Antidepressants are drugs usually used to treat patients with depression. However, some antidepressants have been shown to be effective pain relievers. Though the U.S. Food and Drug Administration (FDA) has not approved most antidepressants for this purpose, they are often prescribed to relieve chronic pain, even in patients who do not have depression.

Studies have shown that tricyclic antidepressants (TCAs) – which appear to increase the levels of certain neurotransmitters that block pain signals – can relieve pain associated with numerous conditions, including the burning or searing pain related to nerve damage (neuropathic pain). Such pain may affect patients with diabetes, shingles, stroke or other conditions. TCAs also appear to be first-line medications for the management of fibromyalgia.

A group of antidepressants called selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) appear to exert their effect by mechanisms similar to TCAs. The FDA has approved an SSNRI for relief of diabetic nerve pain.  

Other conditions that are sometimes treated with antidepressants include chronic fatigue syndrome, migraines and other headaches, cranial neuralgias, arthritis, back pain and pelvic pain.

The FDA has found that antidepressants increased the risk of suicidal thoughts and behavior in individuals with major depressive disorders and other psychiatric conditions, and ordered that warnings to this effect appear on the labeling of these medications. Patients on antidepressants should be closely monitored for any worsening of their condition, suicidal thoughts or behaviors or otherwise unusual behaviors.

Antidepressants are medications that have been approved to treat people diagnosed with depression, a psychiatric disorder characterized by symptoms such as extreme sadness, an inability to concentrate, insomnia, loss of appetite, helplessness and thoughts of death. Many of these drugs also are used in pain management.

Although the U.S. Food and Drug Administration (FDA) has not approved tricyclic antidepressants (TCAs) for use in pain relief, they are commonly prescribed to treat chronic pain conditions.

Many patients with chronic pain have depression as well, so the TCAs can help treat both conditions. These drugs are usually used to relieve depression by blocking the reuptake of the neurotransmitters norepinephrine and serotonin in the central nervous system. They relieve pain regardless of whether or not a patient also has depression. TCAs are not addictive.

For at least 40 years, scientists have known about the analgesic potential of antidepressants. As with all analgesic medications, scientists do not yet understand exactly how antidepressants help relieve pain.

Of the antidepressants, TCAs have the longest history of use in pain relief. It is believed that these drugs increase the number of neurotransmitters in the spinal cord that reduce pain signals. TCAs do not immediately relieve pain. It may take several weeks before the pain-reducing benefits of TCAs are experienced.

Among the other classes of antidepressants are selective serotonin and norepinephrine reuptake inhibitors (SSNRIs). The FDA has approved an SSNRI for relief of painful diabetic neuropathy.

The FDA in 2005 issued a public health advisory for antidepressant medications. Scientific studies found that some antidepressants increased the risk of suicidal thoughts in some people with major depressive disorders and other psychiatric disorders. The agency ordered warnings to be placed on medications.

Patients on antidepressants should be closely monitored for any worsening of their condition, suicidal thoughts or behaviors, or otherwise unusual behaviors.

There are several types of antidepressants, including:

• Selective serotonin and norepinephrine reuptake inhibitors (SSNRIs). Increase the availability of mood-regulating neurotransmitters serotonin and norepinephrine in the brain. The U.S. Food and Drug Administration (FDA) has approved one SSNRI, duloxetine (Cymbalta),  for relief of painful diabetic peripheral neuropathy. This is the only antidepressant specifically approved by the agency to treat pain. It is one of only two drugs approved to treat diabetic neuropathy, the other being an anticonvulsant.
  
  
• Tricyclic antidepressants (TCAs). Increase the availability of serotonin, norepinephrine and (to a lesser extent) dopamine in the brain.
  
  
• Selective serotonin reuptake inhibitors (SSRIs). Increase the availability of serotonin in the brain.
  
  
• Monoamine oxidase inhibitors (MAOIs). Increase the concentration of chemicals that transmit data between nerves in specific regions of the brain, which may lead to increased cognitive functioning.
  
