Gabapentin for the treatment of behavioral and psychological symptoms of dementia

doi:10.4236/aad.2012.12002

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Vol.1, No.2, 13-16 (2012) Advances in Alzheimer ’s Disease

http://dx.doi.org/10.4236/aad.2012.12002

Gabapentin for the treatment of behavioral and

psychological symptoms of dementia*

Rajesh R. Tampi1#, Banu Ozkan2, Deena Williamson3

1Department of Psychiatry, Yale University School of Medicine, New Haven, USA;

*Corresponding Author: [email protected]

2Department of Psychiatry, University of Maryland, Baltimore, USA

3Saint Francis Hospital and Medical Center, Hartford, USA

Received 13 July 2012; revised 18 August 2012; accepted 26 August 2012

ABSTRACT

Objective: To examine th e efficacy of gabapentin

for the treatment of behavioral and psychologi-

cal symptoms of dementia (BPSD). Design: A

retrospective chart review. Settings: Tertiary care

geriatric psychiatry inpatient unit. Participants:

230 patients with BPSD. Measurements: The

socio-demographic information, type of behav-

iors, co-morbid psychiatric and medical diag-

noses, daily doses of medications and side-ef-

fects were recorded. Results: Of the 230 patients,

22 were treated with gabapentin. Twenty of these

patients were on a combination of gabapentin

and an antipsychotic medication while two pa-

tients were treated with gabapentin monother-

apy. Eighteen of the 20 patients in the combina-

tion group tolerated the treatments with little or

no side effects as did the two patients in the

monotherapy group. Conclusions: Gabapentin

may be a safe option for the treatment of BPSD

in combination with antipsychotic medications.

Gabapentin may also be effective as monother-

apy in certain patients with BPSD.

Keywords: Behavioral and Psychological

Symptoms of Dementia; Neuropsychiatric

Symptoms of Dementia; Anticonvulsants;

Gabapentin

1. INTRODUCTION

Behavioral and psychological symptoms of dementia

(BPSD) are a heterogeneous group of non-cognitive

symptoms and behaviors that occur in patients with de-

mentia [1]. BPSD does not reflect a specific diagnostic

entity, but describes an important clinical dimension of

dementia which is often the triggering event for its rec-

ognition and referral to the specialist service [2]. The

development of BPSD is associated with greater impair-

ment in activities of daily living, more cognitive decline

and poorer quality of life, institutionalization and is also

a major risk factor for caregiver burden [3]. In this regard,

BPSD are more important than the progressiv e cognitive

deficits of the disease, and for the care of the patients

with AD [3].

Treatments available for BPSD are currently not stan-

dardized and include various non-pharmacological and

pharmacological approaches [3,4] Pharmacotherapy is

usually initiated when symptoms have failed to respond

to non-pharmacological interventions and are not attrib-

utable to an underlying medical condition or medication

effect [3,4]. A variety of medications have been used to

treat BPSD, including typical and atypical antipsychotics,

antidepressants, anticonvulsant mood stabilizers, choli-

nesterase inhibitors, benzodiazepines and other drugs

[3,4].

While the benefits of antipsychotics and anticonvul-

sants like valproic acid and carbamazepine in the treat-

ment of BPSD are not clear, gabapentin, another anti-

convulsant may be a poten tial treatment for the treatment

of these symptoms [3,4]. Gabapentin is structurally re-

lated to GABA and it probably acts by interfering with

the calcium channels to alter transmitter release. It is

commonly used as an adjunctive therapy for partial sei-

zures. Gabapentin is eliminated unchanged renally, and

its clearance is expected to parallel the age-related de-

crease in glomerular filtration rate. The pharmacokinetics

of gabapentin, specifically the lack of both hepatic me-

tabolism and protein binding, makes gabapentin a drug

that is potentially safer than the other anticonvulsant

agents for the elderly population [5].

