Current Neuropathy Drugs - Their Benefits And Hazards

Today's post from rxeconsult.com (see link below) is from India and presents a list of current medical treatments for neuropathy, with their benefits and side effects without any frills and that's its great value. Most people reading this blog will currently be taking one of these drugs for their neuropathy, or have taken them in the past. That's the reality of a disease which for decades has had very little progression in terms of treatment but the nature of this article means that you can see at a glance why the drugs are used along with all their potentially unpleasant side effects. After reading it, you may wish to have a serious discussion with your doctor because the potential side effects are not to be sniffed at and can end up being more unpleasant that the nerve damage symptoms themselves. Well worth a read but it does make for depressing reading. More effective and safer drugs to treat nerve damage symptoms can't come fast enough as far as I'm concerned and he fact that they are being worked on night and day, is of little consolation to current patients.

Medications For Treating Neuropathy (Nerve Pain)

Category: Neurology: Multiple Sclerosis And More by Chandani Honest, PharmD Intern - June 16, 2016 |



Medications For Treatment Of Neuropathic Pain (Nerve Pain)

What is Nerve Pain?

Neuropathic pain or nerve pain is defined as pain initiated or caused by a primary lesion or dysfunction in the nervous system. Typically, lesions are seen in the pathways of the peripheral and central nervous system. The primary functions of nerves in the nervous system are to instruct muscles to move and to detect physical sensations like pain, temperature, and touch. When the nerves are damaged or diseased, it results in muscle weakness, and/or sensory disturbances. The nerves of the hands, arms, legs, and feet are affected the most, resulting in nerve pain in these areas.

Nerve Pain Medications

First-Line Treatments

1. Tricyclic antidepressants (desipramine, nortriptyline)

Tricyclic antidepressant (TCA) medications work by inhibiting the reuptake of norepinephrine and serotonin. They are first line treatments for nerve pain. There are secondary TCAs and tertiary TCAs. Tertiary TCAs (amitriptyline, and imipramine) were first developed and approved before secondary TCAs. The secondary TCAs desipramine and nortriptyline are preferred for treating nerve pain.

Efficacy of tricyclic antidepressant

There are a large number of placebo-controlled randomized trials (RCTs) that show that TCA’s are effective for treating neuropathic pain. It takes 6 to 8 weeks to the see the full effects of tricyclic antidepressants. One in every 2-3 patients with peripheral neuropathic pain will respond to a tricyclic antidepressant. TCAs are inexpensive and they are commonly used for treating nerve pain, but their use is associated with many side effects.

Common Side Effects of Tricyclic antidepressants
Constipation
Dry mouth
Urinary retention
orthostatic hypotension

Serious Side Effects of Tricyclic antidepressants
Cardiovascular problems: cardiac dysrhythmia, heart block, heart attack, prolonged QT interval, sudden cardiac death
Syndrome of inappropriate antidiuretic hormone secretion (SIADH)
Paralytic ileus
Bone marrow depression
Fulminant hepatic failure, and jaundice (rare)
Seizure
Depression worsening, mania, suicidal thoughts
Angioedema

Side effects can be reduced if lower dosages are administered initially at bedtime and the dose should be slowly increased to a higher dose if needed. Secondary TCA’s (nortriptyline and desipramine) have less severe side effects when compared to tertiary TCA’s (amitriptyline and imipramine).

2. Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs) (duloxetine, venlafaxine)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are recommended as first line therapy for treating neuropathic pain. Duloxetine (Cymbalta) is FDA approved for nerve pain. Venlafaxine (Effexor) is used off-label for treating nerve pain.

Efficacy of Serotonin and Norepinephrine Reuptake Inhibitors for Nerve Pain

SSNRIs will relieve nerve pain in one of every 4-5 patients. They are preferred over TCA’s due to their more favorable side effect profile. In clinical studies, duloxetine has shown consistent efficacy in neuropathic pain. Venlafaxine has shown efficacy in nerve pain as well. Typically, 4 to 6 weeks of treatment is required to adequately judge the response to treatment.

Side Effects of Serotonin and Norepinephrine Reuptake Inhibitors

The most common adverse effect of duloxetine is nausea. Nausea seems to be less if dosing starts at 30 mg once daily for 1 week, then increased to 60 mg once daily. Venlafaxine causes a withdrawal syndrome so it should be tapered when treatment is discontinued.

