Potential mechanisms of action of atypical antipsychotic medications in treatment-resistant depression and anxiety

Pierre Blier; Steve T Szabo

Potential mechanisms of action of atypical antipsychotic medications in treatment-resistant depression and anxiety

J Clin Psychiatry. 2005:66 Suppl 8:30-40.

Authors

Pierre Blier¹, Steve T Szabo

Affiliation

¹ Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada. pblier@rohcg.on.ca

PMID: 16336034

Abstract

The serotonin (5-HT) and norepinephrine neurons have reciprocal interactions at the level of their cell bodies and nerve terminals. As an illustration of such connections, selective serotonin reuptake inhibitors (SSRIs) gradually enhance serotonin transmission not only in the forebrain but also in the locus ceruleus, thereby decreasing norepinephrine neuronal firing. In contrast, blocking 5-HT2A receptors in the presence of serotonin reuptake inhibition using the experimental compound YM992 enhances both serotonin and norepinephrine release. The latter pharmacologic effect may be a main contributor to the robust antidepressant effect of adding atypical antipsychotics in SSRI-resistant patients. In obsessive-compulsive disorder, risperidone has consistently been reported to be an effective augmentation strategy in SSRI-resistant patients. This effect may result in part from its antagonistic actions on dopaminergic receptors and alpha2-adrenoceptors on serotonin terminals.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antipsychotic Agents / pharmacokinetics
Antipsychotic Agents / pharmacology*
Antipsychotic Agents / therapeutic use*
Anxiety Disorders / drug therapy*
Anxiety Disorders / metabolism
Depressive Disorder / drug therapy*
Depressive Disorder / metabolism
Humans
Locus Coeruleus / drug effects
Locus Coeruleus / metabolism
Neurons / drug effects
Neurons / physiology
Norepinephrine / metabolism*
Prosencephalon / drug effects
Prosencephalon / metabolism
Raphe Nuclei / drug effects
Raphe Nuclei / metabolism
Rats
Receptors, Adrenergic / drug effects
Receptors, Adrenergic / metabolism
Receptors, Serotonin / drug effects
Receptors, Serotonin / metabolism
Selective Serotonin Reuptake Inhibitors / pharmacokinetics
Selective Serotonin Reuptake Inhibitors / pharmacology
Selective Serotonin Reuptake Inhibitors / therapeutic use
Serotonin / metabolism*
Synaptic Transmission / drug effects

Substances

Antipsychotic Agents
Receptors, Adrenergic
Receptors, Serotonin
Serotonin Uptake Inhibitors
Serotonin
Norepinephrine