The Intravenous Ketamine Test Predicts Subsequent Response to an Oral Dextromethorphan Treatment Regimen in Fibromyalgia Patients

Harvard University, Cambridge, Massachusetts, United States
Journal of Pain (Impact Factor: 4.01). 06/2006; 7(6):391-8. DOI: 10.1016/j.jpain.2005.12.010
Source: PubMed


Fibromyalgia (FM) is a challenging pain syndrome for which no reliable pharmacologic treatment exists. Recent clinical studies suggest that N-methyl-D-aspartate receptors might play a role in the pathogenesis of this disorder. To determine whether an intravenous (IV) ketamine test predicts the response to a therapeutic trial with an oral N-methyl-D-aspartate receptor antagonist, we performed a low-dose (0.1 mg/kg) IV ketamine infusion on 34 consecutive patients with FM, which was subsequently followed by an oral dextromethorphan (DX) treatment regimen. As per previous guidelines, the cutoff value for a positive response to the IV ketamine test was designated to be 67% pain relief, and a positive response to DX treatment was 50% pain reduction at 4- to 6-week follow-up visits. The degree of correlation between pain relief with ketamine and DX was highly significant (Pearson correlation coefficient, 0.66; P < .001). Ten patients responded positively to both ketamine and DX, 19 responded to neither drug, 3 had a positive response to ketamine but not DX, and 2 obtained good pain relief with DX but not ketamine. The sensitivity of the IV ketamine test was 83%, the specificity was 86%, the positive predictive value was 77%, and the negative predictive value was 91%. An association was also found between the development of side effects to the two treatments. PERSPECTIVE: The response to an IV ketamine infusion was found to predict the subsequent response to an oral dextromethorphan treatment regimen in fibromyalgia patients, with an observed agreement of 83%. Considering the refractory nature of fibromyalgia to conventional pain treatments, the IV ketamine test might enhance patient care by saving time and reducing unnecessary treatment trials.

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    • "al, 2005; Staud et al., 2005; Lynch et al., 2004; Carlsson et al., 2004; Redwine and Trujillo, 2003; Ben et al., 2003; Sawynok and Reid, 2003, 2002; Chang et al., 1999). However, due to its low efficacy, DM is usually combined with other analgesic agents such as morphine and general anesthetics as ketamine (Frymoyer et al., 2007; Cohen et al., 2006; Galer et al., 2005; Elesen et al., 2007). "
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    ABSTRACT: Previous study has shown that administration of melatonin into the anterior cingulate cortex contralateral to peripheral nerve injury prevented exacerbation of mechanical allodynia with a concurrent improvement of depression-like behavior in Wistar-Kyoto (WKY) rats, a genetic variation of Wistar rats. In the present study, we examined the effect of the individual versus combined treatment of melatonin and/or dextromethorphan (DM), a clinically available N-methyl-d-aspartate (NMDA) receptor antagonist, on pain behaviors in WKY rats with chronic constriction sciatic nerve injury (CCI). Pain behaviors (thermal hyperalgesia and mechanical allodynia) were established at one week after CCI. WKY rats were then treated intraperitoneally with various doses of melatonin, DM or their combination once daily for the following week. At the end of this one-week treatment, behavioral tests were repeated in these same rats. While DM alone was effective in reducing thermal hyperalgesia at three tested doses (15, 30 or 60 mg/kg), it reduced mechanical allodynia only at high doses (30 or 60 mg/kg). By comparison, administration of melatonin alone was effective in reducing thermal hyperalgesia only at the highest dose (120 mg/kg, but not 30 or 60 mg/kg) tested in this experiment. Melatonin alone failed to reverse allodynia at all three tested doses (30, 60 and 120 mg/kg). However, the combined intraperitoneal administration of melatonin (30 mg/kg) and DM (15 mg/kg) effectively reversed both thermal hyperalgesia and mechanical allodynia although each individual dose alone did not reduce pain behaviors. These results suggest that a combination of melatonin with a clinically available NMDA receptor antagonist might be more effective than either drug alone for the treatment of neuropathic pain.
    Full-text · Article · Aug 2009 · Brain research
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    • "Although modulation of serotonin and norepinephrine levels is the primary mechanism of TCAs, SSRIs, and SNRIs, these agents act on multiple nociceptive targets (eg, NMDA receptors, potassium channels) at central and peripheral locations, the contribution of which to the clinical outcomes obtained is unknown (Lawson 2002; Mico et al 2006). The NMDA receptor antagonists ketamine and dextromethorphan have demonstrated efficacy (pain score) as analgesics in the treatment of FM (Clark and Bennett 2000; Graven-Nielsen et al 2000; Cohen et al 2006). Due to a lack of specificity and thereby associated adverse effects, however, NMDA receptor antagonists are not widely accepted as treatments of chronic pain. "
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    ABSTRACT: Fibromyalgia (FM) is a common, complex, and difficult to treat chronic widespread pain disorder, which usually requires a multidisciplinary approach using both pharmacological and non-pharmacological (education and exercise) interventions. It is a condition of heightened generalized sensitization to sensory input presenting as a complex of symptoms including pain, sleep dysfunction, and fatigue, where the pathophysiology could include dysfunction of the central nervous system pain modulatory systems, dysfunction of the neuroendocrine system, and dysautonomia. A cyclic model of the pathophysiological processes is compatible with the interrelationship of primary symptoms and the array of postulated triggers associated with FM. Many of the molecular targets of current and emerging drugs used to treat FM have been focused to the management of discrete symptoms rather than the condition. Recently, drugs (eg, pregabalin, duloxetine, milnacipran, sodium oxybate) have been identified that demonstrate a multidimensional efficacy in this condition. Although the complexity of FM suggests that monotherapy, non-pharmacological or pharmacological, will not adequately address the condition, the outcomes from recent clinical trials are providing important clues for treatment guidelines, improved diagnosis, and condition-focused therapies.
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