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Side-effects on gabapentin

Date: Tue, 28 Nov 1995 09:08:03 -0500 (EST)
From: Donald Franklin Klein <dfk2@columbia.edu>
Subject: Hypomania on gabapentin

At the ECNP meeting in Venice, I was told that gabapentin can be strongly stimulating and can produce hypomania in depressed patients.

From: "Steven L. Dubovsky" <Steven.Dubovsky@UCHSC.edu>
Date: Tue, 6 Feb 1996 07:55:14 MST
Subject: Side-effects on new anticonvulsants

US physicians can look up lamotrigine (Lamictal) and felbamate (Felbatol) in the Physicians' Desk Reference. Of these two presentations, felbamate comes with a patient information/consent form that includes the following terrifying statements: "I understand that there is a serious risk that I could develop aplastic anemia and/or liver failure, both of which are potentially fatal, by using Felbatol. I understand that there are no laboratory tests which will predict if I am at increased risk for one of the potentially fatal conditions." The company includes a "Note to Physician: It is strongly recommended that you retain a signed copy of the informed consent with the patient's medical records."

It sure looks like felbamate can be a killer.

I see no similar level of warning or concern with lamotrigine.

I don't think I'll be prescribing any felbamate soon.


On the other hand, both lamotrigine and gabapentin were associated with unexplained deaths in premarketing trials. It is not clear if this was due to epilepsy, other drugs, or the new medications alone or in interaction.

Date: Mon, 13 May 1996 22:29:15 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Overdose on gapapentin

People have survived doses of 49 g. Double vision, slurred speech, drowsiness, lethargy and diarrhea were reported. Supportive care was all that was required.

Date: Tue, 23 Jul 1996 01:15:21 -0400
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Hypomania on gapapentin

I have used gabapentin in a dozen or so pholks with mixed or rapidly cycling bipolar disorder not responsive to other meds. I have not seen anything that has looked like the induction of hypomania.

From: cprice@mem.po.com (Charles Sowle Price, MD)
Date: Sat, 19 Oct 1996 03:12:38 -0400
Subject: Activation on gabapentin

Gabapentin seems to be energizing as opposed to sedating like valproic acid and carbamazepine.

Date: Sun, 17 Nov 1996 01:38:35 -0500
From: Ivan Goldberg <Psydoc@psycom.net>
Subject: Activation on new anticonvulsants

Gabapentin seems less "stimulating" than lamotrigine and has been well tolerated by some patients with mixed bipolar states or rapid cycling bipolar disorder who developed insomnia while taking lamotrigine.

Date: Thu, 9 Jan 1997 22:45:49 -0800 (PST)
From: "Sanford R. Pepper" <peppers@itsa.ucsf.edu>
Subject: Side-effects on gabapentin

The major side-effects that I have encounterred are mild fatigue and dizziness. I start low and go slow in general, so I have not run into difficulties with ataxia, slurred speech, etc.

Liver function tests are not necessary as the medication is not metabolized but renally excreted. That is why you can combine it so nicely with other anticonvulsants. You do have to take care if the creatinine clearance is low or if you are using another medication that is renally excreted -- for example, cimetidine -- and adjust the dosage accordingly. I suppose that combining gabapentin with lithium might be a bit tricky -- in the same way that cimetidine and lithium interact.

Date: Tue, 04 Mar 1997 23: 58: 47 -0800
From: Frank Feiner <NFRANK@pol.net>
Subject: Side-effects on gabapentin

Third Generation Antiepileptic Drugs, 11/3/96

The general consensus on this list, which I have shared, is that both lamotrigine (1-4) and gabapentin (2, 4-8) are safer than their predecessors.

There has been a more benign picture for gabapentin than for lamotrigine with respect to adverse effects. Most instances have been confined to behavioral activation (21-25), and there are single reports of choreoathetosis (26) and an exacerbation of Lennox-Gastaut epilepsy (27). The question of carcinogenicity has been raised, but appears to be a red herring (28, 29). Gabapentin has also been reported to be safe in an overdose (30).

Addendum, 3/4/97

For gabapentin, there was another movement disorder report in the last 4 months, this time that it induced one case each of dystonic and myotonic movement disorder (34), and two reports of weight gain (35, 36) (as opposed to none for lamotrigine).

