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Treatment of prurigo nodularis with pregabalin

Article  in  Journal of Clinical Pharmacy and Therapeutics · February 2013

DOI: 10.1111/jcpt.12005 · Source: PubMed

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Journal of Clinical Pharmacy and Therapeutics, 2013, 38, 16–18 doi: 10.1111/jcpt.12005

Treatment of prurigo nodularis with pregabalin

M. Mazza* MD PhD, G. Guerriero MD, G. Marano* MD, L. Janiri* MD, P. Bria* MD and S. Mazza MD*
*Department of Neurosciences, Università Cattolica del Sacro Cuore di Roma, Roma, Italy and Department of Dermatology, Università Cattolica del
Sacro Cuore di Roma, Roma, Italy

Received 20 November 2011, Accepted 9 August 2012

Keywords: itching, nodules, pregabalin, prurigo

SUMMARY the stress response with strong pruritogenic potential need to be

further explored systematically in order to develop more effec-
What is known and objective: Prurigo nodularis (PN) is a
tive therapeutic combination strategies for PN and other chronic
chronic skin condition that is difficult to treat. Pregabalin is
stress-vulnerable inflammatory skin diseases.6 PN is often
one of the possible treatments for PN but its safety and effi-
refractory to classical treatment with topical corticosteroids and
cacy are not well defined. We aimed to assess the efficacy of
antihistamines. In a number of case series and case reports, sys-
pregabalin in patients with PN.
temic l-opioid receptor antagonists, such as naloxone, nalmef-
Methods: Thirty patients (10 men, 20 women; mean age
ene and naltrexone have been used to treat PN and various
51.6 ± 9.39 years) were treated with pregabalin (75 mg/day) for
forms of chronic pruritus (cholestatic pruritus, chronic urticaria,
3 months. Efficacy was classified as (i) successful (disappear-
atopic dermatitis). However, most of the evidence for efficacy
ance of the pruritus and reduction of nodules); (ii) slight
remains anecdotal.7 Phototherapy, erythromycin, retinoids,
improvement/reduction of the nodules, that is, number and/or
cyclosporine, azathiopurine and other psychopharmacological
flattening, no disappearance of itching; or (iii) unsuccessful.
agents (pimozide and selective serotonin reuptake inhibitor an-
Results: Twenty-three patients (76%) responded successfully
tidepressants) have been tried with some success.8–11 Some
after 3 months of treatment. There was a statistically signifi-
authors have claimed efficacy for thalidomide, a drug that has
cant difference between visual analogue scale scores before
to be carefully monitored because of its neurotoxicity and there-
and after 1 month treatment period (8Æ15 ± 2Æ04 and 1Æ5 ± 1Æ12,
fore is often discontinued by patients.12 Dereli et al.13 have
respectively; P < 0Æ0001). Pregabalin was generally well toler-
described a patient with PN who responded well to the treat-
ated with only six (20%) patients reporting side effects. No
ment with gabapentin and more recently Gencoglan et al.14
patient showed any renal insufficiency.
described five cases of lichen simplex chronicus and four cases
What is new and conclusion: In our study, pregabalin was
of PN who responded well to gabapentin.
effective for the treatment of PN. However, given the open
Pregabalin shares with gabapentin a similar mechanism of
and non-controlled study design used, a properly powered
action, inhibiting calcium influx and subsequent release of excit-
randomized controlled validation study is called for.
atory neurotransmitters.15,16 However, pregabalin appears to
have some distinct pharmacokinetic advantages over gabapentin
WHAT IS KNOWN AND OBJECTIVE that may translate into an improved pharmacodynamic effect.
Orally administered pregabalin is absorbed more rapidly, with
Prurigo nodularis (PN) is a benign dermatitis of unknown aeti-
maximum plasma concentrations attained within 1 h. Absorp-
ology characterized by firm, hyperkeratotic pruritic nodules
tion is linear, with plasma concentrations increasing proportion-
most commonly localized symmetrically on the bilateral exten-
ately with increasing dose and absolute bioavailability of
sor lower extremities.1 It is a difficult-to-treat chronic skin con-
pregabalin remains at > or =90% irrespective of the dosage. It
dition. Interruption of the itch-scratch cycle is difficult and long-
neither bind to plasma proteins nor is metabolized or inhibits
term prognosis remains guarded. Some studies show that symp-
hepatic enzymes that are responsible for the metabolism of
toms of anxiety and depression are often present in patients
other drugs. It is excreted renally, with elimination half-lives of
with PN, along with some specific traits of personality.2 PN in
approximately 6 h.15 We aimed to investigate the efficacy of pre-
fact has also been classified in the category of ‘psychocutaneous
gabalin in patients with PN.
disorders’;3 a recognition of the contribution of psychogenic fac-
tors in this condition.4
Nerve growth factor has been implicated in the pathogenesis METHODS
of PN. Calcitonin gene-related peptide and substance P immu-
We included all patients referred to A. Gemelli Hospital in
noreactive nerves are markedly increased in PN when com- Rome between September 2007 and November 2009 for the
pared with normal skin. These neuropeptides may mediate the treatment of PN. The study included patients diagnosed with
cutaneous neurogenic inflammation and pruritus in PN.5 For
PN who were willing to discontinue their currently prescribed
this reason, some authors argue that key candidate molecules of
treatment. Patients who had been previously treated with pre-
gabalin but failed to improve or did not tolerate this drug were
Correspondence: M. Mazza, Department of Neurosciences, Univer- excluded, as were pregnant or lactating women. All patients
sità Cattolica del Sacro Cuore di Roma, Via Ugo De Carolis, 48 underwent blood analysis as suggested in the data sheet of pre-
00136 Roma, Italy. Tel.: +39 06 35348285; fax: +39 06 35501909; gabalin. No concomitant therapy was allowed or applied. As
e-mail: mariannamazza@hotmail.com; marianna.mazza@rm.unicatt.it rescue medication, antihistamines were recommended with the

