Antidepressant analgesia in rheumatoid arthritis. Management of depression in rheumatoid arthritis: a combined pharmacologic and cognitive-behavioral approach. Comparison of cognitive behavioral and mindfulness meditation interventions on adaptation to rheumatoid arthritis for patients with and without history of recurrent depression. A randomized, within-patient, cross-over, placebo-controlled trial on the efficacy and tolerability of the tricyclic antidepressants chlorimipramine and nortriptyline in central pain. Tailored cognitive-behavioral therapy in early rheumatoid arthritis for patients at risk: a randomized controlled trial. Paroxetine versus amitriptyline for treatment of depression associated with rheumatoid arthritis: a randomized, double blind, parallel group study. Aripiprazole augmentation in major depressive disorder: a double-blind, placebo-controlled study in patients with inadequate response to antidepressants. Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis. A comparison of dothiepin versus placebo in the treatment of pain in rheumatoid arthritis and the association of pain with depression.
Forty-seven patients with definite rheumatoid arthritis (RA) were treated in a 32 week, double blind, crossover trial of amitriptyline, desipramine, trazodone, and placebo. All drug regimens produced significant changes on pain measures relative to baseline, but only amitriptyline exceeded placebo. Amitriptyline was associated with a significant reduction in the number of painful/tender joints. Our study supports the efficacy of a moderate dose of amitriptyline as an adjunct drug for the treatment of pain in both depressed and nondepressed patients with RA. To examine the effectiveness of cognitive-behavioral and pharmacologic treatment of depression in rheumatoid arthritis (RA).
                Subjects (n = 54) with confirmed diagnoses of both major depression and RA were randomly assigned to 1 of 3 groups: 1) cognitive-behavioral/pharmacologic group (CB-PHARM), 2) attention-control/pharmacologic group, or 3) pharmacologic control group. Measures of depression, psychosocial status, health status, pain, and disease activity were collected at baseline, posttreatment (10 weeks), 6-month followup, and 15-month followup. Data were analyzed to compare the treatment effectiveness of the groups; data also were aggregated to examine the effects of antidepressive medication over time. Lastly, a no-treatment control group was defined from a cohort of persons who declined participation.
                Baseline comparisons on demographic and dependent measures revealed a need to assess covariates on age and education; baseline scores on dependent measures also were entered as covariates. Analyses of covariance revealed no statistically significant group differences at postintervention, 6-month followup, or 15-month followup, except higher state and trait anxiety scores for the CB-PHARM group at the 15-month followup. In the longitudinal analyses of the effects of antidepressive medication, significant improvement in psychological status and health status were found at posttreatment, 6-month followup, and 15-month followup, but no significant improvements were shown for pain or disease activity. In addition, the comparison of the aggregated pharmacologic group with a no-treatment group revealed a statistically significant benefit for the 3 groups that received the antidepressive medication.
                In persons with RA, cognitive-behavioral approaches to the management of depression were not found to be additive to antidepressant medication alone, but antidepressant intervention was superior to no treatment. This research examined whether cognitive behavioral therapy and mindfulness interventions that target responses to chronic stress, pain, and depression reduce pain and improve the quality of everyday life for adults with rheumatoid arthritis (RA). The 144 RA participants were clustered into groups of 6-10 participants and randomly assigned to 1 of 3 treatments: cognitive behavioral therapy for pain (P); mindfulness meditation and emotion regulation therapy (M); or education-only group (E), which served as an attention placebo control. The authors took a multimethod approach, employing daily diaries and laboratory assessment of pain and mitogen-stimulated levels of interleukin-6 (IL-6), a proinflammatory cytokine. Participants receiving P showed the greatest Pre to Post improvement in self-reported pain control and reductions in the IL-6; both P and M groups showed more improvement in coping efficacy than did the E group. The relative value of the treatments varied as a function of depression history. RA patients with recurrent depression benefited most from M across several measures, including negative and positive affect and physicians' ratings of joint tenderness, indicating that the emotion regulation aspects of that treatment were most beneficial to those with chronic depressive features.
