Full text of DOI:10.1345/aph.10027

CASE REPORTS
Treatment of Affective Disorder and
Obesity with Topiramate
Christian J Teter, John J Early, and Carol M Gibbs
OBJECTIVE: To report a case of weight loss and mood stabilization in a patient being treated with the antiepileptic drug topiramate.
CASE SUMMARY: A 37-year-old obese white woman with affective instability and obesity was being treated with adjunctive topiramate
therapy. The patient lost 10 kg over 10 weeks of treatment with topiramate and improved clinically, as evidenced by a reduction in
the number of times that she had to be admitted to a management unit for constant observation, and a decrease in the number of
times that mechanical restraints or medication interventions were required for aggressive outbursts. Furthermore, the patient
successfully completed two home visits while receiving topiramate therapy and was out of the hospital on her third home visit at the
time of this writing.
DISCUSSION: This case further strengthens previous reports that topiramate may be useful in treating affective disorders as well as
inducing weight loss in a patient population in which weight gain is common. The patient discussed in this case report had no acute
illnesses or changes in health status, no changes in diet, and no changes in her medications that could have accounted for the
sudden weight loss. In addition, the patient’s behavior did not improve until topiramate was added as adjunctive therapy of valproic
acid, citalopram, and chlorpromazine during an adequate trial period.
CONCLUSIONS: Controlled studies need to be performed to evaluate the use of topiramate in the psychiatric population and, in
particular, the benefits of topiramate therapy in psychiatric patients with an additional diagnosis of obesity.
KEY WORDS: topiramate, weight loss, affective disorder.
Ann Pharmacother 2000;34:1262-5.
15. There are also data from a retrospective chart review6
of 58 patients who had received topiramate for mood dis-
orders that were refractory to previous therapies, including
some of the newer antiepileptic drugs (i.e., lamotrigine,
gabapentin). Thirty-six (62%) of the patients showed
marked or moderate improvement as evidenced by qualita-
tive assessments, using a Likert scale to measure response.
Weight loss has been attributed to topiramate in addition
to these reports of mood stabilization.9-12 In a long-term ex-
tension study9 with topiramate, 14 of 16 patients who re-
mained in the study at six months had weight loss averag-
ing 11%. In a retrospective trial,10 the charts of 40 patients
were reviewed after topiramate had been added to other
antiepileptic drugs (i.e., valproic acid, carbamazepine,
phenytoin). The conclusions from this report indicate that
the addition of topiramate may be accompanied by signifi-
cant weight loss, particularly in patients receiving con-
he novel anticonvulsant topiramate is a sulfamate-sub-
stituted monosaccharide known to block AMPA/
T
kainate-gated ion channels1 and sodium channels,2 posi-
tively modulate γ-aminobutyric acidA receptors,3 and
weakly inhibit carbonic anhydrase.4 This medication has
been approved for use as adjunctive therapy in the treat-
ment of partial-onset seizures in adults.
There are few published data concerning the use of topi-
ramate for psychiatric disorders, but preliminary results
suggest possible benefits in mood disorders.5-8 A recent re-
port5 describes an acutely manic woman who responded
well to the administration of topiramate in small doses
(25–50 mg/d), as evidenced by a decrease in her Young
Mania Rating Scale score from 43 on day 1 to 13 on day
Author information provided at the end of the text.
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Shorvon.12 In these reports, weight loss was described as a dose-
dependent phenomenon, with patients in the lowest topiramate
dosage group (<200 mg/d) losing approximately 1.6 kg (2.2%
decline), and the patients in the highest dosage group (≥800
mg/d) losing approximately 6.5 kg (7.3%). However, our patient
was receiving the combination of topiramate and valproic acid,
which has been associated with even greater weight loss.10
The patient’s behavior improved dramatically after the addi-
tion of topiramate. Over the course of six weeks of topiramate
therapy, with a dosage of at least 200 mg/d, she had no aggres-
sive outbursts, required no mechanical restraints or medication
interventions, and did not need to be sent to a management unit
for stabilization. During this period, the patient successfully com-
pleted two home visits with her family. On a subsequent home
visit, however, the patient was hospitalized for a nonpsychiatric
illness and topiramate was discontinued. It therefore is not possi-
ble to determine whether topiramate produced any further effects.
comitant valproic acid therapy. The average weight loss in
the patients initially treated with valproic acid was 8 kg af-
ter the addition of topiramate. It has been suggested that
the weight-loss effects of topiramate may be attributable to
its antiglutamatergic properties, resulting in “activation.”13
However, the exact mechanism of weight loss with topira-
mate has not been fully elucidated.
