Dr. Bob's Psychopharmacology Tips

Interactions with lamotrigine

Date: 2 Feb 1996 09:49:50 -0500
From: "Mike Johnson" <mike_johnson@smtpgw.musc.edu>
Subject: Interactions with valproic acid

I haven't used it with valproic acid but there has been a lot written about this combination and it is addressed in the PDR. The bottom line is that you get an increase in Lamictal level when you add valproic acid and a decrease in valproic acid level when you add Lamictal.

Date: 7 Feb 1996 16:06:12 -0500
From: "Mike Johnson" <mike_johnson@smtpgw.musc.edu>
Subject: Interactions with other anticonvulsants

By itself, lamotrigine has a half life of 25-35 hours and once a day should be fine. With certain enzyme inducing drugs such as phenytoin (Dilantin) or carbamazepine (Tegretol), the half life is half of that and so bid dosing is used.

Date: Wed, 24 Apr 1996 00:48:49 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Interactions with valproic acid and carbamazepine

There are some pharmacokinetic interactions of lamotrigine that should be kept in mind. Carbamazepine levels are increased by lamotrigine, and valproate levels are decreased somewhat by lamotrigine.

Date: Sun, 28 Apr 1996 12:47:47 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Interactions with valproic acid

At 07:30 AM 4/28/96 -0400, gottlieb@crocker.com wrote:

You mention that you begin with a dose of 25 mg h.s. with patients not taking carbamazepine. How about patients on valproate? The PDR suggests that one begins with a dose of 25 mg every other day for two weeks.

Date: Fri, 18 Oct 1996 17:08:15 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Interactions with valproic acid

As pointed out in my FAQ valproate is an issue as it has the capacity to double lamotrigine plasma levels, making the patient more susceptable to the development of a rash.

Date: Mon, 10 Feb 1997 17:33:02 -0800
From: Peter Lucas <lucas.p@ghc.org>
Subject: Interactions with valproic acid and carbamazepine

Any thoughts on adding lamotrigine to valproic acid and carbamazepine?

--S Karp

Anecdotally, I had a patient on valproic acid (at a stable dose), lithium, and clonazepam to which I then added lamotrigine. At around 150 mg/day, she developed stuttering, a tremor, and diplopia which abated when the dose of valproic acid was decreased but the lamotrigine dose held constant.

From: HRudMD@AOL.COM (Howard Rudominer, M.D.)
Date: Mon, 10 Feb 1997 21:56:46 -0500 (EST)
Subject: Interactions with valproic acid

When adding lamotrigine to valproic acid you must take particular care since valproic acid raises lamotrigine levels two-fold. You can begin with 25 mg bid but must raise it only by 12.5 mg, not the usual 25 mg, per week, otherwise you will be increasing the risk of developing a rash or the much more serious and sometimes life-threatening Stevens-Johnson syndrome.

From: dreise02@interserv.com (David E. Reiser, M.D.)
Date: Tue, 11 Feb 1997 13:12:38 -0800
Subject: Interactions with valproic acid and carbamazepine

It is true that lamotrigine added to valproate too rapidly can be a problem since valproate raises lamotrigine levels two-fold. Hence, the wisdom of going up by 12.5 mg per week instead of the usual 25 mg per week.

The safety of starting off the first week at 50 mg of lamotrigine was news to me. I have been starting at 12.5 mg and going up by that amount weekly. By my calculations, if commencing with 25 mg bid were indeed safe, that would save three weeks.

Carbamazepine also affects the metabolism of lamotrigine, but in the oppositie direction from valproate. It tends to increase the rapidity of lamotrigine's metabolism and shorten its effective half-life. Hence, when a patient is on carbamazepine, it may be necessary to give the drug twice a day instead of just at hs, and, ultimately, the lamotrigine may have to be titrated past the 100 to 200 mg that most of us are getting accustomed to.

