The International College of Neuro-Psychopharmacology (CINP) Treatment Guidelines for Bipolar Disorder in Adults (CINP-BD-2017), Part 2: Review, Grading of the Evidence, and a Precise Algorithm

Abstract

Background:The current paper includes a systematic search of the literature, a detailed presentation of the results, and a grading of treatment options in terms of efficacy and tolerability/safety.Material and Methods:The PRISMA method was used in the literature search with the combination of the words ‘bipolar,’ ‘manic,’ ‘mania,’ ‘manic depression,’ and ‘manic depressive’ with ‘randomized,’ and ‘algorithms’ with ‘mania,’ ‘manic,’ ‘bipolar,’ ‘manic-depressive,’ or ‘manic depression.’ Relevant web pages and review articles were also reviewed.Results:The current report is based on the analysis of 57 guideline papers and 531 published papers related to RCTs, reviews, posthoc, or meta-analysis papers to March 25, 2016. The specific treatment options for acute mania, mixed episodes, acute bipolar depression, maintenance phase, psychotic and mixed features, anxiety, and rapid cycling were evaluated with regards to efficacy. Existing treatment guidelines were also reviewed. Finally, Tables reflecting efficacy and recommendation levels were created that led to the development of a precise algorithm that still has to prove its feasibility in everyday clinical practice.Conclusions:A systematic literature search was conducted on the pharmacological treatment of bipolar disorder to identify all relevant random controlled trials pertaining to all aspects of bipolar disorder and graded the data according to a predetermined method to develop a precise treatment algorithm for management of various phases of bipolar disorder. It is important to note that the some of the recommendations in the treatment algorithm were based on the secondary outcome data from posthoc analyses.

Efficacy and safety of lithium and lamotrigine for the maintenance treatment of clinically stable patients with bipolar disorder: A systematic review and meta‐analysis of double‐blind, randomized, placebo‐controlled trials with an enrichment design

“…Patients with bipolar disorder (BD) repeatedly and irregularly present mania/hypomania or depression during their life course, which can result in social and occupational disability . A meta‐analysis of mood stabilizer usage reported that continuing their use significantly reduced the relapse rate for adult BD patients [risk ratio (RR) = 0.68, 95% confidence intervals (95%CI) = 0.60‐0.77, P < 0.001], and therefore, recent treatment guidelines for BD have recommended their continuation for a long period, even after remission . A network meta‐analysis of randomized controlled trials (RCTs) investigated the comparative efficacy and safety of pharmacological treatments for BD and suggested that lithium should be used as the first‐line treatment for preventing relapse in patients with this disorder .…”

“…2 A meta-analysis of mood stabilizer usage 3 reported that continuing their use significantly reduced the relapse rate for adult BD patients [risk ratio (RR) = 0.68, 95% confidence intervals (95%CI) = 0.60-0.77, P < 0.001], and therefore, recent treatment guidelines for BD have recommended their continuation for a long period, even after remission. 4,5 A network meta-analysis of randomized controlled trials (RCTs) investigated the comparative efficacy and safety of pharmacological treatments for BD and suggested that lithium should be used as the first-line treatment for preventing relapse in patients with this disorder. 6 However, that meta-analysis included both RCTs with an enrichment design (ie which selected patients who had responded acutely to lithium) and those without an enrichment design (ie which included patients who had responded acutely to drugs other than lithium or who had not received any treatment prior to the study).…”

Putative neuroprotective pharmacotherapies to target the staged progression of mental illness

“…In bipolar disorder (n = 43) and major depression (n = 36), add-on EPO leads to improved objective cognition, which lasts 6 weeks post cessation of EPO (Ott, Vinberg, Kessing, & Miskowiak, 2016). Systematic review of the literature suggests schizophrenia may also benefit from EPO-induced cognitive enhancement (Fountoulakis et al, 2017). In a study of socially defeated mice, a bullying induced model of depression, EPO therapy correlated with symptom improvement as indicated by forced swim testing (Osborn et al, 2013).…”

Are antidepressants useful in bipolar disease?

“…The prescription of fi rst-line antidepressants is now strictly contraindicated, not only because of the risk of manic shift, but also and especially for iatrogenic risks on the course of bipolar illness [10]. The addition of an antidepressant to a mood stabilizer should be done cautiously in a resistant bipolar depression, because of the high risk of hypomania and mania.…”