Thank you to Dr Ivan at Depression Central for permission to
print this article
http://psycom.net/depression.central.gabapentin.html
Revised: October 14, 1999
NOTE: Gabapentin is only approved
in the USA
for the treatment of people with seizures.
There are no systematic studies that establish
the safety or efficacy of gabapentin as a treat-
ment for people with mood disorders, anxiety or
tardive dyskinesia. While such studies are in
the planning stages, what is currently known about
the use of gabapentin for the control of mood and
anxiety disorders and tardive dyskinesia comes
from uncontrolled case reports.
1.What is gabapentin (Neurontin)?
Gabapentin is an anticonvulsant
that is chemically unrelated to any other
anticonvulsant or mood regulating
medication.
2. When was gabapentin approved
for marketing in the USA and for what
indications may it be promoted?
Gabapentin received final approval
for marketing in the USA on 30 December
1993 and is labeled for use as
an anticonvulsant.
3. Is a generic version of gabapentin
available?
There is no generic gabapentin
as the manufacturer has patent protection.
4. How does gabapentin differ
from other mood stabilizing drugs?
Gabapentin differs from other
mood stabilizing drugs in two major ways:
1. Gabapentin's frequent effectiveness
for patients who have failed to respond
to antidepressants or mood stabilizers;
2. Gabapentin's relatively benign
side-effect profile.
5. What, if anything, uniquely
distinguishes gabapentin from carbamazepine
and valproate?
Gabapentin has had been successful
in controlling rapid cycling and mixed
bipolar states in some people
who have not received adequate relief from
carbamazepine and/or valproate.
It also appears that gabapentin has
significantly more antianxiety
and antiagitation potency than either
carbamazepine or valproate. Gabapoentin
has also been shown to be useful as
a treatoent for antipsychotic-induced
tardive dyskinesia.
6. People with what sorts of mood
and/or anxiety disorders are candidates for
treatment with gabapentin?
It is too early to be very specific
about which mood disorders are most likely
to respond to treatment with
gabapentin. There are very few published reports
on gabapentin'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, although some people with such
hard to treat unipolar depressions
have been treated with good results. It is
possible that gabapentin will
prove to be a useful treatment for people with
other mood disorders.
Gabapentin also seems to have
significant activity as a way of controlling
various anxiety disorders.
7. Is gabapentin useful for the
treatment of acute depressed, manic and mixed
states, and can it also be used
to prevent future episodes of mania and/or
depression?
The initial use of gabapentin
was to treat people with depressed, manic and
mixed states that did not respond
to existing medications. Some patients are
now being maintained on gabapentin
on a long term basis in an attempt to
prevent future episodes. The
effectiveness of gabapentin as a long-term
prophylactic agent is currently
being established.
8. Are there any laboratory tests
that should precede the start of gabapentin
therapy?
Before gabapentin 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.
9. How is treatment with gabapentin
initiated?
Gabapentin is usually started
at a dose of 300 mg once a day, usually at bed
time. Every three to five days
the dose is increased. In some people a response
is seen with 600 mg/day . . .
other people must increase the dose as high as
4,800 mg/day.
10. Are there any special problems
prescribing gabapentin for people taking
lithium, carbamazepine (Tegretol),
or valproate (Depakote)?
No interactions between gabapentin
and lithium, carbamazepine or valproate
have been reported.
11. What is the usual final dose
of gabapentin?
When used as an antidepressant
or as a mood-stabilizing agent the final dose
of gabapentin is most often between
900 and 2,000. Some people require doses
as high as 4,800 mg/day to achieve
a good results.
As gabapentin has a half-life
of about six hours it must be administered three
or four times a day,
12. How long does it take for
gabapentin to 'kick-in?'
While some people notice the antimanic
and antidepressant effects within a
week or two of starting treatment,
others have to take a therapeutic amount
of gabapentin for up to a month
before being aware of a significant amount
of improvement.
13. What are the side-effects
of gabapentin?
Here is a listing of gabapentin's
side effects that affected 5% or more of the
543 people taking the drug during
clinical trials and the frequency of those
side effects in the 378 people
treated with placebo in those trials:
Adverse Reactions (%)
Adverse Reaction Gabapentin
Placebo
Sleepiness
19
9
Dizziness
17
7
Unsteadiness
13
6
Nystagmus
8
4
Tremor
7
3
Double Vision
6
2
Side-effects are most noticeable
the few days after an increase in dose and
then usually fade.
