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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, 13 May 1996 22:29:15 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Gapapentin for bipolar and borderline personality disorders
There are no studies showing the psychiatric effectiveness of gabapentin. I have used it in patients with borderline personality disorder + bipolar disorder, often combining it with high dose fluoxetine or venlafaxine.
Gabapentin is safe in overdose.
Date: Tue, 09 Jul 1996 00:00:07 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Gapapentin for bipolar disorder
I have been using gabapentin with people with so called "treatment-resistant" bipolar disorder ... especially with individuals who have rapid cycling or mixed states. Most of the people for whom I have prescribed it have not done well on various combinations of lithium, carbamazepine, valproate, and lamotrigine. In this population I would estimate the success rate as around 60-70%. While I have not treated any of the old-old with gabapentin, some of my patients have been over 65.
Date: Tue, 23 Jul 1996 01:15:21 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Gapapentin for bipolar disorder
I have used gabapentin in a dozen or so pholks with mixed or rapidly cycling bipolar disorder not responsive to other meds. It has been useful useful about half the time.
From: cprice@mem.po.com (Charles Sowle Price, MD)
Date: Thu, 29 Aug 1996 01:25:30 -0400
Subject: Gabapentin for bipolar disorder
I wrote to Parke-Davis inquiring about gabapentin in Bipolar Disorder. They responded that they are currently enrolling 100 patients in 13 centers on it as an adjunct treatment with valproate or lithium. The starting dose is 600 mg/day and an increase is not to exceed 600 mg in a single day. They state that doses of 1800 to 2400 mg/day have been well tolerated. Additional information can be obtained from Parke-Davis at (800) 223-0432.
Date: Thu, 21 Nov 1996 11:43:03
From: caclark@gnn.com (cheryl a. clark)
Subject: Gabapentin for bipolar disorder
I have a very small number of patients (2) on gabapentin. One, a woman in her 30s, has an ultra rapid cycling bipolar disorder that began after a pregnancy. Treatment with lithium, valproate, carbamazepine, and various combinations of those drugs was unsuccessful. She began having acute and then maintenance ECT about 1.5 years ago, which helped significantly, but she could never wean from ECT and was only stable for about 2-3 weeks at a time with ECT... Then she decided to try gabapentin and has now been much more stable for the last 15 weeks with no ECT. She is thrilled with the response, sleeps well, has only a few side effects such as sedation that can be worse on some days than others and an odd experience she calls "brain shut down" that happens with some doses of gabapentin. She is now on 300 mgs t.i.d. More than that sedates her throughout the day, less allows breakthrough cycling. The best news is that her cognitive difficulties are now starting to improve without ECT every 2-3 weeks.
For my N of 2, I am pleased with gabapentin and feel more comfortable prescribing it in rapidly titrated doses than lamotrigine.
Date: Wed, 8 Jan 1997 20:41:31 -0800 (PST)
From: "Sanford R. Pepper" <peppers@itsa.ucsf.edu>
Subject: Gabapentin for bipolar disorder
I have now used gabapentin a half dozen times, and it has truly shown itself to be a remarkable medication. Each patient had a good valproic acid trial and looked a lot more stable on gabapentin. Doses used have ended up around 600 tid.
Also I have used it to aid in sleep problems with doses in the 100-300 mg range.
Date: Thu, 10 Apr 1997 02:23:42 -0400
From: Ivan Goldberg <Psydoc@PsyCom.Net>
Subject: Gabapentin for bipolar disorder
I usually start gabapentin at 100 or 300 mg hs and increase the dose by that same amount every 3-5 days. When the people I start with 100 mg get up to 300 mg tid, I then increase them in increments of 300 mg every 5 days.
I have started doing some plasma levels. It looks as if there are some patients who have wonderful responses to plasma levels at below the "therapeutic range" specified by the lab.
Date: Fri, 11 Apr 1997 09:29:20 -0400
From: Ivan Goldberg <Psydoc@PsyCom.Net>
Subject: Gabapentin for bipolar disorder
While I often find a good response to gabapentin at 2700 mg/day or less, there have been some patients who have required 3600 mg/day to respond.