ª 2012 Blackwell Publishing Ltd 16

Pregabalin and prurigo M. Mazza et al.

indication to immediately contact clinicians if used but no
patient used them during the study. Efficacy was classified as
(i) successful (disappearance of the pruritus and reduction of
nodules); (ii) slight improvement/reduction of the nodules, that
is, number and/or flattening, no disappearance of itching; or
(iii) unsuccessful.12 Any side effects arising during treatment
were recorded. The effectiveness of pregabalin was also evalu-
ated using a visual analogue scale (VAS) before and after
3 months of treatment. VAS consisted of a 10-cm horizontal line
scored from 0 (no itch) to 10 (worst imaginable itch).17 All
patients provided written informed consent before beginning
any study activities. The protocol was approved by the local
Ethics Review Board.
RESULTS
Thirty patients (10 men, 20 women; mean age 51.6 ± 9.39 years)
were treated with pregabalin (75 mg/day, at the dosage of
25 mg t.i.d) (Table 1). None of them had any underlying disease
responsible for the PN, and all had responded poorly to previ-
ous treatments. Twenty-three patients (76%) showed complete
response after 3 months of treatment, with 21 continuing on
maintenance treatment of 50 mg/day at the time of last follow-
up (24 months). Six patients (20%) showed slight improvement,
and the treatment was judged to be unsuccessful in only one
patient.
Treatment with pregabalin had to be discontinued in two
patients (6%) because of side effects (sedation and headache).
Pregabalin was generally well tolerated with only six (20%)
patients reporting side effects. No patient showed any renal
insufficiency by the treatment with pregabalin. There was a sta-
tistically significant difference between VAS values before and
after the 3 months treatment period (8Æ15 ± 2Æ04 and 1Æ5 ± 1Æ12,
respectively; P < 0Æ0001).
Pathways for itch and pain are similar, both involving trans-
mission by specialized C-fibres in the dorsal horns of medulla
spinalis and reaching the thalamus and the somatosensory cor-
tex via the lateral spinothalamic tract.18 The close relationship
between these pathways suggests that pregabalin may inhibit
the sensation of itching. In particular, the results of experiments
on mice suggest that pregabalin may exert an antipruritic effect
through a2 d-1 subunit binding of voltage-gated Ca2(+) channels
and the up-regulation of the a2 d-1 subunit in dorsal root gan-
glion.19 There is evidence of successful use of pregabalin in neu-
ropathic itch 20 and in uraemic pruritus in haemodialysis
patients.17
In this study, the dosage of pregabalin can be considered low
with 75 mg/day. In fact, the usual dosage is 150–300 mg per
day for the treatment of seizures, neuropathic pain, fibromyalgia
and generalized anxiety disorder. Usually physicians start the
patient on a low dose of pregabalin and increase it gradually if
the patient reports little or no clinical improvement.15 In this