  
• Serotonin modulators. Block the reuptake of serotonin.
  
  
• Norepinephrine-serotonin modulators. Block certain receptors that accept serotonin and norepinephrine.

TCAs and SSNRIs are known to relieve pain, even in patients who do not suffer from depression. Several TCAs appear to provide roughly the same levels of pain relief, with some subtle variations. Typically, the type of antidepressant prescribed to a patient will depend on the patient’s overall health and susceptibility to side effects.

The most commonly prescribed antidepressant for pain relief, amitriptyline, is also the most sedating of the tricyclics, which may be beneficial in patients who are having problems sleeping.  However, it is associated with a higher incidence of side effects than the other TCAs. Other TCAs commonly prescribed to treat pain include desipramine (Norpramin, Pertofrane) and nortriptyline (Aventyl, Pamelor), which are less sedating than amitriptyline.

In addition to duloxetine, SSNRIs include venlafaxine (Effexor). It appears to provide pain relief at a similar level to that provided by duloxetine.

Lithium, which is prescribed primarily to treat bipolar disorder (manic depression), is also sometimes used in the treatment of cluster headaches.

Although there are many types of antidepressants, selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and tricyclic antidepressants (TCAs) are the ones most likely to relieve pain. They appear to be especially effective in treating burning or searing pain related to nerve damage (neuropathic pain), which may affect patients with conditions including diabetes, shingles, postherpetic neuralgia, stroke and spinal cord injuries but can also provide significant pain relief for a number of other types of pain.  Other symptoms associated with neuropathic pain include numbness, “pins and needles” sensation (paresthesia) and pain that is stabbing, shooting or radiating.

Other conditions for which these antidepressants also appear to relieve and, in some cases, prevent pain include:

• Chronic musculoskeletal pain syndromes such as fibromyalgia, chronic fatigue syndrome and myofascial pain syndrome
  
  
• Headaches including migraines and tension headaches
  
  
• Cranial neuralgias
  
  
• Back pain
  
  
• Arthritis and other sources of joint pain

• Some types of chest pain, abdominal pain and pelvic pain
  
  
• Cancer pain

Studies have produced mixed findings on the effects of antidepressants on bone health. For example, depression has been linked to decreased bone mass, and some research has suggested antidepressants may slow bone loss, thus reducing the risk of osteoporosis and fractures. Yet other research has found that selective serotonin reuptake inhibitors (SSRIs) might increase the risk of fractures.

Tricyclic antidepressants (TCAs) may increase the risk of seizures in patients who are at risk for these, including those with epilepsy. Selective serotonin reuptake inhibitors (SSRIs) and selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) are generally the safest to use in patients with a history of seizures.

The U.S. Food and Drug Administration (FDA) in 2005 instructed all manufacturers of antidepressants to add warnings to their labeling about certain dangers associated with these medications. These dangers include increased risk of suicidal thoughts and behavior in children and adolescents.

In addition, the FDA issued a public health advisory to inform patients and healthcare providers about the link between antidepressants and increased risk of suicidal thoughts and behavior in adults. According to the advisory, adults who take antidepressants should be carefully monitored for an increase in feelings of depression and suicidal thoughts, especially if they are taking a medication for the first time or its dosage has recently been adjusted. Adults who take antidepressants and experience an increase in feelings of depression should seek immediate medical attention.

It should be noted that there is no information demonstrating that there is an increase in suicidal thoughts when antidepressants are used to manage pain in patients who are not depressed.

The agency also directed manufacturers to include information from pediatric and adult trials in the packaging of antidepressant medications.

Patients should consult a physician if they have concerns about taking these medications in light of the FDA’s recent recommendations.

Some recent studies including the Diabetes Prevention Program have found a possible link between antidepressants and elevated glucose (blood sugar) or risk of developing diabetes. Further research would be needed to establish a connection. 

TCAs are commonly used for the relief of pain. Patients who have been diagnosed with heart disease should inform their physician of this fact before taking TCAs. In addition, TCAs may exacerbate glaucoma in some patients. Glaucoma is a group of eye diseases that damage the optic nerve and usually involve abnormally high fluid pressure inside the eye. Glaucoma can result in partial to complete loss of vision.

