What Are Antidepressants?Antidepressants are one of the most commonly prescribed classes of medication the world over. They are primarily used to treat depression, but can be used to treat other psychiatric disorders such as generalized anxiety disorder, social anxiety disorder, obsessive-compulsive disorder (OCD), anorexia, and bulimia. Although not specifically intended to treat pain, antidepressants have become a mainstay in the treatment of chronic pain. Many people with chronic pain suffer from depression, but antidepressants can ease chronic pain whether or not there is underlying depression.
The pain relieving properties of antidepressants are not very well understood. They may increase neurotransmitters, or chemical messengers, in the brain and spinal cord that decrease pain signals. Antidepressant pain-relieving effects are not immediate and may take several weeks to provide maximum benefit. Many people report moderate pain relief from antidepressants. Anti-seizure medications can be added to antidepressants if pain relief is incomplete.
Managing Pain With AntidepressantsAntidepressants are another weapon against chronic pain. They are an integral part of treatment for many chronic pain conditions. Classes of antidepressants include monoamine oxidase inhibitors (MAOIs), atypical antidepressants, tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), and norepinephrine-dopamine reuptake inhibitors (NDRIs).
All classes of antidepressants are not equally effective in the treatment of chronic pain. The two classes of antidepressants that stand out in the treatment of chronic pain are the TCAs and SNRIs. Examples of TCAs include amitriptyline (Elavil), imipramine (Tofranil), nortriptyline (Pamelor), and trimipramine (Surmontil).
Examples of SNRIs include duloxetine (Cymbalta), venlafaxine (Effexor XR), desvenlafaxine (Pristiq), and milnacipran (Savella).
Both of these classes increase levels of the brain neurotransmitters serotonin and epinephrine, which may block pain signals. Only the SNRI antidepressants duloxetine and milnacipran have been approved by the Food and Drug Administration (FDA) for the treatment of pain.
Chronic pain has two basic categories—neuropathic and nociceptive. Neuropathic pain is caused by nerve damage. Nociceptive pain is caused by damage to body tissue. Duloxetine has been approved for the treatment of neuropathic pain, nociceptive pain, and fibromyalgia.
Fibromyalgia is a chronic pain condition characterized by widespread musculoskeletal pain. Milnacipran has been approved for the treatment of fibromyalgia.
Although not FDA-approved for the treatment of pain, tricyclic antidepressants (TCAs) have a large body of literature supporting their use in the treatment of chronic pain. The TCA with the most support for its use in the treatment of chronic pain is amitriptyline (Elavil).
The pain involved in the following medical conditions may be responsive to antidepressants:
- Diabetic peripheral neuropathic pain, which is nerve damage caused by diabetes
- Post herpetic neuralgia, which is nerve damage from shingles
- Nerve pain from other causes
- Facial pain
- Tension headache
- Low back pain
- Pelvic pain
Treatment of diabetic peripheral neuropathic pain is difficult. Currently, there is only one antidepressant with an FDA indication for its treatment—duloxetine.
Chronic low back pain and chronic painful osteoarthritis are frequently treated with antidepressants. Duloxetine also has an FDA indication for the management of chronic musculoskeletal pain.
Fibromyalgia is another condition leading to chronic pain. Currently only two medications have an FDA indication for the treatment of fibromyalgia—duloxetine and milnacipran.
No matter the cause of chronic pain, there are several tenets of treatment when using antidepressants as pain medication:
- Psycho-education, explaining to the patient there is substantial evidence for the use of antidepressants in the treatment of chronic pain
- Awareness of drug-drug interactions
- Slowly increase the antidepressant dose, or titrate, to effect
- Careful management of side effects
- Carefully decrease the antidepressant dose, or taper, when stopping to decrease the chances of serotonin withdrawal
Adverse Effects And Risks Of Antidepressants For Pain MedicationSome of the most common adverse effects (and tips for managing) when using antidepressants are:
- Can be limited or eradicated by starting at a low dose, titrating slower, giving dose at bedtime, or giving dose after food.
- Weight gain. Can be minimized with a plan consisting of education about weight management, frequent weight measurement, and referral to a nutritionist.
- Sexual dysfunction. Can be treated by decreasing dose of antidepressant (if possible) or switching class of antidepressant (if appropriate). If erectile dysfunction (ED) is an adverse effect consideration should be given to medications targeting ED such as sildenafil (Viagra), tadalafil (Cialis), and vardenafil (Levitra).
- Sleep disturbances. If insomnia occurs, consider AM dosing and trazodone for persistent symptoms. If drowsiness, consider PM dosing, no daytime naps, sleep hygiene advice, and switching class of antidepressant.
- Agitation or worsening of anxiety. Can be managed by considering lowering antidepressant dosage and a one to two week limited course of a benzodiazepine such as diazepam (Valium), alprazolam (Xanax), or lorazepam (Ativan). When using benzodiazepines be on the lookout for the development of dependence.
Another concern of antidepressant usage is the chance of increased suicidal thoughts or actions. Thoughtful and immediate management of common adverse effects can lead to increased compliance in patients. In other words, patients will take the medication as directed by their physicians.
Other classes of antidepressants, besides tricyclics, may also be helpful in the management of chronic pain. Serotonin-norepinephrine reuptake inhibitors (SNRIs) such as venlafaxine, duloxetine, and milnacipran can be used to treat fibromyalgia. Selective serotonin reuptake inhibitors (SSRIs) such as paroxetine and fluoxetine can also relieve pain and may be able to boost the pain-killing effects of some tricyclic antidepressants.
ConclusionAntidepressants are primarily used to treat depression, but they can also be an integral part of the management of varied chronic pain conditions.
There are several classes of antidepressants believed to decrease chronic pain.
The classes of antidepressants that have the best track record treating chronic pain are the tricyclic antidepressants (TCAs) and SNRIs. Selective serotonin reuptake inhibitors (SSRIs) do not work as well as TCAs and SNRIs.
Antidepressants have common adverse effects, which can be minimized by timely diagnosis and management. Additional ongoing clinical trials are needed to further shed light on the treatment of chronic pain with antidepressants.
- Greist JH, Greeden JF, Jefferson JW, Grivedi MH. Depression and pain. J Clin Psychiatry. 2008; 69 (12): 1970-1978.
- Park HJ, Wiffen PJ. Antidepressants for neuropathic pain. Korean J Pain. 2010; 23 (2): 99-108.
- Saarto T, Wiffen PJ. Antidepressants for neuropathic pain: a Cochrane review. J Neurol Neurosurg Psychiatry. 2010; 81 (12): 1372-1373.
- Ursini F, Pipicelli G, Grembiale RD. Efficacy and safety of duloxetine in fibromyalgia. Clin Ter. 2010; 161 (4): 391-395.
- Skliarevski V, Desaiah D, Liu-Seifert H et al. Efficacy and safety of duloxetine in patients with chronic low back pain. Spine. 2010; 35 (13): 578-585.
- Chwieduk CM, McCormack PL. Milnacipran: in fibromyalgia. Drugs. 2010; 70 (1): 99-108.
- Hamer M, Batty GD, Marmot HG, Singh-Manoux A, Kivimaki M. Anti-depressant medication use and C-reactive protein: results from two population-based studies. Brain Behav Immun. 2011; 25 (1): 168-173.
- Chappell AS, Ossanna MJ, Liu-Seifert H et al. Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee paon: a 13-week, randomized, placebo-controlled trial. Pain. 2009; 146 (3): 253-260.