Table 1. Patients characteristics and details of pregabalin treatment (75 mg/day)

Patient Age Sex Disease duration (years) Clinical response (after 3 months) Side effects Evolution (24 months)

1 52 F 3 Slight improvement Sedation Stopped because of SE

2 57 F 12 Successful No MD = 50 mg/day
3 50 F 10 Successful No Lesion free
4 39 M 4 Successful No Lesion free
5 61 M 6 Successful No MD = 50 mg/day
6 62 M 6 Successful No MD = 50 mg/day
7 41 M 8 Successful Dizziness MD = 50 mg/day
8 47 M 2 Successful No Lesion free
9 48 M 3 Successful No Lesion free
10 50 M 2 Successful No MD = 50 mg/day
11 53 F 11 Successful No MD = 50 mg/day
12 42 F 12 Successful No MD = 50 mg/day
13 65 M 18 Slight improvement Sedation MD = 50 mg/day
14 66 F 13 Successful No Lesion free
15 37 F 5 Successful No Lesion free
16 44 F 5 Slight improvement No MD = 50 mg/day
17 37 F 8 Unsuccessful Headache Stopped because of SE
18 45 F 10 Successful No MD = 50 mg/day
19 54 F 7 Successful No MD = 50 mg/day
20 54 F 10 Successful No MD = 50 mg/day
21 60 F 4 Successful No MD = 50 mg/day
22 66 F 4 Successful No MD = 50 mg/day
23 63 F 2 Successful No Lesion free
24 55 F 3 Slight improvement No MD = 50 mg/day
25 49 M 7 Slight improvement No MD = 50 mg/day
26 48 F 10 Slight improvement No MD = 50 mg/day
27 61 F 10 Successful No MD = 50 mg/day
28 65 F 15 Successful Sedation MD = 50 mg/day
29 37 F 2 Successful No MD = 50 mg/day
30 40 M 4 Successful No MD = 50 mg/day

F, female; M, male; SE, side effect; MD, maintenance dose.

ª 2012 Blackwell Publishing Ltd Journal of Clinical Pharmacy and Therapeutics, 2013, 38, 16–18
17
 Pregabalin and prurigo M. Mazza et al.

study, patients were seen at baseline and every 2 weeks for
dose adjustments. Clinical investigators responsible for dosage
adjustments and adverse reactions monitoring decided to leave
the dosage at 75 mg/day because of good tolerability and rapid
response seen.
WHAT IS NEW AND CONCLUSION
In our study, pregabalin was effective for the treatment of PN.
However, given the open and non-controlled study design used,
a properly powered randomized controlled validation study is
called for.
This study needs to be interpreted with caution because of
some limitations. First, not using a control group is an important
weakness that tempers the relevance of the results. Second, the
small sample size does not allow firm conclusions to be drawn.
Despite these points, results from this study seem to support the
safety and the potential efficacy of pregabalin for the treatment of
PN. This work should be replicated comparing pregabalin with
placebo and other medications in a larger sample of patients.

