Atypical antipsychotics and mood stabilization in bipolar disorder

Abstract

The available literature on the use of atypical antipsychotics for the treatment of bipolar disorder was reviewed. All uncontrolled and controlled reports were identified through a comprehensive Medline search. Based on the available evidence, olanzapine was found to be the most appropriate atypical antipsychotic agent utilized for the treatment of manic bipolar patients, although there is also preliminary data suggesting the efficacy of risperidone and clozapine. The preliminary data evaluating the efficacy of quetiapine and ziprasidone in bipolar disorder are still very limited. Double-blind controlled studies with atypical antipsychotics in the long-term treatment of bipolar disorder are still largely not available, but will be critical to determine the effectiveness of these agents in the maintenance treatment of bipolar disorder. There are recent uncontrolled suggestions that olanzapine may have beneficial effects in depressed bipolar patients, which deserve further investigation in controlled studies. In conclusion, atypical antipsychotics, due to lower potential for neurotoxicity and preliminary evidence suggesting better efficacy than typical antipsychotics, are increasingly having a more prominent role in the pharmacological management of bipolar patients. Nonetheless, until there is systematic data from long-term controlled follow-up studies on the comparative efficacy of these agents with mood stabilizers, atypical antipsychotics should be cautiously utilized, and preferably in combination with a mood stabilizer for the maintenance phase of treatment.

GABAergic dysfunction in mood disorders

“…Also, GABAergic transmission appears to be involved in the mechanism of action of antidepressants, mood stabilizers, and ECT, in addition to benzodiazepines and new antipsychotics (ie olanzapine and clozapine), which are tools used in the treatment of mood disorders. 216,270 However, these drugs involve several neurotransmitter systems, such as serotonergic, monoaminergic, and GABAergic systems. 33,44,54 Petty argued 87,282 that GABAergic transmission may mediate noradrenergic function in a unified concept of antidepressant mechanism of action that is complement to the noradrenergic theory of mood disorder.…”

“…268,269 Therefore, it is conceivable that some of the effects of these atypical antipsychotics in mood disorder patients would be modulated by effects in GABAergic systems. 270 Electroconvulsive therapy ECT is a tool with a wide application in psychiatry. 271 Particularly, it exerts antidepressant and antimanic effectiveness in resistant mood disorder patients.…”

Receptor crosstalk: haloperidol treatment enhances A2A adenosine receptor functioning in a transfected cell model

“…Using a rat model of focal ischaemia, it has been demonstrated that increases in A 2A AR density may contribute to A 2A AR-mediated neuron death [11]. In addition, an increase in A 2A AR density and/or functionality has also been detected in psychiatric diseases such as schizophrenia [12] and bipolar disorders [13]: in these pathologies, alterations in A 2A AR parameters have been related to the chronic use of antipsychotic drugs, D 2 dopamine receptor (DR) antagonists [14][15][16], and also the functional crosstalk between the adenosine and dopamine systems.…”

1H MRS Study of Dorsolateral Prefrontal Cortex in Healthy Individuals before and after Lithium Administration

“…Lithium is a first-line drug for acute and prophylactic treatment of bipolar disorder (Brambilla et al, 2003;Soares and Gershon, 1998). Its mechanism of action has not been elucidated, although several preclinical studies have tried to better clarify its biological basis (Lenox and Hahn, 2000).…”