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Revisiting the effectiveness of standard antidepressants in bipolar disorder: are monoamine oxidase inhibitors superior?

ABSTRACT: The role of antidepressants in treating bipolar disorder is controversial, and the comparative effectiveness of specific drugs is insufficiently studied.We report here a comparison of monoamine oxidase inhibitors (MAOIs) with the serotonin reuptake inhibitor paroxetine (PAROX).We conducted a retrospective analysis of data from a larger study, using the first antidepressant trial administered either after entry (n = 46) or after a recurrent episode during study participation (n = 6).Twenty two patients were treated with PAROX and 30 with an MAOI. Durable recovery was determined from Hamilton depression and Young mania scores, based on published criteria.PAROX treatment led to durable recovery in 27% of patients, a result very similar to the 24% recovery rate found in a recent STEP-BD trial. In contrast, patients treated with an MAOI had a 53% durable recovery rate. Survival analysis showed a significantly faster onset of durable recovery with MAOIs (x2 = 4.77, p = 0.029). Among subjects who were able to complete an adequate treatment trial of at least four weeks duration, durable recovery was attained in a significantly greater proportion of those treated with an MAOI (16 of 23, 70%) as compared to PAROX (6 of 18, 33%)(Fisher's Exact Test, p = 0.023).In these patients with bipolar depression, the antidepressant effectiveness of PAROX was unacceptably low, but rates of recovery with MAOIs were significantly higher.

SUBMITTER: Mallinger AG

PROVIDER: S-EPMC3570273 | biostudies-literature | 2009

REPOSITORIES: biostudies-literature

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Revisiting the effectiveness of standard antidepressants in bipolar disorder: are monoamine oxidase inhibitors superior?

Mallinger Alan G AG Frank Ellen E Thase Michael E ME Barwell Michelle M MM Diazgranados Nancy N Luckenbaugh David A DA Kupfer David J DJ

Psychopharmacology bulletin 20090101 2

<h4>Objective</h4>The role of antidepressants in treating bipolar disorder is controversial, and the comparative effectiveness of specific drugs is insufficiently studied.We report here a comparison of monoamine oxidase inhibitors (MAOIs) with the serotonin reuptake inhibitor paroxetine (PAROX).<h4>Experimental design</h4>We conducted a retrospective analysis of data from a larger study, using the first antidepressant trial administered either after entry (n = 46) or after a recurrent episode du ...[more]

PMID: 19629023

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Project description:Background: A mild pro-inflammatory status accompanies bipolar disorder (BD). Inflammation can cause a shift in monoamine metabolism, thereby activating more cytotoxic pathways. The extent to which low-grade inflammation in BD interacts with monoamine metabolism and how this accords to aging and clinical course is unknown. Objectives: We evaluated the presence of alterations in inflammation and monoamine metabolism in BD throughout different mood states and the role of aging therein. Methods: Sixty-seven patients with BD were included during an acute mood episode, either depressive (n = 29), (hypo)manic (n = 29), or mixed (n = 9). Plasma levels of inflammatory markers [tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-y), interleukin-6 (IL-6), and C-reactive protein (CRP)] and markers of monoamine metabolism (neopterin, tryptophan, kynurenine, phenylalanine, and tyrosine) were measured repeatedly during a follow-up of 8 months. Levels in patients were compared to controls (n = 35) and correlated to HDRS-17 and YMRS scores. Spearman correlations and linear mixed model analysis were used for statistical analysis. Results: Forty-nine patients and 30 controls (age range: 22-62 years) completed the study. No significant differences in inflammatory markers were found between patients and controls overall. Tryptophan, tyrosine, and phenylalanine levels were lower in patients. In both patients and controls, markers of inflammation correlated only weakly with markers of monoamine metabolism, but correlations representative for activity of cytotoxic pathways in monoamine metabolism were more pronounced in patients. In patients, but not in controls, older age was associated with increases in inflammatory markers (IL-6, CRP, neopterin) and the kynurenine/tryptophan ratio. None of the biological markers correlated significantly with mood symptom severity. Conclusion: Our data suggest an increased susceptibility of patients with BD to develop a pro-inflammatory state and to shift monoamine metabolism toward more cytotoxic pathways. These findings are in support of the theory of neuroprogression and accelerated aging in BD. Since associations between biological markers and clinical characteristics are limited, it remains to be determined if alterations in biological markers are due to a disease effect or rather are a consequence of confounding factors.

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Revisiting the effectiveness of standard antidepressants in bipolar disorder: are monoamine oxidase inhibitors superior?

Publications

Revisiting the effectiveness of standard antidepressants in bipolar disorder: are monoamine oxidase inhibitors superior?

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