Selection of ACD versus Antidepressant Pharmacotherapy

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Both antidepressants and ACDs have demonstrated comparable efficacy in a number of chronic pain conditions, e.g., migraine headache and neuropathic pain. In a review of randomized controlled trials in which TCAs and anticonvulsants were employed to treat pain associated with diabetic and postherpetic neuropathies, it was found that at least 50% of pain relief was achieved in two-thirds of the patient episodes treated with anticonvulsants and in half of those treated with antidepressants (Collins et al. 2000, Sindrup and Jensen 1999, McQuay 2002). However, adverse effects were slightly more common with antidepressant use, particularly TCAs, as compared with anticonvulsants (Collins et al. 2000, McQuay 2002).

Selection of medication options for patients needs to be individualized, taking into consideration the tolerability of side effects and safety of use of particular medications in the context of the patient's comorbid medical and psychiatric conditions (Leo 2006). For example, the patient with comorbid depression and/or anxiety might be best managed with selection of an antidepressant. On the other hand, ACDs have mood-stabilizing effects that benefit patients with bipolar disorder, schizoaffective disorder, and impulsivity arising from dementia (Chandramouli 2002, Leo and Narendran 1999); therefore, ACD selection for patients with these conditions would be ideal. Regarding medical comorbidities, there are several factors to consider. Heart block, arrhythmias, or severe cardiac disease prohibit use of TCAs. For patients with renal dysfunction, doses of duloxetine, venlafaxine, carba-mazepine, gabapentin, pregabalin, and topiramate would need to be reduced, and if the renal dysfunction is severe enough may preclude use of these agents. For patients with hepatic disease, doses of carbamazepine, duloxetine, and lamotrigine should be reduced. TCAs can conceivably exacerbate encephalopathy associated with hepatic disease.

In the treatment decision algorithm, it is plausible that ACDs could be alternatively employed for patients with persisting pain despite optimal antidepressant use or for whom antidepressant use proved intolerable. Because of the differences in presumed mechanisms of action between ACDs and antidepressants, simultaneous co-administration of antidepressants and ACDs may be useful, capitalizing on complimentary mechanisms of action.

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