&I?w!~~~H'\~ 11 -Treatment options improve prospects for patients with central post-stroke pain

Contrary to the beliefs of some, central post-stroke pain can be alleviated.

About two-thirds of patients will show improvement with appropriate antidepressants, such as amitriptyline, with the key to successful treatment being the earliest possible initiation of therapy.fl]

Other therapies, most notably mexiletine, are avail­able should treatment with antidepressants fail.[l]

Family doctor may be responsible for diagnosis Central post-stroke pain, formerly known as 'thalamic

syndrome', occurs in up to 8% of stroke patients.[1] This type of pain is also less frequently observed after sub­arachnoid haemorrhage, head injury, and postoperative infarcts in patients undergoing neurosurgery. More rarely, central pain may be caused by cerebral abscess, tumour or arteriovenous anomaly.f I,2]

Two features are characteristic of patients with central post-stroke pain.

First, the majority of patients who develop central post-stroke pain were relatively young «65 years) when they had their stroke. In addition, strokes in these pa­tients tend not to have produced serious sequelae, so the patients have a fairly long life expectancy with unremit­ting pain.[1] Although the rate of spontaneous recovery from central post-stroke pain is not known, it is thought that it almost never occurs in patients with well estab­lished central post-stroke pain except, very rarely, as a consequence of a further strokeJI]

Second, central post-stroke pain tends not to appear in the majority of patients until well after the stroke (ap­proximately 3 months).[1] Therefore, most patients will have returned to primary care before pain is reported.

Pain syndromes other than central pain may follow stroke. These syndromes are caused by tissue damage (nociceptive pain) whereas central post-stroke pain is caused by CNS dysfunction (neurogenic pain»)I]

Burning pain accompanied by sensory deficit Central post-stroke pain is often described as burning,

although a few individuals describe it as aching or throb­bing)l] Physical (e.g. cold) or mental stress tend to exac­erbate pain; relaxation or distraction often relieve it. [1]

11 72 -0360/96/00017-0011/$01.00 0 Adis International Limited. All rights reserved

Patients with central post-stroke pain experience a dis­sociated sensory deficit, particularly for pinprick and temperature sensation)l] Furthermore, about 60% of pa­tients experience allodynia (the production of pain by a normally painless stimulus).[1]

Treatment choices Conventional analgesics (including morphine) are

largely ineffective in the treatment of central post-stroke pain.[I]

A number of other interventions have been tried over the years (including anticonvulsants, naloxone, guanethi­dine t injection, stellate ganglion blockade and surgical sympathectomy), also with little success, leading to the myth that central post-stroke pain is untreatable.[1]

As with all types of central pain, the goal of treatment should be pain reduction rather than complete allevia­tion.[3]

No one pharmacological agent is successful in the treatment of all patients, and pain relief

is often incomplete

A suggested plan for the drug treatment of central post-stroke pain is given in the Patient care guidelines.

Amitriptyline commonly used In experimental neuropathies, antidepressants that in­

hibit the reuptake of both serotonin and noradrenaline (e.g. amitriptyline, nortriptyline, desipraminet , maprotil­ine t) are the most effective agents in reducing pain.

In contrast, the selective serotonin reuptake inhibitors (SSRIs) have little effect in the treatment of human neu­ropathic pains) I]

Amitriptyline is considered an effective treatment for central post-stroke pain)I,2] In a small randomised, double-blind, placebo-controlled, crossover study, 67% of patients with central post-stroke pain reported improve­ment after 4 weeks' treatment with amitriptyline 25 to 75 mg/day)4] However, while the improvement with amitriptyline was significantly greater than that with placebo, the magnitude was small; a mean reduction in

t In Spain, guanethidine is available only through the Department of Foreign Drugs and, in Germany, it is not available as a parenteral formulation; desipramine is not available in Spain; maprotiline is not available in Australia.

Vol. 8, No.5; September 2, 1996

~prugs 12 CfT/lL'ltlpt/ Prrspe(tn~ -

Patient care guidelines

I Patient with central post-stroke pain I + I Start treatment with amitriptyline I

10-25 mg/day for 1 week

+ I Increase amitriptyline dose by 10-25 mg/week until maximum tolerated dose (e.g. 50-75 mglday) is reached

~ lis pain relief sufficient? I

Yes No

+ + Maintain dosage I Increase dosage by

r- 25mg increments to a total of 150 mg/day

i Yes

I Is pain relief sufficient? I No ~

I Consider adding mexiletine I Either I Or

... 9-High loading dose: Outpatient therapy:

hospitalise patient and administer a small administer mexiletine 400mg initial dose

then 200mg 6-hourly (e.g. mexiletine 50mg for 3 or 4 days twice daily)

+ i ---..j Hypotension or Increase dose by dizziness? 50- 100mg per week

Yes I No until a beneficial

+- effect is seen

~ Reduce (e.g. 200mg 2-3 times

daily if tolerated) dosage

Discharge on highest tolerated dose (e.g. 200mg 2-3 times daily) © Copyright 1996 Adis

International Ltd

Suggested drug therapy for central post-stoke pain!l)

pain intensity of 11 % was observed with amitriptyline compared with 4% for placebo.

