October, 2004 PSYCHOPHARMACOLOGY UPDATE Volume 4 Number 5
The Dual-Mechanism Antidepressant, Cymbalta, in the Treatment of Pain
Almost 45% of patients with major depression have at least one painful physical symptom including limb pain, backaches, joint pain, and headaches. Abnormalities of serotonin and norepinephrine in the somatosensory cortex and the spinal cord contribute to an increase of painful response in depressed patients. Painful stimuli are more actively conducted up the nociceptive neurons of the spinal cord in depressed patients. In addition, the descending neurons of the spinal cord responsible for diminishing pain reception fail to work efficiently in depressed patients.
Studies have shown that dual-mechanism antidepressants—medications that increase the neurotransmitters serotonin and norepinephrine—are effective in treating certain pain syndromes associated with major depression. The dual-mechanism antidepressant, Effexor, targets only serotonin at doses below 150 mg/day and begins to effect norepinephrine (and serotonin) at doses above 150 mg/day.
Cymbalta, (duloxetine), a recently approved dual-reuptake inhibitor, shows relatively equal affinity for binding to both serotonin and norepinephrine across the entire dosage range. This equal affinity for serotonin and norepinephrine seems to enable Cymbalta to be effective in treating a wider range of pain syndromes and have a more rapid onset of action than previous antidepressants.
In one study, Cymbalta proved effective in relief of diabetic neuropathic pain symptoms at a starting dose of 60 mg/day. Several studies of patients with major depression and chronic pain complaints exhibited significantly greater reductions in pain severity after only one week of treatment. Such a rapid improvement in pain severity suggests that Cymbalta has a direct effect on the nociceptive neurons and the somatosensory cortex. Other studies have shown that Cymbalta seems to have a more rapid antidepressant onset of action than other antidepressants making it unclear whether the relief of pain is related to the medication’s antidepressants effects or the pain relief comes from the medication’s direct effects on pain centers.
Regardless of the exact mechanism of action, Cymbalta appears to have several unique characteristics: 1) It is a rapid onset antidepressant; 2) It seems to be an energizing antidepressant; 3) It is more likely to induce full remission of symptoms rather than partial treatment response more commonly produced by other antidepressants; 4) It apparently treats pain syndromes unassociated with depression.
The usual starting and maintenance dose is 60 mg given in the morning. Taking Cymbalta after breakfast can reduce the risk of nausea, a mild side effect most commonly cited during the first week of treatment. Other side effects include insomnia, headaches, somnolence, dry mouth and sweating. Food does not alter Cymbalta’s absorption but delays maximum concentration by about 4 hours. Cymbalta is metabolized by the 2D6 and 1A2 isoenzymes of the cytochrome P-450 system so that co-administration of beta blockers, quinidine, cimetidine, other antidepressants and antipsychotics could elevate plasma levels of Cymbalta or the other agents. Some men taking Cymbalta have more difficulty reaching orgasm. The agent is contraindicated in those patients taking MAO inhibitors, those with narrow-angle glaucoma, hepatic insufficiency and end-stage renal disease. Gradual reduction in the dose is recommended rather than abrupt cessation in order to avoid the occurrence of discontinuation symptoms.
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