The idea it gets worse before it gets better is applicable to certain antidepressants, according to a new paper published in the journal Trends in Cognitive Sciences.

Selective serotonin reuptake inhibitors (SSRIs) are among the most prescribed drugs (or overprescribed depending on who you talk to) for psychiatric disorders, including depression, anxiety, and eating disorders. They work to increase the brain’s level of serotonin — a chemical that work as a neurotransmitter and is responsible for maintaining mood balance — while inhibiting its reuptake (absorption) into the brain’s presynaptic cell. Chemical synapses are what allow neurons to form circuits within the central nervous system, as well as help connect to and control other systems of the body.

While serotonin can increase up to hours after an SSRI is taken, it takes two weeks before patients notice a subside in symptoms. It’s during this delay researchers from Otto-von-Guericke University believe depression gets worse before it gets better. Specifically, this delay stems from the different ways SSRI affects serotonin and another brain chemical called glutamate, which are both released from the serotonin neuron. Glutamate is the brain’s main excitatory neurotransmitter, and it’s important for neural communication, memory formation, learning and regulation.

Researchers culled data from existing studies and found when taking an SSRI, serotonin is immediately amplified while glutamate is suppressed. This balance is only restored after several days of drug treatment, Adrian Fischer, lead study author, said in a press release. Fischer added the serotonin component has been linked to motivation, while the glutamate component has been linked to pleasure and learning.

Put it another way: An SSRI immediately boosts motivation in depressed patients, while at the same time it’s hampering hedonic components (pleasure) of the reward system. The answer isn’t a higher dose of SSRIs either. Instead, researchers found this combination, whatever the dose, “could lead to the facilitation of suicidal thoughts or behavior in the early weeks of SSRI administration,” especially in young adults.

Pharmacology experts refer to this as a “paradoxical reaction.” Medical Daily previously reported this type of reaction is not uncommon among depression sufferers. One study was on par with the current study’s findings: 42 10- to 17-year-olds were compelled to self-harm after taking Prozac, four of which were hospitalized.

Fischer and his team concluded their paper “offers a framework of directly testable predictions for a better understanding and interpretation of studies employing SSRI challenges.” It also opens potentials for new drugs aiming to delay onset of SSRIs in depression. As always, consult with your doctor on the medication that is best suited for your particular symptoms; antidepressant, and otherwise prescription drugs, aren’t one size fits all. And if patients are prescribed medication, be sure to read up on possible side effects.  

Source: Fischer A, Jocham G, Ullsperger M. Dual serotonergic signals: a key to understanding paradoxical effects? Trends in Cognitive Sciences. 2014.