Published On: Fri, Oct 27th, 2023

Understanding the Time Delay in Antidepressant Effects

Understanding the Time Delay in Antidepressant Effects
Understanding the Time Delay in Antidepressant Effects

Managing clinical depression, a highly treatable mood disorder, and the mechanisms of antidepressant drugs, particularly SSRIs (selective serotonin reuptake inhibitors), have long puzzled researchers. While SSRIs aim to enhance serotonin neurotransmission to boost neuronal communication, the enduring transformation of a person’s mood remains a complex puzzle.

Interestingly, SSRIs don’t always yield immediate results. It’s estimated that over 30 percent of patients do not respond positively to this class of antidepressants. Moreover, the mood-altering effects of SSRIs typically take several weeks to manifest, despite their rapid chemical actions, which increase serotonin levels by inhibiting a key “transporter” protein. Gitte Knudsen, a neurobiologist and neurologist at the University of Copenhagen, Denmark, notes, “You take an antibiotic, and it starts working immediately. That’s not been the case with SSRIs.”

Researchers have proposed various theories to explain this delay, with one of the most intriguing theories centering on neuroplasticity—the brain’s capacity to adapt physically over time. While adult brains seldom generate new neurons, they do form new interconnections among existing ones, known as synapses. Essentially, they engage in rewiring, a process akin to what happens when we exercise or learn. Knudsen believes that this rewiring process could help individuals break free from the cycle of negative rumination, a characteristic feature of depressive episodes.

Knudsen’s research suggests that SSRIs may owe their effectiveness, at least in part, to their ability to enhance neuroplasticity. In a recent study published in Molecular Psychiatry this month, her team explored this theory using a specialized PET scan technology. They enlisted 32 participants who took the SSRI escitalopram (also known as Lexapro) or a placebo for a month. Subsequently, participants underwent PET scans with radioactive tracers to monitor the formation of new synapses in the brain.

The results revealed that the longer individuals were on the antidepressant before their brain scan, the more synaptic signals were detected—a potential indicator of increased neural connections. Knudsen remarks, “This is one of the initial pieces of evidence suggesting that these drugs indeed require time to work, and they achieve their effects by enhancing synaptic connections between nerve cells.”

This finding implies that SSRIs enhance neuroplasticity during the initial weeks or months of treatment, contributing to their therapeutic effects and explaining the delay in the onset of improved mood. Jonathan Roiser, a cognitive neuroscientist at University College London, comments on this paradox, stating that although the drugs’ chemical actions are rapid, “there needed to be this extra bit of explanation about why the mood change does not happen immediately.”

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