NOTE: Gabapentin is only approved in the USA for the treatment of people with seizures. There are few systematic studies that establish the safety or efficacy of gabapentin as a treatment for people with mood disorders, anxiety or tardive dyskinesia. While such studies are in the progress, what is currently known about the use of gabapentin for the control of mood and anxiety disorders and tardive dyskinesia comes mostly from uncontrolled case reports. The few double-blind placebo-controlled studies that have been done to date have not demonstrated that gabapentin is an effective mood stabilizer.


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 only for use
as an anticonvulsant. It is also used to treat
individuals suffering from many kinds of pain problems,
tremors, restless legs syndrome, hot flashes associated with
menopause, and various psychiatric disorders.


3. Is a generic version of gabapentin available?

Generic forms of gabapentin are available in the USA as the
manufacturer no longer 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 has been claimed to sometimes be effective 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 claimed to be successful in controlling rapid
cycling and mixed bipolar states in a few 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. Gabapentin also may be useful as a treatment for
people with 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
might respond to treatment with gabapentin.
There are very few published reports on gabapentin’s
use in psychiatry and most of them do not support its use as a
treatment for people with mood disorders. Patients with hard-to-treat bipolar syndromes have been treated more often than patients
with “treatment-resistant” unipolar disorders, although a few
people with such hard to treat unipolar depressions may 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?

There is no good wvidence that gabapentin is a good acute or
long-term treatment for people with bipolar disorder.


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 attempting to use gabapentin as an antidepressant or as a mood-stabilizing
agent the final dose of gabapentin is most often between
900 and 2,000 mg per day. It has ben claimed that 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
Fatigue 11 3
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 of gabapentin 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?

Like other psychopharmacologic agents, gabapentin should be
discontinued gradually. Withdrawal reactions have been
occasionally treported, mostly in people who have abruptly
stopped taking large doses of gabapentin. 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 24 February 2007, the per tablet cost of generic
gabapentin, when ordered in lots of 100 tablets from
an on-line pharmacy (drugstore.com) was:


100 mg – $1.05

300 mg – $1.32

400 mg – $2.20

600 mg – $3.50

800 mg – $7.99



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 or anxiety disorders that have not been adequately
controlled by other medications.


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.

It has been hard to demonstrate in controlled studies the
effectiveness of gabapentin as a mood control agent.

Like other anticonvulsants, gabapentin may increase suicidal thinking.


28. Why might 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, proven
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?

Here are some abstracts of published reports on the psychiatric uses
of gabapentin:

1. Pharmacoepidemiol Drug Saf. 2010 Oct 4. [Epub ahead of print]

Gabapentin and suicide attempts.

Gibbons RD, Hur K, Brown CH, Mann JJ.

Center for Health Statistics, University of Illinois at Chicago, Chicago, IL
60612, USA.

PURPOSE : On 16 December 2008, FDA issued a class warning for antiepileptic drugs
and suicidal thoughts and behavior. The purpose of this study was to determine if
the antiepileptic drug gabapentin increases risk of suicide attempt in patients
to which it was prescribed for various indications. METHODS: We conducted a
pharmacoepidemiologic study in which suicide attempt rates were compared before
and after gabapentin was prescribed. We used the PharMetrics medical claims
database to study the relationship between gabapentin and suicide attempts in a
cohort of 131?178 patients with a 1-year window of information before and after
initial prescription. Patients had diagnoses of epilepsy, pain disorders, bipolar
illness, major depressive disorder, schizophrenia, and other psychiatric
disorders. RESULTS: Overall, there was no significant difference in suicide
attempt rates before (3.48/1000 patient years-PY) versus after (3.45/1000 PY)
gabapentin prescription. Pre-prescription suicide attempt rates were five times
higher in psychiatric populations compared with non-psychiatric populations
leading us to analyze the two groups separately. No drug effect was detected in
the non-psychiatric populations. Significant reductions in suicide attempt rates
were seen for bipolar disorder (47.85/1000 PY versus 31.46/1000 PY), major
depressive disorder (17.30/1000 PY versus 12.66/1000 PY), and other psychiatric
disorders (12.84/1000 PY versus 10.14/1000 PY). Person-time analysis revealed an
overall significant reduction in suicide attempt rates (2.01/1000 PY on drug
versus 2.30/1000 PY off drug). CONCLUSIONS: This study finds that gabapentin does
not increase risk of suicide attempts in non-psychiatric populations and is
associated with a reduction in suicide attempt risk in patients with psychiatric
disorders. Copyright � 2010 John Wiley & Sons, Ltd.

