State of the Art: Treatment of Bipolar Disorders

Abstract

Bipolar disorders are lifelong lasting affective disorders, with an episodic course of the illness in most cases. The lifetime prevalence is around 2-5%, the illness usually appears in early adulthood and causes significant impairment in psychosocial functioning. This is a selective review focusing on recent developments and issues of interest in the psychopharmacological treatment of bipolar disorders. It is based primarily on the results of adequately powered, randomised, controlled trials (RCTs). These studies were systematically retrieved by means of a Medline search. The past 10 years have led to a broadening of the psychopharmacological treatment options for bipolar disorders. The proof of efficacy for the combination of fluoxetine/olanzapine as well as quetiapine in the acute treatment of bipolar I depression were important steps. While lithium remains the gold standard in the maintenance treatment of bipolar disorders, valproate, olanzapine, lamotrigine, aripiprazole, and quetiapine have been shown efficacious for this indication, with quetiapine possessing the broadest approval status of all drugs for the different treatment phases of this illness. Despite this progress there remains a huge demand regarding new compounds for nearly every area in the psychopharmacological treatment of bipolar disorders. In addition new methodological approaches regarding the proof of effectiveness in clinical practice are urgently needed.

Genetic Influences on Response to Mood Stabilizers in Bipolar Disorder

“…Lithium, carbamazepine and valproate also have stronger antimanic than antidepressant activity although, of these three first-generation mood stabilizers, lithium exerts the most pronounced antidepressant action. Quetiapine has turned out to be the most balanced mood stabilizer, being equally effective against both psychopathological poles [13]. Finally, lamotrigine may be placed on the opposite pole of this continuum, as it exerts a predominantly antidepressant effect, being ‘a mood stabilizer from below’ and its administration typically starts during a depressive episode [14].…”

Lithium and valproate prevent methylphenidate-induced mania-like behaviors in the hole board test

“…Interestingly, in our study, the treatment with lithium, but not valproate, was able to prevent the increase in risk-taking behavior induced by methylphenidate. The ineffectiveness of valproate in counteracting this behavioral parameter corroborates its clinical profile, since this drug, despite been an alternative to treat mania, is less effective than lithium [8]. Lithium is considered a goldstandard mood stabilizer; however significant side effects, nephrotoxicity and a narrow therapeutic window are reported, thus limiting the prescriptions and adhesion to the treatment.…”

“…In this case, for acute mania, the pharmacological options of treatment include lithium or valproate plus an antipsychotic, while for acute bipolar depression, therapeutic options more frequently used are atypical antipsychotics [9]. In maintenance treatment, the focus is to delay the occurrence of future episodes, and minimize the severity of episodes that do occur [8]. Lithium and valproate are the most efficient monotherapies for the long-term treatment of bipolar disorder [9].…”

“…During depressive or manic episodes, the treatment aims to resolve an episode that is ongoing [8]. In this case, for acute mania, the pharmacological options of treatment include lithium or valproate plus an antipsychotic, while for acute bipolar depression, therapeutic options more frequently used are atypical antipsychotics [9].…”

Bipolar disorder: A brief examination of lithium therapy

“…[14] Lithium has long been viewed as the cornerstone for the treatment of individuals with bipolar disorder. [15] The current literature suggests that the use of lithium is beneficial during the acute and maintenance phase of bipolar disorder as well as preventing relapse and reducing suicide risk.…”