The efficacy of gabapentin in treating behavioral

symptoms of dementia has been described in several case

reports and open-label trials but its effect as an adjunct to

antipsychotic treatment has not been studied [6,7]. The

*The other authors have no financial disclosures to make and there are

no conflicts of interes t t o report in the conduct of this study.

#Corresponding author.

R. R. Tampi et al. / Advances in Alzheim er’s Disease 1 (2012) 13-16

purpose of this report is to consider the efficacy of

gabapentin as an adjunctive therapy to antipsychotics and

also as monotherapy for behavioral and psychological

sy mptoms of dementia.

2. Methods

The data for this case series is derived from a retro-

spective chart review of 230 demented inpatients, dis-

charged between July 1st, 2002 and March 31st, 2007

from the Geriatric Psychiatry Unit of a University Hos-

pital. All these patients were diagnosed with dementia

according to the Diagnostic and Statistical Manual of

Mental Disorders, Text Revision, 4th edition (DSM-

IV-TR) [8].

Medications given to treat these patients were evalu-

ated and the charts of all patients who had BPSD and

were treated with gabapentin were selected for this re-

view. Patients were treated with gabapentin if they could

not tolerate higher doses of the antipsychotic agents and

need further stabilization of their behavioral problems.

The socio-demographic information, co-morbid psychi-

atric and medical diagnoses, daily doses of gabapentin

and antipsychotics, effects and side-effects of gabapentin

were recorded.

As this was a retrospective chart review, a waiver of

consent was obtained from the University Institutional

Review Board for the conduct of this study.

3. Results

The total number of patients with dementia who were

treated with gabapentin was twenty-two. Twenty of these

patients were on a combination of atypical antipsychotic

medication and gabapentin while two patients were

treated with gabapentin monot herapy.

The average age of the patients in the study was 73 ±

8.69 years. There were 15 male patients with an average

age of 73.78 years and 7 female patients with an average

age of 76.57 years. Of these 22 patients, 16 were Cauca-

sian (M:F, 10:6), 3 were African America (3:0) and 3

Hispanic (2:1) (Table 1).

All patients had a diagnosis of dementia, of these, 12

patients had Alzheimer’s disease, 6 had dementia of

Table 1. Demographic information of the patients.

Sex Male (n = 15) Female (n = 7)

Age (years) 73.78 76.57

Race

African-American 3 0

Hispanic 2 1

Caucasian 10 6

mixed type, 3 had vascular dementia and 1 patient had

Lewy Body Dementia. Of the twenty-two patients, six

had Folstein Mini Mental State Examination (MMSE)

scores available [9]. The average MMSE score for these

patients was 10.87 ± 6.02. Sixteen of the patients were

unable to co-operate with the MMSE because of severe

impairment in cognitive functioning and agitatio n.

Agitation (verbal aggression) was the most common

behavior noted in these patients. Combative behavior

(physical aggression) was seen in 18 of the 22 patients. A

combination of agitation and physical aggression was

seen in 11 of the 22 patients. Paranoid thoughts (5/22,

23%) and inappropriate sexual behaviors (2/22, 9%)

were less commonly noted in these patients. Confusion

as a complaint was noted only in 5 of the 22 patients

(23%).

A combination of gabapentin and an atypical antipsy-

chotic medication was administered to the 20 patients.

Eighteen of them tolerated this combination with no sid e

effects. Two patients developed side-effects. One patient

who was treated with 1800 mg/day of gabapentin and 20

mg/day of olanzapine became lethargic. The dose of

gabapentin was reduced to 400 mg/day with a reduction

in sedation. The other patient was being treated with 300

mg/day of gabapentin and 75 mg/day quetiapine. Be-

cause of sedation, the dose of gabapentin was decreased

to 200 mg/day. None of the patients in the monotherapy

group had any side-effects.