Common Side Effects of SNRIs
High blood pressure
Sweating
Constipation or diarrhea
Decrease in appetite
Nausea
Dizziness
Insomnia
Fatigue
Dry mouth

Serious Side Effects of SNRIs
Orthostatic hypotension
Heart attack
Hypertensive crisis
Gastrointestinal hemorrhage
Abnormal bleeding
Liver failure
Suicidal thoughts
Serotonin syndrome


3. Calcium Channel α2-δ Ligands (Gabapentin and Pregabalin)

Calcium Channel α2-δ Ligands include gabapentin (Neurontin) and pregabalin (Lyrica). They are both FDA approved for first-line treatment of nerve pain. They both work by binding to voltage-gated calcium channels at the fα2-δ subunit and they inhibit neurotransmitter release.

Efficacy of Gabapentin and Pregabalin for Nerve Pain

Gabapentin and pregabalin have shown efficacy versus placebo for treatment of nerve pain. Available data suggest that TCAs are more effective than gabapentin in relieving nerve pain.

Common Side Effects of Gabapentin and Pregabalin
Peripheral edema
Nausea
Vomiting
Ataxia (muscle incoordination)
Nystagmus (involuntary eye movement)
Fatigue
Fever

Serious Side Effects of Gabapentin and Pregabalin
Stevens-Johnson syndrome
Hypoglycemia
Anaphylaxis
Suicidal thoughts
Angioedema

4. Topical Lidocaine 5% Patch=

Lidocaine is a topical analgesic. It works by altering signal conduction in neurons. It blocks fast sodium channels in the cell membrane of neuronal cells, resulting in signal inhibition. With signal blockage, the signal will fail to transmit, ultimately resulting in nerve pain relief.

Efficacy of Lidocaine Patch

Topical lidocaine 5% patch has shown efficacy and excellent tolerability in clinical trials of subjects with nerve pain. It has been shown to reduce nerve pain severity and it has few side effects because of low systemic absorption. Lidocaine gel (5%), which is less expensive than the lidocaine patch, has also shown efficacy as well. Apply up to 3 patches topically only once, for up to 12 hours within a 24-hour period. It takes up to 3 weeks to see the maximum effects.

Common Side Effects of Lidocaine Patch
Edema
Erythema (bumps under the skin)
Local burning
Abnormal sensations
Itching
Application site reactions

Second-Line Treatments

Tramadol and other opioid analgesics such as methadone, oxycodone, and morphine have shown efficacy in patients with nerve pain but are used as second line treatments because they cause addiction and other serious side effects.

Tramadol (Ultram)

Tramadol is a weak opioid μ-receptor agonist that inhibits reuptake of serotonin and norepinephrine. It provides rapid pain relief.

Efficacy of tramadol for nerve pain

It may be somewhat less effective than strong μ-agonists (e.g., morphine and oxycodone). Tramadol is a controlled substance because it has a risk for abuse and dependence. Serious withdrawal effects are associated with the use of tramadol. The body becomes dependent on tramadol and when tramadol is stopped, the body experiences withdrawal symptoms such as:
anxiety
mood swings
brain zaps (shock-like sensations)
sweating or chills
tremors
headaches
insomnia
depression
aggressiveness
hallucinations
nausea
loss of appetite

Common Side Effects of Tramadol
Flushing
Pruritus
Constipation
Nausea/Vomiting
Xerostomia
Dizziness, Headache
Insomnia
Somnolence

Serious Side Effects of Tramadol
Seizures
Difficulty breathing
Respiratory depression
Serotonin Syndrome

References

Peripheral Neuropathy Causes and Types of Neuropathy. Accessed June 4, 2016.

Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the Pharmacological Management of Neuropathic Pain: An Overview and Literature Update. Mayo Clinic Proceedings. 2010;85(3 Suppl):S3-S14.

Finnerup NB, Otto M, McQuay HJ, Jensen TS, Sindrup SH. Algorithm for neuropathic pain treatment: an evidence based proposal. Pain. 2005;118(3):289-305.

Micromedex.com. 2016.Truven Health Analytics. Accessed on June 6, 2016.

Sindrup S, Otto M, Finnerup N, Jensen T. Antidepressants in the treatment of neuropathic pain. Basic & clinical pharmacology & toxicology. 2005;96(6):399–409. Accessed June 12, 2016.

O’Connor AB. Gabapentin versus Tricyclics for Neuropathic pain. 2009;24(6). Accessed June 12, 2016.

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