From: HRudMD@aol.com (Howard Rudominer)
Date: Sat, 12 Apr 1997 13:36:38 -0400 (EDT)
Subject: Gabapentin for bipolar disorder
With gabapentin, I start patients on 300 mg qhs and quickly within days get up to 300 mg tid and see how they do. I think the average dose is around 1800 mg.
Date: Thu, 17 Apr 1997 22:20:22 -0400
From: Ivan Goldberg <Psydoc@PsyCom.Net>
Subject: Gabapentin for bipolar disorder
When using gabapentin for the control of mixed states or rapid-cycling bipolar disorder the dose may have to be increased to 900 mg t.i.d. or q.i.d for a full effect to be seen.
Date: Sun, 15 Jun 1997 22:37:07 -0400
From: Jim Recht <jimrecht@world.std.com>
Subject: Gabapentin for bipolar and borderline personality disorders
I'd like briefly to relate a case of a young (about 30) woman with severe borderline personality disorder, an eating disorder, and symptoms suggestive of bipolar or bipolar II. One of her most troublesome symptoms (to herself as well as to others) has been chronic, nearly continuous suicidal ideation. After unsuccessful trials of three mood stabilizers and several ("countless" in her view) antidepressants, she agreed to a trial of gabapentin 300 mg bid. Within one week, she reported that she'd gone an entire day without suicidal ideation -- this for the first time in several years. She was less irritable and her energy level was improved. I wanted to pass this along as I found it so impressive.
From: cprice@mem.po.com (Charles Sowle Price, MD)
Date: Sun, 15 Jun 1997 23:28:01 -0400
Subject: Gabapentin for bipolar and borderline personality disorders
I have a borderline patient on 1500 mg of gabapentin. She had been chronically suicidal. I thought I might have picked up some bipolarity in her (though difficult for me to tell in a borderline) and added gabapentin to her regimen several months ago. With very good results, much as you described.
From: MZSHRINK@aol.com (Victoria Codispoti, M.D.)
Date: Tue, 17 Jun 1997 23:38:30 -0400 (EDT)
Subject: Gabapentin for bipolar disorder
My n = 2, but gabapentin has worked wonders for them. One woman in her 40s had been on every antidepresssant and mood stabilizer the FDA approved and was constantly suicidal and anxious. On gabapentin and high dose bupropion and trazodone (yes, you read correctly) she is somewhat improved and not calling me in desperation.
The other patient had peripheral neuropathy and depression, and when I increased his gabapentin because of his depression, both his depression and neuropathy improved! He is also on low dose nortryptiline...
From: RMRich1@aol.com (Roberta Richardson, M.D.)
Date: Fri, 20 Jun 1997 16:51:06 -0400 (EDT)
Subject: Gabapentin for bipolar disorder
I recently prescribed gabapentin to a woman with chronic, treatment resistant depression and borderline-type behavior and emotional style. What happened was, the cranky, over-reactive, aggressive, stormy symptoms quickly resolved -- leaving an alarmingly deep, more typical severe major depression! When I stopped the gabapentin, she had a few days of very rapid cycling. Helped me clarify the diagnosis!
Subject: Gabapentin for bipolar disorder
Date: Tue, 24 Jun 97 19:46:56 +0100
From: Michael Levin <mntcastle@earthlink.net>
Here is an abstract from the recent APA meeting in San Diego:
Purpose: An open study was performed to determine if the use of gabapentin, monotherapy or in addition to other psychiatric medications, could be effective in improving concentration, mood, sleep disorder, and appetite in patients with bipolar affective disorder.
Methods: Retrospective analysis of medical records of 47 patients diagnosed with bipolar affective disorder, with or without concomitant diagnosis of OCD or panic disorder was accomplished. Patients had been on gabapentin therapy for at least six months. Patients were asked during monthly medication checks to comment whether concentration, mood, sleep, appetite, or irritability had improved, worsened, or stayed the same over the preceding month. Gabapentin therapy was titrated to an effective dose range from 600 to 4800 mg/day with a mean of 1500 mg/day.
