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Date: Mon, 27 Nov 1995 04:35:11 -0800 (PST)
From: Ivan Goldberg <psydoc@psycom.net>
Subject: New anticonvulsants for bipolar disorder
There have been case reports to this list and the Staff Lounge that felbamate, gabapentin, and lamotrigine have been used to control mood cycling in individuals with bipolar disorder.
Date: Mon, 27 Nov 1995 09:22:23 -0500 (EST)
From: Bill Boyer <wboyer@emory.edu>
Subject: Lamotrigine for bipolar disorder
I can only speak to lamotrigine. Apparently it is showing considerable promise in bipolars, even rapid-cyclers, in open trials and Glaxo Wellcome thinks enough of it to fund clinical studies.
Date: 2 Feb 1996 09:49:50 -0500
From: "Mike Johnson" <mike_johnson@smtpgw.musc.edu>
Subject: Lamotrigine for bipolar disorder
I do not know of any published data on the use of lamotrigine (Lamictal) in bipolar disorder, but there are some reports in preparation and clinical trials are just getting started. I have used Lamictal as a single agent to treat patients with bipolar disorder who have not responded to or could not tolerate the usual mood stabilizers. I have seen a very low rate of side effects, it is apparently safe in overdose, and I have so far seen several good responses. 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 lowest dose of Lamictal is 25 mg and I have been starting with one in the evening and increasing by 25 mg every 5 to 7 days. If you go up too fast there is an increased risk of developing a rash.
Date: Sun, 4 Feb 1996 17:28:08 -0800
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: New anticonvulsants for bipolar disorder
I would start with lamotrigine as there is more experience with its use in people with bipolar disorder. Felbamate should be tried last because of the potential for serious hematological side effects.
Date: 7 Feb 1996 16:06:12 -0500
From: "Mike Johnson" <mike_johnson@smtpgw.musc.edu>
Subject: Lamotrigine for bipolar disorder
In response to questions about dosing and so forth, there is no established effective dose range and serum levels are not currently used or available. We will be doing a study comparing 50 and 200 mg doses. My experience so far has been that 50 mg is sometimes helpful but that higher doses are sometimes needed.
The dosing schedule depends on what other drugs are being used concurrently. 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.
One other thing: data from the seizure trials suggested that the dose should not be titrated up faster than 50 mg every two weeks -- this minimized the risk of rash.
Date: Tue, 23 Apr 1996 07:55:44 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Lamotrigine for bipolar disorder
Antidepressants that once induced mood-cycling do not do so when administered along with lamotrigine (Lamictal). It seems that this newly released (in the USA) anticonvulsant will play at least as large a role as valproate in the treatment of pholks with bipolar mood disorders.
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Lamotrigine for bipolar disorder
I have found lamotrigine often to be effective in the treatment of patients:
Lamotrigine is tolerated best when introduced slowly. A rash that may necessitate discontinuation is more likely to develop in patients started on too high a dose or in those patients in whom the dose is increased too rapidly.
There are some pharmacokinetic interactions of lamotrigine that should be kept in mind.
In a patient not taking carbamazepine I usually initiate treatment with 25 mg h.s. and increase the dose by 25 mg per day per week until a dose of 100 mg h.s. is reached. If a response is not seen after one week at this dose, I then increase the dose to 200 mg h.s. With a few patients I have had to go higher.
Most impressive have been the results with rapidly cycling bipolar individuals who have not responded to valproate and/or carbamazepine. Also, the protection against antidepressant-induced cycling and mania has been very useful.
I have also had good experiences using lamotrigine to treat the mood lability of so called "borderline" patients.
There are no double-blind placebo-controlled studies to confirm the observations above.
See also: general information on lamotrigine and its use in seizure disorders.
From: "David A. Kahn" <kahndav@cpmc3.cpmc.columbia.edu>
Date: Thu, 25 Apr 1996 08:31:46 EDT
Subject: Lamotrigine for bipolar disorder
Charles Bowden has reported worthwhile preliminary results with lamotrigine in bipolar patients, N = about 50, not published yet... The manufacturer reportedly is somewhat concerned about the high incidence of rashes and isn't sure if they are comfortable investigating it for a new use until there is more post-marketing data.
