Chronic pain and depression: Treatment of 2 culprits in common

Gabapentin and pregabalin have been shown to decrease pain intensity and improve quality of life and function in patients with neuropathic pain conditions. Pregabalin also has shown efficacy in treating central neuropathic pain and fibromyalgia. ¹⁶

Added benefits of these drugs is that they have (1) a better side effect profile than TCAs and (2) fewer drug interactions when they are used as a component of combination therapy. Pregabalin has the additional advantage of less-frequent dosing, linear pharmacokinetics, and a predictable dose-response relationship. ¹⁷

Addressing other comorbid psychiatric conditions
Sleep disturbance is common among patients with chronic pain. Sleep deprivation causes a hyperexcitable state that amplifies the pain response. ¹⁸

When a patient presents with chronic pain, depression, and disturbed sleep, consider using a sedating antidepressant, such as a TCA. Alternatively, gabapentin or pregabalin can be added to an SNRI; anticonvulsants have been shown to improve quality of sleep. ¹⁹ Cognitive-behavioral interventions targeting sleep disturbance may be a helpful adjunct in these patients. ²⁰

When anxiety is comorbid with chronic pain, antidepressants with proven efficacy in treating anxiety disorders, such as duloxetine or venlafaxine, can be used. When chronic pain coexists with a specific anxiety disorder (social anxiety disorder, obsessive-compulsive disorder, panic disorder), an SSRI might be more advantageous than an SNRI, ²¹ especially if it is combined with a more efficacious analgesic.

Benzodiazepines should be avoided as a routine treatment for comorbid anxiety and pain, because these agents can produce sedation and cognitive interference, and carry the potential for dependence.

Fatigue. In patients who, in addition to pain and depression, complain of fatigue, an activating agent such as milnacipran or adjunct bupropion might be preferable to other agents. Modafinil has been shown to be a well-tolerated and potentially effective augmenting agent for antidepressants when fatigue and sleepiness are present as residual symptoms ²²; consider them as adjuncts when managing patients who have chronic pain and depression that manifests as excessive sleepiness and/or fatigue.

Cognitive complaints. We have noted that disturbances of cognition are common in patients with depression and chronic pain, and that cognitive dysfunction might improve after antidepressant treatment.

Studies suggest that SSRIs, duloxetine, and other antidepressants, such as bupropion, might exert a positive effect on learning, memory, and executive function in depressed patients. ²³ Beneficial effects of antidepressants may be “pseudo-specific,” however—that is, predominantly a reflection of overall improvement in mood, not on specific amelioration of the cognitive disturbance.

Vortioxetine has shown promise in improving cognitive function in adults with MDD; its cognitive benefits are largely independent of its antidepressant effect. ²⁴ The utility of vortioxetine in chronic pain patients has not been studied, but its positive impact on mood, anxiety, sleep, and cognition might make it a consideration for patients with comorbid depression—although it is uncertain at this time whether putative noradrenergic activity makes it suitable for use in chronic pain disorders.

Last, avoid TCAs in patients who have cognitive complaints. These agents have anticholinergic effects that can have an adverse impact on cognitive function.