Selective serotonin re-uptake inhibitors or serotonin-specific reuptake inhibitor (SSRIs) are a class of compounds typically used as antidepressants in the treatment of depression, anxiety disorders, and some personality disorders. SSRIs are believed to increase the extracellular level of the neurotransmitter serotonin by inhibiting its reuptake.
The most popular type of antidepressant today is the selective serotonin reuptake inhibitor (SSRI), such as Prozac, Zoloft, or Lexapro, introduced in 1987. SSRIs increase synapse concentrations of the neurotransmitter serotonin by binding to and thus blocking serotonin transporters – proteins which normally recycle serotonin molecules back into the neuron that released them.
In order to understand how SSRIs increase the amount of serotonin signaling in the brain, we must first understand how neurotransmitters like serotonin work. Neurotransmitters are important molecules in the brain that help nerve cells communicate with each other.
When the nerve cells of the brain produce less serotonin, there is decreased serotonin signaling. Serotonin signaling is decreased simply because there are not enough serotonin molecules to interact with the receptors on the cells... This mechanism is where SSRIs come in: they block parts of the presynaptic cell so that less serotonin can be recycled, allowing it to spend more time in the synapse to pass on the signal.
The relationship between serotonin levels and mood is by no means straightforward, nor well understood...
Nevertheless, major depression has been very consistently associated with dysfunction in the serotonin system: depressed subjects have fewer serotonin receptors and transporters (assessed using PET imaging) and decreased levels of tryptophan, a metabolic precursor to serotonin, in cerebrospinal fluid.
Contemporary neuroscience research has failed to confirm any serotonergic lesion in any mental disorder, and has in fact provided significant counterevidence to the explanation of a simple neurotransmitter deficiency. Modern neuroscience has instead shown that the brain is vastly complex and poorly understood.
Subsequent work with agents that targeted particular molecular systems, such as the selective serotonin reuptake inhibitors (SSRIs) and the serotonin and noradrenaline reuptake inhibitors (SNRIs), constituted another important step, insofar as the quality of trials and risk:benefit ratio further improved. Indeed, most current treatment guidelines emphasize that SSRIs and SNRIs are the first-line pharmacotherapy agents of choice in generalized anxiety disorder.
There are relatively few maintenance studies of SSRIs and SNRIs in the longer-term treatment of generalized anxiety disorder. However, such trials have consistently indicated that early discontinuation of these agents is associated with a high risk of relapse. Thus, most treatment guidelines suggest that after a response to pharmacotherapy is obtained, treatment should be continued for at least a year, and that discontinuation should be done gradually.
With successful treatment, extinction of recurrent anxiety symptoms is thought to require neuronal plasticity to take effect, similar to other forms of learning. Selective serotonin uptake inhibitors (SSRIs) and other treatment modalities are thought to facilitate these neurochemical and neuroanatomical enhancements, contributing to clinical effectiveness.
It is well documented in the medical literature that SSRIs are used during pregnancy. In general, most epidemiology studies show that adverse events in pregnant patients are similar to those in non-pregnant patients, and many studies find no major fetal abnormalities in excess of the 1-3% found in the general population.
SSRIs have demonstrated better efficacy and tolerability in the treatment of obsessive compulsive disorder (OCD). They have also been found to be effective in the treatment for social anxiety disorder both in reducing total levels of social anxiety and in improving overall clinical condition. The benefit of SSRIs in anorexia nervosa (AN) is apparently short-term unless medication is given in the context of nutritional or behavioral therapy.