The Role of Anti-Depressants

Many people believe that anti-depressants increase the amount of neurotransmitters in the brain that helps to improve mood because there was a shortage of neurotransmitters to begin with. We're not actually sure if this is true. 

Anti depressants, particularly those such as Selective Serotonin Reuptake Inhibitors (SSRI) increase the amount of available serotonin in the brain which can decrease sensitivity and increase indifference. This means that things don't get under your skin so badly, which reduces irritability. Decreased sensitivity can also reduce anxiety, as you are less inclined to worry about stuff,  but there’s a spectrum of effect:

  • Reduced sensitivity (Usually desirable)

  • Increased indifference (sometimes helpful)

  • Emotional numbing (usually undesirable)

  • Zombified (undesirable)

Where you land in that spectrum depends on dose, duration, type of medication and your individual neurochemistry.

When sensitivity is reduced, things don’t feel so bad. Things don’t feel so irksome. Things don’t feel so difficult. The chaos is more tolerable. One feels less defeated. Irritability is improved and thereby relationships can improve. But when one is too numbed out, life feels dreary and joyless.

Other type of anti-depressants, called Selective Noradrenaline Reuptake Inhibitors (SNRI) work by increasing energy to help with motivation, However, if you have an agitated depression it can make things worse. 

In the video above, Dr Al explains this in more detail

Sometimes the drugs make things worse

Not all drugs are created equal. SSRIs work differently to SNRIs. While both work on mood, some SNRIs (like Effexor) can make anxiety worse, creating new problems. 


Dr Al explain how in this video. 

Weight gain and anti-depressants

Antidepressants such as SSRIs can cause weight gain in some people and weight loss in others. We explain how that works:

1. Weight loss is often about their effect of SSRIs on increasing indifference which may then reduce emotional eating.

2. Weight gain is with SSRIs is often about their effects on increasing someone's indifference in their food choices.

This clip explains how SSRI/SNRI affect sensitivity:


Other antidepressants like Tricyclic antidepressants and Mirtazapine can cause sedation because of their antihistamine effects on increasing appetite. Thats why some medications which cause drowsiness also cause increased appetite. SSRIs include aropax/paroxetine, zoloft/sertraline, prozac/fluoxetine, luvox/fluvoxamine, lexapro/escitalopram and cipramil/citalopram. The mostly interact with the SERT protein to increase serotonin residence in the synapse. They minimally affect the Histamine receptor.


Tricyclic antidepressants (TCA) include endep/amitriptyline, anafranil/clomipromine, dothiepin, nortriptyline etc. Generally have significant effect on Serotonin and noradrenaline reuptake (SERT and NET) as well as hitting specific serotonin receptors (e.g. clomipramine avidly binds 5-HT2c and 5-HT6). They bind Alpha1 and potently bind H1.


Mirtazepine (Avanza) is a tetracyclic antidepressant, also called a "noradrenergic and specific serotonergic antidepressant", but it's not very specific. While it has negligible effect on serotonin or noradrenaline reuptake (negligible SERT or NET effect) but strongly interacts with a number of other receptors including serotonergic 5-HT2C, 5-HT3, Alpha2A, Alpha2C and H1.