PMID: 20922708 [PubMed - as supplied by publisher]

2. Med Care. 2010 Apr;48(4):372-9.

The rise and fall of gabapentin for bipolar disorder: a case study on off-label
pharmaceutical diffusion.

Fullerton CA, Busch AB, Frank RG.

Department of Health Care Policy, Harvard Medical School, 180 Longwood Avenue,
Boston, MA 02478, USA. fullerton@hcp.med.harvard.edu

Comment in:
Med Care. 2010 Apr;48(4):285-7.

CONTEXT: Rising drug costs have increased focus on how new pharmaceuticals
diffuse into the marketplace. The case of gabapentin use in bipolar disorder
provides an opportunity to study the roles of marketing, clinical evidence, and
prior authorization (PA) policy on off-label medication use. DESIGN:
Observational study using Medicaid administrative and Verispan marketing data. We
examined the association between marketing, clinical trials, and prior
authorization on gabapentin use. SETTING AND PATIENTS: Florida Medicaid, bipolar
disorder-diagnosed enrollees ages 18 to 64 for fiscal years 1994 to 2004.
RESULTS: Gabapentin prescriptions increased from 8/1000 enrollees per quarter in
1994 to a peak of 387/1000 enrollees in 2002. Its uptake tracked marketing
efforts towards psychiatrists. The publication of 2 negative clinical trials in
2000 and the discontinuation of marketing expenditures towards psychiatrists were
associated with an end to the steep rise in gabapentin prescriptions. After these
events gabapentin use remained between 319/1000 and 387/1000 enrollees per
quarter until the PA policy, which was associated with a 45% decrease in
prescriptions filled. After 1 year, scientific evidence and marketing
discontinuation were associated with a 5.4 percentage point decrease in the
predicted probability of filling a gabapentin prescription and the PA policy, a
7.1 percentage point decrease. CONCLUSIONS: Pharmaceutical marketing can
influence off-label medication prescribing, particularly when pharmacologic
options are limited. Evidence of inefficacy and/or the cessation of
pharmaceutical marketing, and a restrictive formulary policy can alter prescriber
behavior away from targeted pharmacologic treatments. These results suggest that
both information and policy are important means in altering physician prescribing
behavior.

PMID: 20195173 [PubMed - indexed for MEDLINE]

3. N Engl J Med. 2009 Nov 12;361(20):1963-71.

Outcome reporting in industry-sponsored trials of gabapentin for off-label use.

Vedula SS, Bero L, Scherer RW, Dickersin K.

Center for Clinical Trials, Department of Epidemiology, Johns Hopkins Bloomberg
School of Public Health, Baltimore, MD, USA. svedula@jhsph.edu

Comment in:
N Engl J Med. 2010 Apr 29;362(17):1641; author reply 1641-2.

BACKGROUND: There is good evidence of selective outcome reporting in published
reports of randomized trials. METHODS: We examined reporting practices for trials
of gabapentin funded by Pfizer and Warner-Lambert's subsidiary, Parke-Davis
(hereafter referred to as Pfizer and Parke-Davis) for off-label indications
(prophylaxis against migraine and treatment of bipolar disorders, neuropathic
pain, and nociceptive pain), comparing internal company documents with published
reports. RESULTS: We identified 20 clinical trials for which internal documents
were available from Pfizer and Parke-Davis; of these trials, 12 were reported in
publications. For 8 of the 12 reported trials, the primary outcome defined in the
published report differed from that described in the protocol. Sources of
disagreement included the introduction of a new primary outcome (in the case of 6
trials), failure to distinguish between primary and secondary outcomes (2
trials), relegation of primary outcomes to secondary outcomes (2 trials), and
failure to report one or more protocol-defined primary outcomes (5 trials).
Trials that presented findings that were not significant (P > or = 0.05) for the
protocol-defined primary outcome in the internal documents either were not
reported in full or were reported with a changed primary outcome. The primary
outcome was changed in the case of 5 of 8 published trials for which
statistically significant differences favoring gabapentin were reported. Of the
21 primary outcomes described in the protocols of the published trials, 6 were
not reported at all and 4 were reported as secondary outcomes. Of 28 primary
outcomes described in the published reports, 12 were newly introduced.
CONCLUSIONS: We identified selective outcome reporting for trials of off-label
use of gabapentin. This practice threatens the validity of evidence for the
effectiveness of off-label interventions.

