I. Pathogenesis, depression is due to abnormalities in the biochemical aspects of the emotional neural circuitry of the brain, the specific performance is as follows A: emotional neural circuitry 1, the limbic system of the midbrain: amygdala, hippocampus, vomeronasal nucleus. 2, midbrain prefrontal cortex: prefrontal dorsomedial 3, others: hypothalamus, brainstem. B Biochemical 1. Biogenic amines: dopamine (D1 receptors D3 receptors), norepinephrine, 5-hydroxytryptamine 1A, 5-hydroxytryptamine 2A, 5hydroxytryptamine 7A, 2. Hypothalamic-pituitary-adrenal axis (adrenocorticotropic hormone), hypothalamic -Pituitary-thyroid axis (thyroid hormone) 3, other: glutamine, melatonin, prednisolone, neurotrophic brain factor. Among antidepressants, there is no blocking effect on dopamine transporter protein (except in high doses), whether it is on 5-hydroxytryptamine transporter protein (e.g. Prozac) or noradrenaline transporter protein (e.g. Repoxetine), or both (e.g. tricyclics, venlafaxine). Although bupropion is associated with blockade of all three transporter proteins, it occupies only a small number of dopamine transporter sites, so it remains to be investigated whether the antidepressant effects of this drug are dopamine-related. Mirtazapine has blocking effects on 5-HT2A and NE receptors on prominent anterior membrane 5-hydroxytryptamine and noradrenergic neurons and on prominent anterior membrane 5-HT2A receptors. Trazodone has a blocking effect on anterior membrane 5-HT transporter protein, a blocking effect on posterior membrane 5-HT2A, and an activating effect on 5-HT1A. Dapsone i.e. has a facilitative recycling effect on 5-HT transporter proteins. None of the above antidepressants act on dopamine D1 receptors. This is clearly a deficiency of the antidepressants currently used in clinical practice. However, the antidepressant effect of atypical antipsychotics differs from the mechanism of action of antidepressants. Clozapine, olanzapine, quetiapine and risperidone have blocking effects on 5-HT2A receptors on dopamine and norepinephrine neurons and on a2 receptors on norepinephrine and 5-hydroxytryptamine neurons, thus promoting the release of dopamine, norepinephrine and 5-hydroxytryptamine, and aripiprazole has blocking effects on 5-HT2A receptors on anterior membrane dopamine neurons, promoting the release of dopamine while activating posterior membrane D1 receptors. Ziprasidone blocks dopamine prominence at anterior membrane 5HT2A receptors, and sulpiride blocks anterior membrane D2 receptors and promotes dopamine release. These antipsychotics improve depression by promoting the release of 5-hydroxytryptamine, norepinephrine, and especially dopamine, thereby activating dorsomedial D1 receptors in the midbrain prefrontal cortex. This is different from antidepressants for depression. Three principles of using antipsychotic drugs for depression 1. Principle 1:Applicable to the ineffective of antidepressants In clinical practice, depression is common with 5-HT and NE deficiency, while antidepressant psychotropic drugs mainly improve depressive symptoms by antagonizing homologous receptors or heterologous receptors on pre-membrane dopamine neurons and promoting dopamine de-inhibitory release, which in turn activates D1 receptors in the medial prefrontal cortex of the midbrain. Therefore, antipsychotics cannot be used as first-line agents for the treatment of depression. At the same time, dopamine deficiency, mainly manifested as psychomotor block, diminished interest and decreased libido, so antipsychotic drugs are more suitable for delayed depression. 2, principle two: the combination of drugs because antipsychotic drugs act on the anterior membrane of its own receptors and heterologous receptor function is weak, the antidepressant effect is not very strong, so only as a potentiator, need to combine antidepressants to treat depression. 3, principle three: should not be used in large doses large doses of antipsychotic drugs on the hypothalamic funnel pathway D2 receptor antagonism is too strong, so that D2 receptor function is insufficient, causing prolactin deinhibition release, hyperprolactinemia inhibit gonadotropin release, reduce estrogen levels, resulting in monoamine oxidase deinhibition and increase, causing monoamine deficiency, and ultimately lead to pharmacogenic depression. Therefore, the use of high doses of antipsychotics for depression is not advisable. It must be clarified that tricyclic antidepressants also increase dopamine concentration to some extent, monoamine oxidase inhibitors largely increase dopamine in the brain, and amantadine enhances antidepressant efficacy by promoting dopamine release. Bromocriptine, a dopamine agonist, has been shown to be effective in refractory depression when combined with promethazine in small doses. All of the above drugs have therapeutic effects on depression due to dopamine deficiency.