Monoamine specificity of antidepressants and prediction of therapeutic response

The increase of the availability of monoamines on synapses has been one of the proposed modes of action of antidepressants (AD), but few drugs are specific for one neurotransmitter system, there is a time lag of the onset of action and some substances increasing the availability of neurotransmitters do not improve mood. The monoamine hypotheses of AD mode of action seems too simplistic and hypotheses as the beta receptor down regulation theory or the restored efficient regulation of the dysregulated neurotransmitter system theory are more plausible. Prediction of AD treatment response is an important clinical issue due to the time lag of the onset of action. The dubious theory of monoaminergic specificity has been applied to the prediction of AD response. The pretreatment MHPG levels have been used for prediction of treatment response. Results are contradictory and inconclusive probably due to many methodological problems of this approach. Other monoamine pretreatment levels (5-HIAA, HVA) have also been used, again with inconclusive results. Other approaches based loosely on monoaminergic specificity of various AD such as platelet monoamine oxidase inhibition, platelet imipramine binding and monoamine precursors availability have been used without success. Thus the biological markers may not be useful for a successful prediction of the AD treatment outcome at present.