Selective serotonin reuptake inhibitors

Selective Serotonin Reuptake inhibitors, or SSRIs, are mainly used to treat major depressive disorder. This disorder causes a persistent feeling of sadness and loss of interest in everyday activities. Even though the exact cause of depression is still unknown, there's some evidence that suggests it’s related to low levels of neurotransmitters like serotonin, norepinephrine, and dopamine. Selective serotonin reuptake inhibitors work by increasing the levels of serotonin to alleviate the symptoms of depression.

Now, serotonin is a neurotransmitter that helps regulate mood, emotions and feeding behavior. Presynaptic serotonergic neurons use the amino acid tryptophan to synthesize serotonin, which is also called 5-hydroxytryptamine, or 5-HT. Once synthesized, serotonin is stored in small vesicles within the presynaptic neuron. When an action potential reaches the presynaptic membrane, the vesicles fuse with the membrane and release the serotonin into the synaptic cleft. The serotonin drift around until they bind to 5HT2 receptors on the postsynaptic neuron, and cause it to fire off its own action potential. As long as there’s a high enough concentration of serotonin in the synaptic cleft, the postsynaptic neuron will continue to fire. On the presynaptic neuron, there are serotonin reuptake transporters or SERTs. This protein functions like a little trap door on the cell membrane; when a sodium, a chloride and a serotonin binds to the surface of this protein on the extracellular side, it flips over and sends the serotonin and the ions into the cell. When a potassium ion binds to the protein on the intracellular side, the trapdoor resets again, so more serotonin can attach. This way, serotonin is taken back into the presynaptic neuron, its concentration in the synaptic cleft decreases, and the postsynaptic neuron stops firing.

Now, in conditions such as major depressive disorder, where there’s a low serotonin level, selective serotonin reuptake inhibitors are the first-line therapy due to their milder side effects. Common medications in this class include escitalopram, fluoxetine, fluvoxamine, sertraline, paroxetine, and citalopram. They bind to serotonin reuptake transporters and inhibits them, which increases the serotonin level within the synaptic cleft. It's important to note that these medications are slow-acting because it takes time for serotonin to accumulate within the synaptic cleft. Because of this, it usually takes 4-6 weeks before improvements can be seen. Other conditions that can be treated with SSRIs include chronic anxiety, post traumatic stress disorder, or PTSD, obsessive-compulsive disorder, or OCD, and eating disorders like bulimia.

Common side effects of SSRIs include anxiety, insomnia or drowsiness, GI distress, sexual dysfunction, and syndrome of inappropriate antidiuretic hormone or SIADH. The most dangerous, however, are suicidal ideations, especially in individuals under 25, and serotonin syndrome. Serotonin syndrome is a life threatening condition caused by serotonin accumulation which causes overstimulation of the nervous system. This syndrome is characterized by skin flushing, hyperthermia, agitation, muscle rigidity, seizure, and coma. It usually occurs in individuals treated with a combination of SSRIs and other antidepressants that increase serotonin level, such as monoamine oxidase inhibitors.