Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed class of antidepressants, primarily used to treat major depressive disorder and anxiety disorders. By blocking the reabsorption (reuptake) of serotonin into nerve cells, SSRIs increase serotonin levels in the brain, enhancing neurotransmitter signaling associated with mood regulation.

These medications are often first-line treatments due to their relatively favorable safety profile and lower incidence of side effects compared to older antidepressants. Beyond depression, SSRIs are effective for conditions like obsessive-compulsive disorder (OCD), panic disorder, and post-traumatic stress disorder (PTSD), and are sometimes prescribed off-label for chronic pain or premenstrual syndrome. Their therapeutic effects typically emerge over weeks, coinciding with gradual neuroadaptive changes in serotonin receptor activity

Selective serotonin reuptake inhibitors (SSRIs) primarily act by inhibiting the reuptake of serotonin (5-HT) into the presynaptic neuron. Normally, after serotonin is released into the synaptic cleft and transmits a signal to the postsynaptic neuron, about 90% of it is reabsorbed back into the presynaptic cell via serotonin transporters. SSRIs block this reuptake process, causing serotonin to remain longer in the synaptic cleft and thereby enhancing serotonergic neurotransmission.

This increased availability of serotonin in the synapse leads to greater stimulation of postsynaptic serotonin receptors. Over time, chronic SSRI treatment causes adaptive changes such as desensitization of presynaptic 5-HT1A autoreceptors in the dorsal raphe nucleus, which normally inhibit serotonin release. This desensitization results in increased serotonin release and further enhances serotonergic signaling. These neurochemical adaptations are believed to underlie the therapeutic effects of SSRIs, which typically take several weeks to manifest.

In addition to serotonin reuptake inhibition, some SSRIs have secondary actions, such as interaction with sigma-1 receptors, but these are less well understood and not considered the primary mechanism of antidepressant efficacy.

In summary, SSRIs increase synaptic serotonin by blocking its reuptake into presynaptic neurons, leading to enhanced serotonergic neurotransmission and subsequent neuroadaptive changes that contribute to their antidepressant and anxiolytic effects.

*Gastrointestinal issues* : Nausea, indigestion, diarrhea/constipation, flatulence

*Neurological symptoms:* Dizziness, headaches, drowsiness, insomnia

*Sexual dysfunction:* Reduced libido, erectile dysfunction, difficulty achieving orgasm

*Metabolic changes:* Weight gain or loss, dry mouth, excessive sweating

*Mood disturbances:* Agitation, anxiety, nervousness

Serotonin syndrome (rare but serious) involves confusion, muscle twitching, fever, and irregular heartbeat, often triggered by combining SSRIs with other serotonergic substances.

Side effects often improve within weeks, but sexual and weight-related issues may persist. Always consult a doctor before adjusting medication.