Selective serotonin reuptake inhibitors (SSRIs), used for managing depression, anxiety, and other mood disorders, increase serotonin in the brain by blocking its reuptake into nerve cells, allowing more serotonin to remain active in the synaptic space.
Although serotonin is often called the “happy hormone,” the notion that depression is caused by a chemical imbalance, specifically low serotonin levels, has been widely debunked. A comprehensive review by University College London found no clear evidence that serotonin levels or serotonin activity are responsible for depression.
Regardless, SSRIs are still widely prescribed today. Because nothing in the body occurs in isolation, their effects extend far beyond serotonin. SSRIs influence a web of interconnected systems, including hormones, neurotransmitters, and metabolic pathways.
Some noted side effects of SSRIs:
- Weight gain
- Insomnia or excessive drowsiness
- Sexual dysfunction (low libido, anorgasmia, erectile dysfunction)
- Emotional blunting or apathy
- Increased anxiety (especially during initial use)
- Digestive issues
- Restlessness or agitation
- Increased risk of bleeding (gastrointestinal bleeding)
- Muscle weakness or tremors
- Changes in appetite
- Withdrawal symptoms upon discontinuation (dizziness, irritability, etc.)
- Risk of serotonin syndrome (when combined with other serotonergic drugs)
- Potential for increased suicidal thoughts
Some things to consider about SSRIs.
- SSRIs can increase prolactin.
Prolactin, a hormone secreted by pituitary cells in the brain, is unique in that it is continuously produced unless actively suppressed by dopamine. Dopamine binds to receptors in the pituitary gland, effectively inhibiting prolactin secretion to maintain hormonal balance.
By increasing serotonin levels, SSRIs can interfere with dopamine’s ability to suppress prolactin. This occurs because serotonin and dopamine often work in opposition, and higher serotonin activity can reduce dopamine’s inhibitory effects, leading to elevated prolactin.
Elevated prolactin levels are linked to:
- Increased risk of cancers
- Hypothyroidism
- Headaches
- Weight gain
- Infertility
- Erectile dysfunction
- Bone loss
- Muscle loss
- Menstrual irregularities
- SSRIs can increase cortisol.
SSRIs can increase cortisol levels by affecting the hypothalamic-pituitary-adrenal (HPA) axis, which controls the body’s stress response. By boosting serotonin activity, SSRIs stimulate brain regions like the hypothalamus, triggering the release of corticotropin-releasing hormone (CRH). This leads to the pituitary gland releasing ACTH, which signals the adrenal glands to produce cortisol.
While this may help in the short term, consistently high cortisol levels can lead to serious hormone imbalances, disrupt immunity, and other health issues.
- SSRIs can cause weight gain.
In many animals serotonin rises to stimulate hibernation by slowing metabolism, numb their senses, and lower body temperature. For example, in bears, serotonin levels rise to decrease their metabolism by 75%, helping them conserve energy, avoid starvation, and survive the harsh conditions of winter. Similar anti-metabolic effects are found in humans with elevated serotonin. This can lead to increased fat storage and weight gain over time.
When we use any medical intervention, it’s important to understand that it can affect the body in more ways than we might anticipate. This doesn’t mean the intervention isn’t helpful for some—it’s simply a reminder that nothing in the body works in isolation.
Every system is interconnected, and altering one pathway, like serotonin, can create ripple effects throughout the body, influencing hormones, metabolism, mood, and more. There are no “magic bullets” in medicine, only tools that need to be used thoughtfully, with awareness of both their benefits and potential side effects.