Psychiatry - December 2008 - (Page 18)

[the interface] TABLE 1. The authors’ comparison of antidepressants for the treatment of neuropathic pain EVIDENCE -BASED SUPPORT SIDE EFFECT LOADING ANTIDEPRESSANTS EFFICACY DOSE Tertiary amine tricyclic antidepressants (amitriptyline, doxepin, imipramine) Yes +++ Low to Standard +++ Venlafaxine Duloxetine Bupropion Yes Yes Yes ++ ++ + Standard Standard Standard + + + Secondary amine tricyclic antidepressants (desipramine, nortriptyline) Yes ++ Low to Standard +++ Paroxetine, citalopram Fluoxetine +++ = High; ++ = Moderate; + = Low Modest No + -- Standard Standard + + Note: This summary reflects the authors’ interpretation of the available data. demonstrated modest efficacy in the management of neuropathic pain, whereas fluoxetine has not demonstrated any efficacy at all.1 The overall impression is that SSRIs are less effective than other antidepressant options in the treatment of neuropathic pain.2,4,9–11 Indeed, from a conservative perspective, it appears that SSRIs are not superior to the other types of antidepressants used in the treatment of neuropathic pain, such as the TCAs.12 While SSRI side effects are generally mild, there is the risk of weight gain with the long-term use of some (e.g., paroxetine) as well as sexual dysfunction and discontinuation symptoms with abrupt cessation. Venlafaxine. Venlafaxine is an unusual, mixed-action antidepressant 18 Psychiatry 2008 [ V O L U M E 5, NUMBER that predominantly inhibits serotonin reuptake at low doses and norepinephrine reuptake at higher doses. Therefore, unlike SSRIs and like TCAs, venlafaxine affects both of the key neurotransmitters that are hypothesized to be involved in the modulation of neuropathic pain. In support of this theoretical observation, case reports1,13 and empirical studies9,14 indicate that venlafaxine is effective for the management of neuropathic pain at doses of 150mg per day or higher (i.e., typical antidepressant doses). Venlafaxine has also demonstrated efficacy with pain management in a study in which it was added to gabapentin.4 In the treatment of neuropathic pain, venlafaxine is comparable to imipramine,2,10,13 suggesting that it may be comparable to other TCAs as well. 12, DECEMBER] Despite a milder side effect profile than the TCAs, venlafaxine may elevate blood pressure and has a discontinuation syndrome with abrupt cessation. Bupropion. Bupropion inhibits the reuptake of norepinephrine and dopamine. In a double-blind crossover study of patients with various forms of neuropathic pain, at doses of 300mg per day, bupropion SR was similar in efficacy to TCAs.4 According to the proposed theory of how antidepressants work in pain syndromes (i.e., dual effects on serotonin and norepinephrine), bupropion clearly “breaks the rules.” This observation indicates that other types of antidepressants also warrant investigation as potential medications in the treatment of pain. Bupropion has two absolute clinical contraindications (i.e., current or past history of seizures or eating disorder) and may be excessively activating for some patients.15 Duloxetine. Duloxetine is the only antidepressant approved by the US Food and Drug Administration for the treatment of neuropathic pain. It is purportedly a dual-action drug (i.e., it inhibits both serotonin and norepinephrine). Duloxetine has been confirmed in several studies as an effective agent in the treatment of neuropathic pain.13 Doses for the treatment of neuropathic pain as well as depression are between 60mg and 120mg per day. Interestingly, in a study of healthy volunteers who were taking doses of 60mg per day of duloxetine, the drug exhibited a notable effect on serotonin reuptake inhibition, but not on norepinephrine reuptake inhibition.16 If these data can be generalized to clinical populations, they indicate that the neurotransmitter effects of duloxetine may be dose-dependent. If so, then like bupropion, duloxetine may be an unexpected exception to the hypothesized requirement for dual 18

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Psychiatry - December 2008 Editor’s Message Contents Editorial Advisory Board Antidepressant Prescribing by Specialty and Treatment of Premenstrual Dysmorphic Disorder Pain, Pain, Go Away: Antidepressants and Pain Management Why Psychotherapy Helps the Patient in Chronic Pain General Medical Drugs Associated with Depression Katatonia: A New Conceptual Understanding of Catatonia and a New Rating Scale Thermoregulation and the Role of Calcium Signalling in Neurotransmission Cognition and Schizophrenia: Is There a Role for Cognitive Assessments in Diagnosis and Treatment? Journal Watch Information for Authors

Psychiatry - December 2008

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