11 echo chamber suppl 1-08 pp15-27.qxd

Gabapentin in the Treatment of
TIMOTHY S. CAREY, MD, MPH
JOHN W. WILLIAMS, JR., MD, MHS
Mental Illness: The Echo Chamber
JOHN M. OLDHAM, MD, MS
FRANCINE GOODMAN, PharmD, BCPS
of the Case Series
LEAH M. RANNEY, PhD
LYNN WHITENER, DrPH, MSLS
LAURA C. MORGAN, MA
CATHY L. MELVIN, PHD, MPH
Background. Bipolar disorder is a common and debilitating psychiatric illness. Several antiepileptic drugs
(AEDs) have been approved for the treatment of bipolar disorder. Gabapentin gained a large market share of
AED use in the late 1990s in spite of a lack of randomized clinical trial (RCT) evidence and no labeled indica-
tion from the U.S. Food and Drug Administration for its use in psychiatric illness. This article describes the
results of a literature review, the purpose of which was to examine the characteristics of studies conducted in
humans concerning the efficacy of gabapentin in bipolar disorder. Methods.
Publications relevant to this topic
were identified based on a PUBMED search as well as an examination of references from a published system-
atic review and citations from relevant review articles. Results.
The search located 29 studies published
between 1997 and 2007, with the greatest number of articles published in 1998 and 1999. Of these 29 publica-
tions, 15 involved uncontrolled case series, while 6 were single case reports. The sample size in the studies was
generally small, and often we could not identify the funding source. Despite the generally weak study design
in the identified publications, the authors of the articles often commented on the promising nature of
gabapentin therapy for bipolar disorder. However, 4 small, randomized trials in heterogeneous populations
demonstrated little if any evidence of such efficacy. Nine letters to the editor demonstrated a similar pattern.
Conclusions.
The large number of case series concerning gabapentin is striking. The number of reports and
their distribution in many different journals created a type of “echo chamber” effect, through which the sheer
number of publications and citations may give legitimacy to the practice of using gabapentin for bipolar dis-
order. Although the case series were generally of poor quality, their publication in peer-reviewed journals may
have been partially responsible for the widespread use of an ineffective medication.
(Journal of Psychiatric
Practice
2007;14(suppl 1):15–27)
KEY WORDS: gabapentin, bipolar disorder, case series, case studies, efficacy Off-label use of medications generally refers to the CAREY, RANNEY, WHITENER, MORGAN, and MELVIN: The clinical use of a medication or device by a provider for Cecil G. Sheps Center for Health Services Research, The an indication that has not been approved by the U.S.
University of North Carolina at Chapel Hill; WILLIAMS: DukeUniversity School of Medicine, Durham, NC; OLDHAM: Food and Drug Administration (FDA). Off-label use Menninger Department of Psychiatry and Behavioral Sciences, falls within the accepted practice of medicine, which Baylor College of Medicine, Houston, TX; GOODMAN: Veterans gives physicians broad discretion to prescribe treat- Health Administration Pharmacy Benefits Management ments according to their best clinical judgment. A des- Strategic Healthcare Group, Columbia, SC.
ignation of “off-label” does not necessarily mean that a Copyright 2008 Lippincott Williams & Wilkins Inc.
medication or treatment is ineffective for the condition Please send correspondence and reprint requests to: Cathy L. Melvin, it is being used to treat; rather, it might be effective, PhD, MPH, The Cecil G. Sheps Center for Health Services Research, but it has not been demonstrated to have efficacy and The University of North Carolina at Chapel Hill, 725 Martin Luther been approved by the FDA for that indication. When King Jr. Boulevard, CB#7590, Chapel Hill, NC 27599-7590.
medications are under patent, additional randomized trials and regulatory approval are required to expand Funded by a grant administered by a consortium of state attorneys the conditions for which the medication is indicated.
Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES Pharmaceutical companies may not legally advertise authorship may be attributed to academics, a practice or otherwise market their medications for indications generally known as “ghost authorship.”5 other than those for which they have received FDA Gabapentin (Neurontin) is an antiepileptic drug approval. In contrast. case reports, case series, and (AED) that was licensed in June 1993.6 The medication other observational studies examining the use of underwent a very rapid growth in sales in the late already licensed medications for new indications are 1990s in spite of generally narrow FDA indications as routinely published in the clinical literature. Such an AED and a treatment for certain types of neuro- studies and publications are generally considered part pathic pain such as postherpetic neuralgia. However, of the research process of discovering new uses for by 1999, the second most common use of gabapentin was for the treatment of psychiatric conditions,7 Recent literature and court cases have reflected con- despite the absence of FDA indications for such condi- cerns about the origin, intent, and quality of some of tions. In addition, no randomized trials were done in the literature and about inappropriate marketing the 1990s that demonstrated efficacy for mental health activities addressing off-label indications for medica- indications, although multiple articles were published tions.1–3 Studies of off-label use which appear in the during the 1990s discussing the use of gabapentin for peer-reviewed literature may use study designs that bipolar disorder. This wave of publications coincided result in exclusion from systematic reviews of treat- with the rapid growth of off-label use of this agent.
ment efficacy, such as those conducted by the Cochrane Our group was funded by the Neurontin Executive Collaboration, the Drug Effectiveness Review Project, Committee (a consortium of state attorneys general) to or the Evidence-Based Practice Centers sponsored by disseminate evidence-based information on the roles of the Agency for Health Research and Quality (AHRQ).
AEDs, including gabapentin, in the treatment of bipo- Without a contemporaneous control group and ran- lar disorder. A systematic review of the use of AEDs in domization, it is very difficult to assess the efficacy of bipolar disorder conducted by the Drug Effectiveness an intervention, since improvement in the patient’s Review Project (DERP) found minimal acceptable evi- condition may be due to chance, the natural history of dence concerning the efficacy of gabapentin.8 The liter- the illness, or a nonspecific effect of treatment (placebo ature regarding gabapentin included a small number effect). Thus, case series and non-randomized prospec- of negative randomized trials, and the review conclud- tive observational studies are generally excluded from ed that no acceptable evidence existed to support the systematic reviews assessing efficacy and not included use of gabapentin for bipolar disorder. The review did in either the abstract or the full text of the review.
find evidence for the efficacy of three AEDs: carba- Observational studies may be included in systematic mazepine, valproic acid/valproate, and lamotrigine. In reviews that examine adverse events and may also order to better understand the reasons for growth in sometimes be included to provide information on the the prescribing of gabapentin by providers, we exam- effect of a treatment in subpopulations for which no ined the characteristics of the published literature dur- ing the period this occurred. Once a study is published For some medications, off-label use has become much in the peer-reviewed literature, it can be cited and more common than use for the medication’s approved reproduced, giving the conclusions of the study an aura indications—despite a lack of evidence of treatment of authority that is perhaps not warranted by the qual- efficacy for those off-label uses.4 Journalists and court ity of the research. Our qualitative review includes lit- cases have found that in some circumstances off-label erature that is generally excluded from systematic use has been encouraged by pharmaceutical companies reviews addressing efficacy; we are including this lit- working through medical education companies. While erature to better understand how provider behavior some of the activities of medical education companies may be affected by weak, but widely disseminated, resemble conventional continuing medical education (CME), these companies may collaborate withresearchers and influential clinicians to conduct and write case reports and case series, give grand roundsand CME lectures, and serve on speakers bureaus to We searched for literature on PUBMED using Medical promote off-label use of medications. An unknown Subject Headings (MeSH) or key words for gabapentin number of articles may be written in whole or in part and bipolar disorder. Our inclusion criteria were all by employees of the educational company but the English-language studies published between 1966 and Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES 2007 that involved original research on humans exam- Figure 1. Results of literature search
ining the role of gabapentin in bipolar disorder. Wesupplemented the PUBMED searches with hand Titles and abstracts
searches of recent review articles as well as searches of identified through
the Drug Industry Document Archive (DIDA) database searches:
through the University of California-San Francisco n = 125
(UCSF) library. The DIDA database is a compendium Citations excluded:
of documents gathered as part of the discovery process n = 23
during the litigation concerning gabapentin. Articleswere reviewed for relevance to bipolar disorder and Articles published as
inclusion of original data addressing the efficacy of abstract-only:
gabapentin in the treatment of bipolar disorder either n = 10
Full-text articles
as monotherapy or as an adjuvant to other treatments.