REFERENCES
1. Vaidya DC, Schwartz RA. Prurigo nodu-
laris: a benign dermatosis derived from a
persistent pruritus. Acta Dermatovenerol
Croat, 2008;16:38–44.
2. Dazzi C, Erma D, Piccinno R, Veraldi S,
Caccialanza M. Psychological factors
involved in prurigo nodularis: a pilot
study. J Dermatolog Treat, 2011;22:211–214.
3. Elpem DJ. Toward a better understanding
of ‘‘psychocutaneous disorders’’. Int J Der-
matol, 2009;48:1395–1396.
4. Lotti T, Buggiani G, Prignano F. Prurigo
nodularis and lichen simplex chronicus.
Dermatol Ther, 2008;21:42–46.
5. Lee MR, Shumack S. Prurigo nodularis: a
review. Australas J Dermatol, 2005;46:211–218.
6. Arck P, Paus R. From the brain-skin connec-
tion: the neuroendocrine-immune misalli-
ance of stress and itch. NeuroImmuno
Modulation, 2006;6:347–356.
7. Phan NQ, Bernhard JD, Luger TA, Stander
S. Antipruritic treatment with systemic l-
opioid receptor antagonists: a review. J Am
Acad Dermatol, 2010;63:680–688.
8. Slepmann D, Luger TA, Stander S. Anti-
pruritic effect of cyclosporine microemul-
sion in prurigo nodularis: results of a case
series. J Dtsch Dermatol Ges, 2008;6:941–
946.
9. Horiuchi Y, Bae S, Katayama I. Uncontrol-
lable prurigo nodularis effectively treated
by roxithromycin and tranilast. J Drugs
Dermatol, 2006;5:363–365.
10. Hammes S, Hermann J, Roos S, Ockenfels
HM. UVB 308-nm excimer light and bath
PUVA: combination therapy is very effec-
tive in the treatment of prurigo nodularis.
J Eur Acad Dermatol Venereol, 2011;25:799–
803.
11. Wallengren J. Prurigo: diagnosis and man-
agement. Am J Clin Dermatol, 2004;5:85–95.
12. Taefehnorooz H, Truchetet F, Barbaud A,
Schmutz J, Bursztejn A. Efficacy of thalid-
omide in the treatment of prurigo nodu-
laris. Acta Derm Venereol, 2011;91:344–345.
13. Dereli T, Karaca N, Inanir I, Ozturk G.
Gabapentin for the treatment of recalci-
trant chronic prurigo nodularis. Eur J Der-
matol, 2008;18:85–86.
14. Gencoglan G, Inanir I, Gunduz K. Thera-
peutic hotline: treatment of prurigo nodu-
laris and lichen simplex chronicus with
gabapentin. Dermatol Ther, 2010;23:194–
198.
15. Bockbrader HN, Wesche D, Miller R, Cha-
pel S, Janiczek N, Burger P. A comparison
of the pharmacokinetics and pharmacody-
namics of pregabalin and gabapentin. Clin
Pharmacokinet, 2010;49:661–669.
16. Quintero JE, Dooley DJ, Pomerleau F, Hu-
ettl P, Gerhardt GA. Amperometric mea-
surement of glutamate release modulation
by gabapentin and pregabalin in rat neo-
cortical slices: role of voltage-sensitive
Ca2+ a2d-1 subunit. J Pharmacol Exp Ther,
2011;338:240–245.
17. Aperis G, Paliouras C, Zervos A, Arvani-
tis A, Alivanis P. The use of pregabalin in
the treatment of uraemic pruritus in hae-
modialysis patients. J Ren Care,
2010;36:180–185.
18. Paus R, Schmelz M, Biro T, Steinhoff M.
Frontiers in pruritus research: scratching
the brain for more effective itch therapy. J
Clin Invest, 2006;116:117.
19. Tsukumo Y, Matsumoto Y, Miura H, Yano
H, Manabe H. Gabapentin and pregabalin
inhibit the itch-associated response
induced by the repeated application of ox-
azolone in mice. J Pharmacol Sci,
2011;115:27–35.
20. Thielen AM, Vokatch N, Borradori L.
Chronic hemicorporal prurigo related to a
post-traumatic Brown-Sequard syndrome.
Dermatology, 2008;217:45–47.

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