There are multiple lines of evidence that provide a compelling rationale for the “addition” of a dopamine component to a dual uptake inhibitor.
1) Both clinical and preclinical findings link anhedonia, a core symptom of depression, to deficits in mesocorticolimbic dopaminergic function.
2) Homovanillic acid concentrations are lower in the cerebrospinal fluid of depressed patients compared to normal individuals.
3) Imaging studies indicate a lower density of striatal dopamine transporters in depressed patients than in controls.
4) Clinical pharmacology, including the findings that dopamine reuptake blockers and dopamine agonists are antidepressant. Further adjunctive use of a dopamine agonist has been reported to augment the effect of “traditional” antidepressants in refractory patients.
5) In preclinical studies, an increased sensitivity of dopamine receptors is among the most consistent changes produced by chronic antidepressant treatments. These effects can be observed at the behavioral, cellular, and molecular levels. It has been hypothesized that the interval required to affect this increased sensitivity of dopamine receptors may contribute to the therapeutic lag common to biogenic-amine based antidepressants. These preclinical findings, together with the evidence that dopamine plays a key role in hedonic processes, indicate that a compound producing an immediate increase in synaptic dopamine concentrations will result in a more rapid onset of relief, shortening or eliminating the therapeutic lag.
Sorry, im too lazy to USFSE atm. Would anybody have the courtesy to explain wtf "Homovanillic acid concentrations" are please? And what there relevence is to dopamine. Regards
1) Both clinical and preclinical findings link anhedonia, a core symptom of depression, to deficits in mesocorticolimbic dopaminergic function.
2) Homovanillic acid concentrations are lower in the cerebrospinal fluid of depressed patients compared to normal individuals.
3) Imaging studies indicate a lower density of striatal dopamine transporters in depressed patients than in controls.
4) Clinical pharmacology, including the findings that dopamine reuptake blockers and dopamine agonists are antidepressant. Further adjunctive use of a dopamine agonist has been reported to augment the effect of “traditional” antidepressants in refractory patients.
5) In preclinical studies, an increased sensitivity of dopamine receptors is among the most consistent changes produced by chronic antidepressant treatments. These effects can be observed at the behavioral, cellular, and molecular levels. It has been hypothesized that the interval required to affect this increased sensitivity of dopamine receptors may contribute to the therapeutic lag common to biogenic-amine based antidepressants. These preclinical findings, together with the evidence that dopamine plays a key role in hedonic processes, indicate that a compound producing an immediate increase in synaptic dopamine concentrations will result in a more rapid onset of relief, shortening or eliminating the therapeutic lag.
Sorry, im too lazy to USFSE atm. Would anybody have the courtesy to explain wtf "Homovanillic acid concentrations" are please? And what there relevence is to dopamine. Regards