Weight gain is a significant health risk associated with
many psychotropic agents including mood stabilizers, an-
tidepressants, and antipsychotics, both old and new.14 In
addition to health risks, weight gain is a significant cause
of noncompliance in patients being treated for any condi-
tion. It should be noted that there is no standard definition
of clinically significant weight gain, but the Food and
Drug Administration has defined significant weight gain as
a ≥7% increase in total body weight.14 We report the case
of a patient with affective disorder who lost 10 kg (7%
weight loss) after the addition of topiramate to her medica-
tion regimen despite continued treatment with valproic
acid and chlorpromazine, which are both known to con-
tribute to weight gain.15,16
Discussion
The patient had been on a Heart Healthy Carbohydrate
Consistent diet for obesity consistently before and during
topiramate therapy. This diet is a combination of the cur-
rent American Diabetic Association guidelines for carbo-
hydrate-consistent meal plans and the current American
Heart Association guidelines for low saturated fat, low
cholesterol, and moderate sodium meal plans (personal
communication, Laura L Graham BS RD LDN, Clinical
Dietician, Dorothea Dix Hospital, Raleigh, NC, May
2000). In addition to a balanced meal plan, the patient’s
treatment plan remained consistent. The number of off-unit
passes to the vending area was unchanged during her treat-
ment with topiramate. Furthermore, she did not experience
any acute illness during this time period or have any inci-
dences of nausea, vomiting, diarrhea, or loss in appetite
during treatment with topiramate. The patient had been re-
ceiving chlorpromazine and citalopram at constant dosages
for a long period of time previous to and during therapy with
topiramate. As she had not lost weight prior to topiramate
therapy, we do not believe that either of these drugs con-
tributed to the weight loss; valproic acid therapy also was
not a factor. This patient’s weight loss can most likely be ex-
plained as a result of the topiramate therapy rather than any
changes in diet, health status, or medication dosage adjust-
ments.
This case strengthens previous reports that topiramate
may be useful in treating affective disorders as well as in-
ducing weight loss in a patient population in which weight
gain is common. Our patient had no other contributing fac-
tors that could have accounted for her sudden weight loss.
Weight loss occurring in this patient due to topiramate
therapy is probable according to the Naranjo rating scale.18
In addition, the patient’s behavior did not improve until
topiramate was added as adjunctive therapy to an adequate
trial with the combination of valproic acid, citalopram, and
chlorpromazine.
CASE REPORT
A 37-year-old white woman had an extensive history of psychi-
atric diagnoses, including psychosis not-otherwise-specified, de-
pressive disorder not-otherwise-specified, borderline and antiso-
cial personality disorder, dissociative disorder, and chronic dys-
thymia. The patient’s current Axis I diagnosis remains psychotic
disorder not-otherwise-specified complicated by morbid obesity
as well as an Axis II diagnosis of personality disorder (borderline
type). She had been hospitalized in our state psychiatric facility
for approximately eight months prior to this case report (28th ad-
mission).
Since admission in February 1999, the patient frequently de-
veloped aggressive and combative behaviors toward herself and
others. Over a period of six months, she was placed in a manage-
ment unit for safety five times and chemically and mechanically
restrained twice. During this time, the woman had been receiving
the following medications over an adequate trial period: valproic
acid 2250 mg/d since March 1999 for mood stabilization, chlor-
promazine 400 mg/d since April 1999 for psychotic symptoms,
and citalopram 40 mg/d since June 1999 for depressive symp-
toms. No improvement in the behavioral symptoms was noted
with the combination treatment over that approximate eight-week
period.
In August 1999, the patient was started on adjunctive topira-
mate therapy to treat affective instability complicated by morbid
obesity (156 kg, body mass index [BMI] 55.6 kg/m2. Topiramate
25 mg twice daily was begun and was titrated to a dose of 200
mg/d by the beginning of October; the dosage was titrated to 275
mg/d during that month. She began to experience tingling and
weakness in her right arm with that dosage. The valproic acid
dosage had been reduced to 1250 mg/d secondary to tremors be-
tween August and October 1999. These adverse effects resolved
when the dosages were reduced.
Over 10 weeks of topiramate therapy, the patient’s weight
dropped to 146 kg, with a BMI of 52 kg/m2. According to the
National Heart, Lung, and Blood Institute17 a BMI ≥40 kg/m2 is
considered to be extremely obese. The woman’s weight loss oc-
curred despite continued therapy with valproic acid 1250 mg/d,
chlorpromazine 400 mg/d, and citalopram 40 mg/d. The decrease
in the patient’s valproic acid dosage probably had no effect on the
patient’s weight loss, as weight gain secondary to valproic acid
has been shown to be independent of the dose.15
Unfortunately, while home on a trial placement, the pa-
tient was admitted to an outside hospital for a nonpsychi-
atric illness; topiramate was discontinued at that time by a
clinician unfamiliar with her case. Therefore, it is not pos-
sible to describe any sustained weight loss or mood stabil-
The degree of weight loss experienced by this patient is higher
than that reported by Ortho-McNeil11 and data reviewed by
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ization. The literature11 suggests, however, that with pro-
longed topiramate treatment (≥18 mo), patients’ weight
may return to the pretreatment level. As weight gain is a
common adverse effect of many psychotropic medications,
a mood stabilizer that induces some weight loss may be an
important clinical tool in the treatment of psychiatric disor-
ders.