                (c) 2008 APA, all rights reserved Antidepressant drugs are increasingly used in the management of chronic pain. They are mainly prescribed for cancer-related pain and central pain, e.g. phantom or stump pain, post-herpetic neuropathy. However, no controlled clinical trials have validated their in either pathology. Thus, physicians still do not know whether antidepressants are really effective and which might be best. It is still debated whether the effect of antidepressants in the management of chronic pain is limited to the amelioration of frequently concomitant depression or extends to pain itself. To verify both the analgesic effect of tricyclic antidepressants, and the possible relationship between their antidepressant effect and the relief of central pain, we carried out a randomized, within-patient (cross-over) placebo-controlled study in patients suffering from central pain. The results clearly indicate the better analgesic effect of tricyclic antidepressants over placebo (p less than 0.0001). Within the antidepressants tested, chlorimipramine, a blocker of serotonin reuptake, is significantly more effective (p less than 0.0001) than notriptyline, a blocker of noradrenaline reuptake. Finally, the antinociceptive effect is independent of the effects of the two drugs on the symptoms of depression. Recent developments in chronic pain research suggest that effectiveness of cognitive-behavioral therapy (CBT) may be optimized when applying early, customized treatments to patients at risk. For this purpose, a randomized, controlled trial with tailor-made treatment modules was conducted among patients with relatively early rheumatoid arthritis (RA disease duration of <8 years), who had been screened for psychosocial risk profiles. All participants received standard medical care from a rheumatologist and rheumatology nurse consultant. Patients in the CBT condition additionally received an individual CBT treatment with two out of four possible treatment modules. Choice of treatment modules was determined on the basis of patient priorities, which resulted in most frequent application of the fatigue module, followed by the negative mood, social relationships and pain and functional disability modules. Analyses of completers and of intention-to-treat revealed beneficial effects of CBT on physical, psychological and social functioning. Specifically, fatigue and depression were significantly reduced at post-treatment and at the 6-month follow-up in the CBT condition in comparison to the control condition, while perceived support increased at follow-up assessment. In addition, helplessness decreased at post-treatment and follow-up assessment, active coping with stress increased at post-treatment, and compliance with medication increased at follow-up assessment in the CBT condition in comparison to the control condition. Results indicate the effectiveness of tailor-made CBT for patients at risk in relatively early RA, and supply preliminary support for the idea that customizing treatments to patient characteristics may be a way to optimize CBT effectiveness in RA patients. To compare the efficacy and tolerability of paroxetine (a selective serotonin reuptake inhibitor) with that of amitriptyline (a tricyclic antidepressant) in the treatment of depression in 191 patients with rheumatoid arthritis (RA).
                A randomized, double blind, double dummy, parallel group study. A placebo washout period of 3-7 days was followed by an 8 week active treatment phase during which patients received either paroxetine (20-40 mg daily) or amitriptyline (75-150 mg daily). The primary efficacy variable was the change from baseline in Montgomery Asberg Depression Rating Scale score at endpoint.
                Paroxetine was as effective as amitriptyline for the treatment of depression, with similar improvements in RA associated pain and disability also seen in both groups. However, paroxetine was better tolerated than amitriptyline, with an overall frequency of adverse experiences of 56.4% and 67.7% in the 2 groups, respectively. The frequency of anticholinergic adverse experiences was much lower in the paroxetine treatment group (18.1% vs 43.8% taking amitriptyline) and paroxetine treated patients also experienced fewer severe (16.0% vs 21.9%), serious nonfatal (0% vs 4.2%), and drug related adverse experiences (12.8% vs 29.2%).
                Tolerability is an important consideration in this patient population, which is largely composed of elderly patients who are taking additional medications for RA. Paroxetine shows a number of advantages in the management of depression comorbid with RA. Effective management of major depressive disorder (MDD) continues to be a challenging task for psychiatrists and primary care physicians. This trial evaluated the efficacy and safety of adjunctive aripiprazole versus antidepressant monotherapy in patients with MDD and independently replicated the positive findings of two similar trials.
                Patients (N=1,147) with MDD experiencing a major depressive episode and a history of inadequate response to antidepressant monotherapy were enrolled (week 0); 827 received single-blind adjunctive placebo plus open-label antidepressant (escitalopram, fluoxetine, paroxetine controlled release, sertraline, or venlafaxine extended release) for 8 weeks to confirm inadequate response to antidepressants; 349 patients with inadequate response were randomized (1:1) to double-blind, adjunctive placebo (n=172) or adjunctive aripiprazole (n=177; 2-20 mg/day). Primary outcome was the mean change in Montgomery-Asberg Depression Rating Scale (MADRS) Total score from baseline (week 8) to endpoint (week 14).
