Antidepressants

Dimitris Papadopoulos MD Fellow Of Interventional Pain Practice (FIPP)

Updated 03 January, 2011

ΑΝΤIDEPRESSANTS

GENERAL

Antidepressants are one of the very important groups of drugs used in the treatment of chronic pain syndromes. They are drugs administered to treat depression but it is a long time since they have been shown to be also active in the treatment of some chronic pain syndromes. So, patients who take antidepressants do not necessarily suffer from depression. It has been demonstrated that antidepressants are effective in chronic pain in lower doses and within a shorter time period than in depression. This is not always the case and some patients need higher doses to achieve pain relief.

MODE OF ACTION

Antidepressants increase levels of the neurotransmitters serotonin and norepinephrine, which are chemical substances playing a major role in pain reduction by enhancing the action of the descending pathway that restricts the transmission of pain signals to the brain. Antidepressants that increase norepinephrine seem to have stronger analgesic properties in comparison to selective serotonin receptor inhibitors (SSRIs), which are effective in depression but are not equally drastic in pain control.

SIDE-EFFECTS

The most frequent side-effects of antidepressants are drowsiness, constipation, dry mouth (xerostomia), urinary retention, weight gain and blurred vision. In more rare cases, patients may have nightmares or increase in heart rate. Some patients may present serious intolerable side-effects, whereas others may complain only about minimal mild side-effects. Side-effects differ among the various antidepressants and, in general, they arebetter tolerated by patients over time.

Should a patient complain about intolerable side-effects of an antidepressant and at the same time report pain improvement, switching to another antidepressant of the same group may benefit him/her by being equally effective in pain relief but with fewer adverse events.

BENEFICIAL EFFECTS OF ANTIDEPRESSANTS IN CHRONIC PAIN TREATMENT

•    They do not cause stomach irritation or bleeding, as opposed to steroid anti-inflammatory drugs.
• They do not affect the internal body defence system. On the contrary, they enhance the action of chemical neurotransmitters serotonin and norepinephrine in the nervous system inhibiting the transmission of pain signals.

• They act as sedatives improving sleep quality, which is such a major problem in for patients with chronic pain.
• They act effectively in probable concomitant depression.
• They reduce anxiety and panic attacks.
• They do not cause addiction and the phaenomenon of tolerance is not observed when the optimal therapeutic dose is achieved.

CHRONIC PAIN SYNDROMES INDICATED FOR ANTIDEPRESSANTS
•    Postherpetic neuralgia
•    Diabetic neuropathy
•    Νeuropathic pain
•    Peripheral neuropathy after chemotherapy
•    Fibromyalgia
•    Phantom-limb pain
•    Post-stroke pain
•    Complex regional pain syndrome
•    Migraine
•    Tension headache
•    Rheumatoid arthritis
•    Degenerative osteoarthritis
•    Irritable bowel syndrome

MOST COMMONLY USED GROUPS OF ANTIDEPRESSANTS

Α. TRICYCLIC ANTIDEPRESSANTS

•    Αmitriptyline = SAROTEN
•    Νortriptyline = NORTRYLEN
•    Doxepin = SINEQUAN
•    Clomipramine = ANAFRANIL
•    Μirtazapine = REMERON
Tricyclic antidepressants can roughly be divided in the ones with more and the others with fewer sedative side-effects. Patients with excitation and anxiety benefit more from antidepressants with sedating properties than from those with less sedating properties.

Their most common side-effects are:
•    Dry mouth
•    Blurred vision
•    Constipation
•    Difficulty in urination
•    Fatigue
•    Difficulty in concentrating
•    Aggravation of glaucoma

Other probable side-effects are increase of appetite and weight, reduction of arterial blood pressure and the feeling of heart palpitation. Overdosage may cause even death. Patients with Alzheimer disease should not take antidepressants. Patients with heart disease should avoid the use of antidepressants or, if this cannot be avoided, they should be closely followed by the cardiologist.

Β. SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRI”S)

The second group of antidepressants includes the following drugs:

•    Fluoxetine = PROZAC
•    Sertraline  = ZOLOFT
•    Paroxetine = SEROXAT
•    Fluvoxamine= DUMYROX,MYROXINE
•    Citalopram   = SEROPRAM
•    Escitalopram = CIPRALEX

They have fewer adverse events and are less sedative than tricyclic antidepressants. They are effective in headache prevention and less effective for other types of chronic pain. Most studies conducted for neuropathic pain, have shown that their efficacy in the treatment of neuropathic pain is disappointing.

Most common side-effects are the following:
•    Dry mouth
•    Νausea
•    Vomiting
•    Stomach discomfort
•    Hygroma
•    Diarrhoea
•    Poor appetite
•    Τremor
•    Drowsiness
•    Anxiety
•    Νervousness
•    Insomnia
•    Increase of arterial blood pressure
•    Increase of heart rate
•    Cholesterol increase
•    Sexual dysfunction

They should be used with caution by patients with epilepsy, with a history of manic disorder, heart disease, diabetes mellitus, simultaneous use of drugs in risk for gastrointestinal bleeding, haemorrhage, liver and renal disorders. They should not be administered during gestation and lactation.

Sudden discontinuation is followed by side-effects, such as headache, nausea, burning sensation, limb paraesthesias, confusion and pain. Therefore, they should be gradually interrupted.

SEROTONIN & NOREPINEPHRINE REUPTAKE INHIBITORS (SNRI”S)

The third group of antidepressants includes drugs inducing reuptake inhibition of both serotonin and norepinephrine.

The most commonly used agents used in chronic pain are:
•    Duloxetine  = CYMBALTA
•    Venlafaxine = EFEXOR
•    Milnacipran = SAVELLA
Duloxetine has been approved by FDA for the treatment of diabetic peripheral neuropathy, fibromyalgia, anxiety disorder and depression.
Milnacipran has been approved by FDA for the treatment of fibromyalgia. This specific drug causes more selective inhibition of norepinephrine than duloxetine and venlafaxine.
Drugs of this category have no antiholinergic properties and have fewer side-effects.

The most frequently occurring side-effects are:
•    Dry mouth
•    Νausea
•    Vomiting
•    Blurred vision
•    Hygroma
•    Drowsiness
•    Constipation
•    Gases
•    Headache
•    Sexual dysfunction