[Biological mechanisms of drug-resistant depression]

The authors review recent findings concerning biological mechanisms of drug-resistant depression. Treatment-resistant depression may result from the inability of antidepressants to normalize serotonergic transmission. Efficacy of therapeutic strategies enhancing serotonergic function such as potentiation of tricyclic antidepressants with lithium or fluoxetine as well as effectiveness of selective serotonin reuptake inhibitors in drug-resistant depression may support this hypothesis. Limbic-hypothalamic-pituitary-adrenal axis hyperactivity may be also an important factor of the persistence of depression, and so treatment with inhibitors of steroid biosynthesis may bring about readjustment of this axis and remission of depression in some cases of drug-resistant depression with hypercortisolemia. Another subtype of drug-resistant depression may be related to a dysfunction of hypothyroidism. Some evidence suggests also a relationship between drug resistance in depression and changes in the immune system. Research on biological mechanisms of drug-resistant depression may help clinicians to decide on the most appropriate treatment strategy in resistant depression as well as to shed light on the pathomechanism of depression.