrigine treatment for 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.
[MEDLINE abstract]

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.
MEDLINE abstract

Post RM
Schizophrenia Research, 1999, 39, 153-158.
Comparative pharmacology of bipolar disorder and schizophrenia.
[MEDLINE abstract]

Post RM, Denicoff KD, Frye MA, Dunn RT, Leverich GS, Osuch E, Speer A
Neuropsychobiology, 1998, 38, 152-166.
A history of the use of anticonvulsants as mood stabilizers in the last two decades of the 20th century.
[MEDLINE abstract]

Post RM, Frye MA, Denicoff KD, et al.
Neuropsychopharmacology 1998, 19, 206-219.
Beyond lithium in the treatment of bipolar illness.
[MEDLINE abstract]

Post RM, Leverich GS, Denicoff KD, et al.
Depression and Anxiety 1997, 5, 275-189.
Alternative approaches to refractory depression in bipolar illness.
[MEDLINE abstract]

Preda A, Fazeli A, McKay BG et al.
Journal of Clinical Psychiatry 1999, 60, 708-709
Lamotrigine as prophylaxis against steroid-induced mania.
[No MEDLINE abstract available]

Rapport DJ, Calabrese JR, Clegg K et al.
Primary Psychiatry 1999, 6 (4), 41-42.
Lamotrigine in unipolar major depression.
[No MEDLINE abstract available]

Sachs GS, Printz DJ, Kahn DA, et al
Postgraduate Medicine 2000, Spec No 1, 1-104.
The expert consensus guideline series: Medication treatment of Bipolar Disorder 2000.
[ME]DLINE abstract

Sporn J, Sachs G
Journal of Clinical Psychopharmacology 1997, 17, 185-189.
The anticonvulsant lamotrigine in treatment-resistant manic-depressive illness.
[MEDLINE abstract]

Suppes T, Brown ES, McElroy SL, et al.
Journal of Affective Disorders, 1999, 53, 95-98.
Lamotrigine for the treatment of bipolar disorder: A clinical case series.
[MEDLINE abstract]

Walden J, Hesslinger B
Fortschr Neurol Psychiat 1996, 63, 320-335.
Value of old and new anticonvulsants in treatment of psychiatric diseases.
[MEDLINE abstract]

Walden J, Hesslinger B, van Calker D, Berger M.
Pharmacopsychiatry, 1996, 29, 193-195.
Addition of lamotrigine to valproate may enhance efficacy in the treatment of bipolar affective disorder.
[MEDLINE abstract]

Walden J, Normann C, Langosch J et al.
Fortschr Neurol Psychiatr, 1999, 67, 75-80.
Predictors of response to phase prophylactics (mood stabilizers) in bipolar affective disorders.
[MEDLINE abstract]

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.

Walden J, Normann C, Langosch J, Berger M, Grunze H
Neuropsychobiology, 1998, 38, 181-184.
Differential treatment of bipolar disorder with old and new antiepileptic drugs.
[MEDLINE abstract]

Xie X & Hagan RM
Neuropsychobiology 1998, 38, 119-130.
Cellular and molecular actions of lamotrigine: Possible mechanisms of efficacy in bipolar disorder.
[MEDLINE abstract]

Yathammm LN, Kusumakar V, Parikh SV, et al.
Canadian Journal of Psychiatry 1997, 42 (Suppl 2), 87S-91S.
Bipolar depression: Treatment options.
[MEDLINE abstract]

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: + 212-876-7821

Email Psydoc@PsyCom.Net

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