Etiology Antidepressants are currently the most dominant form of depression treatment in China, and are also more economical and convenient. There is a wide range of antidepressants, and although the mechanism of action varies, each drug is effective in only about 70% of patients, and some of them are ineffective. Some of these patients are “refractory to depression”. There are also patients who have achieved clinical recovery on antidepressant therapy, but who have relapsed during maintenance treatment without any change in medication dose or psychosocial stressors. This phenomenon is called “rapid pharmacoresistance to antidepressants”, or tachyphylaxis. The cause of the lapse phenomenon is not well understood. This phenomenon is similar to the development of resistance of bacteria to antibiotics. Foreign studies have found that the incidence of antidepressant resistance in patients with depression is about 25%, usually occurring around the 31st week of maintenance treatment. Allopathic First of all, do not change medication frequently The onset of action of antidepressants is usually 2 to 4 weeks, so choose a drug treatment and use it for at least 4 weeks before judging it ineffective. If depressive symptoms are not relieved after a sufficient therapeutic dose and a sufficient course of treatment (generally occurring in about 30% of cases), a change of medication should be considered. Attention should be paid to the choice of antidepressants with different mechanisms of action and different types of drug structure, which may often appear to be effective again. For example, if certain patients are not treated with selective 5-hydroxytryptamine reuptake inhibitors, newer antidepressants such as venlafaxine, trazodone, mirtazapine, or monoamine oxidase inhibitors such as morclobemide may be considered. Combination therapy can be attempted in refractory depression that has failed after a full course of treatment with more than two mechanisms of action, and in patients who develop a rapid drug resistance response to antidepressants, including the combination of two antidepressants, antidepressants and emotion stabilizers (e.g., lithium salts), and antidepressants and atypical antipsychotics. Recent studies have shown that the combination of antidepressants such as fluoxetine with newer antipsychotics such as olanzapine and risperidone has been shown to be more effective and safe in the treatment of depression. It is important to emphasize here that selective 5-hydroxytryptamine reuptake inhibitors and monoamine oxidase inhibitors should not be combined, otherwise serious adverse effects, i.e. 5-hydroxytryptamine syndrome, may occur, which may lead to death in severe cases. Electroconvulsive therapy is also available for patients with particularly severe symptoms of refractory depression, especially for those with severe suicidal ideation and a history of suicidal behavior. The most commonly used electroconvulsive therapy is the modified non-convulsive electroconvulsive therapy, which uses anesthesia and muscle relaxants during the treatment, so it is relatively safe and painless for the patient. The efficacy of electroconvulsive therapy is determined, and relevant foreign studies show that the efficiency of electroconvulsive therapy for refractory depression can reach about 70%. Other treatment psychotherapy is also an effective method of depression treatment, which can be used to treat depression by changing the irrational beliefs of depressed patients and enabling them to treat themselves objectively. Research data also shows that psychotherapy combined with antidepressant treatment can improve the efficacy of antidepressants. Reminder: Do not stop taking your medication indiscriminately. Depression is a mental illness that is prone to relapse. After three months of effective medication, the symptoms usually disappear and social functioning is restored, reaching the standard of clinical recovery. However, if medication is discontinued at this time, many patients experience recurrent symptoms. Studies have found that the relapse rate in patients not on maintenance medication is up to 60% or more within 1 year. Therefore, patients with first-episode depression who achieve clinical recovery should continue to consolidate treatment for more than 6 months, while patients with relapse should maintain treatment for more than 1 year or even longer, and patients with multiple relapses may need to take medication for life. Patients should have regular outpatient follow-ups during maintenance treatment to adjust their medication. Generally speaking, if patients can take the initiative to seek medical treatment, family and social support, depression patients can get early and clear diagnosis, timely treatment and sufficient dose, full course of antidepressant treatment, generally can achieve better results. For patients with “refractory” depression or those who have failed to respond to antidepressant medication, systematic re-evaluation should be actively conducted to assess the appropriateness of the type, dose, duration and compliance of medication, and after the above treatment measures are adequately dealt with, they can often achieve With the above treatment measures, a more satisfactory outcome is often achieved.