Você está na página 1de 2

WIM, September 1996-Vol 165,

W -IM--

September--

196-o

--

165

No. 3

NoI

Alerts,Notices,

lrs

and

oie,adCs

Case Reports 147

eot

4

Propylthiouracil hepatotoxicity mimicking autoimmune chronic activehepatitisin agirl.JPediatrGastroenterol Nutr 1989;8:547-548

27.

Lee WM: Drug-induced hepatotoxicity. N Engl J Med 1995; 333:

1118-1127

28.

ShiranA, ShechnerC,Dickstein G:

Propylthiouracil-induced agranulocy-

tosis in four patients previously treated with

the drug (Letter). JAMA 1991;

 

266:3129-3130

29.

Amrhein JA, Kenny FM, Ross D: Granulocytopenia, lupus-likesyndrome

andothercomplicationsofpropylthiouraciltherapy.JPediatr 1970;76:54-63

30.Bilezikian SB, Laleki Y,Tsan MF, etal:Immunological reactionsinvolv- ingleukocytes: Agranulocytosisinducedbyantithyroiddrugs.JohnsHopkinsMed

J 1976; 138:124-129 31.BreeseTJ, Solomon IL: Granulocytopenia andhemolytic anemia ascom-

plications of propylthiouraciltherapy. JPediatr 1975; 86:117-119

32.

Aksoy M, Erdem S: Aplasticanaemiaafterpropylthiouracil. Lancet 1968;

1:1379

33.Sammon TJ,Peden VH, WitzlebenC,etal:Disseminatedintravascularco-

agulationcomplicatingpropylthiouraciltherapy-Acasedescriptionofa 16-year- oldgirl.ClinPediatr 1971; 10:739-742

34.

Verdy M, PrettyH, Cadotte M, etal:Vasculitis secondary toantithyroids.

UnionMed Can 1975; 104:576-579

35.

Vasily DB, Tyler WB: Propylthiouracil-induced cutaneous vasculitis.

JAMA 1980; 243:458-461

 

36.Miyazono

K,OkazakiT,Uchida S,etal:Propylthiouracil-induced diffuse

interstitial

pneumonitis. ArchIntemMed 1984; 144:17641765

37.

Movitt E, Gerstl B, Davis A: Needle liverbiopsy inthyrotoxicosis. Arch

InternMed 1953;91:729

38.

Czaja AJ: Autoimmune hepatitis and viral infection. Gastroenterol Clin

NorthAm 1994;23:547-566

Venlafaxine Hydrochloride and Chronic Pain

KIRKTAYLOR, MD MICHAEL C. ROWBOTHAM, MD San Francisco, California

CLINICALTRIALSoftricyclicantidepressants have shown efficacy for both chronic headaches and neuropathic

pain.'Thetricyclicantidepressantsusefulforchronicpain

a -adrenergicreceptorsites,makingitssideeffectprofile

su1bstantiallydifferentfromandtheoreticallymorebenign

thanthatofthetricyclicantidepressants. We reportourinitialopen-labelexperiencewithven-

lafaxineintreatingpatientswithchronicpain,primarily headache andneuropathic pain.Painreliefwas ratedby combining a patient's rating of efficacy with the clini- cian'sglobalimpression afteraminimum offourweeks oftherapy.Ifapatientcompletedlessthanfourweeks of

treatment,efficacywas ratedattheend oftreatment. An

80% orgreaterreductioninpainseveritywas interpreted

ascompletepainrelief,a50% to79% reductionasmod-

eratepainrelief,20% to49% asmildpainrelief,andless

than20% reductioninpainasno painrelief.

Summary of Cases

Table 1 summarizes thecases ofthe first 12 patients we treatedwithvenlafaxine. Allofthem had had inade-

quatepainrelieforintolerablesideeffectswiththeuseof

atleastone antidepressant. These patientscompleted at least two weeks oftherapy with venlafaxine. One case was notincludedintheresultsbecausethepatienthadse- vere nausea aftertaking only two doses. Otherwise, the datawere collected over a seven-month periodafterpa- tientswereexaminedforchronicpainorheadache. Theeightwomen andfourmen had an averageageof

  • 54 yearsand an averagepaindurationof7.7years. Four

patients had headache, seven had neuropathic pain, and

one hadatypicalfacialpain.Patientshadtriedan average

of2.6differentantidepressantsbeforetakingvenlafaxine.

Patients6and 10were on concurrentopioidtherapywith transdermalfentanylcitratepatches.Patients5 and9did not complete fourweeks oftherapy. Patient5 had com-

  • blocktheneuronalreuptakeofbothserotoninandnorepi- pletereliefofchronicdailyheadache fortwo weeks, but

nephrine. Serotonin-selective reuptake-inhibitor antide-

pressantshaveshownlittleornoefficacywhen compared

with placebo or tricyclic antidepressant use for neuro- pathic pain.2 Unfortunately, the use of these drugs for chronicpainislimitedby numerous sideeffectssuch as

sedation,cognitiveimpairment, orthostatichypotension,

cardiacconduction abnormalities,drymouth, andconsti- pation.Many oftheseeffectsareduetotheaffinityoftri-

cyclic antidepressants for the muscarinic-cholinergic, histaminic, and ot1-adrenergicreceptors. Venlafaxinehy- drochlorideisanew antidepressantmedication that,like the tricyclic antidepressants, inhibits the neuronal reup-

takeofboth serotonin and norepinephrine.3 Venlafaxine does notbindtomuscarinic-cholinergic, histaminic, and

(TaylorK,Rowbotham MC: Venlafaxinehydrochlorideandchronicpain.

