Evidence-Based Reviews

Treating affective illness in patients with chronic pain

Current Psychiatry. 2004 May;3(5):51-68

References

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Fluoxetine may help chronic daily headache, and paroxetine and citalopram may be useful for diabetic neuropathy. However, one cannot generalize that all SSRIs are similarly effective as analgesics.¹⁴

SSRIs have fewer side effects than TCAs and are less dangerous in overdose. In general, however, SSRIs are a second-line treatment for pain, to be used when dual-action agents pose disadvantageous side effects (Table 3) or have been poorly tolerated or ineffective.

Table 3

Antidepressant side effects:
Limitations and potential benefits in chronic pain

Side effects/agents	Problems	Conditions potentially benefited	Possible alternatives
Anticholinergic TCAs	Xerostomia, constipation, urinary slowing (esp. when combined with opioids)	Diarrhea-predominant irritable bowel syndrome	SSRIs, nefazodone, venlafaxine
Sedation TCAs, mirtazapine, nefazodone, trazodone	Excessive sedation, cognitive impairment, driving risk (esp. when combined with opioids, benzodiazepines)	Pain with insomnia	SSRIs, venlafaxine, bupropion
Insomnia SSRIs, venlafaxine	Pain with pre-existing insomnia; equivocal analgesic effects	Excess sedation related to depression, polypharmacy for pain	TCAs, mirtazapine, trazodone, nefazodone
Orthostasis TCAs (esp. with methadone), nefazodone	Falls, especially in elderly patients	——	Nortriptyline, SSRIs bupropion, venlafaxine
Weight gain TCAs, mirtazapine	Pain patients are often sedentary, get limited exercise	Pain and depression with weight loss	Bupropion, fluoxetine
Hypertension Bupropion, venlafaxine	Pre-existing hypertension	? Hypotensive state	Citalopram (hypertensive side effects infrequent)
Cardiac TCAs	ECG abnormalities, conduction delays, arrhythmias aggravate pre-existing cardiac abnormalities; avoid if recent MI	———	SSRIs, bupropion
Overdose lethality TCAs	Prominent suicidal ideation	——	SSRIs, venlafaxine
Seizures Esp. maprotiline, clomipramine, bupropion	Lower seizure threshold, aggravation of seizure disorders	——-	SSRIs
Sexual dysfunction SSRIs	Pre-existing sexual dysfunction secondary to pain, medications, stress; equivocal analgesic effects	——-	Bupropion, nefazodone, mirtazapine

Table 4

How psychosocial therapies can help treat chronic pain and depression

Therapies	Purpose/benefits
Behavioral therapy	Increase activity and learn to balance activity with limitations Reduce pain behaviors and analgesic use Decrease dependency and secondary gain
Cognitive-behavioral therapy	Identify automatic thoughts Challenge negative cognitions, catastrophizing Substitute and rehearse positive thoughts, capabilities Transition from patient role to self-care
Couples’ therapy	Assist adaptation to role changes Diminish spousal solicitousness or excessive caretaking Increase communication
Biofeedback, relaxation, imagery	Adjunctive role in pain management Reduce tension, comorbid anxiety
Hypnosis	Dissociate awareness of pain Substitute, displace, reinterpret pain sensations
Vocational rehabilitation	Increase activity, ability to distract Regain sense of control, identity, and productivity Increase socialization
Pain management program	Multiple treatment effects Useful for complex pain with affective states

Monoamine oxidase inhibitors (MAOIs) may have some efficacy for neuropathy and headache, but the need for a tyramine-free diet and potential for drug-drug interactions limit their usefulness. Co-administering an MAOI and meperidine is always contraindicated, as this combination can produce fever, delirium, seizures, circulatory collapse, and death. Similarly, avoid using an MAOI with any other antidepressant.

Others. Evidence is very limited on using other antidepressants such as trazodone, nefazodone, bupropion, and mirtazapine in chronic pain:

Trazodone may help pediatric migraine, but it is not a consistent analgesic and may not be well-tolerated.
Case reports suggest bupropion may help with headaches and chronic low-back pain.¹⁴
Mirtazapine and trazodone may be useful adjuncts for treating insomnia in depressed patients with chronic pain.

Other options

Anticonvulsants appear useful for neuropathic pain and are appropriate for chronic pain patients who cannot tolerate TCAs.²⁴ Like TCAs, anticonvulsants are not addictive. Unlike TCAs, anticonvulsants may help stabilize other affective illnesses that may coexist with chronic pain, including bipolar disorder, schizoaffective disorder, and impulsivity/aggression related to dementia or personality disorder.⁶ If the starting dosage is not effective within 1 week, increase gradually every 2 to 3 days to target dosages comparable to those for anticonvulsant efficacy.

Carbamazepine and gabapentin are recommended first-line medications for neuropathy. Carbamazepine is indicated for treating trigeminal neuralgia, although its cytochrome P-450 3A3/4 isoenzyme induction may reduce serum levels of acetaminophen, opioids, and oral contraceptives. Gabapentin, although not clearly beneficial for bipolar disorder, has anxiolytic effects and a benign side-effect profile, which may help patients with chronic pain.

Valproate can help prevent migraines. Clonazepam can help reduce anxiety and restless legs syndrome but may be habituating. Anticonvulsants’ common adverse effects include sedation, GI upset, dizziness, and fatigue.

Lithium has known efficacy for mood stabilization in bipolar disorder and can ameliorate cluster headaches.

Antipsychotics. Evidence is sparse on whether antipsychotics have analgesic activity. Their side effects generally limit their usefulness to treating pain in patients with psychosis or delirium.⁶

Stimulants such as dextroamphetamine and methylphenidate can be helpful adjuncts for treating depression, especially for medical inpatients who require a rapid therapeutic response. Stimulants may reduce fatigue or excessive sedation and improve concentration in patients receiving opioids for chronic pain. They also may have analgesic effects when combined with opioids. Potential adverse effects include appetite suppression, anxiety or agitation, confusion, tics, and addiction.⁶

Precautions. The muscle relaxant carisoprodol is associated with potential dependence and withdrawal. Cyclobenzaprine, another muscle relaxant, has a TCA-like structure and can be lethal in overdose. Baclofen can be useful for chronic pain related to spasticity, although psychotic depression and mania have been reported with abrupt withdrawal.⁶