Efficacy and Safety of Clonidine in the Treatment of Acute Mania in Bipolar Disorder: A Systematic Review.
Prakamya SingalNicolas A NuñezBoney JosephLeslie C HassettAshok SeshadriBalwinder SinghPublished in: Brain sciences (2023)
Clonidine, an alpha-2 adrenergic agonist, has been proposed as an antimanic agent that acts by reducing noradrenergic transmission. We conducted a systematic review to examine the efficacy and safety of clonidine for acute mania/hypomania. A comprehensive literature search was performed to identify randomized controlled trials (RCT) and non-randomized studies investigating the efficacy and safety of monotherapy/adjuvant treatment with clonidine for acute mania/hypomania in patients with bipolar disorder (BD). Nine studies ( n = 222) met our inclusion criteria, including five RCTs ( n = 159) and four non-randomized studies ( n = 63). Non-randomized studies showed clonidine to help reduce symptoms of mania. However, data from placebo controlled RCTs were inconsistent. One RCT showed adjuvant clonidine as superior to placebo, whereas another RCT reported that clonidine was not better than placebo. In individual RCTs, lithium and valproate offered better antimanic effects compared to clonidine. Studies reported hypotension, depression, and somnolence as common adverse effects. Significant differences in study design and sample size contributed to high heterogeneity. This systematic review suggests low-grade evidence for clonidine as an adjuvant treatment for acute mania with mood stabilizers and inconclusive efficacy as monotherapy, warranting further well-designed RCTs.
Keyphrases
- bipolar disorder
- placebo controlled
- double blind
- major depressive disorder
- liver failure
- systematic review
- phase iii
- open label
- low grade
- early stage
- respiratory failure
- case control
- combination therapy
- drug induced
- phase ii
- aortic dissection
- clinical trial
- replacement therapy
- machine learning
- high grade
- intensive care unit
- deep learning
- depressive symptoms
- physical activity
- phase ii study