Date: Sat, 20 Jul 1996 19:57:10 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Lamotrigine for bipolar disorder
Those who are asked for a reference regarding the innovative use of lamotrigine with patients who have treatment-resistant mood disorders may find Lamotrigine in Treatment-Refractory Bipolar Disorder useful.
Date: Wed, 24 Jul 1996 12:16:04 -0400 (EDT)
From: Bill Boyer <wboyer@emory.edu>
Subject: Lamotrigine for bipolar disorder
"Start low and go slow" to minimize the risk of rash or other significant adverse events.
From: dreiser@interserv.com (David E. Reiser, M.D.)
Date: Wed, 28 Aug 1996 04:49:52 -0700
Subject: Lamotrigine for bipolar disorder
On 27 Aug 1996, Troy Caldwell wrote:
I am happy to report that my first trial of lamotrigine, in a bipolar lady who was unresponsive to all the usual remedies, has resulted in the patient feeling better than she has in years. I'm not convinced this is not just a phase of her cycle yet but am encouraged.I have started five patients on lamotrigine at this point. Four seem to be improving mildly to significantly. All four had been treatment-refractory rapid cycling people and completely unresponsive to ADKH (All Drugs Known to Humankind). Three had had disappointing responses to ECT as well. All of these patients cycled continuously.
Date: Wed, 28 Aug 1996 11:46:26 -0400 (EDT)
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Lamotrigine for bipolar disorder
If there is no response to a couple of weeks at 400 mg/day I consider lamotrigine to be ineffective -- although I would not be surprised if someone were able to show that there were such pholks as "late responders."
From: JoelSHoffm@aol.com (Joel S Hoffman)
Date: Mon, 21 Oct 1996 08:33:51 -0400
Subject: Lamotrigine for bipolar disorder
I am finding lamotrigine very useful in working with hard to treat affective illness but the comment that it is useful for 2/3 of patients either unresponsive to, or unable to tolerate other mood stabilizer meds may be overstating what it can do.
Date: Mon, 21 Oct 1996 20:40:37 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Lamotrigine for bipolar disorder
You may be right, but so far about 2 of 3 hard-to-treat pts to whom I give Lamictal do very well.
Date: Mon, 09 Dec 1996 11:29:43 -0500
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Lamotrigine for bipolar disorder
Lamotrigine has a good deal of antidepressant activity.
For more info check-out my FAQ.
From: "Mark I. Levy, M.D." <milevy@itsa.ucsf.edu>
Subject: Lamotrigine for bipolar disorder
Date: Fri, 30 May 1997 23:36:34 -0700
I too am relying increasingly on lamotrigine. It is my first line mood stabilization choice. I have frequently reduced antidepressant levels from much higher with concomitant lamotrigine (e.g,. Prozac 60 mg to 10-20 mg, bupropion 400 mg to 200 mg, Parnate 50 mg to 20 mg, etc.).
It is apparent that lamotrigine has none of the sedating side effects of Depakote (divalproex) and in my "n" of about 8 cases has some direct antidepressant effect.
Date: Tue, 23 Sep 1997 23:57:47 -0400
From: William Braden <braden@brown.edu>
Subject: Lamotrigine for bipolar disorder
Here is some data on lamotrigine from my practice. I have follow-up on 31 patients. 9 of them stopped it because of side effects.
| N | Diagnosis |
|---|---|
| 8 | Bipolar I |
| 8 | Bipolar II |
| 14 | Depression (with and without "bipolar features") |
| 1 | Depression with complex partial seizures |
| 31 | Total |
| N | Therapeutic effect in those left over |
|---|---|
| 7 | Very helpful |
| 8 | Somewhat or possibly helpful |
| 7* | Not helpful |
| 22 | Total |
| * includes a patient with depression with complex partial seizures whose seizures improved but mood did not | |
Date: Fri, 03 Oct 1997 23:34:07 +0200
From: Leigh Janet <leigh@lia.net>
Subject: Lamotrigine for bipolar disorder
I have used lamotrigine, gabapentin and topiramate extensively over the past 2 years. Most patients managed with these agents suffer from bipolar spectrum disorders, and many also meet diagnostic criteria for borderline personality disorder. Many patients have explosive irritable temperaments, and most have experienced massive interpersonal difficulties, especially in their domestic lives.
