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Hum Psychopharmacol. 2015 May;30(3):132-42. doi: 10.1002/hup.2465. Epub 2015 Feb 17.

Is pindolol augmentation effective in depressed patients resistant to selective serotonin reuptake inhibitors? A systematic review and meta-analysis.

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Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; Institute of Neuroscience, Chongqing Medical University, Chongqing, China; Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing, China.



This systematic review and meta-analysis was conducted to assess the use of pindolol augmentation in depressed patients resistant to selective serotonin reuptake inhibitor (SSRI) therapy.


A comprehensive search of PubMed, Cochrane, Embase, Web of Science, and PsychINFO databases from 1970 through December 2013 was conducted. Only randomized controlled trials (RCTs) studied on unipolar SSRI-resistant depressed adults were included. The primary outcome was mean change scores of depressive symptom on the depression rating scales, assessed with standardized mean differences.


Five RCTs consisting of 154 patients met all inclusion and exclusion criteria. The overall pooled effect size in the primary and secondary efficacy analysis showed no significant effects of pindolol plus SSRI therapy (standardized mean difference = -0.43, p = 0.24; OR = 1.92, p = 0.39, respectively). In terms of acceptability, there was no statistical difference in either tolerability or safety between the two groups (OR = 0.46, p = 0.40; OR = 0.90, p = 0.94, respectively). These estimates remained robust through several sensitivity and subgroup analyses, except 7.5 mg-qd pindolol augmentation did show a significant benefit over 2.5-mg tid pindolol augmentation.


Pindolol augmentation may not be suitable for treatment-resistant depression patients with SSRI-resistant depression. However, once-daily high-dose pindolol (7.5 mg qd) appears to show a promising benefit in these patients.


depression; meta-analysis; pindolol; selective serotonin reuptake inhibitors; systematic review

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