Results: The majority of patients reported improvement. We were able to eliminate one or more concomitant medications for a number of patients. The majority of patients reported no side effects and there were no reports of serious adverse events.
Conclusion: Gabapentin is a safe, effective therapy when used alone or in combination to treat patients with bipolar affective disorder. The need for double-blind, placebo-controlled trials exists.
Subject: Gabapentin for bipolar disorder
Date: Tue, 24 Jun 97 19:54:45 +0100
From: Michael Levin <mntcastle@earthlink.net>
More:
Summary: There is a pressing need for new management options in mood disorders as many patients are commonly seen with illness refractory to conventional mood stabilization treatments, either alone and in various combinations. In this paper, we discuss the emerging evidence that lamotrigine and gabapentin, two drugs recently approved as adjunctive treatment for partial epilepsy, hold promise as adjunctive or alternative therapies for patients with mood disorder.
After a double-blind, two-week washout period,patients with refractory mood disorders received, in a randomized double-blind trial, either gabapentin monotherapy, lamotrigine monotherapy, or placebo for six weeks with two subsequent crossovers so that each individual would receive all three blinded agents. As disease polarity may influence response, both unipolar and bipolar mood disorder patients were studied.
The primary outcome measures were the Clinical Global Impression (CGI-BP), and Life Chart Methodology (LCM). The preliminary monotherapy response data to date (based on a CGI-BP rating of moderate or marked improvement) for lamotrigine was 53% and for gabapentin was 43%. Further response data by diagnostic subtype will be presented.
This preliminary evidence of clinical efficacy suggests that lamotrigine and gabapentin may ultimately become important additions to the mood disorder pharmacopoeia.
The treatment of bipolar depression is not well established. Gabapentin has been suggested to have mood stabilizing and possibly antidepressant properties. Outpatients who met DSM-IV criteria for bipolar disorder type I or II, currently depressed (HamD > 16), and who were refractory to standard mood stabilizers, received gabapentin orally (twice or three times daily for six weeks) in an open fashion alone or in combination with standard mood stabilizers. The mean ± SD age of the subjects (5 men and 10 women) was 39 ± 9 years. The mean dose was 1050 ± 640 mg. There was a significant reduction (T = 3.00, df14, p = 0.01) comparing the six-week and baseline HamD scores in these subjects. Eight subjects (53%) responded (3 marked i.e. > 50% reduction in HamD; 5 partial i.e. 25% to 50% reduction in HamD). In only one subject was the HamD score higher after six weeks of treatment and this same subject was the only subject to experience hypomanic symptoms (Young Mania Scale score of 13) during the trial. This is one of the first reports to provide preliminary evidence for the acute antidepressant efficacy of gabapentin. This case series requires confirmation and extension in larger-scale controlled trials.
From: cprice@mem.po.com (Charles Sowle Price, MD)
Date: Tue, 8 Jul 1997 02:22:02 -0400
Subject: Gabapentin for bipolar disorder
I push gabapentin, using side effects as a ceiling. I have pushed dosages above 5000 mg/d, though only after getting some encouragement from a neurologist.
Date: Sat, 27 Sep 1997 15:17:01 -0700
From: Lee Dante <ldante@pol.net>
Subject: Gabapentin for bipolar disorder
For what it's worth, I've gone as high as 5000 mg without ill effect in an effort to control episodic mood cycling in two patients. It worked well in one case and in the other I had to add lamotrigine while reducing the gabapentin to 4000 mg in an attempt to be conservative.
Both patients had episodes of altered consciousness accompanied by weird autonomic instability, transient hyperemic blotches, pupillary changes, piloerection, and body temperature changes, all of which vanished in the one who is still on the one antiepileptic drug.