Date: Sun, 09 Mar 1997 11:11:43 -0500
From: Ivan Goldberg <Psydoc@PsyCom.Net>
Subject: Interactions with valproic acid

There is a pharmacokinetic interaction between valproate and lamotrigine that results in a higher than usual plasma levels of the latter. If, in patients taking valproate, lamotrigine is started at a dose of 12.5 mg a day, or every other day, and increased very slowly, lamotrigine can be administered without causing rashes. In people taking valproate, the final dose of lamotrigine is often 75-100 mg/day.

Date: Wed, 23 Apr 1997 13:26:31 -0400
From: Mike Johnson <JohnsoMR@smtpgw2.musc.edu>
Subject: Interactions with other anticonvulsants

The estimate of a 1/1000 risk of "potentially dangerous" rash is based on 3 patients of 3000 who developed a rash identified by the clinician as "Stevens-Johnson". All occurred in trials where lamotrigine was being used in combination with Depakote (divalproex), Tegretol (carbamazepine), or Dilantin (phenytoin).

In children there are data to suggest a more concerning problem. The rate of Stevens-Johnson in clinical trials has been 1 in 500. There have been 220 children and adolescents treated with monotherapy in clinical trials and 2 have had a "serious rash" -- i.e., a rash requiring hospitalization. This leaves a rate of monotherapy "serious rash" of 1/110 in children and adolescents.

Combination therapy with Depakote or Tegretol in children and adolescents should probably be avoided.

Date: Thu, 05 Jun 1997 20:28:44
From: "Richard David Brand, MD" <rdb@icu.com>
Subject: Interaction with carbamazepine

In: Dubovsky SL, Buzan RD. Novel alternatives and supplements to lithium and anticonvulsants for bipolar affective disorder. [Review] [221 refs] Journal of Clinical Psychiatry. 58 (5): 224-42; quiz 243-4, 1997 May:

They say "lamotrigine may have a pharmacodynamic interaction with carbamazepine leading to neurotoxicity" and reference:

Messenheimer JA. Lamotrigine. [Review] [64 refs] Epilepsia. 36 Suppl 2: S87-94, 1995.

Date: Fri, 03 Oct 1997 23:34:07 +0200
From: Leigh Janet <leigh@lia.net>
Subject: Interactions with lamotrigine

Some patients on combination therapy have reported increased appetite.

I have noted a few cases of transient increases in liver transaminases, so I do tend to monitor these liver enzymes (especially when using lamotrigine in combination with other drugs known to raise liver enzymes).

Recently I have noted 3 patients to have what appear to be cardiac "symptoms" -- breathlessness, reduced effort tolerance, dizziness -- when adding lamotrigine to existing antidepressants. One patient was on phenelzine (a stable dose for years) and developed marked postural hypotension and dizziness when the lamotrigine dose reached 125 mg. ECG showed prolonged PR and borderline lengthening of QT. A similar problem appeared in another patient stable on clomipramine when I changed to lamotrigine for seizure prophylaxis (from valproate). With valproate the patient was stable cardiac-wise on clomipramine 275 mg/day, but with lamotrigine 150 mg/day, the patient developed incipient tricyclic cardiotoxicity (ECG changes, despite insignificant change in tricyclic blood level). The cardiologist was unable to detect any problem apart from seeming TCA related changes on the ECG. Both patients recovered completely when lamotrigine was withdrawn.

Date: Fri, 07 Nov 1997 05:51:46 -0500
From: Ivan Goldberg <Psydoc@PsyCom.Net>
Subject: Interactions with MAOIs

Lamotrigine and MAOIs may be safely combined. I have trreated many patients with the combination.

Date: Tue, 18 Nov 1997 21:39:33 -0500 (EST)
From: Adele Tutter <jhudak@pobox.com>
Subject: Possible interactions with lithium

I did see this very unexpected response in a 14 year old bipolar with rapid cycling. He had profound short-memory disturbance starting at 25 mg bid and worse at 100 mg daily -- he couldn't go higher than that becuase he was so impaired: he could barely function without constant supervision and was even sent home from a sheltered class as unable to concentrate on anything. But he was not agitated, just perplexed about his inability to think clearly. He had had no similar reaction on other anticonvulsants. He was also on lithum maintenace, risperidone, and chlorpromazine 25-50 mg PRN. We tried to wait it out for 6 weeks, but it did not clear, so we quit.