2. Patsalos PN, Sander JW: Newer antiepileptic drugs. Towards an improved risk-benefit ratio. Drug Saf 1994; 11: 37-67

4. Fogel BS: Medical and neuropsychiatric perspectives on antiepileptic drugs. In: Treatment of Complex Medical-Psychiatric Syndromes. American Psychiatric Association Annual Meeting, 1995

5. The US Gabapentin Study Group: The long-term safety and efficacy of gabapentin (Neurontin) as add-on therapy in drug-resistant partial epilepsy. Epilepsy Res 1994; 18: 67-73

6. Sivenius J, Ylinen A, Kalviainen R, Riekkinen PJ Sr: Long-term study with gabapentin in patients with drug-resistant epileptic seizures. Arch Neurol 1994; 51: 1047-50

7. Beydoun A, Uthman BM, Sackellares JC: Gabapentin: pharmacokinetics, efficacy, and safety. Clin Neuropharmacol 1995; 18: 469-81

8. McLean MJ: Gabapentin. Epilepsia 1995; 36 Suppl 2: S73-86

21. Short C, Cooke L: Hypomania induced by gabapentin. Br J Psychiatry 1995; 166: 679-80

22. Wolf SM, Shinnar S, Kang H, Gil KB, Moshe SL: Gabapentin toxicity in children manifesting as behavioral changes. Epilepsia 1995; 36: 1203-5

23. Hauck A, Bhaumik S: Hypomania induced by gabapentin. Br J Psychiatry 1995; 167: 549

24. Tallian KB, Nahata MC, Lo W, Tsao CY: Gabapentin associated with aggressive behavior in pediatric patients with seizures. Epilepsia 1996; 37: 501-2

25. Lee DO, Steingard RJ, Cesena M, Helmers SL, Riviello JJ, Mikati MA: Behavioral side effects of gabapentin in children. Epilepsia 1996; 37: 87-90

26. Buetefisch CM, Gutierrez A, Gutmann L: Choreoathetotic movements: A possible side effect of gabapentin. Neurology 1996; 46: 851-2

27. Vossler DG: Exacerbation of seizures in Lennox-Gastaut syndrome by gabapentin. Neurology 1996; 46: 852-3

28. Sigler RE, Gough AW, de la Iglesia FA: Pancreatic acinar cell neoplasia in male Wistar rats following 2 years of gabapentin exposure. Toxicology 1995; 98: 73-82

29. Fowler ML, Sigler RE, de la Iglesia FA, Reddy JK, Lalwani ND: Absence of Ki-ras mutations in exocrine pancreatic tumors from male rats chronically exposed to gabapentin. Mutat Res 1995; 327: 151-60

30. Fischer JH, Barr AN, Rogers SL, Fischer PA, Trudeau VL: Lack of serious toxicity following gabapentin overdose. Neurology 1994; 44: 982-3

34. Reeves AL, So EL, Sharbrough FW, Krahn LE: Movement disorders associated with the use of gabapentin. Epilepsia 1996 Oct; 37 (10): 988-90

35. Morris GL 3rd: Efficacy and tolerability of gabapentin in clinical practice. Clin Ther 1995 Sep-Oct; 17 (5): 891-900

36. Gidal BE, Maly MM, Nemire RE, Haley K: Weight gain and gabapentin therapy Ann Pharmacother 1995 Oct; 29 (10): 1048

Date: Tue, 18 Mar 1997 20:22:15 -0500
From: Ivan Goldberg <Psydoc@PsyCom.Net>
Subject: Side-effects on gabapentin

At 10:39 AM 3/18/97 -0800, Sanford R. Pepper wrote:

Over the past month I have encountered two interesting adverse effects associated with the administration of gabapentin.
  1. In a female in her twenties with a history of abuse and anorexia, current phenomenology highly suggestive of rapid cycling bipolar disorder, and a strong family history of affective disorder, administration of the medicine in amounts up to 1500 mg was associated with the onset of dissociative episodes which remitted after the medicine was tapered and discontinued. [She also had a signficant increase in irritability. --Mon, 22 Sep 1997 21:26:49 -0700 (PDT)]

  2. In a male in his fifties with a history of intractable migraine and sertraline-induced hypomanic episodes, administration of gabapentin was associated with feelings of spaciness -- not unlike what he remembers as being "stoned" on cannabis sativa.
I have found that feelings of dissociation and feelings of being "stoned" are not uncommon for about 5-7 days following an increase in the dose of gabapentin in some individuals. If they can be induced to tolerate these feelings, the feelings resolve. Decreasing the dose and increasing it more slowly is an alternative.