                Clinically significant improvements in depressive symptoms as assessed by decreases in the MADRS Total score were greater with adjunctive aripiprazole (-10.1) than placebo (-6.4; P<.001). Remission rates were greater for adjunctive aripiprazole than for adjunctive placebo (week 14, 36.8% vs 18.9%; P<.001). Completion rates with adjunctive aripiprazole and placebo were high (83% vs. 87%) and discontinuations due to adverse events were low (6.2% vs 1.7%).
                For some patients with MDD who do not obtain adequate symptom relief with antidepressant monotherapy, adjunctive therapies can significantly improve depressive symptoms. As reported, adjunctive aripiprazole was associated with a two-fold higher remission rate than adjunctive placebo. This, and previous studies, have shown that discontinuations due to adverse events were low and completion rates were high, and has indicated that both antidepressant and aripiprazole in combination were relatively well-tolerated and safe. This is the third consecutive clinical trial, in the absence of a failed trial, to demonstrate that aripiprazole augmentation to antidepressants is an efficacious and well-tolerated treatment for patients with MDD who do not respond adequately to standard antidepressant monotherapy (ClinicalTrials.gov study NCT00105196). To evaluate RA-1, a standardized plant extract formulation, traditionally considered a safe, effective antiarthritic in the Asian-Indian Ayurvedic medicinal system.
                One hundred eighty-two patients with active-on-chronic rheumatoid arthritis (RA) participated in a 16 week randomized, double blind, placebo controlled, parallel efficacy clinical drug trial in Pune, India. Tenderness, pain, swelling, and several other efficacy measures were assessed by (1) ACR core set 20% and 50% improvement; (2) ACR 20% improvement response. An intent-to-treat analysis was performed; p<0.05 considered significant.
                Seventeen patients withdrew (active = 9; placebo = 8); none withdrew due to drug toxicity. An unprecedented placebo response (often p<0.001 in within-group change) was observed. The active RA-1 group remained numerically superior at all evaluation timepoints. RA-1 demonstrated few significant differences: (1) increased proportion with 50% reduction in swollen joint count (95% CI approximately 1.52, 29.90) and swollen joint score (95% CI approximately 0.91, 28.73); (2) reduced rheumatoid factor (95% CI approximately -303.7, -2.72); 39% in the RA-1 group versus 30% placebo showed ACR 20% improvement (95% CI approximately -5.48, 24.59). Only minor side effects were seen, with no significant differences by treatment group.
                In a trial with sufficient power, RA-1 revealed efficacy that was not significantly superior to the strong placebo response, except for improvement in joint swelling. Further, the effect on RF and good safety profile led to an open label phase. The effectiveness of dothiepin (a tricyclic anti-depressant) at a dose of 75 mg given orally at night was compared with placebo for 4 weeks in alleviating pain in 60 patients with classical or definite active rheumatoid arthritis. Patients were classified as either 'depressed' or 'not depressed'. The week before, during and 2 weeks after the study, 600 mg ibuprofen was given orally three times daily to all patients. Compared with placebo, dothiepin produced a significant reduction in daytime pain by the end of the treatment period. The Hamilton rating scale in 'depressed' patients was significantly improved in patients given dothiepin. The Cassano-Castrogiovanni self-evaluation rating scale in both 'depressed' and 'not depressed' patients showed a tendency (not significant) to be improved following dothiepin treatment compared with placebo. These results suggest that patients with rheumatoid arthritis may experience an increase in pain symptoms due to an alteration of mood. Therapy with tricyclic anti-depressants, such as dothiepin, therefore, may determine an improvement of pain indexes besides having an anti-depressant effect.
There is currently insufficient evidence to support the routine prescription of antidepressants as analgesics in patients with RA as no reliable conclusions about their efficacy can be drawn from eight placebo RCTs. The use of these agents may be associated with adverse events which are generally mild and do not lead to cessation of treatment. More high quality trials are needed in this area.