retrieved:
The articles we identified were then abstracted into n = 92
evidence tables by staff and these abstractions were Full text articles
excluded:
n = 39
We found 29 articles in the peer reviewed literature during the time period examined. Only 4 of these stud- ies were randomized trials, 2 of which were crossover trials. The remaining 25 articles were excluded from previous systematic reviews for the standard reason that they lacked an appropriate comparison group andit was therefore not possible to judge efficacy compared Background articles:
with existing treatments or placebo. The characteris- n = 15
tics of the 29 articles are summarized in Appendix 1.
Nineteen studies were conducted in the United States Articles/letters included in review:
or Canada, and 10 in Europe. Figure 1 summarizes the n = 38
The temporal distribution of the articles is presented in Figure 2. The first articles appeared in 1997, with the most frequent publications in 1998 and 1999.
Publication became less common after 2000, the year in which the first randomized controlled trial (RCT) 2 on double-blind, randomized crossover trials was published demonstrating lack of efficacy of gabapentin as an adjunct to other AEDs in bipolar dis-order.9 Only three articles were published after 2002,the year that Warner-Lambert’s fraudulent promotion 6 months of patient outcome data, which is short for a of off-label uses for gabapentin became public. The chronic disease such as bipolar disorder. Seventeen of most common type of study design was the case series the studies reported outcomes measures such as stan- (15 studies), in which patients were given gabapentin dard scales, while the others reported clinician impres- without blinding of the patients or providers and with- out comparison to any control group. Evidence of effi- The conclusions presented in the articles were cacy was inferred through improvement over time.
almost uniformly optimistic, with the exception of 3 of Sample sizes in these case series were generally small, the 4 controlled studies. Appendix 1 includes conclu- 18 patients on average (range 2–43); 8 of the 15 case sions as reported by the authors. While most of the series contained 20 or fewer subjects. The duration of articles did note the need for additional studies and follow-up was quite variable, sometimes even within randomized trials, there was little discussion concern- the same study. Of the 29 studies, 22 reported less than ing the inability to show causality and other possible Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES Figure 2. Number of articles published per year
lar disorder.”12 These four trials provided no substan-tial evidence of the efficacy of gabapentin in the treat- ment of bipolar disorder, or in preventing recurrence of symptoms. Three of the four trials’ conclusions didmatch their results sections.
One article was a retrospective chart review without collection of information directly from patients.29 Weidentified three prospective studies that did not have contemporaneous comparison groups.41,44,46 Seventeen of the articles (58.6%) had unknown fund- ing sources, 6 studies were funded by private founda- tions or internal university grants, 4 were reported to be funded by industry, and 2 by Canadian governmentagencies.
