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Antidepressants as Analgesics: Test your Adjuvant IQ


Antidepressant classes once considered "adjuvant" analgesics now are first-line therapy for various pain conditions. Test yourself!

The opioid analgesics, nonsteroidal anti-inflammatory drugs, and acetaminophen are often thought of as the primary analgesic medications with other medication classes that may provide relief considered as “adjuvant” medications. However, some of these other medications including certain of the antidepressants can provide marked analgesia and are considered primary analgesics for a number of pain conditions.

Try this short test of your analgesic adjuvant IQ.

1. For which of the following conditions are antidepressants considered to be first line analgesics.

A. Postherpetic neuralgia

B. Fibromyalgia

C. Diabetic peripheral neuropathic pain

D. A and C only

E. All of the above

Answer, discussion, and next question>>>



Answer: E. All of the above.

The antidepressants are recommended as first- line analgesics for most forms of neuropathic pain.


2. Which class of antidepressants usually provides the most analgesia?

A. Tricyclics (TCAs) and other serotonin norepinephrine reuptake inhibitors (SNRIs)

B. Selective serotonin reuptake inhibitors

C. Monoamine oxidase inhibitors (MAOIs)

Answer, discussion, and next question>>>


Answer: A. The TCAs and other SNRIs, and most notably venlafaxine and duloxetine.

MAOIs are not used for analgesia. 


3. In choosing among antidepressants to be prescribed for analgesia, the most important factor to consider, apart from previous response to a medication, is:

A. Level of analgesia     

B. Cost

C. Side effect profile

Answer, discussion, and next question>>>


Answer: C. Side effect profile of each of the drugs.

All of the TCAs and SNRIs appear to be equally analgesic and the TCAs venlafaxine and duloxetine are available in generic forms. However, the TCAs also are associated with more marked potential side effects than the other SNRIs and there is individual variation between the TCAs. Because of their potential effects on cardiac conduction and the anticholinergic effects of the TCAs, their use is generally not recommended for patients age 50 years or older.


4. True or False. The TCAs and other SNRIs only provide analgesia for patients who have clinical depression in addition to their pain.

A. True

B. False

Answer, discussion, and next question>>>


Answer: B. False

These drugs provide analgesia in the absence of depression. 


5. Amitriptyline has often been reported to be the most effective analgesic of the TCAs. What is the one advantage that this drug may have over other TCAs and other SNRIs for patients with pain?

A.  A more benign side effect profile

B.  Is more likely than the others to be sedating

C.  It only needs to be taken once per day

Answer, discussion, and next question>>>


Answer: B. Is more likely than the others to be sedating

Because of its strong antihistaminic effect, amitriptyline is often more sedating than the other TCAs and SNRIs an effect that can be beneficial for the many patients with pain who have problems with sleep. However, it is also more likely to have anticholinergic effects which can cause dry mouth and constipation.


6. Which of the following statements is most accurate regarding dosing of TCAs and other SNRIs as analgesics?

A.Doses less than those needed to treat depression are usually sufficient

B.Doses similar to those needed to treat depression are usually required

C.Doses higher than needed to treat depression are usually required

Answer, discussion, and next question>>>


Answer: B. Doses similar to those need to treat depression are usually required. 

Although it is often stated that lower doses of these drugs are sufficient to treat pain, in fact most of the studies demonstrating their analgesic effects have required doses similar to those needed for depression and the dosing for duloxetine, the only antidepressant FDA approved as both an analgesic and antidepressant, is similar for both conditions.


7. True or False. If antidepressants are combined with opioid analgesics, the analgesic effects of both are likely to be decreased.

A. True

B. False

Answer and discussion>>>


Answer: B. False

In fact there is evidence indicating that providing these drugs together may provide more analgesia than either class alone.



Dharmshakfu P, Tayal V, Kaira BS. Efficacy of antidepressants as analgesics: a review.  J Clin Pharmacol. 2012;52:6-17.

Gilron I, Tu D, Holden RR, et al. Combination of morphine with nortriptyline for neuropathic pain.Pain. 2015;156:1440-1448.

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