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Chronic pain conditions are associated with loss of quality of life,
employment, productivity and increased healthcare costs.
Common examples of neuropathic
pain include diabetic neuropathy,
which has a higher prevalence rate.
Other examples are cancer related
neuropathy, central neuropathic pain,
complex regional pain syndrome (CRPS)
Type II, human immunodeficiency virus
(HIV) neuropathy, phantom limb pain,
postherpetic neuralgia, postoperative or
traumatic neuropathic pain, spinal cord
injury and trigeminal neuralgia.2,3
Imipramine is a tricyclic antidepressant
(TCA) that is most commonly used to
treat depressive illness in adults and
nocturnal enuresis in children. It is also
indicated for chronic pain conditions
at lower doses. It is partially converted
in the body to an active metabolite,
desipramine, which is another tricyclic
antidepressants. The mechanism of
action of imipramine in the treatment
of neuropathic pain remains uncertain,
although it is known to be a strong
reuptake inhibitor of serotonin and,
to a lesser extent, norepinephrine.
Desipramine, on the other hand is
a very strong reuptake inhibitor of
norepinephrine and, to a lesser extent,
serotonin. Imipramine is associated with
anticholinergic adverse events such as
dry mouth, weight gain, and drowsiness.
This evidence summary presents both
the efficacy and adverse events of
imipramine for the management of
The studies included in the above
mentioned review met a minimum
of reporting quality (blinding,
randomisation), validity (duration, dose
and timing, diagnosis, outcomes, etc.)
and size (ideally at least 500 participants
in a comparison in which the number
needed to treat is four or above.
All studies included in the review were
randomised controlled trials (RCTs) with
at least 10 participants per treatment
group and double-blind assessment
of participant outcomes following two
weeks of treatment or longer.
Quality of the research
Studies included in the report were
of moderate methodological quality.
Biases such as incomplete outcome data
(attrition bias) and sample size were the
• The following databases were
searched; CENTRAL, MEDLINE, and
EMBASE as well as the reference lists
of retrieved papers and other reviews.
Moreover, hand searching of database
for older studies, and two clinical trials
databases were undertaken.
• The review included five studies
with a total of 168 participants
with painful diabetic neuropathy
or polyneuropathy. Their mean age
ranged 47 and 56 years.
• Four studies used a cross-over
design, and one a parallel group
design. Imipramine dose ranged
between 25 mg to 350 mg daily
(most took 100 mg to 150 mg
daily). Comparators were placebo
(an active placebo in one study),
paroxetine, mianserin, venlafaxine,
and amitriptyline, and treatment was
given for two to 12 weeks.
The e cacy of imipramine
for neuropathic pain
BY DR HANAN KHALIL
The purpose of this evidence summary is to provide the
best available evidence for the efficacy of imipramine
for neuropathic pain. For the full review, please refer
to: Hearn L, Derry S, Phillips T, Moore RA, Wiffen PJ.
Imipramine for neuropathic pain in adults. Cochrane
Database of Systematic Reviews 2014, Issue 5. Art. No.:
CD010769. DOI: 10.1002/14651858.CD010769.pub2.1
Dr Hanan Khalil is the Director of the Centre for Chronic
Disease Management, a collaborating centre of the
Joanna Briggs Institute, Faculty of Medicine, Nursing and
Health Sciences, Monash University, and a reviewer for
the consumer group of the Cochrane Collaboration.
• The main outcome measures included;
Patient-reported pain relief of 30%
or 50% or greater, Patient Global
Impression of Change (PGIC), any
pain-related outcome indicating some
improvement, withdrawals due to lack
of efficacy and adverse events.
• Pooling of the data from the five
included studies was not possible due
to the heterogeneity of the reported
outcomes. However, individual studies
indicated some improvement in pain
relief with imipramine compared
Implications for research and
Studies addressing imipramine efficacy
in the management of neuropathic pain
are inconclusive due to their low quality
and heterogeneity in reporting pain
outcomes. There is good evidence to
support the use of other anti-epileptic
and antidepressant drugs in the
treatment of chronic neuropathic pain.5
There is little evidence to support the use
of imipramine to treat neuropathic pain.
1. Hearn L, Derry S, Phillips T, et al. Imipramine for neuropathic
pain in adults. Cochrane Database of Systematic Reviews
2014, Issue 5. Art. No.: CD010769. DOI: 10.1002/14651858.
2. McQuay HJ, Smith LA, Moore RA. Chronic Pain. In: Stevens
A, Raftery J, Mant J, Simpson S eds. Health Care Needs
Assessment. 3rd Edition. Oxford: Radcliffe Publishing, 2007.
3. Vos T, Flaxman AD, Naghavi M, et al. Years lived with disability
(YLDs) for 1160 sequelae of 289 diseases and injuries 1990-
2010: a systematic analysis for the Global Burden of Disease
Study 2010. Lancet 2012;380(9859):2163--96.
4. Watson CPN, Gilron I, Pollock BG, et al. Antidepressant
analgesics. In: McMahon SB, Koltzenburg M, Tracey I, Turk
DC eds. Wall and Melzack's Textbook of Pain. 6th Edition.
Philadelphia: Elsevier Saunders, 2013:465--90.
5. Khalil H. Painful diabetic neuropathy management.
International Journal of Evidenced based Health Care. 2013
[P], vol11, issue1, Wiley-Blackwell Publishing Asia, Richmond,
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