Other conditions of concern in regard to use of TCAs include:

• Alcoholism
• Bipolar disorder
• History of seizures
• Enlarged prostate (benign prostatic hyperplasia) or history of urination difficulties
• High blood pressure
• Heart problems including arrythmias
• Schizophrenia
• Kidney disease
• Liver disease
• Overactive thyroid gland (hyperthyroidism)
• Stomach or intestinal problems

Some of these, such as arrhythmias and prostate enlargement, are contraindications for the use of TCAs, but others, such as kidney or liver disease, may merely affect the dosage.

The SSNRIs have much more benign side-effect profiles than the TCAs.  Duloxetine can be associated with nausea and can exacerbate liver disease. Venlafaxine can, in rare cases, exacerbate high blood pressure.

Tricyclic antidepressants (TCAs) are commonly used in pain management. Use of TCAs may cause drowsiness in patients. For this reason, patients are often urged to take these medications just before going to bed. To minimize potential side effects, most physicians will start their patients on a low dose of the medication and gradually increase the amount. Other side effects associated with TCAs include:

• Dry mouth
• Constipation
• Weight gain
• Urination difficulties
• Changes in blood pressure
• Dizziness, lightheadedness and fainting
• Blurred vision

Because of the potential side effects associated with the TCAs, their use is generally not recommended in patients age 50 or older.

The analgesic benefits of TCAs can be experienced at lower doses than are needed for treating depression. This helps to minimize side effects for many patients. However, many patients require doses equivalent to those used for depression in order to obtain pain relief.

Selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) are also frequently prescribed to treat pain. Among the possible side effects are nausea, dry mouth, loss of appetite, fatigue, sleep problems, sweating and tremors.

Patients who discontinue use of antidepressants must do so slowly and under a physician’s close supervision. Tapering off too quickly can cause withdrawal symptoms, including insomnia, restlessness and vivid dreams.

The U.S. Food and Drug Administration (FDA) in 2006 issued a public health advisory warning that a life-threatening condition called serotonin syndrome may result when a class of headache medications called triptans is used together with a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) or a selective serotonin reuptake inhibitor (SSRI). The condition involves excessive amounts of the brain chemical serotonin.  However, research indicates that this very rarely occurs.

Other substances that may contribute to serotonin syndrome include monoamine oxidase inhibitors (MAOIs), meperidine (an opioid painkiller), dextromethorphan (cough medicine) or illegal drugs such as ecstasy or LSD, according to the National Institutes of Health (NIH). There are also reports that St. John’s wort, an herbal supplement taken by some people to relieve depression, may contribute to serotonin syndrome.

Symptoms of serotonin syndrome can include restlessness, hallucinations, incoordination, fast heartbeat (tachycardia), rapid changes in blood pressure, increased body temperature, overactive reflexes, nausea, vomiting and diarrhea. The FDA advises that patients consult their physician before stopping their medications. People experiencing serotonin syndrome should be hospitalized under close observation for at least 24 hours, according to the NIH.

Patients should consult their physician before taking any additional prescriptions, over-the-counter medications, supplements or herbal substances, especially St. John’s wort.

Of particular concern to individuals taking tricyclic antidepressants (TCAs), which have the longest history of use in pain management among antidepressants, are:

• Allergy, asthma, hay fever or cold medications, including antihistamines, bronchodilators and decongestants
  
  
• Amphetamines or other diet pills
  
  
• Antihypertensives including clonidine, guanadrel, guanethidine, methyldopa, metyrosine and rauwolfia alkaloids
  
  
• Antipsychotics
  
  
• Central nervous system depressants
  
  
• MAOIs or SSNRIs
  
  
• Thyroid medications
  
  
• Cimetidine (antiulcer drug)
  
  
• Metoclopramide (antiemetic and gastrointestinal stimulant)
  
  
• Pemoline (central nervous system stimulant)
  
  
• Pimozide (Tourette’s syndrome medication)

With SSNRIs, a major drug interaction of concern besides triptans is MAOIs. In patients taking an SSNRI and an MAOI, there have been reports of serious and sometimes fatal reactions including hyperthermia, rigidity, myoclonus (muscle twitches and jerking), changes in autonomic functions such as blood pressure and heart rate, and changes in mental status such as severe agitation worsening to coma.

