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Gabapentin and pregabalin act at the a28-subunit of presynaptic calcium channels on primary nociceptive endings.56,57 Dizziness and drowsiness are the most commonly reported adverse events, especially during upward titration to targeted doses. Both drugs have a low potential for drug interactions, and no negative impact on cardiac function. Peripheral edema occurs in some patients. Both drugs have been shown to be effective in the management of PHN. Pregabalin has superior bio-availability and dose titration-to-effect seems to produce fewer side effects than gabapentin.58 Gabapentin and pregabalin improve sleep disturbance, overall mood, and other measures of quality of life in neuropathic pain patients.56,59[I]

These features make the a28-subunit ligands suitable for first-line therapy especially for the elderly, a population very often suffering from several comorbidities that need multiple drug therapies. In most situations they are a more costly option than TCAs but their perceived greater safety may overcome this limitation, particularly in elderly or frail patients. Abrupt discontinuation should

Table 32.1 Guidance for use of drugs for postherpetic neuralgia.

Medication

Start dosage

Titration

Maximum dosage

Duration of adequate trial

Gabapentin

100-300 mg every night

Increase by 100-300 mg

1800 mg/day (600 mg

3-6 weeks for titration

or 100 mg 3 x times

3 x daily every 1-7

3 x daily); reduce if

plus 1-2 weeks at

daily

days as tolerated

low creatinine

maximum tolerated

clearance3

dosage

Pregabalin

50 mg 3 x daily

Increase to 100 mg 3 x

600 mg/day (200 mg 3 x

2 weeks for titration

daily within one

daily) reduce if low

plus 1-2 weeks at

week

creatinine clearance

maximum tolerated

dosage

Tricyclic

10-25 mg every night

Increase by 10-25 mg/

75-150 mg/day; if blood

6-8 weeks with at least

antidepressants

day every 3-7 days as

level of active drug

1-2 weeks at

(e.g. nortriptyline,

tolerated

and its metabolite is

maximum tolerated

amitriptyline)

> 100 ng/mL,

dosage

continue titration

with caution

Opioid analgesics

5-15 mg every 4 hours

After 1-2 weeks convert

No maximum with

4-6 weeks

(morphine)

as needed

total daily dosage to

careful titration over

long-acting opioid

time

analgesic and

continue short-

acting medication as

rescue medication

Tramadol

50 mg once or twice

Increase by 50-100 mg/

400 mg/day (100 mg 4

4 weeks

daily

day in divided doses

times daily); in

every 3-7 days as

patients older than

tolerated

75 years, 300 mg/day

in divided doses

5% Lidocaine patch

Maximum of 3 patches

None needed

Maximum of 3 patches

2 weeks

daily for a maximum

daily for a maximum

of 12 hours

of 12 hours

aThis dose is frequently exceeded in specialist clinical practice.

aThis dose is frequently exceeded in specialist clinical practice.

Table 32.2 Number needed to treat (NNT) and number needed to harm (NNH) for effective treatments for postherpetic neuralgia.

Active treatment

Number of patient

Number of

NNT (95% CI)

NNH (95% CI)

NNH (95% CI)

episodes

studies

minor harm

major harm

Combined tricyclic

248

4

2.64 (2.1-3.54)

5.67 (3.34-18.58)

16.9 (8.85-178)

antidepressants

Combined gabapentin

559

3

4.39 (3.34-6.G7)

3.93 (2.64-7.66)

12.25 (7.69-3G.2)

Combined pregabalin

411

3

4.93 (3.66-7.58)

4.27 (2.78-9.18)a

-

Combined opioids

211

2

2.67 (2.G7-3.77)

3.57 (2.16-10.23)a

6.29 (4.16-12.8)

Tramadol

108

1

4.76 (2.61-26.97)

-

-

Topical lidocaine (5%

64

1

2 (1.43-3.31)

-

aData from Ref. 50.

patch)

aData from Ref. 50.

be avoided after a case study reporting encephalopathic Opioid analgesics changes following sudden pregabalin withdrawal.60 There is no convincing evidence for efficacy of sodium-blocker Double-blind placebo-controlled studies have demon-

anticonvulsants, such as carbamazepine, in PHN.61 strated that intravenous infusions of morphine or fentanyl give significant pain relief in PHN.62[II] Controlled trials have demonstrated sustained efficacy for several weeks of oral oxycodone63[II] and tramadol.64[II] Additionally, in a nonplacebo-controlled parallel group study of neuropathic pain management comparing two doses of levorphanol, significant dose-dependent pain relief was found in PHN patients.65[II] In one study, oral morphine was analyzed in a group of PHN patients comparing the effect of tricyclic antidepressants in the same cohort. Both drugs were similarly effective. However, there was no correlation in the response rate between both drugs, indicating that different mechanisms are active in these PHN patients.66 The use of opioids requires caution in elderly patients and those with a history of chemical dependence or pulmonary disease. Standard guidelines for use of strong opioids in nonterminal pain should be followed. After dose titration with a short-acting agent, conversion to long-acting opioid analgesics (e.g. sustained release morphine or oxycodone preparation) is desirable. Prophylactic treatment of common side effects, nausea and constipation, is necessary and improves patient compliance. Further common adverse effects are dizziness, sedation, and pruritus. Psychotic symptoms may occur, in particular in elderly patients. Withdrawal should be by gradual reduction in dosage.

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