From: HRudMD@aol.com (Howard Rudominer)
Date: Sat, 12 Apr 1997 13:36:38 -0400 (EDT)
Subject: Side-effects on new anticonvulsants

Stevens-Johnson syndrome is still a very rare occurrence, and if lamotrigine is effective where all else fails, I think most of us would weigh the risk/benefit ratio way to the the side of the benefit.

I concur that lamotrigine seems to be more activating and gabapentin more sedating.

Date: Sun, 13 Apr 1997 21:40:18 -0700
From: "Kathleen Schilli, PharmD." <DrRx@ix.netcom.com>
Subject: Side-effects on new anticonvulsants

At my facility we have used both lamotrigine and gabapentin. The patients do not like lamotrigine because of the rash (even though we start at a low dose and go up slowly on it) and the hair loss. It seems that gabapentin has a lot fewer drug interactions and side effects.

Date: Tue, 08 Jul 1997 21:31:23 -0700
From: Frank Feiner <nfrank@pol.net>
Subject: Hypomania on gabapentin

Gabapentin has been reported to *induce* mania, although antiepileptic drugs are generally excellent acute anti-manic agents.

Hauck A, Bhaumik S: Hypomania induced by gabapentin. Br J Psychiatry. 1995 Oct; 167 (4): 549

Short C, Cooke L: Hypomania induced by gabapentin. Br J Psychiatry. 1995 May; 166 (5): 679-80

Date: Mon, 22 Sep 1997 22:38:14 -0400
From: "John M. Rathbun" <73162.3513@compuserve.com>
Subject: Activation on gabapentin

With gabapentin, I often see an initial activation similar to what I used to see with fluoxetine. This subsides with increased dose in most cases.

Date: Fri, 03 Oct 1997 23:34:07 +0200
From: Leigh Janet <leigh@lia.net>
Subject: Side-effects on gabapentin

Gabapentin seems at times to sedate (it can be quite significant, 6/10, at higher (> 400 mg) individual doses, but I have had a few patients agitated by gabapentin. Most of the latter group are patients with documented temporal lobe epilepsy, a few of whom seem to deteriorate on gabapentin.

Although it would not surprise me to learn of cases of dependency on gabapentin, I have had no problem withdrawing gabapentin in any patient. I regularly run Medline searches for possible cases of gabapentin dependence -- none so far.

I have seen no serious or life threatening adverse effects of gabapentin, but have had to stop the drug because of skin reactions on at least 6 occasions and because of agitation or sedation in about 10% of cases. About 10% of patients do not settle on the drug during the introduction phase. Nausea does occur, but gradual dose titration seems almost to eliminate this problem.

2% of patients have experienced hypomanic mood, one patient after the first dose of gabapentin. 1 patient experienced marked increase in paranoid ideation on introduction of gabapentin, but another patient with severe OCD and mania, who was also paranoid, settled when gabapentin was added to the combination of risperidone and valproate.

I have seen no major biochemical or lab result changes as a result of gabapentin, except for one patient whose lithium level rose when gabapentin was added. The patient had previously exhibited stable lithium levels.

Increased appetite and weight gain are side effects of gabapentin. There do not appear to be problems with cardiac side effects or hypotension, and drug drug interactions are seldom a problem.

Some patients experience cognitive side effects with gabapentin, but my sense is that these effects are far less frequent than with lithium, carbamazepine, or even valproate.

I have, at times, experienced problems combining gabapentin with antipsychotic agents, especially older agents, where increased motor side effects, and ataxia, seem to occur.

Date: Thu, 13 Nov 1997 07:24:18 -0500
From: Ivan Goldberg <Psydoc@PsyCom.Net>
Subject: Mania on gabapentin

The following is reproduced with the permission of the author:

I would like to report a case of severe mania being induced by gabapentin.

