Treating depression in acute stage: biochemical and clinical aspects

The treatment of depression has advanced dramatically over the last 50 years: electroconvulsion, monoamine oxidase inhibitors (MAOIs), cyclic antidepressants - in chronological order. The amine theories have been giving guidance in the development of new antidepressant drugs and have thus been important in the selectivity of drugs acting, for example, primarily on 5-hydroxytryptamine (5-HT) reuptake. Drugs like citalopram, fluoxetine, fluvoxamine, and paroxetine are very selective in their 5-HT reuptake inhibition, so that in clinical practice they can be tested for the specific importance of this system in depression. Research on cerebrospinal fluid (CSF) has for many years been restricted to amine metabolites, but we have now been able to measure the parent neurotransmitters, thanks to international cooperation. CSF adrenaline was low, noradrenaline normal, and serotonin and dopamine increased in untreated depression. This calls for major revision of the amine theories. In addition, our animal studies have shown marked increase in CSF adrenaline after MAOIs, and long-term effect of citalopram on CSF noradrenaline. This indicates the need for enlargement of the number of transmitters in the elucidation of the biology of depression and its treatment, and that interactive counterregulations may lessen the initial selectivity of antidepressant drugs.