WHY DO DIFFERENT ANTIDEPRESSANTS PRODUCE DIFFERENT SIDE EFFECTS?

Different antidepressants have varied side effects because they act differently in the central nervous system. Specifically, the side effects depend on how the medication interacts with the neurotransmitters released at the nerve synapse and with the receptors located on die nerve cell on the other side of the synaptic gap. Prozac and the other SSRI classical drugs including sertraline (Zoloft) and paroxetine (Paxil) selectively make certain that the neurotransmitter serotonin is not reabsorbed into the nerve, thus causing die brain serotonin levels to increase specifically. In contrast, and as I have already noted, older antidepressants block the uptake of the neurotransmitters norepinephrine and dopamine as well as serotonin. Effexor, the latest antidepressant to be FDA approved, increases both norepinephrine and serotonin levels, but has a mild side effect profile like the SSRIs.

Different mechanisms of action produce different side effects. The blockage of norepinephrine uptake, for instance, can produce tachycardia, tremor, and sexual dysfunction. Blocking dopamine (a process important to the antidepressants Asendin and Wellbutrin) can produce movement disorders and changes in the endocrine system. Blocking serotonin avoids those problems for the most part but can create instead gastric distress, insomnia, and anxiety.

Again, the side effects depend on which receptors (among them Alpha1, Dopamine D7, Histamine H1 and muscarinic receptors) are being blocked. Block the Histamine H1 receptors and you’re likely to see sedation and weight gain. Block the muscarinic receptors, and you can expect blurred vision, a dry mouth, constipation, and an impaired memory.

The more an antidepressant participates in these processes, the more side effects it is likely to produce. Thus, a tricyclic antidepressant such as armtriptyline (Elavil), which blocks the uptake of norepinephrine and serotonin as well as all four receptors listed above, is also associated with a much higher incidence of side effects than is Prozac, which is more limited, and thus more specific in its action.

Unlike older medications, Prozac blocks receptors only minimally, making it the first but not the only antidepressant for which this is true. Other SSRIs and Effexor also interfere very weakly with the receptors.

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