SA JOURNAL OF DIABETES & VASCULAR DISEASE
DRUG TRENDS
VOLUME 9 NUMBER 3 • SEPTEMBER 2012
141
Managing neuropathic pain: first expert recommendation for South
Africa places emphasis on stepwise pharmacological intervention
N
europathic pain, initiated or caused
by a primary lesion or disease in the
peripheral or central nervous system, is best
treated by first defining the aetiology, then
treating the primary cause such as diabetes
or rheumatoid arthritis, and thirdly, initiating
appropriate and adequate doses of pain-
relieving medication. ‘Frequently, patients
are referred to us at the Pain Clinic with
appropriate pain-relieving therapy, but at
very timid doses’, Dr Milton Raff, Christiaan
Barnard Memorial Hospital said at the recent
FCPSA Congress.
In his presentation, Dr Raff dealt with the
basics of the physiology of pain, stressing
the transmission mechanism of pre-synaptic
neurons
releasing
neurotransmitters,
reaching the receptor on the post-synaptic
neuron in onward transmission to the spinal
cord, cortex and the limbic brain, which
integrates pain awareness with subjective
factors such as fear, anxiety and sleep
disturbance. ‘At each physiological level, we
have agents to target the pain mechanism
(
Table 2). We must appreciate that one
aetiology does not cause one symptom but
causes a cluster of symptoms that are shared
with other aetiologies, requiring more than
one therapeutic approach’, Dr Raff noted.
With regard to neuropathic pain, there
are four main drug classes that can be used:
carbamazepine as a sodium channel blocker
plus anti-depressants; the alpha-2 delta-
ligands (pregabalin and gabapentin); SNRIs;
and opioids. ‘The difficulty is that there are
no predictors to guide choice and no-head-
to-head studies to compare agents’, Dr Raff
pointed out. This has led to the development
of a stepwise pharmacological approach of
using agents, first developed by Dickenson,
1
and latterly followed by international
agencies such as the European Federation
of Neuroscience guidelines.
2
Recent South African guidelines have
been published,
3
with input from an expert
panel consisting of specialists from the fields
of psychiatry, neurology, neurosurgery,
anaesthesiology, family medicine and basic
science (Table 1). The expert panel makes
the following recommendations:
First-line therapy is the alpha-2 delta-
•
ligands (pregabalin or gabapentin), TCAs
(
tricyclic antidepressants) or the SNRIs
(
duloxetine and venlafaxine).
Table 1.
Summary of therapeutic agents for peripheral and diabetic neuropathy in South Africa
Contraindications/precautions/drug interactions
Other benefits
α
2
δ
-
ligands
Pregabalin
No significant drug interactions
Linear pharmacokinetics
Dose reduction required in renal insufficiency
Improvement of
sleep disturbance
Anxiolytic
Gabapentin
Dosage reduction required in renal insufficiency
No clinically significant drug interactions
Improvement of
sleep disturbance
SNRIs
Duloxetine
Contraindicated in severe hepatic impairment, end-stage renal
disease, alcohol abuse, concomitant use of tramadol and
MAOIs
Low initial doses for mild to moderate hepatic and renal
impairment
Caution required in patients with history of mania, seizures,
acute narrow-angle glaucoma
Glucose monitoring required as worsening glycaemic control
seen in diabetic patients
Drug interactions with tramadol, TCAs, SSRIs and SNRI.
Inhibition of metabolism of drugs metabolised by CYP2D6
Suicide risk (black-box warning, in line with other
antidepressants)
Improvement
of major
depressive disorder
and generalised
anxiety disorder
Venlafaxine
Caution required in patients with cardiac disease
Risk of hypertension, hence regular blood pressure monitoring
required
Lower dose may be necessary in patients with renal impairment
(
GFR = 10–70 ml/min) or cirrhosis of the liver
Use with caution in patients with history of seizures and history
of mania
Drug interactions with tramadol, TCAs, SSRIs and SNRIs.
Inhibition of metabolism of drugs metabolised by CYP2D6
Suicide risk (black-box warning, in line with other
antidepressants)
TCA: amitrip-
tyline
Contraindicated with MAOI use, antihypertensives, patients
with myocardial infarction/heart block, untreated narrow-angle
glaucoma
Use with caution in patients with glaucoma, cardiovascular
disease, especially in elderly patients, hyperthyroidism, impaired
liver function, epilepsy, urinary retention, prostatic hypertrophy,
constipation, mania
Improvement of
major depressive
disorder
Tramadol
High risk of addiction and abuse, psychomotor impairment
possible
Use with caution in patients with history of substance abuse,
suicide risk, seizure disorder and in elderly patients because of
risk of confusion
Contraindicated with concomitant use of SSRI, SNRI, TCA
Rapid onset of
analgesic benefit
Strong opioids
High risk of addiction and abuse, psychomotor impairment
possible
Use with caution in patients with history of substance abuse,
suicide risk and in elderly patients because of risk of confusion
Contraindicated with concomitant use of SSRI, SNRI, TCA
Rapid onset of
analgesic benefit
SNRIs = serotonin–noradrenalin reuptake inhibitors; MOAIs = monoamine oxidase inhibitors;
TCAs = tricyclic antidepressants; SSRIs = selective serotonin reuptake inhibitors.