In the combination treatment group, 11 patients were

on quetiapine, 6 were on olanzapine, 2 were on risperi-

done and 1 was on clozapine. Of the 22 patients, 10 were

on Donepezil 5 - 10 mg/day and 1 was on memantine

and 1 was on both donepezil and memantine. One of the

patients was on valproic acid for seizure disorder, and 2

of them were on both valproic acid and gabapentin for

agitation a n d b e havioral probl ems (Table 2).

Behavioral issues in of all the patients resolved with

these treatments. Twenty patients were discharged to

skilled nursing facilities, 1 patient went to an assisted

living facility and 1 patient went home. The average

length of stay for these patients was 23.23 ± 5.66 days.

4. Discussion

Although some psychotropic medications have been

found to be helpful in the treatment of BPSD, none of

them have proven efficacy and benign side-effect pro-

files [3,4]. Elderly patients also have more medical

co-morbidities and are taking multiple medications. This

puts them at higher risk for developing medical compli-

cations and medication side-effects along with drug-drug

interactions. These issues must be considered while giv-

ing a new medication to the older patient [3,4].

In this study, we used a cobination of atypical anti- m

R. R. Tampi et al. / Advances in Alzheim er’s Disease 1 (2012) 13-16

Table 2. Diagnosis, comorbidities and psychotropic medications.

Age Diagnosis Comorbid medical illness Comorbid

psychiatric

illness Psychotropic medications (name/daily dosages)