14. Which side-effects are severe
enough to force people to discontinue
gabapentin?
The side effects most often associated
with discontinuation of gabapentin are
sleepiness (1.2%), unsteadiness
(0.8%), fatigue (0.6%), nausea and/or
vomiting (0.6%), and dizziness
(0.6%).
15. Does gabapentin have any psychiatric
side effects?
Among the rarely reported side
effects of gabapentin are depersonalization,
mania, agitation, paranoia, and
increased or decreased libido.
16. How does gabapentin interact
with prescription and over-the-counter
medications?
Only a few interactions between
gabapentin and other drugs have been
identified. Antacids may decrease
the absorption of gabapentin and lover the
blood level by 20% Gabapentin
may increase the concentration of some oral
contraceptives by 13%. This probably
is not clinically significant.
17. Is there an interaction between
gabapentin and alcohol?
Alcohol may increase the severity
of the side-effects of gabapentin.
18. Is gabapentin safe for a woman
who is about to become pregnant, pregnant
or nursing an infant?
Gabapentin is has been placed
in the FDA pregnancy Category C:
"Animal studies have shown an
adverse effect on the fetus but there are no
adequate studies in humans; The
benefits from the use of the drug in pregnant
women may be acceptable despite
its potential risks . . . ."
19. Is gabapentin safe for children
and adolescents?
Gabapentin has been used with
children and young adolescents in other
countries other than the USA.
In the USA gabapentin is only approved for use
in those over the age of 12.
20. Can gabapentin be used in
elderly people?
Older people seem to handle gabapentin
similarly to younger ones. There is
little experience using gabapentin
for the treatment of psychiatric disorders in
the elderly.
21. Do symptoms develop if gabapentin
is suddenly discontinued?
There are no specific symptoms
that have been described following the abrupt
discontinuation of gabapentin,
other than the seizures that sometimes follow
the rapid discontinuation of
any anticonvulsant. Only when necessary because
of a serious side effect, should
gabapentin be suddenly discontinued.
22. Is gabapentin toxic if taken
in overdose?
Data on overdoses are scarce.
Overdoses of up to 49,000 mg of gabapentin
have been survived without sequelae.
23. Can gabapentin be taken along
with MAO inhibitors?
Yes, the combination has been
used without any special problems.
24. What does gabapentin cost?
As of May 1999, the per tablet
cost of gabapentin, when ordered in lots of 100
tablets from a national mail-order
pharmacy was:
300 mg - $1.19
400 mg - $1.44
25. Might gabapentin be effective
in people who have failed to receive benefit
from other psychopharmacologic
agents?
The major use of gabapentin in
psychiatry is with people who have mood
disorders that have not been
adequately controlled by other medications.
26. What are the advantages of
gabapentin?
Gabapentin 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 cycling, or because of the
development of mixed states,
have been able to tolerate therapeutic doses of
anti- depressants when taking
gabapentin.
For most people, gabapentin has
minimal side effects.
27. What are the disadvantages
of gabapentin?
As gabapentin 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 if people who initially
do well on gabapentin continue to do so after
many years of treatment.
The short half-life of gabapentin
makes it necessary for it to be taken in
divided doses over the course
of the day.
Similar to other drugs that have
the ability to reduce depression, gabapentin
can induce mania in some people
with bipolar disorder.
28. Why should physicians prescribe,
and patients take, gabapentin, when there
are mood regulating medications
that have been available for many years and
which have been shown to be effective
in double-blind placebo-controlled
studies?
There are two major reasons why
physicians prescribe and patients take
gabapentin 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.
29. Is gabapentin available in
countries other than the USA?
Gabapentin is currently available
in about 45 countries.
30. Are there any published reports
on the psychiatric uses of gabapentin?
Among the published reports on
gabapentin are:
Blinder BJ, et al.
Advances in mood stabilizing
medications.
West J Med. 1998, 169, 39-40.
Cabras PL, et al.
Clinical experience with gabapentin
in patients with bipolar or schizo-
affective disorder:
results of an open-label study.
J Clin Psychiatry. 1999, 60,
245-248.
Carvill S, et al.
The management of epilepsy in
a hospital for people with a learning
disability.
Seizure. 1999, 8,175-180.
Chouinard G, et al.
