Lamotrigine is currently available in about 60 countries. The drug is currently only approved for the treatment of people with seizures. There are no systematic studies that establish the safety or efficacy of lamotrigine as a treatment for people with mood disorders.While such studies are in the planning stages, what is currently known about the use of lamotrigine for the control of mood disorders comes from uncontrolled casereports.
Lamotrigine is an anticonvulsant that is chemically unrelated to any other anticonvulsant or mood regulating medication.Lamotrigine received final approval for marketing in the USDA on 27 December 1994 and is labeled for use as an anticonvulsant. It has full patent protection and a generic version is not available yet.
The two major differences between lamotrigine and other mood
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.
What sorts of mood disorders might be treated 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 just about no published reports on lamotrigine's use in psychiatry. Patients with hard-to-treat bipolar syndromes seem to 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.
The initial use of lamotrigine was to treat 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.
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.
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.
No interaction between lithium and lamotrigine has been reported.
Carbamazepine induces 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 50% as much as is usually initially prescribed.
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.
Side effects and risks
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:
Side-effects are most noticeable the few days after an increase in dose and then usually fade.
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.
Not everyone who develops a rash wile taking lamotrigine goes on to discontinue the drug, and some people with rashes go on to have a good clinical response to continued therapy.
Psychiatric side effects
Among the rarely reported side effects of lamotrigine are agitation, anxiety, concentration problems, confusion, depression, emotional lability, irritability, and mania.
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
Alcohol may increase the severity of the side-effects of lamotrigine.
While lamotrigine has been safely used with children and young adolescents in other countries. In the USA lamotrigine is only approved for use in those over the age of 16
Discontinuing the drug
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.
Safety in Overdose
Data on overdoses are scarce. Two individuals who took over
As of 3 October 1996, 100 tablets of lamotrigine, when ordered from a well-known mail-order pharmacy in the USA cost:
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
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 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.
Smith RM Lamotrigine in
treatment-refractory bipolar disorder.
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