Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review

Sienaert P, Lambrichts L, Dols A, De Fruyt J.
Evidence‐based treatment strategies for treatment‐resistant bipolar depression: a systematic review.
Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objectives: Treatment resistance in bipolar depression is a common clinical problem that constitutes a major challenge for the treating clinician as there is a paucity of treatment options. The objective of this paper was to review the evidence for treatment options in treatment‐resistant bipolar depression, as found in randomized controlled trials and with special attention to the definition and assessment of treatment resistance. Methods: A Medline search (from database inception to May 2012) was performed using the search terms treatment resistance or treatment refractory, and bipolar depression or bipolar disorder, supplemented with 43 separate searches using the various pharmacologic agents or technical interventions as search terms. Results: Only seven studies met our inclusion criteria. These studies examined the effects of ketamine (n = 1), (ar)modafinil (n = 2), pramipexole (n = 1), lamotrigine (n = 1), inositol (n = 1), risperidone (n = 1), and electroconvulsive therapy (ECT) (n = 2). Conclusions: The available level I evidence for treatment strategies in resistant bipolar depression is extremely scarce, and although the response rates reported are reassuring, most of the strategies remain experimental. There is an urgent need for further study in homogeneous patient samples using a clear concept of treatment resistance.     

A single photon emission computerized tomography (SPECT) study of regional cerebral blood flow in bipolar disorder

Data on functional imaging of bipolar disorder (BD) utilizing single photon emission computerized tomography (SPECT) is limited. This study assessed regional cerebral blood flow (rCBF), using ^99mTc-ECD SPECT, among patients with BD, with mania (N=10) or depression (N=10), compared with 10 patients with unipolar depression and 10 normal controls. Regions of interest were analysed using a semi-automatic brain quantification programme. Compared to controls, patients with mania had significantly reduced perfusion mainly in the left frontal area, also in the left anterior cingulate and parietal cortices; those with bipolar depression had significantly lowered rCBF principally in the anterior temporal regions bilaterally, as well as the left parietal area. Patients with unipolar depression had significantly lowered perfusion than controls in most of the regions examined, chiefly in the anterior temporal and frontal cortices bilaterally; they also had lowered perfusion in the right anterior temporal and frontal areas, as well as the right middle temporal area and the right thalamus, compared to patients with mania. Increased severity of psychotic symptoms was associated with reduced rCBF in patients. These results indicate that altered blood flow in the frontal-subcortical systems characterises patients with BD, as well as those with unipolar depression.