To understand the impact of the 29 articles pub- lished in the peer-reviewed literature, we used the ISIWeb of Science to conduct citation searches. According to this reference database, all 29 studies were cited inother articles. The average number of citations was 35 explanations (e.g., natural history of the disease, effect per article. Even the most recent article, which was of co-interventions, placebo effect) for the improvement published in 2006, had been cited at least twice. Those that had been observed. Six studies were case reports cited most frequently were the randomized trials: Frey of single patients. Several of the cases reported benefit et al. 200010 was cited 196 times, and Pande et al. 20009 of gabapentin in ameliorating the adverse effects of was cited 130 times. The 1,001 citations of the 29 arti- other medications, such as bruxism (teeth grinding) cles appeared in 429 unique articles in 152 unique due to an antidepressant. Most of the case series and journals (any article could cite any number of the orig- single case reports addressed the use of gabapentin as inal 29 studies). The lead authors of the original 29 adjunctive therapy in patients who were taking other articles also co-authored articles that cited the original medications. The rationale for testing gabapentin in 29. For example, Grunze was an author or co-author of bipolar disorder varied among the studies and includ- 20 of the 429 articles in which citations appeared, ed the sometimes refractory nature of the illness, the while Frye was an author or co-author of 19 of the 429 usefulness of other AEDs (class effect), and the per- and McElroy was an author or co-author of 15 of them.
ceived modest incidence of adverse events with In all, the authors of the original 29 articles appeared as authors 130 times for these 429 articles in which Four randomized trials were published between citations of the original studies appeared. More than 2000 and 2006.9–12 The average number of patients in half (15) of the 29 articles were originally published in each trial was 55; only one trial9 studied more than 100 only four journals: Bipolar Disorder, Journal of patients. The quality of this trial was considered fair; Clinical Psychopharmacology, Journal of Affective the other trials all had significant design or conduct Disorders, and Journal of Clinical Psychiatry. The problems and were rated as poor. The trials by Frye10 tracking of citations and authors done for this study and Obrocea11 both had crossover designs, which can indicated that a few authors, often writing together be problematic in diseases which may be influenced by and appearing in a limited number of journals, can the order in which medications are provided, leading to appear in other research for a much broader audience.
attenuation of effect. Both of these small crossover tri- We did search the University of California at San als found that gabapentin was not distinguishable Francisco’s digital archive of documents regarding the from placebo. The fourth trial12 was very small with case of United States of America ex. rel David Franklin only 25 randomized patients, and only half of the sub- vs Pfizer Inc and Parke Davis, Division of Warner- jects were followed for the duration of the study. In Lambert Co (http://dida.library.ucsf.edu). These docu- spite of the high attrition and generally negative ments, which mostly date from the late 1990s, results, the author concluded that “gabapentin might document pharmaceutical marketing strategies for provide some benefit on the long-term outcome of bipo- gabapentin for multiple indications, including bipolar Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES disorder. We found authors of 8 of the 29 articles refer- Case series and other observational study designs do enced in the archives, with involvement such as pres- have a role in the medical literature. Clinical observa- ence at a company-sponsored meeting, being a paid tions, and their report in series of cases, are often the speaker, or a reference to working with ghostwriters.
first way hypotheses are generated and transmitted to We were unable, based on these documents, to directly the research and the clinical communities. Case series tie specific involvement or payment to specific publica- may be useful in settings of initial reports of innovative treatment, hospital reports of outcomes, or multi-insti- In addition to the 29 peer reviewed articles, we iden- tutional registries. Although relatively little guidance tified an additional 9 letters to the editor published in has been published on quality grading of case series, journals that contained patient information.38,48–55 readers are referred to one publication in this area by Three were case reports, while 6 were case series with our group.56 Characteristics of good case series reports a mean sample size of 24. Four letters were published in 1997; the most recent letter, which was a case report, appeared in 2006 and stated that “Gabapentin showed preliminary efficacy as an add-on mood stabilizer to divalproex for adults with mental retardation and bipolar mood disorder or schizoaffective disorder, bipo- Discussion/conclusions supported by the dataAcknowledgment of funding source if any.