Date: Fri, 03 Oct 1997 23:34:07 +0200
From: Leigh Janet <leigh@lia.net>
Subject: Gabapentin 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 Gabapentin, N > 500
The two main clinically beneficial effects of gabapentin, in my hands, are mood elevation -- seldom more than 2 or 3 points on a scale of 10 -- and anxiolysis -- often 5 or 6 on the same scale.
My initial use of the drug was in a core group of ultra rapid cycling bipolar patients in whom monotherapy with gabapentin was disappointing, but where gabapentin often (in about 4 of 10 patients) gives a useful stability to mood swings or elevation in mood from below the line to within normal limits. Most of these patients are on valproate, sometimes combined with lithium. So I use lithium-valproate-gabapentin or valproate-gabapentin combinations quite frequently. More recently I have found that patients with chronic low grade depression may benefit from gabapentin monotherapy, as may patients that experience marked agitation on initiation of SSRIs.
I have frequently used gabapentin to augment SSRIs, MAOIs and atypical antidepressants. I augment with gabapentin when there has been a partial response, but marked agitation or tremor are noted, often as side effects of the "high" dose of antidepressant.
I have had some patients with alcohol or benzodiazepine dependence problems report that their intake of alcohol or benzodiazepine is reduced when they take gabapentin. I have had some patients use additional gabapentin on a prn basis to control anxiety (not much success with panic attacks, though) and would say that gabapentin 200 mg is 6/10 versus 15 mg oxazepam in efficacy versus anxiety -- for those patients in whom gabapentin is anxiolytic.
I seldom see sustained benefit above 1800 mg per day and recently have confined most prescriptions to 1200 mg per day or less. Many early high dose responders developed marked sedation over time, necessitating dose reduction.
I frequently use gabapentin as an adjunctive medicine for benzodiazepine withdrawal states.
I note that gabapentin is being used increasingly in pain clinics and headache clinics, as well as clinics treating fibromyalgia, where the doses used are often high (up to 7000! mg). I do not have much experience with gabapentin in primary pain disorders.
Date: Wed, 06 May 1998 11:48:00 -0700
From: "James W. Hawkins" <jwh@creative.net>
Subject: Gabapentin dosing
The elimination half-life of gabapentin is 5 to 7 hours which might suggest a need to dose the drug at least 3 times a day. Has anyone's experience with gabapentin confirmed a need to dose this drug at least three times a day, or have you had success with other dosing regimens?I have been giving the drug both bid and tid. I've noticed little difference in those patients who respond. All of my patients, however, are elderly. I'm not sure we know the half-life of this drug in older patients. It is my impression that most half-life studies are done in younger, healthier people.--Ritchie Applewhite Rph
Date: Wed, 06 May 1998 13:59:28 -0700
From: Randall Riggs <riggs@workmind.com>
Subject: Gabapentin dosing
I reported before on this list a single case of a previously stable bipolar patient, about 30 years old, who -- without my knowledge -- consolidated her tid gabapentin into a single evening dose. She deteriorated greatly over the month on this regimen. She stabilized rapidly when returned to the tid doses. (She has rapid cycling, lithium resistant disorder and is also on high doses of valproate.)
Date: Wed, 23 Sep 1998 03:01:30 EDT
Subject: Gabapentin efficacy
I recently read that Parke-Davis abandoned their efforts to seek FDA indications for gabapentin to treat bipolar disorders and anxiety disorders due to lack of efficacy in their preliminary trials.I would certainly say I've seen inconsistent efficacy.--Mark Rosenberg, MSN, RN, CS
Date: Wed, 23 Sep 1998 06:31:21 -0700
From: Charles Price <cprice@pol.net>
Subject: Gabapentin efficacy
I do not see it as a wonder drug, but it has some benefit on occasion. I wonder if the reason for the loss of interest by Parke-Davis has to do with the timing of the expiration of the patent.