Date: Wed, 19 Nov 1997 00:03:11 -0500
From: William Braden <braden@brown.edu>
Subject: Possible interactions with lithium

I recently had 2 cases suggesting additive toxicity.

1. A man, in his 30s, bipolar depressed. On lamotrigine 150 mg plus his long-standing dose of lithium, his lithium level essentially unchanged at 0.7, he began stuttering and shaking, felt spacy, and having fits of weeping. With lowered dosages of both meds he cleared (he was on carbamazepine also).

2. A woman, in her 50s, bipolar depressed. On lamotrigine 50 mg plus her long-standing dose of lithium, her lithium level 0.6, she began stuttering. This went on for months, then she was hospitalized for acute confusion, with no satisfactory diagnosis made. She's doing well now on 100 mg of lamotrigine and no lithium.

Date: Tue, 25 Nov 1997 22:06:51 -0500 (EST)
From: Adele Tutter <jhudak@pobox.com>
Subject: Possible interactions with lithium

An update: My patient, a bona fide rapid cycling bipolar woman, sounded a lot like Bill's first case except that she didn't stutter. (However, her voice did develop a shaky quaver.) She had minor memory problems on lithium alone. Lamictal, then Nardil, were added for cycling and depression. A month or so after raising her Lamictal to 150, she got more depressed, with weepiness; she was on lithium 1200 (level 1.1), Lamictal 150, Nardil 45, and T-4 0.225. I increased the Nardil to 60, and she got worse, labile and confused, really disoriented. Lowering the Nardil didn't seem to help. After reading about Bill and Jane's cases, I cut her lithium in half and within four days she is much less labile, less shaky and mentally much clearer. The common denominator in these cases seems like a delirium associated with the lithium and Lamictal combination.

Many thanks!

From: Burns Woodward, M.D. <WoodwardB1@aol.com>
Date: Sun, 7 Dec 1997 16:00:02 EST
Subject: Possible interactions with lithium

A number of years ago there was an article on "neurotoxicity" with the combination of lithium and carbamazepine. I have seen it several times -- cognitive disturbance and impaired motor coordination, much worse than with either drug alone. It is manageable by titrating the dose of the second drug upward very slowly and carefully.

I have not seen and am not aware of such an interaction between lithium and valproate. It is interesting that this may be occurring with lamotrigine.

Date: Fri, 27 Feb 1998 23:38:36 -0600
Subject: Interactions with gabapentin
From: abartists.lex@juno.com (A J Cohen)

I know of no problem with gabapentin and lamotrigine.

Date: Sat, 28 Feb 1998 09:55:52 -0500
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Interactions with gabapentin

There does not seem to be a pharmacokinetic interaction between gabapentin and lamotrigine.

Date: Tue, 31 Mar 1998 00:04:06 -0500
From: William Braden <braden@brown.edu>
Subject: Interactions with carbamazepine

Burns Woodward wrote:

I did a PubMed search and found a couple of articles indicating that lamotrigine does not increase levels of carbamazepine or its metabolites.

Actually the package insert is a little confusing. Lamotrigine is only approved by the FDA as an add-on to other antiepileptic drugs, so the dosing is given for various combinations of antiepileptic drugs but not for lamotrigine alone.

The package insert confirms that lamotrigine doesn't influence blood levels of carbamazepine.

Date: Wed, 24 Jun 1998 20:46:00 -0600
From: "Cheryl A. Clark, MD" <cclarkmd@earthlink.net>
Subject: Possible interactions with tranylcypromine

I have had one patient on Lamictal and Parnate (tranylcypromine) quite successfully for about 8 months until she developed a "lupus-like syndrome" and had to stop the Lamictal.

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