PMID: 19907043 [PubMed - indexed for MEDLINE]

4. Gen Hosp Psychiatry. 2009 May-Jun;31(3):279-87. Epub 2009 Apr 5.

How reviews covered the unfolding scientific story of gabapentin for bipolar
disorder.

Williams JW Jr, Ranney L, Morgan LC, Whitener L.

Center for Health Services Research in Primary Care, Durham VAMC and Center for
Clinical Health Policy Research, Duke University, Durham, NC 27705, USA.
jw.williams@duke.edu

BACKGROUND: Despite the lack of randomized controlled trials (RCTs), gabapentin
use increased rapidly in the 1990s for mental health conditions. Subsequent RCTs
did not demonstrate efficacy for bipolar disorder (BD). We examined the
characteristics of review articles to determine their potential role in the
growth of gabapentin for BD. METHODS: We searched MEDLINE, the International
Pharmaceutical Abstracts and LexisNexis for review articles or commentaries
examining the role of gabapentin for BD. Electronic searches were supplemented by
manual searches of reference lists. Articles were abstracted for the types of
evidence cited, source of evidence, the proportion of available RCTs cited and
narrative blurbs discussing the role of gabapentin for BD. Review articles were
classified as narrative versus systematic and positive, neutral or negative
regarding the role of gabapentin in BD. RESULTS: We included 27 review articles
published between 1998 and 2008, but no commentaries met eligibility criteria.
Most did not describe potential conflicts of interest or a funding source, and
the 3 systematic reviews were of low quality. The 11 reviews published prior to
the first RCT of gabapentin for BD cited uncontrolled trials or case series
(n=9), basic science (n=6), chart reviews (n=3) or unpublished RCTs (n=2). Six
recommended gabapentin, 3 were neutral and 2 were negative. The 16 articles
published after the first gabapentin RCT continued to cite uncontrolled trials
and basic science; only 5 cited all the available RCTs. However, more of these
reviews (n=10) reached negative conclusions about the role of gabapentin for BD.
CONCLUSIONS: Narrative and low-quality systematic reviews, principally those
published prior to RCTs, may have contributed to the growth of gabapentin use for
BD. High-quality systematic reviews are needed to inform clinicians and
policymakers about the effectiveness of new treatments.

PMID: 19410108 [PubMed - indexed for MEDLINE]

5. J Clin Psychiatry. 2006 Mar;67(3):473-7.

A double-blind, randomized, placebo-controlled, prophylaxis study of adjunctive
gabapentin for bipolar disorder.

Vieta E, Manuel Goikolea J, Mart�nez-Ar�n A, Comes M, Verger K, Masramon X,
Sanchez-Moreno J, Colom F.

Bipolar Disorders Program, Institute of Neuroscience, Hospital Clinic, University
of Barcelona, IDIBAPS, Barcelona, Spain. evieta@clinic.ub.es

OBJECTIVE: To conduct the first randomized, controlled trial assessing the
prophylactic efficacy of gabapentin in bipolar disorder. METHOD: We conducted a
1-year, double-blind, randomized, comparative, placebo-controlled,
parallel-group, multicenter study. As this was a pure prophylactic trial, only
euthymic bipolar I and II patients (DSM-IV) were randomly assigned in a 1:1 ratio
to gabapentin (N = 13) or placebo (N = 12) added to the current treatment
(lithium, valproate, carbamazepine, or any combination but not antipsychotics or
antidepressants). Subjects participated in the study for 12 months. The primary
efficacy parameter was the Clinical Global Impressions scale for Bipolar Illness,
Modified (CGI-BP-M), which was assessed at all visits. Other assessments were the
Young Mania Rating Scale (YMRS), Hamilton Rating Scale for Depression (HAM-D),
Hamilton Rating Scale for Anxiety (HAM-A), Pittsburgh Sleep Quality Index (PSQI),
and the systematic collection of reported adverse events. Data were collected
from May 1999 to February 2004. RESULTS: The change from baseline to month 12 in
mean CGI-BP-M scores between groups was statistically significant (p = .0046).
Mean score change from baseline to endpoint in the gabapentin group was -2.1, and
the mean score change in the placebo group was -0.6. No emerging manic or
depressive symptoms were seen in either group as measured with the YMRS, HAM-D,
HAM-A, and PSQI. In the PSQI-6 subscale (use of sleeping medication), the mean
score change at month 12 in the gabapentin group was 0.9, and the mean score
change in the placebo group was 0.05 (p = .0267). Overall, gabapentin was well
tolerated. CONCLUSION: This small, randomized clinical trial comparing the
prophylactic efficacy of adjunctive gabapentin to placebo suggests that, despite
lack of acute efficacy, treatment with gabapentin might provide some benefit on
the long-term outcome of bipolar disorder.