Gabapentin: long-term antianxiety
and hypnotic effects in psychiatric
patients with comorbid anxiety-related
disorders.
Can J Psychiatry. 1998, 43, 305.
Cora-Locatelli G, et al.
Rebound psychiatric and physical
symptoms after gabapentin discontinuation.
J Clin Psychiatry. 1998, 59,
131.
Cramer JA, et al.
New antiepileptic drugs: comparison
of key clinical trials.
Epilepsia. 1999, 40, 590-600.
Review.
Dimond KR, et al.
Effect of gabapentin (Neurontin)
[corrected] on mood and well-being in
patients with epilepsy.
Prog Neuropsychopharmacol Biol
Psychiatry. 1996, 20, 407-417.
Dodrill CB, et al.
Cognitive abilities and adjustment
with gabapentin: results of a multisite
study.
Epilepsy Res. 1999, 35, 109-121.
Dopheide JA, et al.
Gabapentin and lamotrigine in
the treatment of bipolar disorder.
J Am Pharm Assoc (Wash). 1998,
38, 632-634.
Dunn RT, et al.
The efficacy and use of anticonvulsants
in mood disorders.
Clin Neuropharmacol. 1998, 21,
215-235. Review.
Erfurth A, et al.
An open label study of gabapentin
in the treatment of acute mania.
J Psychiatr Res. 1998, 32, 261-264.
Ferrier IN.
Lamotrigine and gabapentin. Alternative
in the treatment of bipolar disorder.
Neuropsychobiology. 1998, 38,
192-197. Review.
Freeman MP, et al.
Mood stabilizer combinations:
a review of safety and efficacy.
Am J Psychiatry. 1998, 155, 12-21.
Review.
Frye MA, et al.
Gabapentin does not alter single-dose
lithium pharmacokinetics.
J Clin Psychopharmacol. 1998,
18, 461-464.
Frye MA, et al.
Possible gabapentin-induced thyroiditis.
J Clin Psychopharmacol. 1999,
19, 94-95.
Ghaemi SN, et al.
Gabapentin treatment of mood
disorderss: A preliminary study.
J Clin Psychiatry. 1998, 59,
426-429.
Grunze H, et al.
Renal impairment as a possible
side effect of gabapentin. A single case
report.
Neuropsychobiology. 1998, 38,
198-199.
Grunze H, et al.
[Gabapentin in the treatment
of mania].
Fortschr Neurol Psychiatr. 1999,
67, 256-260. German.
Harden CL, et al.
A beneficial effect on mood in
partial epilepsy patients treated with
gabapentin.
Epilepsia. 1999, 40, 1129-1134.
Hardoy MC, et al.
Gabapentin as a promising treatment
for antipsychotic-induced movement
disorders in schizoaffective
and bipolar patients.
J Affect Disord. 1999, 54, 315-317.
Hatzimanolis J, et al.
Gabapentin as monotherapy in
the treatment of acute mania.
European Neuropsychopharmacology.
1999, 9, 257-258.
Hauck A, et al.
Hypomania induced by gabapentin.
British Journal of Psychiatry.
1995, 167, 549.
Kaufman KR.
Adjunctive tiagabine treatment
of psychiatric disorders: three cases.
Annals of Clinical Psychiatry.
1998, 10, 181-184.
Keck PE Jr, et al.
Anticonvulsants and antipsychotics
in the treatment of bipolar disorder.
Journal of Clinical Psychiatry.
1998, 59 (Suppl 60),74-81; discussion 82. Review.
Ketter TA, et al.
Positive and negative psychiatric
effects of antiepileptic drugs in
patients with seizure disorders.
Neurology. 1999, 53 (5 Suppl
2), S53-67. Review.
Ketter TA, et al.
Metabolism and excretion of mood
stabilizers and new anticonvulsants.
Cell Mol Neurobiol. 1999, 19,
511-532. Review
Knoll J, et al.
Clinical experience using gabapentin
adjunctively in patients with a
history of mania or hypomania.
Journal of Affective Disorders..
1998, 49, 229-233.
Labbate LA, et al.
Gabapentin-induced ejaculatory
failure and anorgasmia.
American Journal of Psychiatry.
1999, 156, 972.
Letterman L, et al.
Gabapentin: a review of published
experience in the treatment of bipolar
disorder and other psychiatric
conditions.