My wife began taking gabapentin about 7 months ago for treatment of bipolar disorder. The very first day she took it she claims that her depression was completely gone and she felt like she was going to get a cure. But, the mania began to escalate day by day.

In the beginning she was taking the gabapentin along with her regular lithium but this had to be stopped as when the two were taken together she would develop lithium toxicity. Was gabapentin potentiating the lithium?

Anyway, at first it was nice and pleasant but after a few months irritability, annoyance, and volatility began to emerge. Her psychiatrist didn't believe her when she told him that the gabapentin was inducing the mania, and he told her it was a placebo effect. My wife and I followed her mood swings, timing it with the taking of the gabapentin, and each day it followed the same pattern. She would take the gabapentin, and within one-half hour the euphoria would begin and would last for about two hours. Then she would begin to grow irritable until she would take her next dose of gabapentin.

After a few months in this fashion the mania became more and more irritable and hostile, culminating in her having to be hospitalized three times: once for an attempted overdose and twice for extreme mania. At the psychiatric hospital here the psychiatrist had never heard of gabapentin being used for bipolar disorder, and the last time she was hospitalized she had to wait for four days until they would attempt to begin administration of valproate to try and combat the mania. During this wait she became very delusional and psychotic. Hypersexuality set in and she became involved with a male co-patient and the resulting relationship caused a tremendous amount of grief for her, as well as myself. She had absolutely no control. She understood what she was doing but she didn't understand her motivation to act in such a manner. She couldn't see the wrongness in her activity. She possesses high moral values, we have been married for 25 years, and she had never been unfaithful. Now she was and there was absolutely nothing wrong with it. I believe that it had to be a psychotic episode.

Along with the valproate she is now taking lorazepam, and the mania is almost gone, but still lingers under the surface. She would never give up the gabapentin for she would rather die than go back into the depression, which the gabapentin is keeping her out of at the moment. I thought that I would pass this on as I was just reading the letter in the British Journal of Psychiatry by Hauch and Bhaumik.

[ Hauck A, Bhaumik S. Hypomania induced by gabapentin. British Journal of Psychiatry. 167 (4): 549, 1995 Oct. Comment on: 1995 May; 166 (5): 679-80. ]

Date: Wed, 26 Nov 1997 22:19:38 +0200
From: Leigh Janet <leigh@lia.net>
Subject: Side-effects on gabapentin

A fiftyish guy is under treatment for chronic pain and depression with nefazodone 300 bid and gabapentin 1500 qhs, which he tolerates well. Because of some breakthrough of the pain, his gabapentin is increased to 1800 qhs. The next afternoon, after abruptly straightening up in the garden, this patient briefly loses consciousness and slightly injures himself.

Blood pressures in hospital run from 70 to 90 systolic, with marked postural drops. The EKG is normal, and the cardiology consultation is unproductive. EKG monitoring and metabolic studies are now in progress.

I've now had 4 patients experience syncopal episodes on gabapentin. No obvious cause was found in any of the cases, but all were on more than 2 drugs at the time. Sedative medications may be implicated, but none of my cases was taking nefazodone.

2 patients experienced "blackouts" within the first week of initiating treatment, at very low doses.

My guess is that this is a gabapentin adverse event, but I did not re-challenge any of the patients.

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.

From: Roberta M. Richardson, M.D. <RMRich1@aol.com>
Date: Wed, 1 Apr 1998 15:07:53 EST
Subject: Side-effects on gabapentin

I had one patient who definitely got more depressed on gabapentin, although she was not taking any antidepressant at the time.

I have become more concerned recently about gabapentin's potential to stimulate irritability and aggression. Here are some quotes from three different patients:

In all three cases, those particular symptoms resolved immediately upon stopping the gabapentin.

Date: Wed, 01 Apr 1998 19:37:39 -0500
From: Jim Ellison MD <jellison@InterServ.Com>
Subject: Irritability on gabapentin

That is very interesting, since there are case reports in the literature of children who took gabapentin for epilepsy and developed rage attacks!

From: Ron Podell <ConEmo@aol.com>
Date: Sat, 4 Apr 1998 01:00:12 EST
Subject: Irritability on gabapentin

I have recently added gabapentin 400 qid to the regimen of a bipolar 30-something-year-old. He called me up and told me he felt like killing someone. I am quickly tapering him off. I probably will try lamotrigine.