Other potential drug interactions with SSNRIs include TCAs, SSRIs, quinolone antibiotics and certain antiarrhythmics.

Symptoms of overdose can be similar to the medication’s side effects but are usually more severe. Patients exhibiting any of these symptoms should contact their physician immediately:

• Confusion
• Seizures
• Inability to concentrate
• Severe drowsiness
• Enlarged pupils
• Fast, slow or irregular heartbeat
• Fever
• Hallucinations
• Restlessness and agitation
• Shortness of breath or breathing difficulties
• Unusual tiredness, fatigue or weakness
• Vomiting

Tricyclic antidepressants (TCAs) are the type of antidepressant most commonly prescribed to relieve pain. Studies of the effects of TCAs in pregnant women have not been conducted. However, some reports have suggested that newborns may suffer from muscle spasms and heart, breathing and urinary problems when their mothers take TCAs immediately prior to a child’s birth.

TCAs are known to pass into breast milk and may cause drowsiness in a nursing infant.

Selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) also pass into breast milk and are not generally recommended when breastfeeding.

The U.S. Food and Drug Administration (FDA) cautioned in December 2005 that early results from new studies suggested that use of a selective serotonin reuptake inhibitor (SSRI), paroxetine (Paxil), during the first three months of pregnancy may increase the risk of heart defects and other problems in the baby. Recent research also suggests that use of SSRIs late in pregnancy might increase the infant’s risk of a serious lung condition called pulmonary hypertension of the newborn. 

In light of such findings, the American College of Obstetricians and Gynecologists issued a recommendation in 2006 that pregnant women not be treated with paroxetine and that other SSRIs and selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) be used cautiously during pregnancy.  The benefits of these drugs to the individual patient must be considered when deciding whether to continue use of antidepressants during pregnancy and when breastfeeding is being considered. 

Elderly patients are more susceptible than younger adults to side effects associated with tricyclic antidepressants (TCAs). Symptoms that may affect elderly patients include:

• Drowsiness
• Dizziness
• Confusion
• Vision problems
• Dryness of mouth
• Constipation
• Urination difficulties

Preparing questions in advance can help patients have more meaningful discussions with their physicians regarding their conditions. Patients may wish to ask their doctor the following questions about antidepressants:

1. Can my pain be treated with antidepressants?
   
   
2. Can antidepressants still help relieve my pain even if I don’t have depression?
   
   
3. How do antidepressants work in reducing my pain?
   
   
4. I take the newer antidepressants known as selective serotonin reuptake inhibitors (SSRIs). Do these help relieve pain?
   
   
5. I understand that a selective serotonin and norepinephrine reuptake inhibitor (SSNRI) has been approved for relief of diabetic neuropathy. Can it also treat other pain that I have?
   
   
6. What are my potential side effects when taking antidepressants for pain relief?
   
   
7. Is it safe for me to take antidepressants if I take triptans for my headaches? Can any of the other medications I take interact badly with antidepressants?
   
   
8. Is it safe for me to take more than one type of antidepressant? Is it safe for me to use antidepressants while taking herbs or other supplements that may help treat depression, such as St. John’s wort?
   
   
9. What is the name of my medication and its dosage?
   
   
10. How and when do I take my medication?
    
    
11. What should I do if I miss a dose or take an extra dose?
    
    
12. At what point should I notify you of side effects?
    
    
13. Do these drugs raise special concerns for children, the elderly or women who are pregnant? Can they cause me problems if I have or am at risk of developing diabetes, heart conditions, glaucoma, kidney disease, liver disease, prostate enlargement, osteoporosis or other disorders?