Thank you to Ivan Goldberg, MD - Psydoc@PsyCom.net for permission to use this FAQ.

FAQ: Gabapentin for Depression and/or Mania.

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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