Dement ia; mixe d

type (AD an d

vascular type),

moderate

anemia, post CVA, CAD,

chronic orthostatic hypotension,

hypertension, AF, CRI no Gabapentin

400 mg Memantine

20 mg

64 Dementia;

AD type, severe

DM type2, CAD, post MI,

hyperlipidemia, vitamin

B12 deficiency,

alchohol

dependence

with full

remission

Gabapentin

800 mg Donepezil

10 mg Olanzapine

15 mg

73 Dementia;

AD type vitamin B12 deficiency MDD with

anxiety Gabapentin

600 mg Donepezil

5 mg Quetiapine

400 mg

76 Dementia;

AD type,

moderate

hypertension, DM type II,

CRI, BPH, gout no Gabapentin

800 mg Olanzapine

15 mg

67 Dementia;

AD type hypertension, urinar y

incontinence, BPH no Gabapentin

500 mg Olanzapine

15 mg Donepezil

5 mg Memantine

15 mg

85 Dementia;

AD type, severe

CRI, osteoarthritis, recurrent

UTI, dejenarative joint disease,

hypertension, stress urinary

incontinence, chronic leg edema

no Gabapentin

300 mg Olanzapine

7.5 mg

64 Dementia;

AD type, severe

DM type II, seizure disorder ,

tinea corporis of the right buttock,

anemia of chronic disease no Gabapentin

1200 mgValproic acid

1250 mg

83 Dementia;

vascular type,

moderate

hypertension, CAD, CHF,

anemia, NIDDM, hyperlipidemia no Gabapentin

100 mg Quetiapine

150 mg Donepezil

10 mg Citalopram

30 mg

90 Dementia;

vascular type hypertension, glaucoma,

post left CVA, post cyst removal in her br e astno Gabapentin

200 mg Quetiapine

100 mg Donepezil

10 mg

64 Dementia;

vascular type,

moderate

hypertension, CAD, DM , post

bilateral above knee amputation,

MRSA and vancomicyn

resistant enterococci wound

infection left thigh

no Gabapentin

400 mg Risperidole

2.5 mg Donepezil

5 mg Valproic acid

1000 mg

68 Dement ia; mixe d

type (AD and

alcohol induced), severe BPH, hypercholesterolemia History of

alcohol

dependence

Gabapentin

1200 mgOlanzapine

10 mg Donepezil

10 mg

78 Dementia;

AD type, severe hypertension, hyper t hyroidism,

NIDDM no Gabapentin

900 mg Quetiapine

25 mg prn Donepezil

10 mg

79 Dement ia; mixe d

type, severe chronic pain, CVA, post UTI,

fungal groin infection no Gabapentin

600 mg Memantine

5 mg

67 Dementia; AD

type, severe

hypertension, bronchitis, GERD,

hypocholesterolemi a, Raynaud’s

disease, post lung ca, post left

lung-upper lobe lobectomy

no Gabapentin

400 mg Clozapine

200 mg Valproic acid

500 mg

82 Dementia; AD

type, severe arthritis no

Gabapentine

200 mg Quetiapine

75 mg

81 Dementia; AD

type, severe hypertension, BPH, history

of diverticulosis no Gabapentin

600 mg Quetiapine

200 mg Donepezil

10 mg

84 Dementia; mixed type

(AD and

Vascular)

delirium due to multiple medical

causes, NIDDM, rapid AF,

hypothyroidism, chronic anemia,

post epidural hematoma ,

post left breast mastectomy

no Gabapentin

1200 mgQuetiapine

200 mg Donepezil

5 mg

R. R. Tampi et al. / Advances in Alzheim er’s Disease 1 (2012) 13-16

Continued

67 Dementia; Lewy

body type

hyperkalemia, MRSA-positive,

coccygeal decubitus, resolving,

dysphagia secondary to deme ntia no Gabapentin

3000 mgOlanzapine

20 mg Donepezil

10 mg

83 Demen tia; mixed

type (AD

and Vascular)

recurrent UTI, CVA with

hemiplegia and aphasia, AF,

cardiomegaly, degenarative

joint disease

no Gabapentin

2000 mgRisperidole

2.5 mg

59 Dementia; AD

type, severe hypertension no

Gabapentin

2400 mgQuetiapine

37.5 mg Valproic acid

100 mg

78 Dementia;

AD type GERD, Parkinson’s disease,

hypertension

BAD type II,

hypomanic

episode

Gabapentin

1800 mgQuetiapine

250 mg

77 Dementia; mixed type

(AD and Vascular),

severe

IDDM, hypertension, GERD,

phimosis & balanitis with penile

discharge positive for MRSA no Gabapentin

200 mg Quetiapine

400 mg

AD = Alzheimer’s Disease; CVA = Cerebral Vascular Accident; CAD = Coronary Artery Disease; CRI = Chronic Renal Failure; MI = Myo-

cardial Infarctus; BPH = Benign Prostate Hypertrophy; UTI = Urinary Tract Infection; CHF = Chronic Heart Failure; NIDDM = Non-Insulin

Dependent Diabetes Mellitus; MRSA= Methicillin Resistant Staphylococcus aereus; GERD = Gastroesophageal R e f l ux D i se a s e ; A F = Atrial

Fibrillation; MDD = Major Depressive Disorder; BAD = Bipolar Affective Disorder.

psychotic medication and gabapentin, which appears to

be effective and well tolerated in the treatment of BPSD.

Gabapentin was also effective as monotherapy for the

treatment of two cases of BPSD. Side-effect profile was

relatively benign and no drug-drug interactions were

noted. Our finding is in keeping with the case-series by

Moretti et al. [6], Herrmann et al. [7], where they found

that gabapentin monotherapy was well tolerated and ef-

fective for the treatment of BPSD. However, our study

also indicated that gabapentin was well tolerated even in

combination with atypical antipsychotics.

As this study is a retrospective chart review and has

potential for bias, further controlled studies are necessary

to confirm the efficacy of the combination treatments for

BPSD. However, this current study provides the proof

that elderly patients with BPSD tolerate a combinatio n o f

psychotropic medications, if these medications are dosed

appropriately and monitored carefully.

5. Conclusion

Behavioral and psychological symptoms are common

in dementia. The treatment for these important symptoms

is not standardized and is limited by the side-effect pro-

file of the various drugs. Gabapentin, an anticonvulsant

medication may be beneficial in combination with an-

tipsychotic agents or as monotherapy for patients pre-

senting with these behaviors.

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