10. Rosenfeld WE, Schaefer PA, Pace K. Weight loss patterns with topira-
mate therapy (abstract). Epilepsia 1997;38(suppl 3):58.
11. Data on file, RW Johnson Pharmaceutical Research Institute, Raritan,
NJ, Document ID No. 420105:1, 1996.
12. Shorvon SD. Safety of topiramate: adverse events and relationships to
dosing. Epilepsia 1996;37(suppl 2):S18-22.
13. Ketter TA, Post RM, Theodore WH. Positive and negative psychiatric
effects of antiepileptic drugs in patients with seizure disorders. Neurolo-
gy 1999;53(suppl 2):S53-67.
Our patient experienced possible parasthesia in her right
arm during a dosage increase from 275 to 325 mg/d (target
maximum dose 400 mg/d). This reaction was eliminated
following dosage reduction and the patient did not report
any other adverse effects. This response is contrary to the
data provided by Ortho-McNeil, which states that pares-
thesias are not dose-related.19
14. Sachs GS, Guille C. Weight gain associated with use of psychotropic
medications. J Clin Psychiatry 1999;60(suppl 21):16-9.
15. Dinesen H, Gram L, Andersen T, Dam M. Weight gain during treatment
with valproate. Acta Neurol Scand 1984;70:65-9.
16. Amdisen A. Drug-produced obesity: experiences with chlorpromazine,
perphenazine and clopenthixol. Dan Med Bull 1964;11:182-9.
17. National Heart, Lung, and Blood Institute (NHLBI). Am Pharmaceut
Assoc Highlights News 1999;2(1):1-6.
18. Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, et al. A
method for estimating the probability of adverse drug reactions. Clin
Pharmacol Ther 1981;30:239-45.
Summary
19. Package insert. Topamax (topiramate). Raritan, NJ: Ortho-McNeil, 1998.
Controlled studies need to be performed to evaluate the
use of topiramate in the psychiatric population and, in par-
ticular, the benefits of topiramate therapy in psychiatric pa-
tients with an additional diagnosis of obesity.
EXTRACTO
OBJETIVO: Informar el caso de una paciente que experimentó pérdida de
peso y estabilización en su estado de ánimo al ser tratada con el
medicamento anticonvulsivo topiramate.
Christian J Teter PharmD, Research Fellow, Substance Abuse,
College of Pharmacy, University of Michigan, Ann Arbor, MI
RESUMEN DEL CASO: Una mujer blanca y obesa de 37 años con
inestabilidad afectiva y obesidad, fue tratada con topiramate como
terapia adjunta. La paciente perdió 10 kg en diez semanas de tratamiento
y mejoró clínicamente. Esto último fue evidenciado por el número de
veces que la paciente tuvo que ser enviada a una unidad de manejo para
observación constante y por una disminución en el número de veces que
fue necesario restringir mecánicamente o intervenir con medicamentos
para crisis agresivas. Además, esta paciente completó exitosamente dos
visitas a su hogar y se encontraba fuera del hospital en su tercera visita
al hogar al escribirse este artículo.
John J Early MPA BS Pharm, Clinical Assistant Professor, Divi-
sion of Pharmacotherapy, The University of North Carolina at Chapel
Hill; Director of Pharmacy, Dorothea Dix Hospital
Carol M Gibbs MD, Psychiatrist, Adult Psychiatry, Dorothea Dix
Hospital
Reprints: Christian J Teter PharmD, College of Pharmacy, Univer-
sity of Michigan, 428 Church St., Ann Arbor, MI, 48109-1065, FAX
734/763-4480, E-mail cjteter@umich.edu
We thank Valerie Brooks PharmD BCPP for her contributions to this case report.
DISCUSIÓN: Este informe fortalece aún más la literatura previa que indica
que el topiramate puede ser una herramienta útil tanto en el tratamiento
de trastornos afectivos como en inducir pérdida de peso en la población
psiquiátrica en la cual la ganancia en peso es un problema común. La
paciente discutida en este informe de caso no tuvo enfermedad aguda,
cambios en salud, cambios en dieta ni cambios en medicamentos que
pudieran ser responsables de su pérdida súbita en peso. Además, el
comportamiento de la paciente no mejoró hasta que se añadió el
topiramate como tratamiento adjunto a la combinación de ácido
valproico, citalopram, y clorpromacina.
