CASE 2 Patient with long-standing CPP, multiple diagnoses, and sleep problems
A 30-year-old woman (G2P2) reports having had CPP for 17 years. She is amenorrheic with continuous OCP treatment. She had experienced some improvement with pelvic PT. The patient reports that she has daily pain with intermittent pain flares and that she is exhausted and has poor sleep quality, which she attributes to pain. She has been diagnosed with interstitial cystitis, irritable bowel syndrome, and temporomandibular joint disorder. She has a history of depression, which she feels is well controlled with bupropion. Physical examination reveals that the patient has diffuse but mild pain in the pelvic floor and abdominal wall muscles.
What further pain management options can you offer for this patient?
Managing pain, sleep disturbance, and depression
This patient has been living with CPP for many years, and she has sleep difficulties that might be exacerbating pain or result from pain (or both). She is already on continuous OCPs and has had some relief with pelvic PT. Other options that may help with her multiple issues include antidepressants, cyclobenzaprine, and calcium channel blockers.
Antidepressants
Several classes of antidepressants have been used in the treatment of chronic pain conditions, specifically, tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Commonly used TCAs include amitriptyline, nortriptyline, desipramine, and doxepin. Commonly used SNRIs are duloxetine and milnacipran. Both TCAs and SNRIs increase the availability of norepinephrine and serotonin, which are thought to act on the descending pain inhibitory systems to decrease pain sensitivity. Of note, most selective serotonin reuptake inhibitors (SSRIs) at typical doses do not exert a significant enough impact on norepinephrine to be useful for chronic pain.22
Evidence is limited on the use of antidepressants for treating CPP. Amitriptyline is the most extensively studied antidepressant. Amitriptyline treatment resulted in modest pain improvement in patients with CPP and fibromyalgia.23,24 Bothersome anticholinergic effects, including fatigue, dry mouth, and constipation, often are reported with TCAs. Adverse effects tend to be less with nortriptyline or desipramine compared with amitriptyline, but possibly at the expense of efficacy.
While SNRIs have not yet been studied in CPP, several investigations have shown that they improve pain and quality of life in fibromyalgia patients.22,25
Antidepressant therapy may be appropriate for patients with suspected central pain amplification, widespread pain, and sleep disturbances. Best practices include patient education and careful discussion of this option with your patient. We suggest that clinicians explain that antidepressant medications alter the function of neurotransmitters, which modulate pain signals. While neurotransmitters also are involved in mood modulation, this is not the therapeutic goal in this circumstance. In addition, the doses used for the effective treatment of chronic pain are significantly lower than those needed to treat depression effectively.
Patients often need to hear that you believe that their pain is real and is not a manifestation of depression or another mood disorder. If you suspect that the patient also has untreated depression, address this as its own issue and use medications that have greater efficacy for mood symptoms.
Because many antidepressants can cause sedation, they are best taken before bedtime. Also, slow dose titration over several weeks will reduce the chance of bothersome adverse effects. Counsel patients that efficacy is not generally seen until at goal dose for several weeks. Be aware of interactions with other medications that can cause serotonin syndrome.
Cyclobenzaprine
Cyclobenzaprine is a muscle relaxant that also has activity in the central nervous system. The drug’s precise mechanism of action is not known, but it appears to potentiate norepinephrine and bind to serotonin receptors. Thus, it also likely has some TCA-like activity.
Cyclobenzaprine has not been studied in patients with CPP. In fibromyalgia patients, however, it produced significant improvements in pain, sleep, fatigue, and tenderness.26,27 In our anecdotal experience with CPP patients, cyclobenzaprine has been one of the most impactful therapies. It hits the “chronic pain triad,” meaning that it helps with myofascial pain, neuropathic pain, and sleep disturbances.
Cyclobenzaprine treatment may be considered for patients with myofascial pain, sleep disturbances, and clinical symptoms of central pain amplification. Best practices include starting with low (5 mg) scheduled doses at bedtime and slowly titrating the dose. Drowsiness is a very common side effect, so we try to use that to the patient’s advantage to help with sleep quality.
Notably, sleep disturbances are highly prevalent in patients with chronic pain.28 The relationship appears to be bidirectional, meaning that chronic pain negatively impacts sleep quality, and poor sleep quality causes amplified perception of pain.28–30 Interventions that improve sleep quality have been associated with improvements in pain, coping, mood, and functional status.31 Helping a patient to improve her sleep generally requires a multifaceted approach. It always involves “sleep hygiene” or a behavioral component, and pharmacologic assistance may be considered when improved sleep hygiene does not provide adequately improved sleep quality.
Calcium channel blockers
Gabapentin and pregabalin are calcium channel blockers that inhibit the reuptake of glutamate, norepinephrine, and substance P, which helps to decrease pain sensitivity. They also act as membrane stabilizers, reducing hyperexcitability of peripheral and central nerves. Studies have shown that in patients with CPP, gabapentin resulted in improved pain and mood symptoms with few adverse effects.23,32 Patients with fibromyalgia had improvements in pain, sleep, quality of life, fatigue, and anxiety with both gabapentin and pregabalin.33
It is appropriate to consider use of gabapentin or pregabalin in patients with central pain amplification and sleep disturbances. Best practices include starting with a low dose at bedtime. Traditionally, gabapentin is given in 3 equal doses throughout the day. In our experience, patients report less daytime drowsiness and better sleep quality if two-thirds of the daily dose is given at night, with the remaining daily dose broken up into 2 smaller daytime doses. Slow titration over several weeks will reduce risk of bothersome adverse effects. Patients should be counseled that efficacy is not generally seen until treatment is at goal dose for several weeks.
CASE 2 Treatment recommendations
For this patient with daily pelvic pain, multiple diagnoses that have a pain component, and poor sleep quality, consider a treatment plan that includes scheduled cyclobenzaprine, improved sleep hygiene, and, if needed, gabapentin.