If you’ve ever started medication for depression, anxiety, or another mental health condition, you’ve probably heard the frustrating phrase: “It might take a few weeks to start working.” But why? In a world where many other medications take minutes or even seconds to start working, why do these medications move so slowly?

In this post, we’ll explore the neuroscience behind this phenomenon and provide a more encouraging perspective on how these medications work.

Not Just a Chemical Imbalance

For decades, depression was oversimplified and hypothesized to be a “chemical imbalance,” particularly described as a lack of the brain chemical messengers (neurotransmitters) serotonin, and to a lesser extent, dopamine and norepinephrine. While these neurotransmitters do play a role, the full picture is far more complex.

When someone takes the most common class of antidepressant, a selective serotonin reuptake inhibitor (SSRI) such as Prozac, serotonin levels in the brain increase within hours. However, the antidepressant effect is usually delayed for several weeks, suggesting that downstream mechanisms, rather than immediate serotonin levels, are responsible for symptom improvement.

The Brain Needs Time to Adapt

Brain medications do not produce rapid changes in mood because they operate through long-term adaptive processes. The 3 main ways this is achieved are through:

1. Receptor desensitization:

When serotonin levels increase, the brain responds by gradually altering receptor sensitivity and density. For instance, perhaps seemingly counterintuitively, there is a type of serotonin receptor which detects the initial increase in serotonin and causes a response of less serotonin release, effectively cancelling the effects of the medication. However, over time, these receptors downregulate and stop suppressing the system (Blier & de Montigny, 1999).

2. Gene expression:

Many antidepressants influence which genes are activated (or inactivated) within neurons, altering the production of biomolecules involved in brain signalling (Duman & Aghajanian, 2012). Turning genes on and off is a slow but effective method of treating various conditions!

3. Neuroplasticity:

This is the brain’s ability to reorganize and form new connections, and it is essential for recovery. For example, antidepressants are thought to enhance plasticity through increased levels of brain-derived neurotrophic factor (BDNF), a molecule which promotes the growth and survival of neurons (Castrén & Hen, 2013). Once again, you may notice that reasonably, these structural and functional changes take time to accumulate.

It’s Not Just the Drug, It’s What the Brain Does With It

Putting aside all this information on how these medications work, I would like to think that it is beneficial to think of brain medications as setting the conditions for healing, not directly causing it. Elevated neurotransmitter levels may help improve sleep, energy, and emotional regulation. However, these changes, in turn, make it easier to engage in therapy, build routines, or reconnect socially. Over time, these reinforcing experiences become part of recovery.

What Can You Do While You Wait?

Though it is difficult, the waiting period can be productive:

• Some early improvements may include better sleep or energy. These signs can signal that the brain is beginning to respond. Continuing therapy during this time often leads to better outcomes, as the medication may enhance your ability to engage with therapeutic material.
• It is also critical to stay connected with your healthcare provider. Side effects, dosage adjustments, or the need to switch medications are all part of finding the right fit.
• Finally, support from family or friends can help buffer the frustration and loneliness of the waiting period.

References

Blier, P., & de Montigny, C. (1999). Serotonin and drug-induced therapeutic responses in major depression, obsessive–compulsive and panic disorders. Neuropsychopharmacology, 21(2), 91–98. https://doi.org/10.1016/S0893-133X(99)00036-6
Castrén, E., & Hen, R. (2013). Neuronal plasticity and antidepressant actions. Trends in Neurosciences, 36(5), 259–267. https://doi.org/10.1016/j.tins.2012.12.010
Duman, R. S., & Aghajanian, G. K. (2012). Synaptic dysfunction in depression: Potential therapeutic targets. Science, 338(6103), 68–72. https://doi.org/10.1126/science.1222939