PMID: 16649836 [PubMed - indexed for MEDLINE]

6. Menopause. 2003 May-Jun;10(3):214-7.

Gabapentin for the management of hot flushes: a case series.

Albertazzi P, Bottazzi M, Purdie DW.

Centre for Metabolic Bone Disease, Hull Royal Infirmary, England.
p.albertazzi@hull.ac.uk

OBJECTIVE: To audit the effectiveness of the anticonvulsant gabapentin on hot
flushes in postmenopausal women. DESIGN: This was an open case series involving
11 postmenopausal women who were willing to take gabapentin for the relief of
their hot flushes and were willing to keep a diary recording the number and
intensity of their hot flushes, both before and during treatment. Gabapentin was
started at a dose of 300 mg, to be taken at night, and the women were instructed
to increase the dose up to 1,200 mg, according to symptom behavior. RESULTS:
Eleven women agreed to participate for on average 53.22 days (range, 2-79 days),
but two discontinued participation-one before starting treatment and one after 2
days-so there are complete data sets for nine women. Gabapentin was found to be
extremely effective in reducing hot flush activity (P < 0.001; Fig. 1). A significant reduction in symptoms was observed with a dose of 300 mg/day (P < 0.001). Scores on the Green Climacteric Scale were significantly improved from a mean of 25.72 (range, 12-42) to 19.25 (range, 13-31; P < 0.001). Palpitations (P = 0.001), panic attacks (P = 0.0001), mood (P = 0.023), muscle and joint pains (P = 0.021), and paresthesias and loss of sensation in the extremities (P = 0.001) were also shown to improve with treatment. CONCLUSIONS: In the present case series, gabapentin was well tolerated and could be a valuable alternative for the treatment of hot flushes in women with contraindications to hormonal replacement therapy. It would be particularly beneficial for women in whom aches and pains and paresthesias are also a significant feature of the climacteric syndrome. PMID: 12792292 [PubMed - indexed for MEDLINE] 7. Bipolar Disord. 2002 Oct;4(5):296-301. Gabapentin augmentation therapy in bipolar depression. Wang PW, Santosa C, Schumacher M, Winsberg ME, Strong C, Ketter TA. Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, Stanford, CA 94305-5723, USA. wangp0@stanford.edu BACKGROUND: Gabapentin (GBP) may be useful in bipolar disorders, including as adjunctive therapy for bipolar depression, although controlled studies suggest inefficacy as primary treatment for mania or treatment-resistant rapid cycling. METHODS: We performed a 12-week trial of open GBP (mean dose 1725 mg/day) added to stable doses of mood stabilizers or atypical antipsychotics in 22 (10 women, mean age 38.4 years) depressed (28-item Hamilton Depression Rating Scale (HDRS) >
18] bipolar (10 bipolar I, 12 bipolar II) disorder outpatients. Mean illness
duration was 18.6 years, current depressive episode duration was 18.0 weeks.
Prospective 28-item HDRS, Young Mania Rating Scale (YMRS) and Clinical Global
Impression-Severity (CGI-S) ratings were obtained. RESULTS: Overall, HDRS ratings
decreased 53% from 32.5 +/- 7.7 at baseline to 16.5 +/- 12.8 at week 12 (p < 0.0001). Twelve of 22 (55%) patients had moderate to marked improvement (HDRS decrease = 50%) with HDRS decreasing 78% from 27.9 +/- 6.2 to 6.2 +/- 4.5 (p < 0.0001). Eight of 22 (36%) patients remitted (HDRS > or = 8). In non-responders,
HDRS decreased from 38.0 +/- 5.4 to 28.9 +/- 6.7 (p = 0.005). Ten of 13 (77%)
mild to moderately depressed (baseline HDRS > 18 and <35) patients responded, while only two of nine patients (22%) with severe depression (HDRS > or = 35)
