Take aim at most—or all—of the patient's symptoms
In treating a patient with multiple comorbidities, it is best to initiate treatment with an agent that will address most—or all—of his or her symptoms. Using one drug whenever possible will reduce costs, prevent drug-drug interactions, and limit the likelihood of adverse effects. The American Psychiatric Association recommends the use of tricyclic antidepressants (TCAs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) for treating chronic pain and comorbid depression.18 There is evidence of the effectiveness of “unconventional” analgesics, including anticonvulsants and antidepressants, for the treatment of chronic pain, as well. Opioids are, of course, an option too. In addition, nonpharmacologic treatments, such as cognitive-behavioral therapy (CBT), are recommended.19
Start with an anticonvulsant?
The anticonvulsants gabapentin and pregabalin have been shown to be effective in reducing certain types of neuropathic pain and alleviating insomnia.20,21 In studies investigating the use of these drugs in patients with GAD, both gabapentin and pregabalin led to improvement in anxiety symptoms, as well as in pain and sleep.20,21 At a dose of about 600 mg/d, pregabalin has been shown to significantly reduce pain levels in patients diagnosed with diabetic peripheral pain syndrome22; it has also been found to help prevent relapse23 and reduce sleep disturbances associated with GAD.24
The most common adverse effects of pregabalin are mild-to-moderate somnolence, dry mouth, headache, dizziness, and peripheral edema20,22; dizziness, somnolence, peripheral edema, and gait disturbance are most commonly associated with gabapentin treatment.25 These tend to stabilize over time, but occasionally the dose must be lowered or the drug discontinued.
Lamotrigine has been shown to reduce pain in patients with diabetic and sensory neuropathy compared with placebo,26 but was not effective in treating patients with pain due to spinal cord injury. The drug should be initiated at a low dose and slowly titrated to minimize the risk of serious adverse effects such as Stevens-Johnson syndrome.26
Try a tricyclic or an SNRI
TCAs, including amitriptyline, nortriptyline, desipramine, and imipramine, are recommended by the Canadian Pain Society as first-line therapy for chronic pain and often have benefit in the treatment of comorbid mood or anxiety disorders.27 Noradrenergic antidepressants—including TCAs—appear to have particular efficacy in treating moderate to severe neuropathic pain in patients with a comorbid substance disorder who take the drugs regularly, while undergoing frequent assessments.15
Overdose is a risk associated with TCAs, which have higher toxicity than other classes of antidepressants.28 Thus, it is essential to avoid prescribing TCAs for depressed patients until you carefully assess their risk of overdose. TCAs should not be prescribed for any patient at increased risk for cardiac arrhythmias.29
If you do prescribe a TCA… The doses of TCAs used to treat mood and anxiety symptoms often are much higher than doses needed for pain relief. As a result patients are often at risk of experiencing side effects.
What about an SNRI? In general, SNRIs, which target both serotonin and norepinephrine, have a greater analgesic effect than antidepressants targeting either neurotransmitter alone.30 Duloxetine, an SNRI, has been shown to effectively reduce symptoms in patients with pain disorders and comorbid depression.31 Other SNRIs studied in the treatment of pain and associated symptoms include venlafaxine, which has been effective in treating patients in a primary care setting who had both pain and depression,32 and milnacipran, which has been used successfully to treat pain associated with fibromyalgia.33
SNRIs may interfere with sleep. SNRIs have been associated with an increase in arousal and in rapid eye movement sleep suppression.34 Thus, another type of medication may be preferable for patients with pain and a sleep disturbance or, if an SNRI is prescribed, it may be necessary to lower the dose or add a sleep aid.
The role of SSRIs
Despite the recognized utility and widespread use of selective serotonin reuptake inhibitors (SSRIs) in the treatment of depressive and anxiety disorders, their role in managing neuropathic pain is less clear. Although some agents, such as escitalopram, have demonstrated mild pain-relieving effects in patients with painful polyneuropathy, the magnitude of the effect was clinically relevant at best for only a small number of patients.35 The effectiveness of other SSRIs in painful diabetic neuropathy has been shown to be less than that of TCAs.36 SSRIs generally are not recommended for the treatment of chronic neuropathic pain, even when it is associated with mood and anxiety symptoms.27
Opioids for which patients?
Chronic pain often is treated with opioids. Particular caution is required, however, when treating patients with pain and substance abuse or dependence.15,37 In order to prevent relapse in such individuals when they’re suffering from chronic pain, opioids should be used only if:15,38
• the pain is moderate to severe and has a significant impact on the patient’s functioning and overall quality of life;
• nonopioid medications have been tried but were unsuccessful; and
• the patient agrees to be closely monitored while taking opioids.