ANTIDEPRESANTS USED IN THE

TREATmENT OF NEUROPATHIc PAIN

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OBJEcTIVES• Back Ground Information On Depression

• Synopsis of Pain

• Types And Classification Of Pain• Neuropathic Pain• Pain and depression• Antidepressants used to treat pain

• Tricyclic antidepressants used to treat pain

• MOA of Tricyclic Antidepressants• Side effects Of TCAs• Pharmacology Of TCAs

• Contraindications/ Precautions Of TCAs

• SNRI- serotonin-norepinephrine reuptake inhibitors used to treat pain• Pharmacology Of Duloxetine• Side Effects Of Duloxetine• Pharmacology Of Venlafaxine

• Adverse effects and Contraindicated of Venlafaxine

• References2

Back Ground Information On Depression

According to Rang et al., 2012 Depression is the most common form of affective disorders.

This affective disorder of the mood, thought or cognition is considered a heterogeneous disorder with individuals presenting with one or more symptoms.

It is characterized by lethargy, sadness, and a loss of interest or pleasure in normal activities.

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Synopsis of Pain

Pain is an unpleasant sensory or emotional experience associated with actual or potential tissue damage.

Pain originates in the primary sensory neurons and terminates in the dorsal horn of the spinal cord; at the dorsal horn pain signals activate many brain structures through the ascending pathways.

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Types And Classification Of Pain

Acute pain is short-lasting and can be described, as it is usually the result of an injury, surgery or illness. It last lesser than six months.

Chronic pain is a constant or intermittent pain that persists beyond the expected healing time and seldom attributed to a specific cause or injury. It lasts longer than six months. Eg cancer pain

Nociceptive pain: stimuli from somatic (skin and deep tissue) and visceral (internal organs) structures.

Neuropathic pain: stimuli abnormally processed by the nervous system

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NEUROPATHIC PAIN Neuropathic pain is caused by a problem with one

or more nerves. The function of the nerve is affected in a way that it sends pain messages to the brain. Neuropathic pain is often described as burning, stabbing, shooting, aching, or like an electric shock.

Some common causes of neuropathic pain include: Alcoholism, Amputation, Chemotherapy, Diabetes, HIV infection or AIDS, Multiple sclerosis, Shingles and Spine surgery.

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Pain and depression There are link between

depression and pain biologically, where there is a dysfunction of the neurotransmitters serotonin hydroxytryptamine (5HT), Norepinephrine (NE) and dopamine. Thus causing a dysfunctional pathway.

Persons with chronic pain are prone to depression because of the continuous disease burden impose by the pain.

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Antidepressants Used To Treat Pain

Tricyclic antidepressants

– Analgesic effects separate from anti-depressant effects.

– Amitriptyline: most studied, but has most side effects

– Nortriptyline & desipramine: better tolerated, less well studied.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs

– inhibit both norepinephrine and serotonin reuptake

– efficacy in neuropathic pain syndromes or pain associated with depression (duloxetine [Cymbalta®], venlafaxine [Effexor®])

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Tricyclic antidepressants used to treat pain

Tricyclic antidepressants particularly Amitriptyline, Nortriptyline and Desipramine are widely used in the treatment of neuropathic pain. These drugs act centrally by inhibiting noradrenaline reuptake and are highly effective in relieving neuropathic pain in some cases, but not all, cases. Their action is however, independent of the antidepressant effects.

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MOA Of Tricyclic Antidepressants

The MOA of TCA’s is to block the uptake of amines on nerve terminals, by competition for the binding site of the amine transporter. Most TCAs inhibit noradrenaline and 5-HT uptake but have much less effect on dopamine uptake. It has been suggested that the improvement of emotional symptoms reflects mainly an enhancement of 5-HT mediated transmission, whereas relief of biological symptoms results from noradrenergic transmission.

In addition to their effects on amine uptake, most TCAs

affects other receptors, include muscarinic acetylcholine receptors, histamine receptors and 5-HT receptors.

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Side Effects Of TCAs

Sedation. (30% amitriptyline/2% nortriptyine)

postural hypotension .This is due to blockade of H2 and musacarinc receptors

Anticholoinergic effects includes: (dry mouth: 30% amitriptyline/10% nortriptyline), constipation, urinary retention, blurred vision, tachycardia, cognitive impairment)

Cardiac arrhythmias ( especially in overdose)

Weight gain 11

Pharmacology Of TCAs

Dose: start with 10 mg at bedtime with Gradual escalation every three days in 10 mg increments.

( Analgesic response typically seen with 10 – 75 mg daily)

Given Orally

Half life 10-20 hrs

90-95% PPB12

Contraindications/ Precautions Of TCAs

Should not administered to persons with cardiovascular disease and low blood pressure

Should not be given to elderly people as they consist of many side effects.

Precautions: Benign prostatic hypertrophy, closed angle

glaucoma, CV disease Screening EKG for cardiac conduction

abnormalities if > 40 yo Risk of suicide by overdose (> 750 mg or 15 - 20

mg per kg)13

SNRI- Serotonin-norepinephrine Reuptake Inhibitors Used To Treat Pain

Duloxetine is primarily used to treat major depression. It is also used to treat pain and tingling caused by diabetic neuropathy (damage to the nerves) and fibromyalgia. Its also used to treat on going bone or muscle pain such as lower back pain or osteoarthritis.

MOA of SNRI : increase levels of norepinephrine ( and serotonin) to stimulate the descending pain pathway

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Pharmacology Of Duloxetine

Duloxetine (Cymbalta ®) Start at 15 mg once daily and titrate slowly up to 60 mg daily

Dosage adjustment not necessary in renal dysfunction; caution with hepatic insufficiency

It is given orally

Half life: 12 hours (range 8-17 hours)

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Side Effects Of Duloxetine

 Signs of an allergic reaction: skin rash or hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Agitation, hallucinations, fever, fast heart rate.

Headache, trouble concentrating, memory problems

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Pharmacology Of Venlafaxine

Start at 15 mg once daily and titrate slowly up to 60 mg daily

It is given orally

Half life: 5 hours

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Adverse Effects And Contraindicated Of Venlafaxine

SE: nausea, headaches, sedation, sweating, increased blood pressure

Minimal anticholinergic side effects

Contraindicated in alcohol and St.John's Wort.

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References

Rang H.P., Dale M.M., Ritter J.M., Flower R.J., Henderson G. (2012). Rang and Dale’s Pharmacology. The Nervous System Pages 506 & 521

Rang H.P., Dale M.M., Ritter J.M., Flower R.J., Henderson G. (2012). Rang and Dale’s Pharmacology. Antidepressant drugs Page 564

Tricyclic Antidepressants and Tetracyclic Antidepressants . Retrieved on September 19, 2014 from http://www.mayoclinic.org/diseases-conditions/depression/in-depth/antidepressants/art-20046983

Skapinakis, P.(2008).Tricyclic Antidepressants - Effects and Contraindications. Retrieved on September 19, 2014 from http://web4health.info/en/answers/bipolar-depr-med-tcas-effect.htm

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THAT MOMENT JUST BEFORE PAIN

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