responded (p < 0.03). Both groups, however, had similar, statistically significant HDRS decreases. GBP was well tolerated. CONCLUSION: Open adjunctive GBP was effective and well tolerated in patients with mild to moderate bipolar depression. This open pilot study must be viewed with caution, and randomized controlled studies are warranted. PMID: 12479661 [PubMed - indexed for MEDLINE] 8. Ann Pharmacother. 2001 Oct;35(10):1264-9. Gabapentin treatment for bipolar disorders. Maidment ID. Pharmacy Department, Kent and Canterbury Hospital, England. ian.maidment@ekh-tr.sthames.nhs.uk OBJECTIVE: [corrected] To review the effectiveness data on the use of gabapentin in bipolar disorders. DATA SOURCES: Clinical literature was accessed through MEDLINE (January 1985-November 2000). Key search terms included gabapentin, mood stabilizer, and bipolar disorder. DATA SYNTHESIS: Bipolar disorder is a complex condition that can be difficult to treat effectively. Mood stabilizers are increasingly being used to manage bipolar disorder. Studies that used gabapentin in bipolar disorders are evaluated. CONCLUSIONS: From the data presented, gabapentin cannot be recommended for treatment of bipolar disorder. Further studies are required to determine whether gabapentin has any role in the management of bipolar disorder. PMID: 11675857 [PubMed - indexed for MEDLINE] 9. J Clin Psychopharmacol. 2000 Dec;20(6):607-14. A placebo-controlled study of lamotrigine and gabapentin monotherapy in refractory mood disorders. Frye MA, Ketter TA, Kimbrell TA, Dunn RT, Speer AM, Osuch EA, Luckenbaugh DA, Cora-Ocatelli G, Leverich GS, Post RM. Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1272, USA. There is a pressing need for additional treatment options for refractory mood disorders. This controlled comparative study evaluated the efficacy of lamotrigine (LTG) and gabapentin (GBP) monotherapy versus placebo (PLC). Thirty-one patients with refractory bipolar and unipolar mood disorders participated in a double-blind, randomized, crossover series of three 6-week monotherapy evaluations including LTG, GBP, and PLC. There was a standardized blinded titration to assess clinical efficacy or to determine the maximum tolerated daily dose (LTG 500 mg or GBP 4,800 mg). The primary outcome measure was the Clinical Global Impressions Scale (CGI) for Bipolar Illness as supplemented by other standard rating instruments. The mean doses at week 6 were 274 +/- 128 mg for LTG and 3,987 +/- 856 mg for GBP. Response rates (CGI ratings of much or very much improved) were the following: LTG, 52% (16/31); GBP, 26% (8/31); and PLC, 23% (7/31) (Cochran's Q = 6.952, df = 2, N = 31, p = 0.031). Post hoc Q differences (df = 1, N = 31) were the following: LTG versus GBP (Qdiff = 5.33, p = 0.011); LTG versus PLC (Qdiff = 4.76, p = 0.022); and GBP versus PLC (Qdiff = 0.08, p = 0.70). With respect to anticonvulsant dose and gender, there was no difference between the responders and the nonresponders. The agents were generally well tolerated. This controlled investigation preliminarily suggests the efficacy of LTG in treatment-refractory affectively ill patients. Further definition of responsive subtypes and the role of these medications in the treatment of mood disorders requires additional study. PMID: 11106131 [PubMed - indexed for MEDLINE] 10. Pharmacopsychiatry. 1999 Jul;32(4):136-41. Clinical experience using adjunctive gabapentin in treatment-resistant bipolar mixed states. Perugi G, Toni C, Ruffolo G, Sartini S, Simonini E, Akiskal H. Institute of Psychiatry, University of Pisa, Italy. gperugi@psico.med.unipi.it OBJECTIVE: Open studies and case observations have suggested that gabapentin may be effective in the treatment of bipolar disorder. However, the adjunctive use of the drug in bipolar mixed states has not been specifically addressed before. METHODS: Twenty-one patients with bipolar I mixed episodes as defined by Diagnostic and Statistical Manual of Mental Disorders (Revised) (DSM-III-R), who were admitted to the outpatient department at the Psychiatry Clinic of the University of Pisa, were treated adjunctively with gabapentin for a period of eight weeks. All patients had been resistant to therapeutic levels of standard mood stabilizers, and had a mean clinical global impression (CGI) of 5.2+/-0.8 when entering the study. Gabapentin treatment was started at 300 mg/day and increased up to 2000 mg/day. Patients were evaluated using the Hamilton Rating Scale for Depression (HRSD), the Young Mania Rating Scale (YMRS), and CGI. Patients with final CGI scores of 1 or 2 were regarded as responders. RESULTS: Only one patient had to interrupt the drug treatment, due to irritability and ataxia. Negative interactions between gabapentin and concomitant psychotropic medications were not observed. The condition deteriorated in only