The studies on gabapentin were limited, even as case DISCUSSION
series, in that they often did not describe the study We identified a large number of studies reporting on population or patient selection. The discussion sections the use of gabapentin in bipolar disorder that were were also limited, and there was a lack of clarity con- published in the late 1990s and early in the current cerning funding sources. Drawing inferences regarding decade. The studies were characterized by small sam- treatment efficacy from pre-post case series may be ple sizes, poor description of the patient populations, especially fraught with difficulties in a chronic condi- and relatively brief follow-up. Most of the studies did tion such as bipolar disorder, which is characterized by not report sponsorship or potential conflicts of interest a waxing and waning clinical course. Yet limitations in by the authors. The DIDA database did indicate that drawing inferences from such small samples were the manufacturer of gabapentin at that time contract- often unacknowledged in these publications. Patients ed with medical education companies in the late 1990s with bipolar disorder are also often taking a number of to produce peer reviewed publications on off-label use medications, including other AEDs or antipsychotic of the medication.7 The timing and type of publications medications. Unless such co-interventions are careful- we identified are consistent with just such a campaign.
ly assessed and their equal distribution across the The reduction in the number of publications examin- intervention and comparison groups is assured, treat- ing the use of gabapentin in bipolar disorder in recent ment effect will be difficult to distinguish from years may be due to a number of factors, such as the improvement due to natural history, placebo effect, or disclosure of the manufacturer’s fraudulent marketing the effect of the co-interventions. Use of contempora- scheme, lapsing of the contracts with medical educa- neous controls and randomization are the only ways in tion companies, or consensus in the academic psychia- which treatment effect can be assessed in these cir- try community regarding the lack of utility of cumstances. In the case of gabapentin, RCTs were not gabapentin for these indications. The number of publi- conducted for some years after this agent began to be cations from European authors in recent years may widely used for mental health indications, and the reflect attempts to increase market share outside the studies that were done were often small and some- The number of times this limited literature was cited The large number of case series and case reports is remarkable. Simple citation counts do not, of course, reported encouraging results that were not confirmed describe how the citation was used in this secondary by later small randomized trials. The number of literature and an examination of the 429 articles in reports and their distribution in a number of journals which these citations appeared was beyond the scope of created a type of “echo chamber” effect, through which the sheer number of publications and citations may Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES have given legitimacy to the practice of using time we recommend that gabapentin be used only in gabapentin for bipolar disorder. Although pharmaceu- the setting of a randomized trial among patients tical representatives visiting providers’ offices are pro- refractory to other agents.” We recognize that circum- hibited from distributing copies of articles addressing stances might arise in which patients are truly refrac- off-label use of their products, such practices did occur tory to the multiple treatments available, and in the past,1 and the large number of available publi- clinicians do need some flexibility to address such dif- cations may have made such practices easier. The cita- ficult clinical situations. The role of the research liter- tion of such publications during grand rounds or CME ature should be to encourage appropriate clinical use, conferences by clinical experts who may have relation- not inappropriate prescribing in settings in which ships with pharmaceutical companies is another other efficacious treatments are available. Clinicians potential route of dissemination. The case of may prescribe medications off label for appropriate gabapentin, a medication that has modest benefit for reasons, including lack of data or FDA evaluation in seizures and neuropathic pain, but which has been certain populations (e.g., children) or in patients whose used for many other indications, is one of the most illness is refractory to treatment or who are unable to striking examples of coordinated off-label marketing. A recent settlement regarding olanzapine is another.57 A cursory examination of the literature identified in The clinical community knows about these activities this review reveals repeated references to a promising only through the public availability of documents new treatment. Our more detailed examination obtained in the discovery process of litigation. Other demonstrates multiple poor quality observational examples of the use of the medical publication system studies which collectively represent an echo chamber for off-label marketing purposes may exist but have encouraging utilization of the medication based on not yet been similarly uncovered. While the fines from minimal evidence. The literature on gabapentin repre- litigation were imposed on the pharmaceutical compa- sents a cautionary tale for industry, researchers, and ny (Warner-Lambert and Pfizer), the clinicians and fac- ulty who were the authors of record of the reportsshould also bear responsibility. How many case reportsor case series are needed to generate a hypothesis that References
