Prophylactic lithium treatment and cognitive performance in patients with a long history of bipolar illness: no simple answers in complex disease-treatment interplay

Abstract

Cognitive impairment in patients with bipolar disorder (BD) is not restricted to symptomatic phases. It is also present in euthymia. There is evidence of differences in the brain’s structure between bipolar patients and healthy individuals, as well as changes over time in patients. Lithium constitutes the gold standard in long-term prophylactic treatment. Appropriate therapy that prevents new episodes improves the disease’s course and reduces the frequency of harmful outcomes. Interestingly, preclinical data suggest that lithium has a (additional) neuroprotective effect. There is limited data on its related effects in humans and even less on its long-term application. In this multi-center cross-sectional study from the International Group for the Study of Lithium-treated Patients (IGSLi), we compared three groups: bipolar patients without long-term lithium treatment (non-Li group; <3 months cumulative lithium exposure, ≥24 months ago), bipolar patients with long-term lithium treatment (Li group, ongoing treatment ≥24 months), and healthy subjects (controls). Strict inclusion and exclusion criteria were defined; the inclusion criteria for patients were diagnosis of BD types I or II, duration of illness ≥10 years, ≥5 episodes in patient’s history and a euthymic mood state. Neurocognitive functioning was assessed using the Wechsler Adult Intelligence Scale-Revised (WAIS-R), the California Verbal Learning Test (CVLT), and a visual backward masking (VBM) task. A total of 142 subjects were included, 31 in the non-Li and 58 in the Li group, as well as 53 healthy controls. Treated patients with long-standing BD and controls did not differ significantly in overall cognitive functioning and verbal learning, recall, and recognition; regardless of whether lithium had been part of the treatment. Patients, however, demonstrated poorer early visual information processing than healthy controls, with the lithium-treated patients performing worse than those without. Our data suggest that bipolar patients with a long illness history and effective prophylactic treatment do not reveal significantly impaired general cognitive functioning or verbal learning and memory. However, they are worse at processing early visual information. Accompanying volumetric and spectroscopic data suggest cell loss in patients not treated with lithium that may be counterbalanced by long-term lithium treatment.

A specific group of patients with diagnostic conversion from depression to bipolar disorder and finally to dementia as a mental GSK‐3 disease: A hypothesis

“…On the other hand, a meta‐analysis examining the trajectory of cognitive impairment in bipolar disorder indicated that bipolar patients' performance on 14 cognitive measures remained stable, but the mean follow‐up period was relatively short (4.62 years) . Also, Pfennig et al showed that lithium‐treated patients with a long‐standing bipolar disorder and controls did not differ significantly in neurocognitive performance in overall cognitive function and verbal learning, recall, and recognition, regardless of whether lithium was part of their long‐term treatment. Very recently, Seelye et al demonstrated a steeper aging‐related decline specific to cognitive control processes of cognitive flexibility in bipolar adults to nonbipolar adults.…”

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness

“…Lithium has received more clinical assessment of its neuroprotective capacity than any other agent, most notably in bipolar disorder. Crosssectional studies of bipolar patients have associated lithium treatment with: (a) attenuation of cortical grey matter loss and (b) maintained white matter integrity (Table 1) (Giakoumatos et al, 2015;Gildengers et al, 2015;Hajek et al, 2012Hajek et al, , 2014Hartberg et al, 2015;Pfennig et al, 2014;Poletti, Locatelli, Radaelli, Colombo, & Benedetti, 2014;Simonetti et al, 2016;van Erp et al, 2012;Zung et al, 2016), though few have correlated lithium's structural benefits with a similar improvement in brain function.…”

Efficacy and tolerability of lithium for the treatment of acute mania in children with bipolar disorder: A systematic review

“…Therefore, a cautionary approach in using centrally active medication during the formative years of the nervous system is wise, but at the same time, it is also important to evaluate the potential benefits and adverse effects of an effective treatment such as lithium, and research its use in children that may be suffering from a serious form of the same illness. This is particularly important because recent evidence suggests that lithium may have several benefits including neuroprotective effects, and a delay in the initiation of treatment has been found to be associated with poor outcomes …”

“…This is particularly important because recent evidence suggests that lithium may have several benefits including neuroprotective effects, and a delay in the initiation of treatment has been found to be associated with poor outcomes. [8][9][10] Therefore, as a joint effort between IGSLi (www.igsli.org) and the ISBD Task Force on Lithium Treatment (www.isbd.org/active-taksforces), the objective of this study was to summarize the available evidence concerning the effectiveness and tolerability of lithium in the treatment of paediatric mania using a systematic review.…”