WestJMed 1996; 165:147-148)

From thePain

Management

Center,theDepartments

ofNeurology and Anes- SchoolofMedicine

thesia,UniversityofCalifornia,SanFrancisco(UCSF),

Thisworkwas

supportedinpartbyNationalInstitutesofHealthPainResearch

TrainingGrantNS07265.

Reprint requests

Center,2233

to Michael C. Rowbotham, MD,

UCSF Pain Management

PostSt,Ste 104,SanFrancisco,CA 94115.

whenpainbegantoreturn,sheelectedtodiscontinueven-

lafaxineinsteadofadjustingthedose. Patient9was tak- ing several medications-mexiletine hydrochloride,

carbamazepine, and valproatesodium-forpaindue toa

posteriorfossaarteriovenousmalformation aftera stroke. With thestartofvenlafaxinetherapy, an increasedblood

pressurerequiredthecessationoffludrocortisoneacetate

used forthe control oforthostatic hypotension. The pa-

tientexperiencedpersistentdrowsiness and unsteadygait

afterthreeweeks oftherapy,andvenlafaxinewas discon- tinued. In theotherten patients,painreliefwas ratedas moderate inseven andmildinthreeattotaldailydosages from 18.75 to 250 mg perday (average, 99 mg perday). The most common side effect was nausea, which was

made manageable by starting therapy at 18.75 mg per

day. Patient 10 had moderate reliefofperipheralneuro- pathicpainatadoseof37.5 mg perdaybutlaterreduced thedoseto 18.75mg perdaybecauseofsubjectivehyper-

thermia and impotence, with onlya slightdiminution of painrelief.Patient 12laterrequiredadosereductionfrom

  • 75 mg twice a day to 37.5 mg twice a day because of

worsenedhypertension. Shebecame normotensivewith-

out a loss ofpain control. Based on these results, ven-

148 WIM, September 1996-Vol 165, No. 3 Alerts,Notices, and Case Reports Alerts, Notices, and Case Reports
148
WIM, September 1996-Vol 165, No. 3
Alerts,Notices,
and
Case
Reports
Alerts, Notices,
and Case
Reports
TABLE .-Patients TreatedWith VenlafaxineHydrochloride(HCI)
Antidepressant
VenlafaxineHCI
Patient
Age, yr
Sex
Diagnosis
Durcition,yr
Drug Trials
Dosage, mg/d
DoseResponse
1.
30
Female
Reflex dystrophy
1
Desipramine HCI
75, 2x
Mild relief
2.
42
Female
Migraine
10
Nortriptyline HCI,
amitriptyline HCI
37.5
Moderate relief
3.
44
Male
Intercostal neuralgia
9
Amitriptyline, fluoxetine,
nortriptyline
125, 2x
Moderate relief
4.
45
Female
Atypicalfacial pain
11
Desipramine, imipramine
HCI,
doxepin HCI,
nortriptyline
37.5
Moderate relief
5.
47
Female
Mixed headache
18
Nortriptyline, amitriptyline,
paroxetine
75, 4x
Complete relief
6.
50
Female
Multiple sclerosis
5
Amitriptyline
37.5
Mild relief
7.
52
Female
Mixed headache
15
Amitriptyline, fluoxetine,
sertraline,
paroxetine
75
Moderate relief
8.
53
Male
Peripheral neuropathy
3
Amitriptyline, fluoxetine
50, 4x
Moderate relief
9.
65
Male
Poststroke pain
S
Amitriptyline, desipramine
37.5
Moderate
relief
10.
70
Male
Peripheral neuropathy
6
Desipramine, amitriptyline,
doxepin
37.5
Moderate relief
11.
71
Female
Mixed headache
2
Nortriptyline, paroxetine
37.5
Mild relief
12.
74
Female
Postzoster pain
7
Desipramine,
amitriptyline,
imipramine, sertraline
75, 2x
Moderate relief

lafaxineprovided substantialreliefinpatientswho were refractoryto treatment withotherantidepressants.

Conclusion

Venlafaxine appears to be a useful additionto thelist

of antidepressants with efficacy in pain management. Like otherantidepressants, sideeffectsare minimized by

startingatthelowestpossibledose. Increasedbloodpres-

sure and nausea seen with venlafaxine are uncommon

withtheuse oftricyclicantidepressants, and antidepres- sant-like cognitive impairment and anticholinergic side

effectswere uncommon withtheuse ofvenlafaxine.This open-label experience supports the need for controlled, randomizedclinicaltrialsofvenlafaxineforchronicpain.

REFERENCES

1.Max M: Antidepressants as analgesics, In Fields HL, LiebeskindJC (Eds):

Progress in Pain Research and Management, Vol 1. Seattle, Wash, International Association fortheStudyofPainPress, 1994,pp 229-246

2.Max MB, Lynch SA, MuirJ,ShoafSE, SmollerB,DubnerR: Effectsofde-

sipramine, amitriptyline, and fluoxetine on painin diabetic neuropathy. N EnglJ

Med 1992; 326:1250-1256

3.Montgomery SA: Venlafaxine: A new dimension inantidepressantpharma- cotherapy. JClinPsychiatry 1993;54:119-126