The main treatment for depression is still antidepressant therapy, and the safety and tolerability problems of traditional drugs are more prominent. With the development of antidepressants, traditional tricyclic antidepressants (TCAs) and tetracyclic antidepressants have a tendency to be replaced by newer drugs. Although the newer drugs are more effective, safer, and have a lower risk of death from overdose, there are still safety issues that may lead to patient agitation, increased suicidal ideation, and drug interactions, in addition to the usual adverse effects during the acute phase of treatment. Even the same class of new antidepressants has its own characteristics, and clinicians should be familiar with the adverse effect characteristics of the selected drugs so that they can be used more purposefully according to the symptoms. In addition to discussing traditional drugs, this section focuses on the safety of new drugs. A common adverse drug reactions antidepressant adverse reactions are mainly due to the role of drugs on cholinergic receptors, histamine receptors, alpha receptors, etc. If the drug has a strong affinity for these receptors, it will produce the corresponding adverse reactions, especially in the acute phase of treatment, drug titration process adverse reactions may be more prominent, and sometimes patients stop the drug for this reason and lead to treatment failure. 1, the effect of drugs on the cardiovascular system: various antidepressants, TCAs have the most prominent effect on the cardiovascular system, which can lead to arrhythmias, tachycardia, postural hypotension, etc. TCAs are more cardiotoxic and even cause sudden cardiac death, so patients with significant risk of heart disease and patients aged > 50 years should have an electrocardiogram before taking the drug, and in the course of treatment (especially in the early stage of treatment) to follow up the ECG and observe the changes in cardiac conduction. Atrioventricular block may occur after administration of TCAs even in patients with normal ECGs prior to treatment. Because TCAs have similar effects to class Ia antiarrhythmics (quinidine, procainamide), they may have additional toxic effects on cardiac conduction when combined with other class I antiarrhythmics, and patients with ventricular arrhythmias on class I antiarrhythmics should be monitored more carefully when treated with TCAs. In patients with pre-existing heart disease, it is safer to use selective 5-hydroxytryptamine (5-HT) reuptake inhibitors (SSRIs), 5-HT and norepinephrine (NE) reuptake inhibitors (SNRIs), or bupropion. Monoamine oxidase inhibitors (MAOI) do not affect cardiac conduction, rhythm and contractile function, but can cause postural hypotension and must follow strict dietary restrictions or be prone to harmful drug interactions, so their use should be limited. 2. Anticholinergic effects: The anticholinergic effects of antidepressants are most obvious with TCAs. All TCAs act on M1 receptors and produce anticholinergic effects. Among the newer drugs, paroxetine is more obvious. The most common are dry mouth, constipation, urinary difficulties, exacerbation of narrow-angle glaucoma, cardiac arrhythmias, and sexual dysfunction. When used for central M1 receptors, it can impair cognitive function and even cause delirium, especially in elderly patients, those with concomitant somatic diseases or those taking other anticholinergic drugs. 3. Convulsions: TCAs, bupropion, and maprotiline can lower the convulsion threshold in relation to drug dose. overdose of TCAs can cause seizures, and some susceptible patients develop seizures even at therapeutic doses of TCAs (especially clomipramine and maprotiline). Avoidance of high doses of bupropion (>450 mg/d), avoidance of rapid dose increases, and use of extended-release dosage forms or split-dose immediate-release dosage forms may reduce the risk of seizures. Bupropion in patients with anorexia nervosa and bulimia nervosa may increase the risk of seizures. 4. Sedation: Patients with depression often have sleep disturbances in the acute phase. There is some value in selecting drugs with strong sedative-hypnotic effects for acute treatment, and patients often experience significant improvement in depression and anxiety when their sleep status improves. Of course, the sedative effect of drugs is also a common adverse effect that may significantly affect work efficiency. reduced arousal after H1 receptor blockade may affect the ability to drive and operate machinery and equipment, posing a potential risk, so the assessment should be strengthened before the use of drugs to select the appropriate drug, such as patients with a significant reduction in normal driving or work ability, the medication should be adjusted. 5, other adverse reactions: the blocking effect of new drugs such as SSRIs on 5-HT reuptake can cause agitation of a variety of postsynaptic 5-HT receptor subtypes and produce significant adverse reactions, such as common neurological effects such as headache, dizziness and insomnia, gastrointestinal reactions such as nausea, vomiting, diarrhea and sexual dysfunction, etc. Other adverse reactions such as hypoglycemia and hyponatremia have also been reported. Second, some special problems of acute treatment 1. Overdose and suicide: Before the widespread use of new antidepressants, suicide by overdose of antidepressants was relatively common in clinical practice. TCAs such as amitriptyline and promethazine have direct toxic effects on the heart, and the risk of death by overdose of these drugs is high, so the prescribed amount of drugs should be strictly controlled and drug management should be strengthened. With the widespread use of newer drugs, the risk of suicide due to drug overdose has been greatly reduced, and most newer antidepressants are less likely to cause death even in overdose, largely reducing the risk of suicide by overdose. The possibility of increased suicidal ideation at the beginning of newer medications, especially in children and adolescents, is still warned in black boxes in newer medication instructions. The mechanism of increased suicidal ideation due to drug treatment is complex and may be related to drug-induced agitation and anxiety, although no increase in suicide mortality was found in patients using drugs in clinical studies, it still deserves the attention of clinicians. 2-HT syndrome: Generally, it is common to use more than 2 kinds of 5-HT drugs at the same time. Patients can show nausea, vomiting, sweating, tachycardia, irritability and agitation, and in severe cases, high fever, respiratory distress and convulsions. There are neurological signs such as tremor, increased muscle tone, and hyperactive tendon reflexes. The clinical manifestations are similar to those of malignant syndrome. 5-HT syndrome, although uncommon, carries the risk of secondary renal failure, shock and death with serious consequences, and should be avoided as much as possible by combining antidepressants, paying attention to prevention, and prompt diagnosis and management.