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Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES lusions
linical utility of these widely used anticonvulsants appeared most effective in those with younger age and, y thus emerge as an important addition to the anticonvul- ith respect to anticonvulsant dose and gender TG in treatment-refractory affectively ill patients uthor conc
effective adjunctive treatment when administered to outpa- difference between the responders and the nonresponders controlled investigation preliminarily suggests the efficacy of TG appeared most effective for male patients with fewer prior with GP might provide some benefit for the long-term outcome study in bipolar disorder conducted to date sants used for treating bipolar disorder….Future double-blind patients with antidepressant-induced bruxism… GP w scribed to this patient on the basis of literature reports of effi- cacy in treating anxiety and mood symptoms controlled trials of GP in patients with iatrogenic idiopathic bruxism are needed to substantiate this anecdotal A
“The findings of this study did not demonstrate that GP is an “Initial reports of GP for mood stabilization are fa from randomization to first new episode ( began valproate and anorgasmia resolved 12 atient with bipolar I disorder on venlafaxine and on GP as adjunctive therapy (other medications continued) bruxism resolved within 4 weeks Results
No significant differences between groups for PSQI-6 subscale (use of sleep medication) at 12 No significant differences between groups for time 72% of patients showed overall positive response Bipolar symptoms resolved but patient developed Adj?
N
y design
Summary of studies located by literature search
Stud
y
Appendix 1.
Stud
Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES hotic patients with affective features of those linical utility in the management of tardive lusions
GP in conjunction with other effective mood stabilizers uthor conc
of our study must be regarded as preliminary and in need of replication in double-blind or placebo-controlled trials stabilizer and its usefulness as adjunctive therapy patients with ID…the present data seem to confirm the previ- ous evidence reported in the open trials….
patients to treat modest but not severe manic states seems to be safe and efficacious in the treatment of severe neous sample of non-refractory bipolar spectrum illness subgroup of patients with mood disorders in a naturalistic set- mood stabilizing and/or antidepressant properties of GP in the setting of bipolar spectrum disorders…this agent could be A
“These data in 25 patients suggest that GP ma “The present results suggest a possible role for GBP as a mood “It is suggested that GP monotherapy might be useful in selected “GP appears to be somewhat effective as add-on treatment in a “It is suggested that the possibility of renal dysfunction should be “Controlled studies are needed to evaluate the possible antimanic “Our report suggests that the possible antimanic properties of GP with statistically nonsignificant differ-, y 21 in the add-on group and from 27.8 to 9.0 in as moderately to markedly effective in 30% of bipolar disorder type II and not otherwise speci- as reversible after discontinuation of GP as remarkable within 3 weeks of start of treat- decreased after being given medication.
Improvement in scores on scales of anxiety markedly effective in 43% of patients for overall ences between patients with bipolar disorder type the total sample discontinuing treatment due to ment and remained so for 6 months of follow-up signs of tardive dyskinesia diminished until they accompanied by reduction of tardive dyskinesia in Results
Number of patients with mood disorder recurrence Improvement and stabilization of mood symptoms After 2 weeks of treatment a moderate improvement Adj?
N
ued
y design
contin
Stud
y
Appendix 1.
Stud
Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES ve antimanic and mood-stabilizing effects ve utility as an adjunctive medication.
lusions
hoice as an adjunctive therapy…This investigation Controlled studies of BP in bipolar disorder appear to ve antidepressant and anxiolytic properties uthor conc
moderate response must be considered a relative success in some patients with bipolar disorder and is generally well tol- ing that GP is an effective and well tolerated treatment in a large proportion of bipolar patients who are resistant to tradi- of GBP in resistant bipolar disorder resides in its effectiveness against comorbid panic disorder and alcohol abuse resistant bipolar mixed states…The major weakness of the placebo response or spontaneous remissions must be regarded effective as an augmenting agent in the maintenance phase of treatment of some bipolar spectrum patients “The data from this small study is quite preliminary should be validated by the standard researc who only partially respond to other mood stabilizers able side-effect profile and rapid action make this drug an A
“The results of the present study replicate prior studies indicat- “…GP appears to be an effective adjunctive treatment for drug- “The results of this small open study suggest that GP ma “This case series suggests that controlled studies are w ment 1 to 3 months after the addition of GP; responses over subsequent periods of time score showed significant reduction during 8 weeks a statistically significant reduction.
