Antidepressant drugs, 5HT-2C receptor antagonist, exerts the same disinhibition effect as agomelatine , thereby increasing the concentration of dopamine and norepinephrine in the brain, and its effect of blocking norepinephrine recovery ranks second in SSRIS (paroxetine>fluoxetine>sertraline>fluvoxamine>escitalopram). This leads to the fact that although fluoxetine is a single-channel serotonin drug, it can actually increase the content of norepinephrine and play a role in invigorating the spirit. It is suitable for blockade depression, but it will be prone to anxiety, reduce appetite, insomnia, and lose weight. The blockade of 5HT2C receptors can also play a role in treating bulimia and anorexia.
Sertraline :
In addition to the normal function of SSRIs to increase serotonin content, sertraline also has a special effect on increasing dopamine. Its effect of inhibiting dopamine recycling is the highest among SSRIs (sertraline>paroxetine>fluoxetine>fluvoxamine>escitalopram). The increase of prefrontal dopamine will improve people’s emotions, cognition, and interests. The disadvantage is that it will make people feel nauseous, prone to diarrhea, and in severe cases, hallucinations will occur. Next, I want to talk about the biggest problem of sertraline. It antagonizes sigma 1 receptors. Sigma receptors can be understood as IQ receptors. Stimulating it increases IQ, while antagonizing it damages cognition. Sertraline is the drug I least recommend. Although it can increase dopamine, the effect is minimal. In SSRIS, serotonin always has the upper hand.
The increase of serotonin will stimulate 5HT-2A receptors to inhibit dopamine norepinephrine. In addition, its dopamine protein binding rate is high, which greatly affects the effect of DA reuptake inhibition. So thinking of taking sertraline to promote cognition with this dopamine is a step in the wrong direction. In the antidepressant category, it is almost the most cognitively damaging drug. There is an error in the “Clinical Manual of Psychiatry” written by Yu Dongshan, where antagonism σ is written as excitement σ. Be careful to distinguish.
Escitalopram :
Combining the above two rankings of SSRIs in brackets about the inhibition of dopamine norepinephrine recycling, it can be found that citalopram affects almost nothing except serotonin, which leads to the least side effects and is the purest SSRI. The most expensive drug now, vortioxetine, is an upgraded version of citalopram.
Paroxetine :
In contrast to fluoxetine, it is suitable for anxiety-related depression and increases the ranking of serotonin (paroxetine>escitalopram>sertraline>fluoxetine>fluvoxamine). It is more calming and has anticholinergic effects, which manifest as dry mouth, anorexia, cognitive impairment (the actual probability of cognitive impairment caused by paroxetine is not high, because depression and anxiety themselves can damage cognition. Paroxetine has a high efficacy in treating depression and restores cognition to a certain extent), constipation, etc.
Fluvoxamine :
In contrast to sertraline, fluvoxamine stimulates sigma 1 receptors and exerts the same nootropic effect as methylphenylpiracetam. It is also the antidepressant with the lowest probability of cognitive impairment. The sigma 1 stimulatory effect also gives it a special way to fight obsessive-compulsive disorder, which is different from the traditional anti-obsessive-compulsive disorder by increasing serotonin and norepinephrine. It has a certain hypnotic and sedative effect, and can also treat insomnia when taken at night, but it should be noted that its peak effect time is 5 hours. The ranking of cognitive impairment (mirtazapine 35%> sertraline 16%> fluoxetine 13%> venlafaxine 9%> citalopram 5.5%> paroxetine 4.9%> fluvoxamine 1.2%) data comes from a foreign survey paper, which is for reference only, because there are too many factors that affect cognition.
SNRIS
What patients need to recover is not only depression, but also social function, and norepinephrine and dopamine are equally indispensable.
Venlafaxine :
Although all SNRIs are dual-channel drugs, because norepinephrine and dopamine share a common transporter, SNRIs are actually triple-channel. They also have a significant effect on dopamine. Venlafaxine increases serotonin and norepinephrine in a ratio of 30:1. SNRs are more helpful for blockade depression and make people more energetic, but only about 150 mg of venlafaxine can play the role of the other two channels. Therefore, two upgraded products were born, toludivenlafaxine and desvenlafaxine succinate (also called desvenlafaxine, a metabolite of venlafaxine), which can more strongly block the common transporter of norepinephrine and dopamine, thereby increasing these two neurotransmitters.
Duloxetine :
This is one of the drugs I recommend most. It increases the ratio of serotonin and norepinephrine to about 10:1. A small dose can achieve the same effect as toruloxetine and desvenlafaxine succinate, and its price is quite cheap compared to toruloxetine, only 0.5 cents per pill. It is better in treating anxiety and somatic symptoms. The disadvantages are high nausea rate, inability to drink alcohol (worsening alcoholic liver damage), sweating, and constipation.
Milnacipran :
Increases the ratio of serotonin to norepinephrine to 1:1, has a stronger psychoactive effect, and causes irritability and anxiety, so it is not used to treat anxiety disorders, but can treat adult attention disorders, negative symptoms of schizophrenia, and obsessive-compulsive disorder. Its effect in treating depression is roughly equivalent to that of venlafaxine and duloxetine.
Specificity
Mirtazapine :
Antagonizes 5-HT2A, 5-HT2C, and 5-HT3 receptors, and α2 autoreceptors to release NE and 5-HT from inhibition. It also has an antihistamine H1 receptor, making people sleepy and treating insomnia. 15-22.5 mg is the best dose for sleep. It is a mild anticholinergic. The antagonism of 5ht2c, 5ht3, and H1 will greatly promote appetite and weight gain.
Trazodone :
Blocks 5ht2a receptors and alpha 1 receptors (reduces stress response) at 1mg and above, blocks H1 receptors at 50mg (can be used as a hypnotic), blocks alpha 2 receptors at 100mg (same as mirtazapine), antagonizes serotonin transporters at 100mg to 300mg, increases serotonin content, and then antagonizes 2c receptors, dopamine D2 receptors, etc. The highest dose is 400mg, and it is not recommended to use more than 300mg
Bupropion :
It does not affect the serotonin content, but only affects norepinephrine and dopamine, with a ratio of 1.3:1 . I personally recommend it as an antidepressant enhancer to improve social function. It is also a second-line drug for the treatment of attention disorders, with the lowest rate of transition to mania. It is mostly used to treat bipolar disorder, sexual dysfunction, and PSSD.
Vortioxetine :
Stimulates 5HT1a receptors . Long-term low-dose stimulation can desensitize 5ht1a receptors, thereby increasing the concentration of serotonin to accelerate the onset of action and enhance the effect. It can also enhance the function of dopamine in the raphe nucleus-prefrontal system, improve the cognitive function of patients with negative symptoms of depression and schizophrenia, and enhance sexual function, which has the same effect as buspirone. Antagonizes 5ht-3 receptors . Ondansetron is an antiemetic drug, and its principle is also 5ht-3 receptor antagonism. The purpose of vortioxetine antagonizing this receptor is to prevent nausea and vomiting caused by drugs, and antagonizing 5-HT3 receptors can inhibit GABA function and enhance dopamine release, which is conducive to cognitive improvement. So basically vortioxetine is citalopram + buspirone + ondansetron or mirtazapine + buspirone.
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