Pramipexole Augmentation for Treatment-Resistant Unipolar and Bipolar Depression in the Real World: A Systematic Review and Meta-Analysis.

BACKGROUND: Pramipexole is a dopamine full agonist approved for the treatment of Parkinson's disease and restless legs syndrome. Its high affinity for the D3 receptor and neuroprotective, antioxidant, and anti-inflammatory activity provides a rationale for the treatment of depression. In this paper, we review studies on the effectiveness and safety of antidepressant pramipexole augmentation in treatment-resistant depression. METHODS: This comprehensive systematic review and meta-analysis of observational studies on pramipexole-antidepressant augmentation included patients with resistant unipolar and bipolar depression. The primary outcome measure was the treatment response, measured at the study endpoint. RESULTS: We identified 8 studies including 281 patients overall, 57% women and 39.5% with bipolar disorder and 60.5% with major depressive disorder. The mean follow-up duration was 27.3 weeks (range 8-69). The pooled estimate of treatment response was 62.5%, without significant differences between unipolar and bipolar depression. Safety was good, with nausea and somnolence the most frequent side effects. CONCLUSIONS: The findings of this systematic review, needing further confirmation, show that off-label use of pramipexole as augmentation of antidepressant treatment could be a useful and safe strategy for unipolar and bipolar treatment-resistant depression.

Continuous circular cycling in bipolar disorder as a predictor of poor outcome.

OBJECTIVE: This prospective study aims to determine if patients with bipolar disorder with a continuous circular course (CCC) are significantly different on clinical characteristics and response to long-term treatment from those with a non-continuous circular course (N-CCC). CCC was defined as the alternation of depression and (hypo)mania without a completely free interval, and N-CCC as the presence of free intervals after the sequence mania-depression or depression-mania. METHOD: The study sample includes 140 consecutive patients with bipolar I or II disorder according to DSM-IV criteria, aged 18-65 years and receiving prophylactic treatment for. Treatment was based upon international guidelines and clinical experience at the time of patient's enrollment (from January 1998 to January 2006). Primary outcome was the absence of new episodes during the follow-up. Significance level was set at p<0.05. RESULTS: Twenty-eight percent of the sample has CCC. Compared with N-CCC, CCC patients were older, had a later onset, a higher number of total, depressive and (hypo)manic episodes, and of switches, and spent a higher percentage of time ill in the year before entering the study. Polarity at onset and subsequent recurrences were more frequently mixed in N-CCC than in CCC patients. The proportion of patients in the CCC group who had no recurrences during the follow-up was significantly lower than in the N-CCC group. CONCLUSION: The presence or absence of a free intervals over the course of illness identifies two subtypes of bipolar disorder that differ in clinical presentation, outcome, and response to long-term treatment.

Treating bipolar depression - antidepressants and alternatives: a critical review of the literature.

OBJECTIVE: Although depressive symptoms are preponderant in the course of bipolar (BP) disorders, the treatment of BP depression remains a controversial issue with different clinical approaches available. This review addresses the issues of whether antidepressants (ADs) are effective in treating acute and long-term BP depression, risks linked to ADs and what alternatives to ADs are available. METHODS: We searched the MEDLINE databases using the following syntax: [bipolar depression AND unipolar depression AND (antidepressants OR anticonvulsants OR lithium OR antipsychotics OR dopamine-agonists OR psychoeducation OR psychotherapy OR electroconvulsive therapy OR transcranial magnetic stimulation)]. The search included studies published up to 31 May 2009 and conducted on adults. RESULTS: In the acute treatment of BP depression ADs are effective with no differences among drug classes. However, neither the switch into (hypo)mania induction rate nor the suicide risk linked to AD use are definitely established. The effectiveness of long-term AD use is limited to highly selected samples of patients with positive acute response. The risk of long-term ADs causing cycle acceleration and rapid cycling induction concerns a subpopulation of patients. Valid alternatives to ADs in treating acute BP depression are quetiapine, an olanzapine-fluoxetine combination, and electroconvulsive therapy for more severe patients. Lamotrigine is effective and safe in preventing depressive relapses. Psychotherapy and psychoeducation represent effective adjunctive treatments. CONCLUSION: In the treatment of BP depression there is not a specific effective treatment for all the patients. Interventions should therefore be personalised and the scientific evidence should be adapted to each patient's clinical features.