Date: Wed, 23 Sep 98 23:31:27
From: Phyllis Edelheit, MD <edelheit@nassau.cv.net>
Subject: Gabapentin efficacy
Gabapentin is an interesting medication -- as a mood stabilizer, it is limited -- although there are patients who do well with it. As an antidepressant, its effects are quite good and should be considered in the depressed patient with seizure disorder or the depressed patient who is unable to tolerate antidepressants for any of the many varieties of reasons or due to drug interactions. Gabapentin's interaction profile is good as well.
Date: Thu, 24 Sep 1998 07:37:23
From: "Richard Brand, M.D." <rdb@icu.com>
Subject: Gabapentin efficacy
I have been using gabapentin in combination with divalproex and/or lamotrigine in low doses to minimize their side effects while taking advantage of its different mechanism of action. Some have found gabapentin less sedating than divalproex or carbamazepine, although this is not universal. I have several patients with bipolar depression doing well with gabapentin in combination with other stabilizers and sometimes an antidepressant (generally bupropion), although I try to minimize the antidepressant use to hedge my bets against the possibility of triggering mania or rapid cycling. I have found that using gabapentin along with lamotrigine for bipolar depression allows me to limit the dose and rapidity of dose increase of the latter, theoretically lowering the likelihood of producing the dreaded rash.
Date: Thu, 24 Sep 1998 23:03:00 -0400
From: Mark and Cathy <mcrosen@erols.com>
Subject: Gabapentin efficacy
This article is the one mentioned in a previous post which reported that Parke-Davis abandoned gababapentin studies of bipolar and anxiety disorders due to lack of efficacy.
Date: Fri, 13 Nov 1998 18:04:02 -0500 (EST)
From: David Tobolowsky <dmtmd@dc.seflin.org>
Subject: Gabapentin dosage
At the University of Miami grand rounds today, Lewis Brodsky, M.D., shared his experience in using gabapentin in over 300 patients with bipolar disorder. His usual dosage range is 1600-2400 mg daily, and he opines a therapeutic window effect as an explanation for a NIMH group which used higher doses not finding good efficacy. He also avoids blood levels in excess of 10 (I don't know the units). (Dr. Brodsky is affiliated with the University of Florida and with the Florida State University School of Nursing.)
Date: Fri, 13 Nov 1998 21:46:39 -0500
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Gabapentin dosage
I have probably prescribed gabapentin for about a hundred patients with Bipolar Disorder. I am not impressed that there is a therapeutic window of any sort, but it is clear that the dose has to be individualized. While some people do well on 900 mg/day, others clearly require over 4000 mg/day for mood stabilization. I have not gotten many plasma levels, but in a few individuals in whom the impact upon bipolar mood swings has been gratifying, the plasma levels have been all over the place.
Date: Sun, 15 Nov 1998 10:31:12 -0600
From: Ereshefsky <Ereshefsky@uthscsa.edu>
Subject: Gabapentin dosage
It is important to remember that gabapentin has saturable absorption: higher doses must be further divided into frequent daily dosing to maximize absorption.
Stated another way, the bioavailability of gabapentin decreases as the size of the single dose increases. Single doses > 600 mg/day demonstrate dramatically poorer absorption. Some patients need to be on 5-6 x/day dosing!
From: RKolli@aol.com (Ravi Kolli, MD)
Date: Tue, 17 Nov 1998 23:43:06 EST
Subject: Gabapentin dosage
I wanted to elaborate a bit. Gabapentin (Neurontin) is absorbed via the neutral amino acid transport process, which is saturable. So:
| for a single dose of (mg) | the bioavailability is about (%) |
| 100 | 80 |
| 300 | 70 |
| 600 | 50 |
| 900 | 40 |
and so on at a diminishing rate. That is why any single dose > 600 mg will result in less drug being absorbed and the dose has to be divided. I hope this explanation makes sense.
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Dr. Bob is Robert Hsiung, MD,
dr-bob@uchicago.edu
URL: http://www.dr-bob.org/tips/split/Gapapentin-bipolar.html
Original tips copyright 1994-98 original authors.
Web page copyright 1995-98 Robert Hsiung.