Repost of FAQ: Neurontin (Gabapentin) for Depression and/or Mania

[James D. Milton]

"FAQ: Neurontin (Gabapentin) for Depression and/or Mania"
Revised 8/24/97

Ivan K. Goldberg, M.D.
1346 Lexington Avenue
New York, NY 10128

Voice: 212 876 7800
Fax: 212 737 0473
Email: Psy...@PsyCom.Net

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 treatment for people with mood disorders.
While such studies are in the planning stages, what is currently known
about the use of gabapentin for the control of mood disorders 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:

a. Gabapentin's frequent effectiveness for patients who have failed
to respond to antidepressants or mood stabilizers;

b. Gabapentin's relatively benign side-effect profile.

5. What, if anything, uniquely distinguishes gabapentin from
carbamazepine and valproate?

Gabapentin has been successful in controlling rapid cycling and mixed
bipolar states in 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.

6. People with what sorts of mood 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 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 mg/day. Some
people require doses as high as 4,800 mg/day to achieve good results.

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 lower
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 12 April 1997, the per tablet cost of gabapentin, when ordered in
lots of 100 tablets from a national mail-order pharmacy was:

100 mg - $0.40
300 mg - $0.92

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.

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 impact of gabapentin on mood?

Among the published reports on gabapentin are:

Ayd FJ
International Drug Therapy Newsletter 1997 32, 23-24.
Gabapentin -- Another mood stabilizer?

Diamond KR, Pande AD, LLamoraux L, Pierce MW
Prog Neuropsychopharmacol Biol Psychiat 1996, 20, 407-417.
Effect of gabapentin on mood and well-being in patients with epilepsy.

Bennett J Goldman WT Suppes T
Journal of Clinical Psychopharmacology 1997, 17, 141-142.
Gabapentin for treatment of bipolar and schizoaffective disorders.

Hauck A, Bhaumik S
British Journal of Psychiatry 1995, 167, 549.
Hypomania induced by gabapentin.

McElroy SL, Soutullo CA, Keck PE, Kmetz GF
Annals of Clinical Psychiatry 1997, 9, 99-103.
A pilot trial of adjunctive gabapentin in the treatment of bipolar
disorder.

Regan WM, Gordon SM
Journal of Clinical Psychopharmacology 1997, 17, 59-60.
Gabapentin for behavioral agitation in Alzheimer's Disease.

Ryback RS, Brodsky L, Munasifi F
Journal of Neuropsychiatry and Clinical Neuroscience
1997, 9, 301.
Gabapentin in bipolar disorder.

Ryback R, Ryback L
American Journal of Psychiatry 1995, 152, 1399.
Gabapentin for behavioral dyscontrol.

Saletu B, Grunberger J, Linzmayer L
International Journal of Clinical Pharmacology,
Therapeutics and Toxicology 1986, 24, 362-373.
Evaluation of encephalotropic and psychotropic properties of gabapentin
in man by pharmaco-EEG and psychometry.

Schaffer CB, Schaffer LC
American Journal of Psychiatry 1997, 154, 291-292.
Gabapentin in the treatment of bipolar disorder.

Short C, Cooke L
British Journal of Psychiatry 1995, 166, 679-680.
Hypomania induced by gabapentin.

Stanton SP, Keck PE, McElroy SL
American Journal of Psychiatry 1997, 154, 287.
Treatment of acute mania with gabapentin.

31. Additions and corrections?

Please address additions and corrections to:

Ivan K. Goldberg, M.D.
1346 Lexington Avenue
New York, NY 10128

Voice: + 212 876 7800
Fax: + 212 737 0473

Email: Psy...@PsyCom.Net
--

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