References
1. Severt L, Coulter DA, Sombati S, DeLorenzo RJ. Topiramate selectively
blocks kainate currents in cultured hippocampal neurons (abstract 2.16).
Epilepsia 1995;36(suppl 4):38.
2. Sombati S, Coulter DA, DeLorenzo RJ. Effects of topiramate on sus-
tained repetitive firing and low Mg2+-induced seizure discharges in cul-
tured hippocampal neurons (abstract 2.15). Epilepsia 1995;36(suppl
4):38.
3. White HS, Brown SD, Woodhead JH, Skeen GA, Wolf HH. Topiramate
enhances GABA-mediated chloride flux and GABA-evoked chloride
currents in murine brain neurons and increases seizure threshold. Epilep-
sy Res 1997;28:167-79.
4. Maryanoff BE, Costanzo MJ, Nortey SO, Greco MN, Shank RP, Schup-
sky JJ, et al. Structure–activity studies on anticonvulsant sugar sulfa-
mates related to topiramate. Enhanced potency with cyclic sulfate
derivatives. J Med Chem 1998;41:1315-43.
5. Normann C, Langosch J, Schaerer LO, Grunze H, Walden J. Treatment
of acute mania with topiramate (letter). Am J Psychiatry 1999;156:12.
6. Marcotte D. Use of topiramate, a new anti-epileptic as a mood stabilizer.
J Affect Disord 1998;50:245-51.
7. Calabrese JR, Shelton MD III, Keck PE Jr, McElroy SL, Werkner JE.
Topiramate in severe treatment-refractory mania. In: Proceedings of the
151st Annual Meeting of the American Psychiatric Association, Toronto,
May 30–June 4, 1998:121-2.
8. Suppes T, Brown ES, McElroy SL, Kmetz GF, Frye M, Keck PE, et al.
A pilot trial of adjunctive topiramate in the treatment of bipolar disorder:
application of the Stanley Foundation Bipolar Network (SFBN) prospec-
tive protocol (abstract). In: Proceedings of the 37th Annual Meeting of
the American College of Neuropsychopharmacology, Los Croabas,
Puerto Rico, December 14–18, 1998:306.
CONCLUSIONES: Se necesita llevar a cabo estudios controlados para
evaluar el uso de topiramate en la población psiquiátrica, y en particular,
los beneficios del tratamiento con este medicamento en pacientes
psiquiátricos con el diagnóstico adicional de obesidad.
Lydia González
RÉSUMÉ
OBJECTIF: Décrire un cas de perte pondérale et de stabilisation de
l’humeur chez une patiente recevant du topiramate, un médicament
anti-convulsivant, comme thérapie adjuvante pour le traitement de
troubles affectifs multiples.
RÉSUMÉ DU CAS: Une femme blanche de 37 ans, obèse et présentant une
instabilité affective a été traitée par une thérapie adjuvante au topira-
mate. La patiente a perdu 10 kg sur une période de dix semaines de
traitement par le topiramate et on a noté une amélioration clinique,
amélioration mise en évidence par une diminution du nombre de fois
que la patiente a du être mise en observation sur une unité de surveil-
lance intensive et par une diminution du nombre de fois que des con-
traintes mécaniques ou des interventions pharmacologiques ont été req-
uises pour contrôler des épisodes d’agressivité aiguë. De plus, on a
constaté lors de trois visites subséquentes à domicile chez la patiente,
9. Norton J, Potter D, Edwards K. Sustained weight loss associated with
topiramate (abstract). Epilepsia 1997;38(suppl 3):60.
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Case Reports
alors qu’elle recevait toujours du topiramate, qu’elle ne nécessitait plus
d’hospitalisations, ce qui est toujours le cas au moment de la rédaction
de cette histoire de cas.
auraient pu expliquer la perte pondérale soudaine. De plus, le comporte-
ment de la patiente ne s’était pas amélioré sous un traitement optimal
par l’association d’acide valproïque, de citalopram, et de chlorpromazine
jusqu’à l’addition du topiramate comme thérapie adjuvante.
DISCUSSION: Ce cas vient illustrer le fait que le topiramate, tel que rap-
porté précédemment dans la littérature, peut être un outil pharma-
cologique utile pour traiter des troubles affectifs et aussi induire une
perte de poids chez une population de patients chez lesquels la surcharge
pondérale est un problème fréquent. La patiente dont le cas est discuté
ici, ne présentait aucunes maladies aiguës ni aucuns changements ré-
cents dans son état de santé, sa diète ou sa médication, changements qui
CONCLUSIONS: Des études contrôlées sont nécessaires pour évaluer l’em-
ploi du topiramate chez une population de patients psychiatriques, et en
particulier, pour évaluer les bénéfices lors d’obésité concomitante.
Denyse Demers