Date: Sat, 1 Jul 1998 22:33:10 +0500
From: Niraj Ahuja <niraj@giasdl01.vsnl.net.in>
Subject: Side-effects on gabapentin

Some of the adverse effects of gabapentin include gingivitis, glossitis, gum hemorrhage, stomatitis, increased salivation, blisters in the mouth, tooth discoloration, salivary gland enlargement, and lip hemorrhage (1996 Physicians GenRx).

Date: Wed, 2 Sep 1998 09:38:33 -0700 (PDT)
From: Ellen Haller <ehaller@itsa.ucsf.edu>
Subject: Side-effects on gabapentin

I have a 40-something overweight female with recurrent depression and probable atypical bipolar disorder who finally stabilized on combination of paroxetine and gabapentin. She then asked for switch to fluoxetine due to some sedation as well as a fairly distant history of response to fluoxetine. Now (about one month later), she's complaining of feeling severely bloated, stating, "even my lymph nodes are swollen." No other complaints.

Date: Wed, 02 Sep 1998 13:21:55 -0600
From: "Cheryl Clark, MD" <cclarkmd@earthlink.net>
Subject: Side-effects on gabapentin

I too have seen this with gabapentin in moderate doses. One of my bipolar patients had severe pedal edema with gabapentin which went away when discontinued. She is very sensitive to most medications, so I restarted her at 100 mg per day, which she tolerated OK, and we have been very, very slowly increasing the dose. She has now made it back to 300 mg per day, but if we increase that at all she has edema again. We stick with it only because she can't tolerate lithium, valproic acid, carbamazepine or verapamil. If she worsens and we need additonal mood stability I suppose we will be moving on to other alternatives like nimodipine or lamotrigine.

From: RKolli@AOL.COM (Ravi Kolli,MD)
Date: Wed, 18 Nov 1998 00:10:29 EST
Subject: Side-effects on gabapentin

I have a patient with Bipolar-II who had elevated liver function tests on valproate, anemic indices so I could not try carbamazepine, and severe diarrhea on lithium. So I started him on gabapentin, and now he reports a couple of episodes of nocturnal enuresis. His gabapentin dose was only 300 mg qid. He was also on Klonopin (clonazepam) 1.5 mg bid for panic attacks. He absolutely denies any alcohol abuse related these episodes of enuresis.

From: AMIROT@aol.com (Adam Mirot, M.D.)
Date: Thu, 19 Nov 1998 01:50:46 EST
Subject: Side-effects on gabapentin

I had recently one patient (in her early 60s, with depression) whom I began on 100 hs of gabapentin as a sleeper -- she developed enuresis the first night of treatment and refused all subsequent doses.

From: JoelSHoffm@aol.com (Joel S Hoffman, M.D)
Date: Sat, 21 Nov 1998 08:23:10 EST
Subject: Side-effects on gabapentin

I use this medication extensively and have found enuresis the most troubling side effect. Weight gain and sedation or cognitive impairment may be more common, but patients want to stop the medication when enuresis occurs. I would be guessing about the occurrence rate, but would estimate 10%. It is dose related and sometimes alleviated by decreasing the dosage or oxybutynin (Ditropan).

Date: Fri, 16 Apr 1999 19:13:07 -0400
From: Cyrus Wolfman <cwolfman@optonline.net>
Subject: Side-effects on gabapentin

I've had patients with peripheral edema on gabapentin which did not decrease in a few days, so I lowered the dose. I did not try diuretics.

--Fred Brown

I have spoken to someone with a good amount of experience with gabapentin.

He said that he, as well as the neurologists who use the drug frequently, simply try reducing the dose. If the edema does not remit, they add a diuretic such as furosemide (Lasix) prn without problems.

My patient's edema was reduced but did not remit on my lowering the gabapentin to 300 mg qd.

So I just raised the dose back to 300 mg tid and added Lasix 20 mg bid yesterday. She reported by phone today that the edema has reduced a good bit. We shall continue with the Lasix, titrating it upward if need be. We will repeat the lab study for electrolytes and add potassium if indicated.

The impression I get from those with a lot of experience with the drug is that it is exceptionally safe to use despite the side effect of edema.

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