When prescribing antidepressants, it is very important that the patient is aware that:

• no effect on pain may be seen until the maximal dose has been taken for at least 4 weeks

• amitriptyline (and other adrenergically active antide­pressants) have an independent action on 'nerve pain'

VoL 8, No.5; September 2, 1996

and are not being prescribed because the doctor thinks the patient's pain is 'psychological'.[l] The greatest cause of noncompliance with the antide­

pressants used to treat central post-stroke pain is dry mouth; this may be overcome by the use of artificial saliva or chewing gum.l1]

Treatment with antidepressants should be started as soon as the diagnosis of central

post-stroke pain is made

Other common adverse effects include drowsiness or tiredness, and constipation.l1,2] These effects may be minimised by taking the daily dose at bedtime and start­ing with a low dose followed by gradual dosage titra­tion.[2)

Mexiletine an alternative Mexiletine, a class Ib anti-arrhythmic agent that is

structurally related to lignocaine, has been reported to be effective in treating pain of neurogenic origin such as central post-stroke pain and diabetic neuropathy.

In patients with central post-stroke pain, mexiletine may be used both as a first-line treatment (especially in younger patients) and after failure to respond to antide­pressants.[l]

Electrocardiography and frequent check-ups are man­datory in patients receiving mexiletine.[1] Approximately one-third of patients will develop nausea or dizziness of sufficient intensity to require discontinuation of the drug.[lJ

Mexiletine added to antidepressant therapy may be more effective than mexiletine alone.l l ]

Nondrug measures available Positive relaxation can be helpful and should be used

as an adjuvant to drug therapy.l5J Some patients have also found transcutaneous electrical nerve stimulation (TENS) to be helpful as an adjuvant therapy.[l]

Patients who fail to respond to drug treatment may benefit from deep brain or motor cortex stimulation through surgically implanted electrodes.l1]

References I . Bowsher D, Nurmikko T. Central post-stroke pain: drug treatment

options. CNS Drugs 1996 Mar; 5 (3): 160-5

2. Bryson HM, Wilde Ml. Amitriptyline: a review of its pharmacological properties and therapeutic use in chronic pain states. Drugs Aging 1996 Jun; 8 (6): 459-76

3. Gonzales GR. Central pain: diagnosis and treatment strategies. Neurology 1995 Dec; 45 Suppl. 9: S II-S 16

1172 ·0360/96/00017-0012/$0 1.00 © Adis International Limited. All rights reserved

~prugs CJ'TIwffl/7IJ Perspectives 13

4. Leijon G, Boivie J. Central post-stroke pain - a controlled trial of amitriptyline and carbamazepine. Pain 1989 Jan; 36: 27-36

5. Bowsher D. The management of central post-stroke pain. Postgrad Med J 1995; 59: 127-33

Incidence of dose-related adverse effects of anticonvulsants can be minimised

Treating patients with epilepsy has always been a bal­ance of obtaining the maximum seizure control while minimising the emergence of dose-related adverse ef­fects.

Traditional anticonvulsants are associated with a range of dose-related adverse effects. Recently a number of new anticonvulsants have been introduced, and al­though these new agents tend to be better tolerated, dose­related adverse effects may still prevent the maximum effective dosage being used.

With care most patients can achieve effective seizure control while avoiding the majority of

dose-related adverse effects

Types of adverse effects Anticonvulsants produce a range of dose-related ad­

verse effects that can generally be divided into 5 catego­ries:[1]

• motor effects • cognitive effects • gastrointestinal effects • appetite and bodyweight changes

• headache and dizziness These effects can range from mild, causing minor

irritation for the patient, to severe, necessitating discon­tinuation of therapy. However, even mild adverse effects can decrease quality of life in patients who have to take anticonvulsant medication for life. The effects of anticon­vulsants on quality of life in patients with epilepsy are becoming an important outcome measure in this patient population. [2]

The older traditional anticonvulsants appear to have approximately equivalent adverse effects on cognitive function. Recent data that suggests that some of the newer anticonvulsants (lamotrigine, gabapentin and vigabatrin t) may have beneficial effects on cognitive function.[3]

t Vigabatrin has not yet been approved in the US.

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Importance of adverse effects Dose-related adverse effects commonly prevent the

maximum effective dosage being given to patients with epilepsy and may result in treatment failure. Individuals vary in their response to a particular anticonvulsant dosage both in efficacy achieved and the occurrence of adverse effects.

Monitoring plasma anticonvulsant concentrations may be of assistance for some of the traditional anticon­vulsants (e.g. phenytoin, carbamazepine) as these can give a guide to the concentration necessary to achieve seizure control or at which dose-related adverse effects appear.

In contrast, for some of the newer anticonvulsants (e.g. lamotrigine), plasma concentrations do not relate to efficacy or onset of adverse effects, and are therefore of little value.l4]

Minimising the occurrence of adverse effects The best way of minimising the occurrence of adverse

effects associated with anticonvulsant therapy is to pre­vent their emergence, and this may be easier to achieve by using a single anticonvulsant.[!]

Adverse effects often occur when therapy is started, and are more common and severe in patients who are being treated with an anticonvulsant for the first time, especially if they have never taken medications that af­fect the CNS.

Initiation of therapy In anticonvulsant drug-naive patients, the CNS effects

of anticonvulsant therapy can be quite distressing. The consequences of these effects can be limited if therapy is initiated with care.[1]

It has been suggested that anticonvulsant therapy should be started at a quarter to a third of the target dose and gradually increased every few days until the target dose is reached.[l]

This dosage titration allows the body to adjust to the drug effects, and, for some drugs, allows a degree of autoinduction of metabolism to occur. For example,

Vol. 8, No.5; September 2, 1996

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