A Brief Summary of the Biochemistry and Pharmacology of FM-associated Depression

By: Jessica Franke
Reprinted from FM Online

Depression and fibromyalgia often occur together, and that’s not just because being tired and in pain is depressing. Both are diseases of the nervous system involving dysregulation of some of the same neurotransmitters. To be an educated patient of either disease requires basic knowledge of the nervous system.
The nervous system is made up of two main systems, the central nervous system (brain and spinal cord) and the peripheral nervous system (all the nerves in the rest of the body). All the nerves in both systems talk to each other with neurotransmitters; however, specific neurotransmitters are used by specific nerves for certain messages in certain parts of the body. For example, one function of acetylcholine is to tell muscles to contract, while one function of oxytocin is to cause milk to be produced by breast cells.

Both depression and fibromyalgia involve problems with the neurotransmitters in the central nervous system. In fibromyalgia the nerves of the brain and spinal cord are too sensitive to stimuli, a condition called “central sensitization.” For example, research has shown that fibromyalgia patients have too much of a neurotransmitter called Substance P, which tells nerves to transmit pain signals to the brain. In contrast, depression occurs when signals to “feel good” are lost because there aren’t enough of the monoamine neurotransmitters (like serotonin) around to deliver the message.

Sometimes, upregulating a parallel pathway can compensate for one defective pathway. That is, an excess of “feel good” signals from serotonin could cancel out the pain signals transmitted by Substance P. But when the two pathways malfunction simultaneously, the unfortunate owner of that nervous system feels very poorly indeed. Luckily, there are many ways to positively affect the balance of neurotransmitters in the brain, such as exercise, proper nutrition, and medication.
Disorders of the glands of the endocrine system, such as the thyroid, pancreas, and adrenals, can lead to neurotransmitter dysregulation and depression. Make sure to consult with a doctor to rule out or treat these and other serious problems that may exacerbate FM and depression symptoms.


There are many types of medications available to treat both fibromyalgia and depression, and fortunately some of these drugs treat both at the same time. Feeling better may be a side effect of other medications that allow patients to get better sleep, feel less pain, or feel less anxious.

Commonly, certain antidepressant drugs are used to treat both conditions. For FM relief, they are often prescribed at a low dose to capitalize on the sedating and analgesic side effects of the drug. The dose can be increased to treat depression as well.  Drugs like Prozac (fluoxetine) and Paxil (paroxetine) are SSRIs (selective serotonin reuptake inhibitors), while Elavil (amitriptyline) and Pamelor (nortriptyline) are examples of TCAs (tricyclic antidepressants). Both classes of drugs act to increase the amount of serotonin in the brain. TCAs are especially effective in promoting sleep and pain relief at smaller doses.

Some newer drugs increase the levels of the other monoamine neurotransmitters related to serotonin that also participate in the transmission of pleasure and pain signals. Effexor (venlafaxine) targets serotonin and norepinephrine reuptake (SNRI), while Wellbutrin (bupropion) acts on norepinephrine and dopamine (NDRI). By targeting the other neurotransmitters, these drugs may provide the added boost that some depressed individuals need to feel better. Take care and consult with a doctor when taking any antidepressant, as neurotransmitters have multiple functions in the brain and can have serious side effects.

Even if these common classes of drugs do not provide depression relief, do not despair! There are drugs that work in nontraditional ways to improve monoamine neurotransmitter chemistry, including Deseryl (trazodone), Adapin (doxepin), or Remeron (mirtazapine).

In some cases, it may be necessary to explore medication targeting a different class of neurotransmitters to find relief. Glutamate and GABA are involved in controlling the general sensitivity of the nervous system, and are beginning to be recognized as important in FM. Drugs that affect this pathway can help with sleeping, pain relief, and muscle spasticity, and include Lyrica (pregabalin), Neurontin (gabapentin), and Klonopin (clonazepam), among others. Lamictal (lamotrigine), a closely related drug, has been approved for use in the treatment of bipolar disorder, indicating the potential usefulness of this class of drugs in treating psychological disorders.

The bottom line is that antidepressant medications can address a number of different issues. Certain antidepressants also are especially useful in decreasing pain, anxiety, insomnia, or in treating other ailments (such as obsessive-compulsive disorder) as determined by a doctor. Antidepressant medication should be utilized in conjunction with a comprehensive treatment plan for controlling FM symptoms, as decreasing pain and improving sleep quality is virtually guaranteed to improve an individual’s mood.

It may take some trial and error to find the medication regimen with the greatest efficacy and least side effects for any given individual, but once the right combination is found, the results can be well worth the effort.