Question

You are developing a new drug to treat Major Depressive Disorder (MDD). You know that patients do not show clinical signs of improvement when they begin taking an SSRI. Your goal is to create a drug that will result in immediate improvement for patients, and can be used with SSRIs initially, and discontinued once the SSRI becomes fully effective. a. Explain how SSRIs affect transmission at serotonin synapses, and why clinical effects are not seen immediately after a patient starts taking this medication. b. What part of neuronal transmission would you target with your drug? Why would this alleviate the issue with SSRIs?

Answer 1

a. SSRIs or Selective Serotonin Reuptake Inhibitors are used as pharmocologicla tretament for symptoms of depressive disorders. SSRIs act by increasing the level of the neurotransmitter serotonin which is associated with creating feeling so of pleasures and well being in the human body. SSRIs typically function by limiting the reuptake mechanism or reabsorption of the excess serotonin molecules into the presynaptic neuron, thereby increasing the level of serotonin in the synaptic cleft and this excess serotonin is then available to bind to the postsynaptic receptor of the next neuron and generate action potentials.

Although, SSRIs are the most common drug treatment for depression, there are many debates about its effectiveness in alleviating th esymptoms. Most researchers have shown that SSRI anti-depressants like paroxetine and fluoxetine offer no significant advantage over placebo in the treatment of short-term mild depression.

The initial changes in the serotonin reuptake and the increase in the functioning of the post-synaptic serotonin receptors, signal the pre-synaptic neuron to synthesize and release less serotonin. This leads to a reduction in the levels of serotonin available in the synapse, and this ultimately leads to a reduction of the post-synaptic neuron’s sensitivity to serotonin. Thus, this gradual and slow process of absorption and reuptake in the serotonergic neurons helps to explain why clinical effects of the SSRI drug cannot be measured after immediate consumption of the medication by patients.