tinued to experience benefit from maintenance GP improve with further treatment while manic symp- stabilized with no significant side effects for peri- Results
Eight patients showed moderate or marked improve- All 7 patients experienced improvement in manic GP exerted potent early effect on initial, Adj?
N
ued
y design
contin
Stud
y
Appendix 1.
Stud
Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES as effective and well tolerated in patients parallel control group…Contrary to prior the main benefits of GP seemed to involve linical trials…Depressive symptomatology lusions
y be beneficial in bipolar depression.
GP responders compared with non-responders had y be a useful drug for the add-on treatment of bipolar uthor conc
wide therapeutic index with few side effects and drug interac- tion of GP…Unique to this case is that this geriatric patient week-long taper…GP taper should follow a course similar to that of a benzodiazepine taper—slowly and over a period of patients with poor response to mood stabilizers improved more than manic or hypomanic features with mild to moderate bipolar depression.
icance and generalizability of our findings to other patients are A
“Controlled studies are needed to evaluate the possible anti- and 4 showed no therapeutic effects (outcome atient showed marked response within 1 month and remained euthymic 7 months after addition of GP dropped to 9 after 1 month of treatment.
atient had moderate upper respiratory tract infec- tion symptoms and somatic complaints 1 da improvement (defined as a decrease of at least 2 with bipolar II disorder and severe agoraphobia and depression subscale in mean CGI-BP scores ences remained significant for improvements in Results
Adj?
N
ued
y design
contin
Stud
y
Appendix 1.
Stud
Journal of Psychiatric Practice Vol. 14, Suppl. 1 GABAPENTIN: THE ECHO CHAMBER OF THE CASE SERIES at least in a subgroup of patients…longer fol-, lusions
Small sample size and the use of an open uncon- uthor conc
cy of GP in both phases of bipolar disorder trolled design limit interpretation of results” term prophylactic efficacy in bipolar disorder low-up of patients who initially present in the depressed phase of bipolar disorder and are treated with GP is needed to c continued efficacy of this drug in depression and whether it leads to longer term mood stabilization.
A
“These findings are consistent with others establishing the effica- linical Global Impressions Scale fC Clinical Global Impressions of Improvement Clinical Global Impressions Severity Scale atients experienced significant reduction in depres- during a depressive episode showed significant decrease in depressive symptoms over 12 weeks Subgroup of manic patients had significant reduc- depressed group to determine effect of GP on mood versus anxiety symptoms (using HAM-D) showed significant overall reduction in both anxiety and depression after treatment and this subject w Results
Significant but modest reduction from baseline in Adj?
N
ued
y design
contin
Stud
Clinical Global Impressions Scale f y
Appendix 1.
Stud
Journal of Psychiatric Practice Vol. 14, Suppl. 1

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Short Communication Characteristics of the Turkish Isolates of Francisella tularensis ¸aban Gürcan*, O˘guz Karabay1, Aynur Karadenizli2, Çi˘gdem Karagöl, Trakya University, Faculty of Medicine, Department of Microbiology and Clinical Microbiology, Edirne; 1˙Izzet Baysal University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Bolu; 2Kocaeli Un

Section6uk.pmd

The following table is only meant as guidance. Under normal domistic conditions an acceptable life span can beexpected, if those in the table indicated polymered medicaments are used. Character explanation: A : good, suitable for continuous usage. B : satisfactory, suitable for periodic usage. F : above average, suitable for periodic or seldom usage. O : no information available at this mo

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