The usual presentation is treatment refractory mood disorder, mostly depression, but many have, in addition, histories of significant anxiety disorders (usually OCD, panic disorder with or without agoraphobia, or multiple social phobias), substance abuse, prior hypomanic episodes, and brain trauma, and many have abnormal EEGs, especially temporal lobe electrical abnormalities.
Some (female) patients have post partum onset or worsening of their disorders, and many have thyroid anomalies. All patients have been extensively worked up from a medical perspective at some stage. All patients have extensive prior psychiatric treatment histories, with failure to respond to multiple prior interventions.
Common features almost inevitably include rapid shifts in mood, from depression to euthymia, from hypomania to depression, etc., and many have developed ultra-rapid mood cycling, even patients that were maintained well for years on antidepressants or lithium. Reversed vegetative features are common in many (but not all) episodes -- even within individual patients' histories.
Many patients are notably dysphoric during their mood episodes.
All patients are fully informed about the current status of these drugs as far as their use in mood disorders is concerned. Generally I am dealing with a well informed population, but many are prepared to undergo management with novel treatments as they have failed to respond to multiple other treatments. I give each patient a detailed exposition of the side effects of each drug. All patients are able to give informed consent.
Experience with Lamotrigine
Because of the well described dangers with lamotrigine, I initially used lamotrigine almost exclusively as monotherapy.
I have about 1/4 of patients initiated on lamotrigine convert to stable good outcome -- not bad results really in the context of the cases that I treat, where no drug (over time) generates a greater than 25% response rate, except tranylcypromine, which I use in highly selected cases.
I have tended to avoid combining lamotrigine with valproate, but have combined lamotrigine with lithium, carbamazepine, gabapentin, topiramate, and with antidepressants, especially SSRIs and MAOIs. For the last year or so I have tended to combine lamotrigine more frequently with low(ish) doses of antipsychotics, especially olanzapine, risperidone and clozapine.
My sense is that lamotrigine may offer a long term alternative to lithium and valproate in patients with bipolar spectrum disorders. I have a number of patients stable and well at twelve months on lamotrigine monotherapy. Yet, I worry about the lamotrigine patients because of the dangers of the drug.
Recently I have increased numbers of patients on combined lamotrigine and gabapentin.
Date: Thu, 23 Oct 1997 10:12:39 -0400
From: Mike Johnson <johnsomr@smtpgw2.musc.edu>
Subject: Lamotrigine for adolescents
I have used lamotrigine sucessfully with several adolescents with no significant problems. It worked well in all cases. The combination of a good side effect profile and being able to take it once daily really makes it more palatable to adolescents. The absence of toxicity in overdose is also appealing.
It is true that the risk of rash is higher in children and adolescents, although it isn't clear to me that this isn't simply a problem with the rate of dose titration, as seems to be true with adults. It may be that adolescents should be started at half the usual dose (ie, at 12.5 mg) and titrated up from there.
I would certainly avoid using it with divalproex under any circumstance as this will increase the risk of rash.
I have never heard of a child or adolescent dying from lamotrigine complications. Their warning of two deaths per 1,000 is not correct. It may have been they meant two incidences of a "potentially" life threating rash. All the deaths I am aware of have been the result of toxic epidermal necrolysis in adults who were on combination therapy and were experiencing serious medical illnesses at the same time. There has never, to my knowledge, been a fatality from lamotrigine used as a single agent (in fact it isn't clear that there has ever been a case of Stevens-Johnson syndrome from monotherapy).
Date: Tue, 28 Oct 1997 04:42:41 -0500
From: Stephen Bazire <SBazire@compuserve.com>
Subject: Lamotrigine for bipolar disorder
Our web site has a page about lamotrigine for patients.
This topic is indexed under the following subjects:
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Dr. Bob is Robert Hsiung, MD,
dr-bob@uchicago.edu
URL: http://www.dr-bob.org/tips/split/Lamotrigine-bipolar.html
Original tips copyright 1994-98 original authors.
Web page copyright 1995-98 Robert Hsiung.