Article

A double-blind study comparing idazoxan and bupropion in bipolar depressed patients

{ "0" : "Lilly Research Laboratories, Lilly Corporate Center, Drop Code 2033, Indianapolis, IN 46285, USA" , "1" : "Lilly Research Laboratories, Lilly Corporate Center, Drop Code 0532, Indianapolis, IN 46285, USA" , "2" : "Olsten Health Services, 30 South 15th Street, Philadelphia, PA 19102, USA" , "3" : "Biomedical Statistical Consultants, 1357 Garden Road, Wynnewood, PA 19096, USA" , "5" : "Idazoxan" , "6" : "Bupropion" , "7" : "Bipolar" , "8" : "Depression" , "9" : "Biologic effects" , "10" : "Bipolar depressed"}
Journal of Affective Disorders (Impact Factor: 3.38). 01/2000; 56(2):237-243. DOI: 10.1016/S0165-0327(99)00041-5

ABSTRACT

Background: There is a small body of evidence indicating that idazoxan, a potent and selective alpha-2 antagonist, may be effective in treating bipolar depressive disorder. The purpose of this prospective controlled study is to compare idazoxan to bupropion, an antidepressant which has been suggested to have some advantages over other antidepressants in treating bipolar depressed patients. Methods: Bipolar I depressed patients were randomly assigned in this 6-week double-blind out-patient study to receive either idazoxan, titrated to 240 mg/day and placebo bupropion, or bupropion, titrated to 450 mg/day and placebo idazoxan. These doses were achieved after 2 weeks. Depression severity was assessed with the Hamilton Depression Rating Scale and possible psychosis with the Brief Psychiatric Rating Scale. Side effects, heart rate, weight, and orthostatic blood pressure were also monitored. Results: Fourteen patients completed this study (seven in each group). Both idazoxan and bupropion demonstrated significant improvement over time with reductions in Hamilton scores of 50%. Limitations: Limitations of this study include lack of a placebo group and small sample size. Conclusion: In light of our preliminary findings suggesting the usefulness of idazoxan in bipolar depression, larger more rigorous studies are indicated.

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    • "In addition, van der Loos et al. (2009) compared adding lamotrigine or placebo to lithium (responders : 33/64 vs. 19/60 ; p=0.025) ; non-responders also failed to respond to later, unblinded addition of paroxetine (van der Loos et al., 2010). Finally, several trials compared different antidepressants in bipolar depression and found no differences in responses, but lacked placebo controls (Bocchetta et al., 1993 ; Sachs et al., 1994 ; Grossman et al., 1999 ; Young et al., 2000 ; Silverstone, 2001 ; Post et al., 2006). "

    Full-text · Dataset · Jul 2013
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    • "In addition, van der Loos et al. (2009) compared adding lamotrigine or placebo to lithium (responders : 33/64 vs. 19/60 ; p=0.025) ; non-responders also failed to respond to later, unblinded addition of paroxetine (van der Loos et al., 2010). Finally, several trials compared different antidepressants in bipolar depression and found no differences in responses, but lacked placebo controls (Bocchetta et al., 1993 ; Sachs et al., 1994 ; Grossman et al., 1999 ; Young et al., 2000 ; Silverstone, 2001 ; Post et al., 2006). "
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    ABSTRACT: Bipolar depression remains a major unresolved challenge for psychiatric therapeutics. It is associated with significant disability and mortality and represents the major proportion of the approximately half of follow-up time spent in morbid states despite use of available treatments. Evidence regarding effectiveness of standard treatments, particularly with antidepressants, remains limited and inconsistent. We reviewed available clinical and research literature concerning treatment with antidepressants in bipolar depression and its comparison with unipolar depression. Research evidence concerning efficacy and safety of commonly used antidepressant treatments for acute bipolar depression is very limited. Nevertheless, an updated meta-analysis indicated that overall efficacy was significantly greater with antidepressants than with placebo-treatment and not less than was found in trials for unipolar major depression. Moreover, risks of non-spontaneous mood-switching specifically associated with antidepressant treatment are less than appears to be widely believed. The findings encourage additional efforts to test antidepressants adequately in bipolar depression, and to consider options for depression in types I vs. II bipolar disorder, depression with subsyndromal hypomania and optimal treatment of mixed agitated-dysphoric states - both short- and long-term. Many therapeutic trials considered were small, varied in design, often involved co-treatments, or lacked adequate controls.
    Full-text · Article · Feb 2013 · The International Journal of Neuropsychopharmacology
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    • "Finally, there are no double-blind placebo-controlled studies demonstrating clinical antidepressant action for an a 2 -adrenergic antagonist lacking biologically significant 5-HT 2A receptor affinity. Evidence reported thus far for the selective a 2 -adrenergic antagonist idazoxan suggests that the suspected beneficial effects of this drug for mood disorders may be mostly restricted to bipolar depression (Osman et al, 1989; Potter et al, 1994; Grossman et al, 1999). Taken together, it is far from clear that the beneficial effects from combining mirtazapine or mianserin with SSRIs in depressed patients (discussed below) is due to a 2 -adrenergic blocking activity of these compounds. "
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    ABSTRACT: Recently, the addition of drugs with prominent 5-HT(2) receptor antagonist properties (risperidone, olanzapine, mirtazapine, and mianserin) to selective serotonin reuptake inhibitors (SSRIs) has been shown to enhance therapeutic responses in patients with major depression and treatment-refractory obsessive-compulsive disorder (OCD). These 5-HT(2) antagonists may also be effective in ameliorating some symptoms associated with autism and other pervasive developmental disorders (PDDs). At the doses used, these drugs would be expected to saturate 5-HT(2A) receptors. These findings suggest that the simultaneous blockade of 5-HT(2A) receptors and activation of an unknown constellation of other 5-HT receptors indirectly as a result of 5-HT uptake inhibition might have greater therapeutic efficacy than either action alone. Animal studies have suggested that activation of 5-HT(1A) and 5-HT(2C) receptors may counteract the effects of activating 5-HT(2A) receptors. Additional 5-HT receptors, such as the 5-HT(1B/1D/5/7) receptors, may similarly counteract the effects of 5-HT(2A) receptor activation. These clinical and preclinical observations suggest that the combination of highly selective 5-HT(2A) antagonists and SSRIs, as well as strategies to combine high-potency 5-HT(2A) receptor and 5-HT transporter blockade in a single compound, offer the potential for therapeutic advances in a number of neuropsychiatric disorders.
    Full-text · Article · Mar 2003 · Neuropsychopharmacology
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