one patient (final CGI = 5). Ten patients were regarded as responders: four showed marked improvement (CGI = 1), and six had moderate improvement (CGI = 2). The mean dose of gabapentin at week 8 was 1130 mg (range 600-2000 mg). The mean final CGI score for all patients (responders and nonresponders combined) was 3.7+/-1.1 (the mean change in CGI was significant, t=6.1, P<0001). The reduction in the mania score was minimal and statistically insignificant. However, the mean HRSD score showed a statistically significant reduction from 18.2 to 10.6 (t=5.73, P<0.0001), irrespective of the baseline severity of the mania. All but one of the responders maintained these therapeutic improvements over 4-12 months, in most cases requiring less concomitant antidepressant and neuroleptic medications. CONCLUSIONS: These results show that gabapentin appears to be potentially useful in the adjunctive treatment of drug-resistant bipolar mixed states, and that it was particularly effective in relation to depressive symptomatology. PMID: 10505483 [PubMed - indexed for MEDLINE] 11. Pharmacotherapy. 1999 May;19(5):565-72. Gabapentin: a review of published experience in the treatment of bipolar disorder and other psychiatric conditions. Letterman L, Markowitz JS. Department of Pharmacy Practice, Medical University of South Carolina, Charleston 29425, USA. Successful therapy with valproate and carbamazepine in patients with psychiatric disorders led to investigation of other anticonvulsants for similar indications. Gabapentin is a relatively new anticonvulsant being investigated for potential use in the treatment of bipolar disorder (BD), anxiety disorders, behavioral dyscontrol, and substance use disorders. Its favorable side effect profile, absence of the need for therapeutic drug monitoring, and minimal drug interactions give gabapentin a potential role in these indications. Computer searches of the biomedical literature were undertaken to identify all pertinent case reports, case series, and studies of the drug as monotherapy or adjunctive therapy for BD; 10 reports were retrieved. In the treatment of various anxiety disorders, one study, one case report, and one case series were identified. At least one case series described gabapentin therapy for alcohol withdrawal and one case report of the drug for agitation associated with dementia. Published, well-designed studies evaluating the agent's effectiveness as monotherapy for BD are lacking. Its benefit as an adjunctive treatment with other mood stabilizers is also unestablished. Data regarding its efficacy in the treatment of anxiety disorders or manifestations of substance abuse are limited. These areas may deserve further investigation. PMID: 10331819 [PubMed - indexed for MEDLINE] 12. J Clin Psychiatry. 1998 Aug;59(8):426-9. Gabapentin treatment of mood disorders: a preliminary study. Ghaemi SN, Katzow JJ, Desai SP, Goodwin FK. Psychopharmacology Research Center, Department of Psychiatry, The George Washington University, Washington, DC 20037, USA. OBJECTIVE: To determine if gabapentin is effective either as adjunctive treatment or as monotherapy for major affective disorders in a naturalistic setting. METHOD: All charts of patients meeting DSM-IV criteria for bipolar disorder or unipolar major depressive disorder treated with gabapentin in a private psychiatric practice were reviewed and clinical response was assessed retrospectively using the Clinical Global Impressions scale for Improvement (CGI-I). RESULTS: Gabapentin was moderately to markedly effective in 30% (15/50) of patients, with statistically nonsignificant differences between patients with bipolar disorder type I, bipolar disorder type II and NOS, and unipolar major depressive disorder. 70% reported side effects, mainly sedation, with 16% of the total sample discontinuing treatment due to adverse events. CONCLUSION: Gabapentin appears to be somewhat effective as add-on treatment in a subgroup of patients with mood disorders in a naturalistic setting. Prospective, controlled studies are required to clarify these pilot data. PMID: 9721823 [PubMed - indexed for MEDLINE]



30. Additions and corrections?

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