Pharmacotherapy. 1999, 19, 565-572.
Review.
Lovell RW.
Mood stabilizer combinations
for bipolar disorder.
American Journal of Psychiatry.
1999, 156, 980-981.
McElroy SL, et al.
A pilot trial of adjunctive gabapentin
in the treatment of bipolar disorder.
Annals of Clinical Psychiatry.
1997, 9, 99-103.
Magnus L.
Nonepileptic uses of gabapentin.
Epilepsia 1999, 40 (suppl 6)
S66-S72.
Marcotte D.
Use of topiramate, a new anti-epileptic
as a mood stabilizer.
J Affect Disord. 1998, 50, 245-251.
Martin R, et al.
Cognitive effects of topiramate,
gabapentin, and lamotrigine in healthy
young adults.
Neurology. 1999, 52, 321-327.
Mortimore C, et al.
Effects of gabapentin on cognition
and quality of life in patients with
epilepsy.
Seizure. 1998, 7, 359-364.
Pande AC, Davidson JR, Jefferson
JW, et al.
Treatment of social phobia with
gabapentin: a placebo-controlled
study.
Journal of Clinical Psychopharmacology.
1999, 19, 341-348.
Perugi G, et al.
Clinical experience using adjunctive
gabapentin in treatment-resistant
bipolar mixed states.
Pharmacopsychiatry. 1999, 32,
136-141.
Post RM, et al.
A history of the use of anticonvulsants
as mood stabilizers in the last
two decades of the 20th century.
Neuropsychobiology. 1998,38,
152-166.
Post RM, et al.
Beyond lithium in the treatment
of bipolar illness.
Neuropsychopharmacology. 1998,
19, 206-219. Review.
Post RM.
Comparative pharmacology of bipolar
disorder and schizophrenia.
Schizophr Res. 1999, 39, 153-158;
discussion 163.
Rosebush PI, et al.
Catatonia following gabapentin
withdrawal.
J Clin Psychopharmacol. 1999,
19, 188-189.
Ryback RS, et al.
Gabapentin in bipolar disorder.
J Neuropsychiatry Clin Neurosci.
1997, 9, 301.
Saletu B, et al.
Evaluation of encephalotropic
and psychotropic properties of gabapentin
in man by pharmaco-EEG and psychometry.
Int J Clin Pharmacol Ther Toxicol.
1986, 24, 362-373.
Schaffer CB, et al.
Gabapentin in the treatment of
bipolar disorder.
Am J Psychiatry. 1997, 154, 291-292.
Sheldon LJ, et al.
Gabapentin in geriatric psychiatry
patients.
Can J Psychiatry. 1998, 43, 422-423.
Short C, et al.
Hypomania induced by gabapentin.
Br J Psychiatry. 1995, 166, 679-680.
Soutullo CA, et al.
Gabapentin in the treatment of
adolescent mania: a case report.
J Child Adolesc Psychopharmacol.
1998, 8, 81-85.
Stanton SP, et al.
Treatment of acute mania with
gabapentin.
Am J Psychiatry. 1997, 154, 287.
Thijs RD, et al.
The outcome of prescribing novel
anticonvulsants in an outpatient setting:
factors affecting response to
medication.
Seizure. 1998, 7, 379-383.
Walden J, et al.
[Value of old and new anticonvulsants
in treatment of psychiatric diseases].
Fortschr Neurol Psychiatr. 1995,
63, 320-335. Review. German.
Walden J, et al.
[Predictors of response to phase
prophylactics (mood stabilizers) in
bipolar affective disorders].
Fortschr Neurol Psychiatr. 1999,
67, 75-80. Review. German.
Wolf SM, et al.
Gabapentin toxicity in children
manifesting as behavioral changes.
Epilepsia. 1995, 36, 1203-1205.
Young LT, et al.
Acute treatment of bipolar depression
with gabapentin.
Biol Psychiatry. 1997, 42, 851-853.
.
Young LT, et al.
Gabapentin as an adjunctive treatment
in bipolar disorder.
J Affect Disord. 1999, 55, 73-77.
30. Additions and corrections?
Please address additions and corrections
to:
Ivan K. Goldberg, M.D.
1556 Third Avenue
New York, NY 10128-3100
Voice: + 212 876 7800
Fax: + 914 362 9267
Email Psydoc@PsyCom.Net
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